Presentation at the Fourth International Conference of Advanced Cardiac Sciences, 2012, by Carlos Monteiro. An overview about the new pathophysiological and therapeutic concepts of the myogenic theory of myocardial infarction, developed by Quintiliano H. de Mesquita in 1972, by reviewing the following topics: Coronary thrombosis: cause or consequence of myocardial infarction?; Introduction and fundamentals; Mechanism and sequence of events; Stress and acute myocardial syndromes; The benefits of cardiotonic drugs in patients with stable heart disease, unstable angina and acute myocardial infarction; The role of the cardiotonic completing the effects of coronary collateral circulation; The cardiotonic sympatholytic properties; Endogenous cardiotonic steroids; etc..

1. TheThe MyogenicMyogenic TheoryTheory
ofof MyocardialMyocardial InfarctionInfarction
Fourth International Conference on
Advanced Cardiac Sciences
KingKing ofof OrgansOrgans, 2012, 2012
KingdomKingdom ofof SaudiSaudi ArabiaArabia
Carlos MonteiroCarlos Monteiro
InfarctInfarct CombatCombat ProjectProject
http://infarctcombat.orghttp://infarctcombat.org

2.  ""The coronary patientThe coronary patient does not die from coronary disease, hedoes not die from coronary disease, he
dies from myocardial disease.“*dies from myocardial disease.“*
 *Burch GE and col., Ischemic*Burch GE and col., Ischemic cardiomyopathycardiomyopathy, Am Heart J. 1972 Mar;83(3):340, Am Heart J. 1972 Mar;83(3):340--5050

3.  It isIt is importantimportant toto notenote thethe coronarycoronary thrombosisthrombosis theorytheory,, introducedintroduced byby
James BryanJames Bryan HerrickHerrick, in 1912,, in 1912, remainsremains sufferingsuffering seriousserious doubtdoubt onon itsits
causecause andand effecteffect relationshiprelationship..
 ThisThis hashas ledled FriedbergFriedberg andand HornHorn toto suggestsuggest in 1939in 1939 thatthat thethe termterm coronarycoronary
thrombosisthrombosis shouldshould bebe abandonedabandoned in favorin favor ofof thethe moremore genericgeneric oneone ofof
acuteacute myocardialmyocardial infarctioninfarction. In. In theirtheir paperpaper theythey saysay thatthat ““thethe clinicalclinical andand
electrocardiographicelectrocardiographic featuresfeatures ofof coronarycoronary thrombosisthrombosis maymay bebe observedobserved inin
patientspatients inin whomwhom aa coronarycoronary arteryartery thrombusthrombus isis subsequentlysubsequently notnot foundfound
atat necropsynecropsy asas hashas beenbeen notednoted byby LibmanLibman,, ObendorferObendorfer,, BuchnerBuchner,,
HamburgerHamburger andand SaphirSaphir, Dietrich, Levy, Dietrich, Levy andand BruennBruenn andand othersothers.”.”
 AfterAfter thatthat timetime manymany otherother investigatorsinvestigators camecame toto thethe samesame conclusionconclusion asas
wewe willwill seesee followingfollowing......
 ** FriedbergFriedberg CKCK andand Horn H.Horn H. AcuteAcute myocardialmyocardial infarctioninfarction notnot duedue toto coronarycoronary
arteryartery occlusionocclusion. J.. J. AmAm MedMed AssocAssoc 1939;112(17):1939;112(17):16751675--16791679

4.  (1941) Hermann(1941) Hermann andand colleaguescolleagues foundfound thethe thromboticthrombotic occlusionocclusion couldcould
occuroccur withoutwithout infarctioninfarction whenwhen thethe collateralcollateral circulationcirculation appearedappeared
adequateadequate andand ifif anan infarctinfarct hashas happenedhappened, it, it couldcould bebe attributedattributed toto anan
occlusiveocclusive thrombusthrombus atat aa criticalcritical locationlocation inin thethe coronarycoronary treetree..
 (Angina(Angina PectorisPectoris,, coronarycoronary failurefailure andand acuteacute myocardialmyocardial infarctioninfarction: The role: The role ofof
coronarycoronary occlusionsocclusions andand collateralcollateral circulationcirculation, JAMA 1941;116(2):91, JAMA 1941;116(2):91--97;97; MultipleMultiple
freshfresh coronarycoronary occlusionsocclusions inin patientspatients withwith antecedentantecedent shockshock,, ArchArch InternIntern MedMed
1941;68(2):1811941;68(2):181--198; Experimental198; Experimental studiesstudies onon thethe effecteffect ofof temporarytemporary occlusionocclusion ofof
coronarycoronary arteriesarteries; The; The productionproduction ofof myocardialmyocardial infarctioninfarction, American Heart, American Heart
JournalJournal 1941 V22;I31941 V22;I3 --374374--389)389)
 (1951) Miller(1951) Miller andand colleaguescolleagues pointedpointed outout thatthat subendocardialsubendocardial infarctsinfarcts
werewere rarelyrarely associatedassociated withwith coronarycoronary thrombithrombi..
 ((MyocardialMyocardial infarctioninfarction withwith andand withoutwithout acuteacute coronarycoronary occlusionocclusion: A: A pathologicpathologic
studystudy. AMA. AMA ArchArch InternIntern MedMed 1951;88(5):5971951;88(5):597--604)604)

5.  (1960) Spain(1960) Spain andand BradessBradess foundfound completecomplete coronarycoronary obstructionobstruction ofof
atheroscleroticatherosclerotic naturenature,, representingrepresenting aroundaround ofof 75%75% ofof thethe casescases andand recentrecent
coronarycoronary thrombosisthrombosis inin justjust 25%25% ofof thethe autopsiedautopsied cases.cases. AlsoAlso,, theythey havehave
observedobserved crescentcrescent incidenceincidence ofof coronarycoronary thrombosisthrombosis withwith thethe crescentcrescent
durationduration ofof survivalsurvival afterafter thethe myocardialmyocardial infarctioninfarction.. LessLess thanthan a houra hour withwith
16%16% ofof thrombosisthrombosis,, betweenbetween 11 andand 24 hours24 hours withwith 37%37% andand in morein more thanthan
24 hours24 hours withwith 52%52% ofof coronarycoronary thrombosisthrombosis*.*.
 (Spain, DM(Spain, DM andand BradessBradess VA. TheVA. The relationshiprelationship ofof coronarycoronary thrombosisthrombosis toto coronarycoronary
atherosclerosisatherosclerosis andand ischemicischemic heartheart diseasedisease –– aa necropsynecropsy studystudy coveringcovering aa periodperiod ofof
2525 yearsyears,, AmAm JJ MedMed SciSci, 240:7, 240:7--1, 1960; Spain DM1, 1960; Spain DM andand BradessBradess VA.VA. FrequencyFrequency ofof
coronarycoronary thrombosisthrombosis relatedrelated toto durationduration ofof survivalsurvival fromfrom onsetonset ofof acuteacute fatalfatal
episodesepisodes ofof myocardialmyocardial ischemiaischemia.. CirculationCirculation, 22:816, 1960), 22:816, 1960)

6.  (1970)(1970) HellstromHellstrom demonstrateddemonstrated experimentallyexperimentally thethe coronarycoronary thrombosisthrombosis
secondarysecondary toto acuteacute myocardialmyocardial infarctioninfarction causedcaused byby ligatureligature ofof thethe
coronarycoronary arteryartery..
 ((HellstromHellstrom, HR., HR. MyocardialMyocardial infarctioninfarction as a causeas a cause ofof coronarycoronary thrombosisthrombosis..
CirculationCirculation, 42,, 42, SupplSuppl. III); 165, 1970). III); 165, 1970)
 (1972) William Roberts(1972) William Roberts suggestedsuggested thatthat thethe coronarycoronary arterialarterial thrombithrombi areare
consequencesconsequences ratherrather thanthan causescauses ofof acuteacute myocardialmyocardial infarctioninfarction. In. In hishis
studystudy iinvolvingnvolving 107107 patientspatients whowho werewere submittedsubmitted toto necropsynecropsy hehe foundfound
thatthat onlyonly 54%54% ofof thosethose withwith aa transmuraltransmural infarctioninfarction,, andand onlyonly 10%10% ofof thosethose
withwith subendocardialsubendocardial necrosisnecrosis,, hadhad aa thrombusthrombus inin thethe infarctinfarct relatedrelated
arteryartery..
 ((FrequencyFrequency of coronary thrombosis related to duration of survivalof coronary thrombosis related to duration of survival fromfrom onset ofonset of
acute fatal episodes of myocardial ischemia, Circulation,acute fatal episodes of myocardial ischemia, Circulation, 22:816, 196022:816, 1960;; RobertsRoberts,,
W.CW.C.:;.:; Coronary arteries in fatal acute myocardial infarction,Coronary arteries in fatal acute myocardial infarction, Circulation,42:215Circulation,42:215,,
1972, Roberts W. C1972, Roberts W. C.).)

7.  (1980)(1980) DeWoodDeWood and colleagues demonstrated the prevalence of totaland colleagues demonstrated the prevalence of total
coronary occlusion during the early hours ofcoronary occlusion during the early hours of transmuraltransmural infarction byinfarction by
means of coronary arteriography. Their results were accepted by themeans of coronary arteriography. Their results were accepted by the
cardiology community as the definitive clinical evidence about the causalcardiology community as the definitive clinical evidence about the causal
role of thrombosis in acute myocardial infarction.role of thrombosis in acute myocardial infarction.
 ((DeWoodDeWood MA, Spores J,MA, Spores J, NotskeNotske R et al. Prevalence of total coronaryR et al. Prevalence of total coronary oclusionoclusion
during the early hours ofduring the early hours of transmuraltransmural myocardial infarction. Nmyocardial infarction. N EnglEngl J MedJ Med
1980;303:8971980;303:897--902)902)
 (1996)(1996) QuintilianoQuintiliano H. deH. de MesquitaMesquita pointed out that the interpretationpointed out that the interpretation
given bygiven by DeWoodDeWood about the angiographic image, suggestive ofabout the angiographic image, suggestive of
intracoronary thrombus, do not correspond to the absolute realityintracoronary thrombus, do not correspond to the absolute reality
whether it represents a true thrombus or just aggregated platelets that arewhether it represents a true thrombus or just aggregated platelets that are
precocious, unstable or reversible commonly registered in the first hoursprecocious, unstable or reversible commonly registered in the first hours
of unstable angina and in the course of the acute myocardial infarction.of unstable angina and in the course of the acute myocardial infarction.
 (Book:(Book: RemédioRemédio boicotadoboicotado substituisubstitui cirurgiacirurgia dede ponteponte dede safenasafena,, CompsetCompset,,, 1996), 1996)

8.  ((2005) Giorgio2005) Giorgio BaroldiBaroldi andand colleagues,colleagues, discussing the findings fromdiscussing the findings from
DeWoodDeWood,, told that the first main question is how many of the 87%told that the first main question is how many of the 87%
cineangiocineangio occlusion areocclusion are pseudopseudo--occlusionocclusion and whether the "layered"and whether the "layered"
thrombus recovered at bypassthrombus recovered at bypass surgerysurgery was a true thrombus or awas a true thrombus or a
coagulum which frequently show a layering of blood elements not seen incoagulum which frequently show a layering of blood elements not seen in
thrombus formation. Also saying that "Red" thrombus, namely athrombus formation. Also saying that "Red" thrombus, namely a
coagulum, is frequently and erroneously considered as thrombuscoagulum, is frequently and erroneously considered as thrombus..
 In another paper from the same year they sayIn another paper from the same year they say thatthat thethe frequency of anfrequency of an
occlusive thrombus is significantly higher in theocclusive thrombus is significantly higher in the largest infarctslargest infarcts
supportingsupporting its secondaryits secondary formation.formation.
 ((BaroldiBaroldi G,G, BigiBigi R,R, CortigianiCortigiani L: Ultrasound imaging versusL: Ultrasound imaging versus morphopathologymorphopathology inin
cardiovascular diseases: coronary collateralcardiovascular diseases: coronary collateral and myocardialand myocardial ischemia.ischemia. CardiovascCardiovasc
Ultrasound 2005, 3:6; GiorgioUltrasound 2005, 3:6; Giorgio BaroldiBaroldi, Riccardo, Riccardo BigiBigi andand LauroLauro CortigianiCortigiani..
Ultrasound imaging versusUltrasound imaging versus morphopathologymorphopathology in cardiovascularin cardiovascular diseases.diseases.
Myocardial cell damage. Cardiovascular Ultrasound 3:32Myocardial cell damage. Cardiovascular Ultrasound 3:32., 2005)., 2005)

9.  (2001(2001) In a significant number of cases) In a significant number of cases angioscopicangioscopic examination continuesexamination continues
to find thrombus onto find thrombus on the presumedthe presumed culprit lesion, at 6 months afterculprit lesion, at 6 months after
myocardialmyocardial infarction.infarction.
 ((YasunoriYasunori Ueda, MasanoriUeda, Masanori AsakuraAsakura, et al. 2001. The healing process of infarct, et al. 2001. The healing process of infarct--
related plaque: Insights fromrelated plaque: Insights from 18 months18 months of serialof serial angioscopicangioscopic followfollow--up. Amup. Am CollColl
CardiolCardiol, 38:1916, 38:1916--19221922.).)
 ((1998) Murakami and colleagues from Japan using intracoronary1998) Murakami and colleagues from Japan using intracoronary
catheters to aspirate occlusive tissues, performed during the acutecatheters to aspirate occlusive tissues, performed during the acute
myocardialmyocardial infarction,infarction, have confirmed the pathological findings thathave confirmed the pathological findings that
intracoronary thrombus is absent in a substantial number of patientsintracoronary thrombus is absent in a substantial number of patients
indicating it contributes little to the pathogenesis of averageindicating it contributes little to the pathogenesis of average acuteacute
myocardial infarction.myocardial infarction.
 (Murakami(Murakami T. Intracoronary aspirationT. Intracoronary aspiration thrombectomythrombectomy for acute myocardialfor acute myocardial
infarction, Am. J Cardiology 1998 Oct 1;82(7):839infarction, Am. J Cardiology 1998 Oct 1;82(7):839--44)44)

10.  (2005(2005)) RittersmaRittersma and colleaguesand colleagues examined retrieved thrombus materialexamined retrieved thrombus material
aspirated using the percutaneousaspirated using the percutaneous thrombectomythrombectomy catheter in 211 patientscatheter in 211 patients
undergoingundergoing primaryprimary ppercutaneous coronary interventionercutaneous coronary intervention within six hourswithin six hours
of symptom onset. They then established,of symptom onset. They then established, byby histological indicators, thehistological indicators, the
age of the aspirated thrombi. Theage of the aspirated thrombi. The researchersresearchers found thrombus infound thrombus in 199 of199 of
the 211the 211 patients, of whom fresh thrombus waspatients, of whom fresh thrombus was identifiedidentified in just underin just under
half. By contrast, 51% of patient samples containedhalf. By contrast, 51% of patient samples contained thrombusthrombus that hadthat had
lytic or organized changes suggesting that it had originatedlytic or organized changes suggesting that it had originated daysdays oror
weeks before the occlusive event.weeks before the occlusive event. They said that “StrikinglyThey said that “Strikingly, clinical, clinical
characteristicscharacteristics did not differ between the patients with fresh thrombusdid not differ between the patients with fresh thrombus
and thoseand those with ‘older’with ‘older’ thrombus, although men were more likely to havethrombus, although men were more likely to have
freshfresh thrombus thanthrombus than werewere women.”women.”
 ((RittersmaRittersma SZH, van derSZH, van der WalWal AC, Koch KT, et al. PlaqueAC, Koch KT, et al. Plaque instabilityinstability frequentlyfrequently
occurs days or weeks before occlusive coronary thrombosis.occurs days or weeks before occlusive coronary thrombosis. AA pathologicalpathological
thrombectomythrombectomy study in primary percutaneousstudy in primary percutaneous coronary interventioncoronary intervention. Circulation. Circulation
2005; 111:11602005; 111:1160--11651165

11.  The PASSIONThe PASSION trialtrial,, recentlyrecently publishedpublished,, foundfound thatthat thethe useuse ofof thrombusthrombus
aspirationaspiration inin adjunctadjunct toto primaryprimary percutaneouspercutaneous coronarycoronary interventionintervention
(PPCI)(PPCI) diddid notnot affectedaffected ratesrates ofof major adversemajor adverse cardiaccardiac eventsevents atat 22 yearsyears
followfollow--up, asup, as comparedcompared withwith convencional PPCI.convencional PPCI. SoSo,, basedbased inin thisthis studystudy,,
it is fair toit is fair to saysay thatthat thrombusthrombus aspirationaspiration dodo notnot preventprevent thethe occurrenceoccurrence ofof
thethe myocardialmyocardial infarctioninfarction..
 Martin AMartin A VinkVink,, MauritsMaurits TT DirksenDirksen, et al., et al. LackLack ofof longlong--termterm clinicalclinical benefitbenefit ofof
thrombusthrombus aspirationaspiration duringduring primaryprimary percutaneouspercutaneous coronarycoronary interventionintervention withwith
paclitaxelpaclitaxel--elutingeluting stentsstents oror barebare--metalmetal stentsstents: Post: Post--hochoc analysisanalysis ofof thethe PASSIONPASSION
trialtrial.. CatheterizationCatheterization andand CardiovascularCardiovascular InterventionsInterventions, 1 May 2012;Volume 79:, 1 May 2012;Volume 79:
IssueIssue 66,, pagespages 870870--877877

12.  MyocardialMyocardial infarction associated with normal coronary arteries is ainfarction associated with normal coronary arteries is a
well known conditionwell known condition. The overall prevalence rate of myocardial. The overall prevalence rate of myocardial
infarction with normalinfarction with normal coronary arteriescoronary arteries is considered to be low,is considered to be low,
varying from 1%varying from 1% to 12to 12% depending on the definition of "% depending on the definition of "normal“normal“
coronary arteries.coronary arteries.
 ((LegrandLegrand V,V, DeliegeDeliege M,M, HenrardHenrard L, Boland J,L, Boland J, KulbertusKulbertus H:H: PatientsPatients withwith
myocardialmyocardial infarctioninfarction andand normalnormal coronarycoronary arteriogramarteriogram.. ChestChest 1982,1982,
82(6):82(6):678678--685; Raymond685; Raymond R, Lynch J,R, Lynch J, UnderwoodUnderwood D,D, LeathermanLeatherman J,J, RazaviRazavi
M:M: MyocardialMyocardial infarctioninfarction andand normalnormal coronarycoronary arteriographyarteriography: a: a 1010 yearyear
clinicalclinical andand riskrisk analysisanalysis ofof 7474 patientspatients. J. J AmAm CollColl CardiolCardiol 19881988, 11(3):471, 11(3):471--
477477.).)

13.  (1993)(1993) ArbustiniArbustini and colleagues found inand colleagues found in a series of 132 autopsies ofa series of 132 autopsies of
hearts from patientshearts from patients who diedwho died ofof noncardiacnoncardiac causes,causes, that coronarythat coronary
thrombi were shownthrombi were shown to overlayto overlay the intima of a coronary vesselthe intima of a coronary vessel
independentlyindependently of plaqueof plaque type andtype and severity.severity.
 ArbustiniArbustini E, Grasso M,E, Grasso M, DiegoliDiegoli M, et al.M, et al. CoronaryCoronary thrombosisthrombosis in nonin non--cardiaccardiac deathdeath..
CoronCoron ArteryArtery DisDis 1993;4:7511993;4:751––9.9.

14.  AA recentrecent ““StateState--ofof--thethe--ArtArt”” reviewreview andand commentarycommentary publishedpublished atat thethe
JournalJournal ofof thethe AmericanAmerican CollegeCollege ofof CardiologyCardiology mademade thethe followingfollowing
conclusionconclusion::
 “A“A largelarge bodybody ofof evidenceevidence conclusivelyconclusively suggestssuggests thatthat coronarycoronary arteryartery
obstructionobstruction isis onlyonly 11 elementelement in ain a complexcomplex multifactorialmultifactorial
pathophysiologicalpathophysiological processprocess thatthat leadsleads toto IschemicIschemic HeartHeart DiseaseDisease (IHD)(IHD)
andand thatthat thethe presencepresence ofof obstructiveobstructive lesionslesions inin patientspatients withwith IHD doesIHD does notnot
necessarilynecessarily implyimply aa causativecausative role. A morerole. A more comprehensivecomprehensive approachapproach
seemsseems necessarynecessary toto refocusrefocus preventivepreventive andand therapeutictherapeutic strategiesstrategies andand toto
decreasedecrease morbiditymorbidity andand mortalitymortality.. ToTo thisthis effecteffect,, wewe proposepropose a shift ina shift in
approachapproach toto includeinclude thethe myocardialmyocardial cellcell asas wellwell asas thethe coronarycoronary vesselvessel””
 MarioMario MarzilliMarzilli,, C. NoelC. Noel BaireyBairey MerzMerz,, William,, William E.E. BodenBoden, Robert, Robert O.O. BonowBonow,,
 Paola G.Paola G. CapozzaCapozza,, William M.William M. ChilianChilian,, AnthonyAnthony N.N. DeMariaDeMaria,, GiacintaGiacinta GuariniGuarini,,
AldaAlda HuqiHuqi,, DoralisaDoralisa MorroneMorrone,, ManeshManesh R.R. PatelPatel,, WilliamWilliam S.S. WeintraubWeintraub.. ObstructiveObstructive
coronarycoronary atherosclerosisatherosclerosis andand ischemicischemic heartheart diseasedisease:: AnAn elusiveelusive link!. JACClink!. JACC VolVol 60,60,
No. 11, 2012;No. 11, 2012; SeptemberSeptember 11: 95111: 951--66

15. OneOne of the majorof the major developmentsdevelopments ofof DoctorDoctor MesquitaMesquita
was the Myogenic Theory of Myocardial Infarction,was the Myogenic Theory of Myocardial Infarction,
fromfrom 1972. The1972. The MyogenicMyogenic Theory supports the useTheory supports the use
of cardiac glycosides (of cardiac glycosides (cardiotonicscardiotonics) for the) for the
prevention and clinical treatment of acute coronaryprevention and clinical treatment of acute coronary
syndromes. Among other developments are thesyndromes. Among other developments are the
Ventricular Aneurism Surgery of the HeartVentricular Aneurism Surgery of the Heart
performed by Charles Bailey in 1954 and the firstperformed by Charles Bailey in 1954 and the first
diagnosis of Right Ventricular Infarction, in vivo, bydiagnosis of Right Ventricular Infarction, in vivo, by
ECG, made in 1958. (He did more than 30 pioneerECG, made in 1958. (He did more than 30 pioneer
contributions to medical literaturecontributions to medical literature))
Dr.Dr. MesquitaMesquita deceased in 2000 with 82 years olddeceased in 2000 with 82 years old
His memorial is at the following webpage:His memorial is at the following webpage:
http://www.infarctcombat.org/qhm/homepage.htmlhttp://www.infarctcombat.org/qhm/homepage.html

16.  TheThe coronary atherosclerosis and slow coronary flow in the normalcoronary atherosclerosis and slow coronary flow in the normal
extramural coronaries develop myocardial ischemic process through theextramural coronaries develop myocardial ischemic process through the
imbalance between demand and blood supply to the myocardialimbalance between demand and blood supply to the myocardial
segments, dependent on the right and left coronary arteries. Basically, thesegments, dependent on the right and left coronary arteries. Basically, the
large extramural coronary arteries are responsible for nutrition of thelarge extramural coronary arteries are responsible for nutrition of the
segmental myocardium and mainly by the contractile balance of eachsegmental myocardium and mainly by the contractile balance of each
segment of the ventricular wall.segment of the ventricular wall.
 EveryEvery time when is developed a relative coronary insufficiency throughtime when is developed a relative coronary insufficiency through
physical or psychophysical or psycho--emotional stress results inemotional stress results in anan immediate loss ofimmediate loss of
contractility of the ischemic area and simultaneous exaltation of othercontractility of the ischemic area and simultaneous exaltation of other
unaffected contractile ventricular segments.unaffected contractile ventricular segments.
 TheThe continuity of such repetitive ischemic manifestations tend tocontinuity of such repetitive ischemic manifestations tend to
contribute to the installation ofcontribute to the installation of nonsynergicnonsynergic segments, by ischemia + losssegments, by ischemia + loss
of contractility and overload imposed by the remaining intact ventricularof contractility and overload imposed by the remaining intact ventricular
segments, during the ventricular ejection phase.segments, during the ventricular ejection phase.
 Thus,Thus, thethe coronariopathycoronariopathy contributes to the deterioration of thecontributes to the deterioration of the
ventricular segment, constituting areas ofventricular segment, constituting areas of myocardiosclerosismyocardiosclerosis oror
segmental myocardial disease, possible future site of the myocardialsegmental myocardial disease, possible future site of the myocardial
infarction.infarction.
 Book “Book “MyogenicMyogenic TheoryTheory ofof MyocardialMyocardial InfarctionInfarction”, 1979.”, 1979.

17.  CoronaryCoronary AtherosclerosisAtherosclerosis
 SlowSlow CCoronaryoronary FFlowlow
 ↓↓
 StableStable AnginaAngina PectorisPectoris –– SilentSilent CoronariopathyCoronariopathy
 11-- RelativeRelative MyocardialMyocardial IschemiaIschemia
 22-- ReciprocalReciprocal ContractileContractile LossLoss
 ↓↓
 PhysicalPhysical andand PsychoPsycho--EmotionalEmotional StressStress FactorsFactors
 // oror
 PharmacologicalPharmacological FactorsFactors -- NegativeNegative InotropicInotropic AgentsAgents
 ↓↓
 SegmentalSegmental MyocardialMyocardial DiseaseDisease

18.  SegmentalSegmental MyocardialMyocardial DiseaseDisease
 ↓↓
 UnstableUnstable Angina/Angina/ IntermediateIntermediate SyndromeSyndrome
 InfarctingInfarcting ClinicalClinical PicturePicture
 11-- RegionalRegional MyocardialMyocardial InsufficiencyInsufficiency
 22-- ReciprocalReciprocal MyocardialMyocardial IschemiaIschemia
 ↓↓
 PrimaryPrimary MyocardialMyocardial NecrosisNecrosis
 ((InfarctionInfarction))
 ↓↓
 CoronaryCoronary StasisStasis oror FragmentationFragmentation andand
 DisplacementDisplacement ofof AtheromatousAtheromatous PlaquePlaque byby EdemaEdema
 ↓↓
 SecondarySecondary CoronaryCoronary ThrombosisThrombosis
 ((NotNot ObligatoryObligatory))

19.  TheThe termterm ““coronarycoronary”” hashas becomebecome synonymoussynonymous withwith ischemiaischemia andand it isit is
usedused to defineto define anan atheroscleroticatherosclerotic occlusiveocclusive lesionlesion thatthat isis believedbelieved toto bebe
responsibleresponsible forfor allall clinicalclinical patternspatterns..
 SoSo,, insideinside thethe sensesense ofof thethe myogenicmyogenic theorytheory ofof myocardialmyocardial infarctioninfarction II willwill
taketake thethe libertyliberty toto use someuse some termsterms moremore adequatedadequated to itto it likelike ““coronarycoronary--
cardiomyopathycardiomyopathy”” oror ““coronarycoronary--myocardialmyocardial diseasedisease”” ratherrather coronarycoronary heartheart
diseasedisease,, coronarycoronary arteryartery diseasedisease andand”” acuteacute myocardialmyocardial syndromessyndromes””
ratherrather acuteacute coronarycoronary syndromessyndromes..

20.  SeveralSeveral studies have shownstudies have shown aa close connectionclose connection between catecholaminebetween catecholamine
and myocardialand myocardial infarction.infarction. The hyperactivity of the sympathetic nervousThe hyperactivity of the sympathetic nervous
system, withsystem, with an intense outflowan intense outflow ofof catecholaminescatecholamines
(adrenaline/epinephrine and(adrenaline/epinephrine and noradrenalinenoradrenaline//norepinephrinenorepinephrine) also occur) also occur
in unstable angina, alternatively calledin unstable angina, alternatively called preinfarctionpreinfarction angina orangina or
intermediate syndrome, being smaller and less long than in acuteintermediate syndrome, being smaller and less long than in acute
myocardial infarctionmyocardial infarction.. TakotsuboTakotsubo cardiomyopathy, also known as brokencardiomyopathy, also known as broken
heartheart syndromesyndrome,, a suddena sudden temporary weakening of thetemporary weakening of the myocardium,myocardium,
which simulates an evolving myocardial infarction clinical picture,which simulates an evolving myocardial infarction clinical picture,
likewiselikewise hashas am intenseam intense outflow ofoutflow of catecholaminescatecholamines..
 ((IncreasedIncreased cardiaccardiac sympatheticsympathetic nervousnervous activityactivity inin patientspatients withwith unstableunstable coronarycoronary
heartheart diseasedisease,, McCanceMcCance AJ, Thompson PA,AJ, Thompson PA, ForfarForfar JC.JC. EurEur Heart J 1993Heart J 1993
Jun;14(6):751Jun;14(6):751--7 ;7 ; SympatheticSympathetic neuralneural hyperactivityhyperactivity andand itsits normalizationnormalization followingfollowing
unstableunstable anginaangina andand acuteacute myocardialmyocardial infarctioninfarction, Graham LN, Smith PA et al., Graham LN, Smith PA et al. ClinClin
SciSci ((LondLond) 2004 Jun;106(6):605) 2004 Jun;106(6):605--11)11)

21.  Acute stress (or stressAcute stress (or stress overload)overload)
 Beyond intense physicalBeyond intense physical activity, particularly in sports competition,activity, particularly in sports competition, oror
unusualunusual efforts, surpassing the limits of his/her heart conditionsefforts, surpassing the limits of his/her heart conditions, or else, or else
the heavy use of stimulant drugs, therethe heavy use of stimulant drugs, there are many risk factors for acuteare many risk factors for acute
myocardialmyocardial syndromes, based on recentsyndromes, based on recent severe stress situations orsevere stress situations or suddensudden
emotionalemotional stress, like:stress, like:
 Marital separation or divorce, loss of work or retirement, loss of revenueMarital separation or divorce, loss of work or retirement, loss of revenue
or business failure, important family conflicts, important personal injuryor business failure, important family conflicts, important personal injury
or illness, death or illness of a close family member, shock of a surpriseor illness, death or illness of a close family member, shock of a surprise
party, armed robbery or other kind of violence, heated discussion, threatsparty, armed robbery or other kind of violence, heated discussion, threats
or acts of war, earthquakes, to trackor acts of war, earthquakes, to track the team of preference in matches livethe team of preference in matches live
footballfootball, etc…, etc…

22.  The recent discovery of endogenousThe recent discovery of endogenous cardiotoniccardiotonic hormones (digitalis,hormones (digitalis, strophanthinstrophanthin,,
proscillaridineproscillaridine, etc..), isolated from human tissues and body fluids,, etc..), isolated from human tissues and body fluids, may representmay represent aa
strong newstrong new argumentargument for the myogenic theory of myocardial infarction.for the myogenic theory of myocardial infarction.
 An elevated concentration of endogenousAn elevated concentration of endogenous cardiotonicscardiotonics have been found underhave been found under
different conditions such as sodium imbalance, hypertension, cardiac arrhythmias,different conditions such as sodium imbalance, hypertension, cardiac arrhythmias,
chronic renal failure, congestive heart failure and acute myocardial infarction.chronic renal failure, congestive heart failure and acute myocardial infarction.
Vigorous physical exercises as well physiological stress situations may also elevateVigorous physical exercises as well physiological stress situations may also elevate
the concentration of endogenousthe concentration of endogenous cardiotonicscardiotonics in the body.in the body.
 WeWe think thethink the cardiotonicscardiotonics found in nature may complement a deficient productionfound in nature may complement a deficient production
of endogenousof endogenous cardiotoniccardiotonic hormones produced by the human body and thushormones produced by the human body and thus
support cardiac metabolism and protect the heart from the infarction, as proposedsupport cardiac metabolism and protect the heart from the infarction, as proposed
in Myogenic Theory.in Myogenic Theory.
 TwoTwo quotesquotes relatedrelated toto thesethese findingsfindings::
 “The“The diseaseddiseased heartheart isis avidavid forfor cardiotonicscardiotonics””
 QuintilianoQuintiliano H. de Mesquita, 1997H. de Mesquita, 1997
 ““CardiotonicsCardiotonics areare thethe insulininsulin for cardiovascularfor cardiovascular diseasedisease””
 Carlos Monteiro, 2005Carlos Monteiro, 2005

23.  (1912) James Herrick: Proclaimed the myocardial infarction (MI) as(1912) James Herrick: Proclaimed the myocardial infarction (MI) as
consequence of coronary thrombosis andconsequence of coronary thrombosis and cardiotonicscardiotonics (digitalis and(digitalis and
strophanthinstrophanthin) as the best therapy. He declared: "The timely use of this) as the best therapy. He declared: "The timely use of this
remedy may occasionally save live".remedy may occasionally save live".
 (1926) Louis(1926) Louis HammanHamman: Shared in same concepts and enthusiasm of: Shared in same concepts and enthusiasm of
Herrick regarding the use ofHerrick regarding the use of cardiotonicscardiotonics to treat the MI. He said: "Theto treat the MI. He said: "The
patient should be promptly and fully digitalized... not only is thepatient should be promptly and fully digitalized... not only is the
digitalized heart better prepared to withstand the added burden ofdigitalized heart better prepared to withstand the added burden of
certain arrhythmias should they come on, but it is also stimulated to putcertain arrhythmias should they come on, but it is also stimulated to put
forth its better efforts. How desirable the best efforts may be when a largeforth its better efforts. How desirable the best efforts may be when a large
area of heart muscle is infarcted, needs no further comment"area of heart muscle is infarcted, needs no further comment"
 ((JAMA,59: 2015,JAMA,59: 2015, 1912 ;1912 ; BullBull Johns Hopkins Hosp.; 38: 273,Johns Hopkins Hosp.; 38: 273, 19261926))

24.  ((1934) Ernst1934) Ernst EdensEdens: After 3 years using: After 3 years using strophanthinstrophanthin by intravenous wayby intravenous way
in angina pectoris and MI in more than 100 patients he declared: "in angina pectoris and MI in more than 100 patients he declared: "
Subsequently to the recognition of theSubsequently to the recognition of the strophanthinstrophanthin as the best and safestas the best and safest
medicine for the myocardial infarction we don't have the right to use it inmedicine for the myocardial infarction we don't have the right to use it in
a patient only for scientific reasons and tests, giving preference to othera patient only for scientific reasons and tests, giving preference to other
remediesremedies losinglosing precious time for the cure". He also told that will comeprecious time for the cure". He also told that will come
the moment in which the omission of the use ofthe moment in which the omission of the use of strophanthinstrophanthin wouldwould bebe
seen as a professional malpracticeseen as a professional malpractice..
 (Munchener(Munchener Medizinischen Wochenschrift; 37, 1934)Medizinischen Wochenschrift; 37, 1934)

25.  (1950) Ferdinand(1950) Ferdinand R.R. SchemmSchemm:: Preconized the use free from restraintPreconized the use free from restraint ofof
digitalis for MI treatment. He used digitalis in 265 patients recording adigitalis for MI treatment. He used digitalis in 265 patients recording a
mortality of 10%. In practice he noticed that instead of any myocardialmortality of 10%. In practice he noticed that instead of any myocardial
damages, thedamages, the cardiotoniccardiotonic presented compatibility with the acutepresented compatibility with the acute
myocardial infarction, reason of salutary effects and lower mortality.myocardial infarction, reason of salutary effects and lower mortality.
 (1951) John(1951) John MartinMartin AskeyAskey: Applied: Applied digitalis in 50 consecutive patientsdigitalis in 50 consecutive patients
with acute MI. Citing the results achieved bywith acute MI. Citing the results achieved by SchemmSchemm with digitalis referswith digitalis refers
that the medical profession was unable to take full advantage of thisthat the medical profession was unable to take full advantage of this
valuable drug, offering the Henry Thoreau thought: "It is never too late tovaluable drug, offering the Henry Thoreau thought: "It is never too late to
give up our prejudices. No way of thinking however ancient, can begive up our prejudices. No way of thinking however ancient, can be
trusted without proof". This affirmation fromtrusted without proof". This affirmation from AskeyAskey was stated duringwas stated during
the presentation about his results and to appreciate the clinical andthe presentation about his results and to appreciate the clinical and
experimental proceedings realized at that time. Likewise he demonstratedexperimental proceedings realized at that time. Likewise he demonstrated
a healthy apprehension in front of the accommodation and disinteresta healthy apprehension in front of the accommodation and disinterest
regarding so exciting theme.regarding so exciting theme.
 ((PostgradPostgrad Med.; 385, 1950; JAMA; 146: 1008, 1951)Med.; 385, 1950; JAMA; 146: 1008, 1951)

26.  (1955) Norman(1955) Norman H.H. Boyer:Boyer: Mentioned that after an unexpected butMentioned that after an unexpected but
fortunate experience using digitalis by intravenously way ceased his fearfortunate experience using digitalis by intravenously way ceased his fear
about the use of digitalis applying it starting from this moment in aabout the use of digitalis applying it starting from this moment in a
sequence of 50 patients with MIsequence of 50 patients with MI..
 (1970) Berthold Kern: Wrote that he used sublingual(1970) Berthold Kern: Wrote that he used sublingual strophanthinstrophanthin in morein more
than 15.000 cardiac patients during the period of 1947 tillthan 15.000 cardiac patients during the period of 1947 till 1968 resulting1968 resulting inin
a very low mortality rate and few myocardial infarctions.a very low mortality rate and few myocardial infarctions.
 (New(New EnglandEngland J.J. MedMed; 252: 536,; 252: 536, 1955; Der1955; Der MyokardMyokard--InfarktInfarkt.. HaugHaug VerlagVerlag..
HeidelbergHeidelberg, 1970), 1970)

27.  (1972)(1972) QuintilianoQuintiliano H. deH. de MesquitaMesquita:: Advocated that treatment withAdvocated that treatment with
cardiotonicscardiotonics should be started the earliest possible in order to correct theshould be started the earliest possible in order to correct the
regional myocardial collapse in progress. He alsoregional myocardial collapse in progress. He also statedstated thatthat cardiotoniccardiotonic
administration protects the myocardial fibers in collapse, ischemic, butadministration protects the myocardial fibers in collapse, ischemic, but
viable to be kept from the necrosis whichviable to be kept from the necrosis which wouldwould certainly occur in case ofcertainly occur in case of
nonnon--use of this remedy. Surpassing the acute period, theuse of this remedy. Surpassing the acute period, the cardiotoniccardiotonic
should be used, according him, as a maintenance treatment, which blendsshould be used, according him, as a maintenance treatment, which blends
with the MI prophylaxis, in order to defend the ischemic myocardium inwith the MI prophylaxis, in order to defend the ischemic myocardium in
its functional side. During 7 years appliedits functional side. During 7 years applied cardiotonicscardiotonics by intravenouslyby intravenously
way (way (digitalis anddigitalis and strophanthinstrophanthin) in 1183 patients with acute MI, recording) in 1183 patients with acute MI, recording
a survival of almost 90%.a survival of almost 90%. ProfessorProfessor MesquitaMesquita was awarded in 1975 withwas awarded in 1975 with
the Ernstthe Ernst EdensEdens TraditionspreisTraditionspreis by the International Society Againstby the International Society Against
Myocardial InfarctMyocardial Infarct locatedlocated in Stuttgartin Stuttgart-- GermanyGermany..
 (Mesquita(Mesquita, QH De: Angina de esforço e síndrome de enfarte miocárdico iminente:, QH De: Angina de esforço e síndrome de enfarte miocárdico iminente:
aspectos sintomáticos dependentes de insuficiência miocárdica regional. Notaaspectos sintomáticos dependentes de insuficiência miocárdica regional. Nota
prévia. Trabalho apresentado ao XXVIII Congresso Brasileiro de Cardiologia,prévia. Trabalho apresentado ao XXVIII Congresso Brasileiro de Cardiologia,
Curitiba (PR), Julho deCuritiba (PR), Julho de 1972)1972)

28.  (1974)(1974) PritpalPritpal PuriPuri havehave demonstrateddemonstrated thatthat thethe intermediateintermediate
hypocontractilehypocontractile areaarea betweenbetween thethe infarctioninfarction andand normalnormal myocardiummyocardium
respondedresponded toto thethe cardiotoniccardiotonic StrophanthinStrophanthin maintainingmaintaining normalnormal
contractilitycontractility startingstarting fromfrom thethe thethe myocardialmyocardial ischemiaischemia andand
hypocontractilityhypocontractility..
 (1975)(1975) BankaBanka andand colcol,, confirmedconfirmed thethe experimentsexperiments fromfrom PuriPuri usingusing
DigitalisDigitalis andand recordingrecording thethe samesame resultsresults..
 ((PritpalPritpal SS PuriPuri. Modification of experimental myocardial infarct size by cardiac. Modification of experimental myocardial infarct size by cardiac
drugs, Am Jdrugs, Am J CardiolCardiol, 33 :52, 1974; Banka, VS,, 33 :52, 1974; Banka, VS, BodenheimerBodenheimer, MM,, MM, HelfantHelfant, RH e, RH e
ChaddaChadda, KD: Digitalis in experimental acute myocardial infarction. Differential, KD: Digitalis in experimental acute myocardial infarction. Differential
effects on contractile performance of ischemic, border andeffects on contractile performance of ischemic, border and nonischemicnonischemic ventricularventricular
zones in the dog, Am Jzones in the dog, Am J CardiolCardiol, 35:801, 1975), 35:801, 1975)

29.  (1975)(1975) PizarelloPizarello etet alal andand MorrisonMorrison etet alal in 1976in 1976 havehave shownshown thethe serialserial
enzymaticenzymatic reactionsreactions usingusing digitalisdigitalis thethe infarctioninfarction waswas haltedhalted andand,, thusthus,,
thethe cardiotoniccardiotonic mightmight bebe consideredconsidered asas ableable toto rescuerescue thethe viableviable
myocardialmyocardial fibersfibers..
 (1980) Morrison(1980) Morrison etet alal confirmedconfirmed nono changechange in serialin serial creatininecreatinine MBMB
isoenzymeisoenzyme in ain a groupgroup ofof patientspatients withwith heartheart failurefailure afterafter myocardialmyocardial
infarctioninfarction takingtaking digitalisdigitalis, in, in contrastcontrast withwith pastpast observationsobservations mademade inin
animalsanimals followingfollowing coronarycoronary arteryartery ligationligation,, whichwhich havehave shownshown anan
extensionextension ofof thethe areaarea ofof infarctioninfarction afterafter digitalisdigitalis administrationadministration..
 ((PizarelloPizarello R,R, RedutoReduto L, Geller K,L, Geller K, GullotaGullota S, Morrison JS, Morrison J –– Protection of the ischemicProtection of the ischemic
myocardium in man by digitalis. Circulation 1975; 51myocardium in man by digitalis. Circulation 1975; 51--52 (52 (supplsuppl III): 895; MorrisonIII): 895; Morrison
J,J, PizarelloPizarello R,R, RedutoReduto L,L, GullotaGullota SS –– Effect of digitalis on predicted myocardialEffect of digitalis on predicted myocardial
infarct size. Circulation 1976; 53infarct size. Circulation 1976; 53--54 (54 (SupplSuppl II): 102II): 102;; Morrison J,Morrison J, CoromilasCoromilas J, RobbinsJ, Robbins
M et alM et al –– Digitalis and myocardial infarction in man. Circulation 1980; 62: 8Digitalis and myocardial infarction in man. Circulation 1980; 62: 8--16)16)

30.  (1980) Peter(1980) Peter SchmidsbergerSchmidsberger, medical, medical journalistjournalist:: ReportReport thethe resultsresults
obtainedobtained byby Professor Mesquita inProfessor Mesquita in BrazilBrazil informinginforming thatthat RolfRolf DorhmanDorhman
fromfrom thethe BerlinerBerliner WaldkrankenhausesWaldkrankenhauses in Berlinin Berlin -- GermanyGermany,, achievedachieved
duringduring 55 yearsyears similarsimilar resultsresults ofof thethe BrazilianBrazilian professorprofessor applyingapplying thethe samesame
treatmenttreatment withwith strophanthinstrophanthin duringduring thethe acuteacute myocardialmyocardial infarctioninfarction..
 (1993)(1993) QiaoQiao DR told that from the hemodynamic studies the beneficialDR told that from the hemodynamic studies the beneficial
effect ofeffect of cedilanidcedilanid is greater than its adverse effect, concluding thatis greater than its adverse effect, concluding that
digitalis can be safely and effectively used in the treatment of AMI.digitalis can be safely and effectively used in the treatment of AMI.
 (In This Manner a Brazilian Fights Against The Infarction "(In This Manner a Brazilian Fights Against The Infarction "-- BUNTE magazine,BUNTE magazine,
OffenburgOffenburg –– Germany;Germany; R.E.DohrmannR.E.Dohrmann;; H.D.JanischH.D.Janisch && M.KesselM.Kessel:: KlinischKlinisch--
poliklinischepoliklinische StudieStudie überüber diedie WirksamkeitWirksamkeit von gvon g--StrophanthinStrophanthin beibei Angina pectorisAngina pectoris
undund MyokardinfarktMyokardinfarkt,;,; CardiolCardiol Bull (Bull (CardiologischesCardiologisches Bulletin) 14/15: 183Bulletin) 14/15: 183--187, 1977;187, 1977;
QiaoQiao DR. A study on the hemodynamic effect ofDR. A study on the hemodynamic effect of cedilanidcedilanid in the treatment of acutein the treatment of acute
myocardial infarction,myocardial infarction, ZhonghuaZhonghua XinXin XueXue GuanGuan BingBing ZaZa ZhiZhi. 1993. 1993 AprApr;21(2):83;21(2):83--4)4)

31.  (1995) Leor J and colleagues found in patients recovering from(1995) Leor J and colleagues found in patients recovering from
myocardial infarction that one year mortality was significantly highermyocardial infarction that one year mortality was significantly higher
among patients treated with a full dose [19 of 112 (17%)] than patientsamong patients treated with a full dose [19 of 112 (17%)] than patients
treated with a low dose oftreated with a low dose of digoxindigoxin [1 of 41 (2%)][1 of 41 (2%)]
 ((LeorLeor J,J, GoldbourtGoldbourt UU etet al.al. DigoxinDigoxin andand increasedincreased mortalitymortality amongamong patientspatients
recoveringrecovering fromfrom acuteacute myocardialmyocardial infarctioninfarction:: importanceimportance ofof digoxindigoxin dose,dose,
CardiovascCardiovasc DrugsDrugs TherTher 19951995 OctOct;9(5):723;9(5):723--9)9)

32.  “I wish it was as easy to write upon the Digitalis“I wish it was as easy to write upon the Digitalis –– I despair of pleasing myself orI despair of pleasing myself or
instructing others in a subject so difficult. It is much easier to write upon ainstructing others in a subject so difficult. It is much easier to write upon a
disease than upon a remedy. The former is in the hands of nature and a faithfuldisease than upon a remedy. The former is in the hands of nature and a faithful
observer with an eye to tolerable judgment can not fail to delineate a likeness; theobserver with an eye to tolerable judgment can not fail to delineate a likeness; the
latter will ever be subject to the whims, the inaccuracies and the blunders oflatter will ever be subject to the whims, the inaccuracies and the blunders of
mankind". William Withering, Letter, Sep 29, 1778mankind". William Withering, Letter, Sep 29, 1778
 “Digitalis: A God“Digitalis: A God--given remedy” by Friedrich Ludwiggiven remedy” by Friedrich Ludwig KreysigKreysig –– Berlin, 1814Berlin, 1814
 “Digitalis: The opium of the heart” by Jean“Digitalis: The opium of the heart” by Jean BaptisteBaptiste BouillaudBouillaud –– Paris, 1841Paris, 1841

33.  The risk of a heart attack or other acute myocardial events is not proportionalThe risk of a heart attack or other acute myocardial events is not proportional
to the severity of coronaryto the severity of coronary stenosisstenosis. Several studies in which more than one. Several studies in which more than one
angiography was performed in patients who developed acute syndromesangiography was performed in patients who developed acute syndromes
showed that most of these syndromes appear to be developed from lesionsshowed that most of these syndromes appear to be developed from lesions
that on the first angiography caused not significantthat on the first angiography caused not significant stenosisstenosis. These less severe. These less severe
stenoticstenotic lesions lead to myocardial infarction because they have not developedlesions lead to myocardial infarction because they have not developed
a sufficient collateral circulation around that would prevent or limit the extenta sufficient collateral circulation around that would prevent or limit the extent
of myocardial necrosis. This means that a 30% reduction in arterial caliber mayof myocardial necrosis. This means that a 30% reduction in arterial caliber may
have an increased risk for a myocardial infarction than an obstruction 90%.have an increased risk for a myocardial infarction than an obstruction 90%.
 (Ambrose J A,(Ambrose J A, TannenbaumTannenbaum M A et al, Angiographic progression of coronary arteryM A et al, Angiographic progression of coronary artery
disease and the development of myocardial infarction, J Amdisease and the development of myocardial infarction, J Am CollColl CardiolCardiol 1988; 12:561988; 12:56--62;62;
Little W C et al, Can coronary angiography predict the site of a subsequent myocardialLittle W C et al, Can coronary angiography predict the site of a subsequent myocardial
infarction in patients with mild to moderate coronary artery disease?, Circulation 1988;infarction in patients with mild to moderate coronary artery disease?, Circulation 1988;
78:115778:1157--66; John A Ambrose,66; John A Ambrose, ValentinValentin FusterFuster, The risk of coronary occlusion is not, The risk of coronary occlusion is not
proportional to the prior severity of coronaryproportional to the prior severity of coronary stenosesstenoses, Editorial, Heart 1998; 79:3, Editorial, Heart 1998; 79:3--4)4)

34.  Dr.Dr. QuintilianoQuintiliano dede MesquitaMesquita, said in his book ", said in his book "MyogenicMyogenic Theory ofTheory of
Myocardial Infarction, 1979:Myocardial Infarction, 1979:
 "The collateral coronary circulation is absolutely prevalent in cases of total"The collateral coronary circulation is absolutely prevalent in cases of total
obstruction of theobstruction of the coronary artery.coronary artery. He also told: "The net of coronary collateralHe also told: "The net of coronary collateral
circulation is not always able to prevent myocardial infarction, because it developscirculation is not always able to prevent myocardial infarction, because it develops
depending on the anatomical features of the obstructive process, and is not alwaysdepending on the anatomical features of the obstructive process, and is not always
sufficient to face the demands of the physical activity of the coronary patient. Thesufficient to face the demands of the physical activity of the coronary patient. The
role of therole of the cardiotoniccardiotonic is to complete the effects of collateral circulation and ensureis to complete the effects of collateral circulation and ensure
functional preservation of the ischemic myocardium, thus avoiding the infarction."functional preservation of the ischemic myocardium, thus avoiding the infarction."
 A recent metaA recent meta--analysis confirmed that heart disease patients with a wellanalysis confirmed that heart disease patients with a well--
developed collateral coronary circulation have an improved survivaldeveloped collateral coronary circulation have an improved survival
compared with patients with less developed collaterals*.compared with patients with less developed collaterals*.
 *Meier P, Hemingway H, Lansky AJ, et al. The impact of the coronary collateral*Meier P, Hemingway H, Lansky AJ, et al. The impact of the coronary collateral
circulation on mortality: a metacirculation on mortality: a meta--analysis.analysis. EurEur Heart J 2011; DOI:Heart J 2011; DOI:
10.1093/10.1093/eurheartjeurheartj/ehr308*/ehr308*

35. InIn mymy viewview, in, in additionaddition ofof positivepositive inotropicinotropic effectseffects overover thethe heartheart musclemuscle
contractilitycontractility,, cardiotonicscardiotonics maymay alsoalso havehave possiblepossible beneficbenefic effectseffects forfor
cardiovascularcardiovascular diseasedisease,, includingincluding inin haltinghalting acuteacute myocardialmyocardial syndromessyndromes,,
throughthrough thethe reductionreduction ofof heightenedheightened catecholaminecatecholamine levelslevels inin bloodblood andand inin
reductionreduction ofof thethe resultingresulting elevatedelevated lactatelactate productionproduction andand accumulationaccumulation byby
thethe cardiaccardiac musclemuscle..
 ((SchobelSchobel HP et al. 1991HP et al. 1991.. ContrastingContrasting effectseffects ofof digitalisdigitalis andand dobutaminedobutamine onon
baroreflexbaroreflex sympatheticsympathetic controlcontrol inin normalnormal humanshumans,, CirculationCirculation V84,V84, 11181118--1129;1129;
 MM GheorgiadeGheorgiade andand D Ferguson, 1991.D Ferguson, 1991. DigoxinDigoxin: A: A neurohormonalneurohormonal modulatormodulator inin
heartheart failurefailure? 84: 2181? 84: 2181--2186;2186; GutmanGutman Y,Y, BoonyavirojBoonyaviroj P.P. NaunynNaunyn SchmiedebergsSchmiedebergs..
1977.1977. MechanismMechanism ofof inhibitioninhibition ofof catecholaminecatecholamine releaserelease fromfrom adrenaladrenal medullamedulla byby
diphenylhydantoindiphenylhydantoin andand byby lowlow concentrationconcentration ofof ouabainouabain (10 ((10 (--10) M).10) M). ArchArch
PharmacolPharmacol Feb;296(3Feb;296(3):):293293--6);6); SchadeSchade DS. The role ofDS. The role of catecholaminescatecholamines in metabolicin metabolic
acidosis. Ciba Foundacidosis. Ciba Found SympSymp. 1982;87:235. 1982;87:235--53)53)

36.  The myogenic theory recommends the use of theThe myogenic theory recommends the use of the cardiotoniccardiotonic + coronary+ coronary
dilator in stable coronarydilator in stable coronary myocardiopathymyocardiopathy, with or w/out previous, with or w/out previous
infarction in the longinfarction in the long run, complementingrun, complementing thethe beneficialbeneficial and protectiveand protective
effects of collateral coronary circulation in front ofeffects of collateral coronary circulation in front of severe coronarysevere coronary
obstructions.obstructions.
 In short, according the myogenic theory,In short, according the myogenic theory, cardiotonicscardiotonics are theare the antianti--
infarctioninfarction drugs.drugs.
 Excerpts from the paper fromExcerpts from the paper from MesquitaMesquita QHdeQHde et al Effects of theet al Effects of the CardiotonicCardiotonic ++
Coronary Dilator in Chronic Stable CoronaryCoronary Dilator in Chronic Stable Coronary--Myocardial Disease, with andMyocardial Disease, with and
without Prior Myocardial Infarction, in the Long Runwithout Prior Myocardial Infarction, in the Long Run”,”, Ars Cvrandi 2002Ars Cvrandi 2002
(setembro);(setembro);35:7. Text available at the following webpage:35:7. Text available at the following webpage:
http://www.infarctcombat.org/CMDhttp://www.infarctcombat.org/CMD--CE.pdfCE.pdf

37. Dr.Dr. MesquitaMesquita and colleagues say that theand colleagues say that the following effects should befollowing effects should be
highlightedhighlighted from thefrom the uninterrupted use ofuninterrupted use of cardiotoniccardiotonic ++ coronarycoronary dilatordilator inin
chronicchronic stablestable coronarycoronary--myocardiopathymyocardiopathy,, withwith oror w/outw/out previousprevious myocardialmyocardial
infarctioninfarction::
 To counteractTo counteract the negative inotropic effects ofthe negative inotropic effects of ischemia;ischemia;
 To preserve the ventricularTo preserve the ventricular function, leveling over the ischemic segmentsfunction, leveling over the ischemic segments --
contractilecontractile deficientdeficient -- withwith nonnon--ischemicischemic segments,segments, annullingannulling thethe
deleterious segmental confrontation;deleterious segmental confrontation;
 To preventTo prevent Unstable Angina, Myocardial Infarction, Heart Failure andUnstable Angina, Myocardial Infarction, Heart Failure and
Sudden DeathSudden Death -- symptomaticsymptomatic and myocardial instability, ensuringand myocardial instability, ensuring
permanent state ofpermanent state of stability;stability;
 To Increase and to provide peaceful survival,To Increase and to provide peaceful survival, comfortable and long,comfortable and long,
predominantlypredominantly asymptomatic, in front of the commonasymptomatic, in front of the common efforts and accordingefforts and according
to theto the achieved parameters.achieved parameters.
Again, they have said that “theAgain, they have said that “the coronary collateral circulation has its role in the fate ofcoronary collateral circulation has its role in the fate of
coronary artery disease and representscoronary artery disease and represents the compensatory reinforcementthe compensatory reinforcement ofof the "Naturethe "Nature",",
complemented bycomplemented by thethe cardiotoniccardiotonic,, in the preservationin the preservation of myocardialof myocardial contractility.”contractility.”

38.  In a paper published in 2002,In a paper published in 2002, QuintilianoQuintiliano MesquitaMesquita and his assistant,and his assistant,
CláudioCláudio BaptistaBaptista, have prospectively analyzed data from a period of 28, have prospectively analyzed data from a period of 28
years (1972years (1972 -- 2000) using cardiac2000) using cardiac glycosidesglycosides at low concentration (lowat low concentration (low
dose) indose) in patients with stable coronary artery diseasepatients with stable coronary artery disease with or withoutwith or without
previous infarction *. Their results have showedprevious infarction *. Their results have showed very low rates invery low rates in
mortality and morbiditymortality and morbidity.. The patients were divided in twoThe patients were divided in two groups...groups...
 CardiotonicCardiotonic: Insuperable in preservation of myocardial stability, as preventive of: Insuperable in preservation of myocardial stability, as preventive of
acute coronary syndromes and responsible for aacute coronary syndromes and responsible for a prolonguedprolongued survival. Casuistry ofsurvival. Casuistry of
28 years (197228 years (1972--2000)2000)”,”, QuintilianoQuintiliano H. de Mesquita e Cláudio A S Baptista,H. de Mesquita e Cláudio A S Baptista, ArsArs
CvrandiCvrandi 2002 (maio); 35:32002 (maio); 35:3 .. Text available at the following webpage:Text available at the following webpage:
httphttp://://www.infarctcombat.org/28years/digitalis.htmlwww.infarctcombat.org/28years/digitalis.html

39. TheThe first group included 994 patients w/out priorfirst group included 994 patients w/out prior infarction,infarction,
presentingpresenting in 28 years the following morbidity and mortalityin 28 years the following morbidity and mortality::
 -- Myocardial infarction: 14 cases (1.4Myocardial infarction: 14 cases (1.4%)%)
 -- Heart failure: 35 cases (3.5%)Heart failure: 35 cases (3.5%)
 -- Heart failure mortality: 32 cases (3.2%)Heart failure mortality: 32 cases (3.2%)
 -- Sudden Death:Sudden Death: 7272 cases (7.2%)cases (7.2%)
 -- Stroke mortality: 13 cases (1.3%)Stroke mortality: 13 cases (1.3%)
 -- Cancer mortality: 14 cases (1.4Cancer mortality: 14 cases (1.4%)%)
 -- Other causes of mortality: 11 cases (1.1%)Other causes of mortality: 11 cases (1.1%)
 -- Total Mortality: 142 cases (14.2%)Total Mortality: 142 cases (14.2%) -- (0.5% per(0.5% per year!)year!)
 -- Mean Age at Death: 76 yearsMean Age at Death: 76 years

40. TheThe second group included 156 patients with prior infarction,second group included 156 patients with prior infarction,
presenting in 28 years the following morbidity and mortality:presenting in 28 years the following morbidity and mortality:
 -- ReRe--infarction: 8 cases (5.1%)infarction: 8 cases (5.1%)
 -- Heart failure: 17 cases (10.8%)Heart failure: 17 cases (10.8%)
 -- Heart failure mortality: 17 cases (10.8%)Heart failure mortality: 17 cases (10.8%)
 -- Sudden Death: 31 cases (20.5%)Sudden Death: 31 cases (20.5%)
 -- Stroke mortality: 7 cases (4.4%)Stroke mortality: 7 cases (4.4%)
 -- Cancer mortality: 3 cases (1.9%)Cancer mortality: 3 cases (1.9%)
 -- Other causes mortality: 5 cases (3.2%)Other causes mortality: 5 cases (3.2%)
 -- Total Mortality: 64 cases (Total Mortality: 64 cases (40.8%)40.8%) -- (1.45% per(1.45% per year!)year!)
 -- Mean Age at Death: 72 yearsMean Age at Death: 72 years

41.  PermanentPermanent TherapeuticTherapeutic MaintenanceMaintenance
 CardiotonicsCardiotonics employedemployed::
 ProscillaridinProscillaridin--AA 0.750.75--1.50mg/1.50mg/dayday
 AcetildigoxinAcetildigoxin 0.50mg/0.50mg/dayday
 LanatosideLanatoside--C 0.50mg/C 0.50mg/dayday
 DigitoxinDigitoxin 0.1mg/0.1mg/dayday
 DigoxinDigoxin 0.1250.125--0.25mg/0.25mg/dayday
 BetamethildigoxinBetamethildigoxin 0.100.10--0.20mg/0.20mg/dayday
 CoronaryCoronary dilatorsdilators :: CalciumCalcium antagonistsantagonists::
 VerapamilVerapamil 120120--240mg/240mg/dayday
 PrenilaminePrenilamine 120120--180mg/180mg/dayday
 NifedipineNifedipine 2020--30mg/30mg/dayday
 FendilineFendiline 100100--150mg/150mg/dayday
 DiltiazemDiltiazem 9090--180mg/180mg/dayday
 TextText availableavailable atat http://http://www.infarctcombat.org/CMDwww.infarctcombat.org/CMD--CE.pdfCE.pdf

42.  The myogenic theory recommends theThe myogenic theory recommends the useuse of theof the cardiotoniccardiotonic + coronary+ coronary
dilator indilator in the treatment of unstable angina,the treatment of unstable angina, forfor correction ofcorrection of regionalregional
myocardialmyocardial insufficiency, presented as theinsufficiency, presented as the determinant factor in thedeterminant factor in the
pathophysiologicalpathophysiological mechanismmechanism of this alarming clinical syndrome,of this alarming clinical syndrome,
usually characterizing the preusually characterizing the pre--infarctioninfarction..
 ExcerptsExcerpts fromfrom thethe articlearticle ofof MesquitaMesquita QHdeQHde etet alal ““Effects of theEffects of the CardiotonicCardiotonic ++
Coronary Dilator in Unstable AnginaCoronary Dilator in Unstable Angina”” TextText availableavailable atat thethe followoingfollowoing webpagewebpage::
http://http://www.infarctcombat.org/UAwww.infarctcombat.org/UA--CE.pdfCE.pdf

43.  ResultsResults
 Perfect drug tolerancePerfect drug tolerance..
 ImmediateImmediate disappearance ofdisappearance of spontaneousspontaneous anginalanginal episodesepisodes sincesince the firstthe first
injection andinjection and in ain a shortshort--termterm following the administration of the drug byfollowing the administration of the drug by
oral route.oral route.
 InterruptionInterruption of unstable angina in 199of unstable angina in 199 ptspts;;
 OnlyOnly 1 case1 case evolvedevolved to myocardial infarctionto myocardial infarction in thein the eighth day.eighth day.
 NoNo deaths.deaths.
 ECG alterationsECG alterations with rapid disappearance.with rapid disappearance.
 ArrhythmicArrhythmic benignbenign transitional manifestationstransitional manifestations (20.5%).(20.5%).
 MildMild enzymatic changes in the first 24 hours.enzymatic changes in the first 24 hours.

44.  TherapeuticTherapeutic attackattack ofof unstableunstable anginaangina duringduring 66 daysdays
 CardiotonicsCardiotonics::
 SStrophanthintrophanthin--KK :: 0.250.25--0.34 mg/0.34 mg/dayday, IV, IV
 StrophanthinStrophanthin--GG :: 0.250.25--0.50 mg/0.50 mg/dayday, IV, IV
 LanatosideLanatoside--CC :: 0.40 mg/0.40 mg/dayday, IV, IV
 DigoxinDigoxin :: 0.50 mg/0.50 mg/dayday, IV, IV
 MethildigoxinMethildigoxin :: 0.200.20--0.30 mg/0.30 mg/dayday, PO, PO
 ProscillaridinProscillaridin--AA :: 1.501.50--2.0 mg/2.0 mg/dayday, PO, PO
 CoronaryCoronary dilatorsdilators::
 Dipiridamol : 20Dipiridamol : 20 mg/mg/dayday, IV, IV
 VerapamilVerapamil : 240: 240 mg/mg/dayday, PO, PO
 PrenilaminePrenilamine : 180: 180 mg/mg/dayday, PO, PO
 NifedipineNifedipine : 30: 30 mg/mg/dayday, PO, PO
 * The* The strophanthinstrophanthin K or G (IV) was employed in 150 patients, Digitalis (IV) in 30K or G (IV) was employed in 150 patients, Digitalis (IV) in 30
patients and,patients and, exceptionally,exceptionally, by oral route,by oral route, MethildigoxinMethildigoxin in 1 patient andin 1 patient and
ProscillaridinProscillaridin--A in 18 ptsA in 18 pts..
 IVIV: Intravenous route PO: Oral route: Intravenous route PO: Oral route

45.  WhyWhy infarctinginfarcting clinical picture?clinical picture?
 Because with the use ofBecause with the use of cardiotonicscardiotonics the myocardial infarction can bethe myocardial infarction can be
halted ashalted as occurredoccurred in 63.5%in 63.5% of the casesof the cases as shown in the studies by Dr.as shown in the studies by Dr.
MesquitaMesquita..
 MesquitaMesquita QHdeQHde et al “Effects of theet al “Effects of the CardiotonicCardiotonic + Coronary Dilator in the+ Coronary Dilator in the
InfarctingInfarcting Clinical Picture“. TextClinical Picture“. Text available atavailable at the following webpagethe following webpage
httphttp://://www.infarctcombat.org/ICPwww.infarctcombat.org/ICP--CE.pdfCE.pdf

46. ResultsResults
 AbsoluteAbsolute tolerancetolerance fromfrom thethe drugdrug
 ReductionReduction inin administrationadministration ofof analgesicsanalgesics andand narcoticsnarcotics
 LowLow incidenceincidence ofof cardiaccardiac arrhythmiasarrhythmias
 LowLow incidenceincidence ofof cardiaccardiac insufficiencyinsufficiency
 LowLow incidenceincidence ofof cardiogeniccardiogenic shockshock
 RelativeRelative loweringlowering ofof enzymaticenzymatic reactionreaction peakspeaks
 LowLow mortalitymortality
 ClinicalClinical picturepicture moremore calmcalm andand safesafe

47.  TherapeuticTherapeutic attackattack ofof thethe infarctioninginfarctioning clinicalclinical picturepicture duringduring 66 daysdays
 CardiotonicsCardiotonics::
 StrophanthinStrophanthin--K :K : 0.250.25--0.340.34 mg/mg/dayday, IV, IV
 StrophanthinStrophanthin--G :G : 0.250.25--0.500.50 mg/mg/dayday, IV, IV
 LanatosideLanatoside--C :C : 0.400.40 mg/mg/dayday, IV, IV
 DigoxinDigoxin :: 0.500.50 mg/mg/dayday, IV, IV
 CoronaryCoronary dilatorsdilators::
 Dipiridamol : 20 mg/Dipiridamol : 20 mg/dayday, IV, IV
 VerapamilVerapamil : 240 mg/: 240 mg/dayday, PO, PO
 PrenilaminePrenilamine : 180 mg/: 180 mg/dayday, PO, PO
 NifedipineNifedipine : 30 mg/: 30 mg/dayday, PO, PO
 * The* The strophanthinstrophanthin KK oror G (IV)G (IV) waswas employedemployed inin 962962 patientspatients,, andand ddigitalisigitalis (IV) in(IV) in 147147
patientspatients,, duringduring thethe firstfirst phasephase ofof treatmenttreatment..
 IV:IV: IntravenousIntravenous routeroute PO: OralPO: Oral routeroute

48.  Results (Results (IndicesIndices ofof clinicalclinical complicationscomplications):):

-- VentricularVentricular extrasystolesextrasystoles: 24.1%: 24.1%
-- PartialPartial AVAV blockblock: 5.8%: 5.8%
-- Complete AVComplete AV blockblock: 4.6%: 4.6%
-- AtrialAtrial tachycardiatachycardia: 1.7%: 1.7%
-- FlutterFlutter -- AtrialAtrial fibrillationfibrillation: 4.4%: 4.4%
-- TachycardiaTachycardia + Ventricular+ Ventricular FibrilationFibrilation: 2.7%: 2.7%
-- AsystoleAsystole: 4.5%: 4.5%
-- CardiogenicCardiogenic shockshock: 2%: 2%
-- AcuteAcute pulmonarypulmonary edema: 1.3%edema: 1.3%
-- HeartHeart failurefailure: 1%: 1%
-- OverallOverall mortalitymortality: 12.2%: 12.2%
-- MortalityMortality byby age: 9.4% inage: 9.4% in patientspatients underunder 7070 yearsyears andand 26.6% in26.6% in patientspatients
over 70over 70 yearsyears

49. ThisThis book inbook in PortuguesePortuguese languagelanguage maymay bebe downloadeddownloaded freefree ofof
charge.charge. TheThe summarysummary andand conclusionsconclusions inin EnglishEnglish areare atat
http://www.infarctcombat.org/LivroTM/parte8.htmhttp://www.infarctcombat.org/LivroTM/parte8.htm

50.  YouYou cancan findfind recentrecent videosvideos andand powerpointpowerpoint presentationspresentations asas wellwell
articlesarticles andand otherother informationinformation aboutabout thethe myogenicmyogenic theorytheory atat::
 http://www.infarctcombat.org/MyogenicTheory.htmlhttp://www.infarctcombat.org/MyogenicTheory.html