Myocardial protection DR NIKUNJ R SHEKHADA (MBBS ,MS GRN SURG , DNB CTS SR

1. MYOCARDIAL PROTECTION
BY DR NIKUNJ
(CTS RESIDENT STAR HOSPITAL)
(Coordinator:DR P.SATYENDRANATH PATHURI)
(22/10/18)

2. HISTORICAL DEVELOPMENT
• After the initiation of open heart surgery with use of extra- corporeal circulation by
Gibbon, it soon became obvious that aortic cross-clamping was necessary to
provide a bloodless field to facilitate the precise repair of intracardiac defects, to
prevent air embolism when the left side of the heart was opened, and to avoid a
turgid myocardium resistant to retraction.
• To overcome the difficulties of operating on a rheumatic mitral valve in a patient
with aortic regurgitation, Melrose and colleagues introduced the concept of
“elective cardiac arrest” by rapidly injecting into the aortic root, after aortic cross-
clamping, a 2.5% potassium citrate solution in warm blood to arrest the heart.
• myocardial necrosis associated with the Melrose technique.

3. MYOCARDIAL PROTECTION
• Involves strategies and methods used to reduce or prevent post-ischemic
myocardial dysfunction during and after heart surgery.

4. NON-CARDIOPLEGIC TECHNIQUES
FIBRILLATORY ARREST
• Electrically induced ventricular brillation with coronary perfusion was introduced
by Glenn and Sewell and Senning as a means of avoiding air embolism.
• subendocardial ischemia and necrosis with this technique.
• Not applicable for intracardiac procedures
• Field may be obscured by blood during revascularization
• Ventricular fibrillation is associated with increased muscular tone (can limit
surgeon’s ability to position the heart for optimal exposure)

5. CONTINUOUS CORONARY PERFUSION
• In an attempt to mimic the physiologic state, continuous coronary perfusion with a
beating heart at normothermia or mild hypothermia at 32°C to prevent the onset
of ventricular fibrillation became the preferred technique of myocardial
preservation in the late 1960s and early 1970s,
• particularly after the report by McGoon and colleagues17 of 100 consecutive
aortic valve replacements with no deaths.
• continuous perfusion became intermittent as coronary perfusion was often
discontinued to achieve better visualization of the operative field during critical
portions of the procedure.
• In addition, problems with the coronary cannula, such as poor fixation, leaking
associated with calcified ostia, early division of the left main coronary artery
resulting in high perfusion pressure necrosis, and damage to the coronary artery
such as dissection and late stenosis, continued to occur.

6. HYPOTHERMIA
• The earliest attempts to perform open heart surgery before the advent of the heart-
lung machine used systemic hypothermia produced by surface cooling not only to
protect the heart but to protect the brain and other organs during circulatory arrest
• Hypothermia protects the ischemic myocardium by decreasing heart rate, slows the
rate of high-energy phosphate degradation,24 and decreases myocardial oxygen
consumption .
• concept of profound local (topical) hypothermia by filling the pericardial sac with ice-
cold saline.
• this technique is still used as an adjunct to other methods of myocardial protection, it is
rarely used as the sole protec- tive method because of the problem of warm bronchia
collateral flow reaching the heart cavity, resulting in transmyocardial temperature
gradients and resultant ischemia.
•

7. • Hypothermia and potassium infusions remain cornerstone of myocardial
protection during on- pump heart surgery
• Other cardioprotective techniques and methods are available.
•
• Ideal cardioprotective technique, solution, and method of administration have yet
to be found

8. BIOLOGY OF SURGICALLY INDUCED MYOCARDIAL ISCHEMIA
• Myocardial Oxygen Consumption :
• Myocardial oxygen reserve is exhausted within 8 seconds after the onset
of normothermic global ischemia.
• Myocardial oxygen consumption ( MVO2) is compartmentalized into the
oxygen needed for external work of contraction (80% to 90%) and the
unloaded contraction, such as basal metabolism, excitation-contraction
coupling, and heat production.
• A unique aspect of myocardial energetics is that 75% of the coronary
arterial oxygen presented to the myocardium is extracted during a single
passage through the heart;

9. BIOLOGY OF SURGICALLY INDUCED MYOCARDIAL ISCHEMIA
• Biochemical Alterations:
• Under aerobic conditions, the heart derives its energy primarily from
mitochondrial oxidative processes, using substrates such as glucose, free
fatty acids, lactate, pyruvate, acetate, ketone bodies, and amino acids.
However, oxidation of fatty acids provides the major source of energy
production and is used in preference to carbohydrates.
• as tissue PO2 falls, oxidative phosphorylation, electron transport, and
mitochondrial adenosine triphosphate (ATP) production cease.
• Reduced mitochondrial activity leads to the accumulation of glycolytic
intermediaries, reduced NADH, and the reduction of pyruvate to lactate.
The resultant severe intracellular acidosis impairs contractile function,
enzyme transport, and cell membrane integrity.
• This results in a cellular loss of potassium and pathologic accumulation of
sodium, calcium, and water

11. ISCHEMIA-REPERFUSION INJURY

12. CALCIUM HYPOTHESIS
• Inability of myocyte to modulate
intracellular and intraorganellar calcium
homeostasis.
•
• Cascade of events culminating in cell
injury and death is induced .
• Calcium.
• if given as patients come off of bypass,
it can lead to contracture of heart
(maximally contracted heart)
• Therefore, it is desirable to avoid
calcium when heart is recovering from
arrest

14. FREE RADICAL
HYPOTHESIS
• Accumulation of reactive oxygen
species (ROS) – during early stages
of reperfusion – causes myocardial
cellular damage and cell death
through microscomal peroxidation
of cellular phospholipid layer
• Leads to loss of cellular integrity
and function

15. • Stunning: “describes the mechanical dysfunction that persists after reperfusion
despite the absence of myocellular damage and despite the return of normal or
nearnormal perfusion.”
• Hibernation:, which is a syndrome of reversible, chronically reduced contractile
function as a result of one or more recurrent episodes of acute or persistent
ischemia, referred to as chronic stunning

16. IRREVERSIBLE CELL INJURY
• necrosis and apoptosis.
• Necrosis is initiated by noncellular mechanisms with cell swelling, depletion of
ATP stores, and disruption of the cellular membrane involving uid and electrolyte
alterations.
• In contrast, apoptosis (programmed cell death) is an evolution-based mode of cell
death characterized by a discrete set of biochemical and morphologic events
involving the regulated action of catabolic enzymes (proteases and nucleases) that
results in the ordered disassembly of the cell, distinct from cell death provoked by
external injury.

17. ISCHEMIA-REPERFUSION INJURY
• INFLAMMATION
• In ammation has been implicated as a secondary mecha- nism contributing to
injury after reperfusion. It is initi- ated through complement activation leading to
the sequential formation of a membrane attack complex, which creates a cellular
lesion and eventual cell lysis.
• EFFECTS OF AGE
• The vulnerability of the heart to ischemia-reperfusion injury is altered with
temporal development. The newborn heart is more resistant to the effects of
ischemia- reperfusion.
• in the adult heart, functional recovery is significantly delayed
• CYANOSIS
• Cyanosis signi cantly increases the vulnerability of the myocardium to ischemia-
reperfusion injury.
• VENTRICULAR HYPERTROPHY
• Hypertrophied hearts have an increased vulnerability to ischemic injury

18. • All patients undergoing cardiac surgery have varying degrees of myocardial
stunning
• Evidence:
• Requirement of inotropic support for separation from bypass
• Support may last from hours to days after surgery
• Patients are eventually weaned from these drugs as the stunning abates, without
objective evidence of MI

19. CARDIOPLEGIA: BASIC PRINCIPLES
• (1) rapid induction of arrest,
• (2) mild or moderate hypothermia,
• (3) appropriate buffering of the cardioplegic solution,
• (4) avoidance of myocardial edema, and
• (5) avoidance of substrate depletion.

20. (1) RAPID INDUCTION OF ARREST
• Rapid cardiac arrest remains the mainstay of adequate myocardial protection and
is “achieved by targeting various points in the excitation-contraction coupling
pathway”

21. DEPOLARIZED ARREST
• Potassium is the most common agent used for chemical cardioplegia and produces
rapid diastolic arrest.
• As the extracellular potassium concentration increases, the resting myocardial cell
membrane becomes depolarized; the voltage-dependent fast sodium channel is
inactivated, arresting the heart in diastole; and the slow calcium channel is
activated, resulting in cytosolic calcium overload
• The optimum concentration of potassium is thought to vary between 15 and 40
mmol/liter although it has been suggested that concentrations exceeding 20
mmol/liter promote calcium overload and subsequent injury.
• Because the heart will remain arrested until the concentration of extracellular
potassium or other cardioplegic ingredient is decreased by noncoronary collateral
mediastinal blood flow, reinfusions of cardioplegia are necessary every 15 to 30
minutes
•

23. POLARIZED ARREST
• Agents inducing polarized arrest, in which the cell membrane potential remains
close to resting potential, have significant advantages by limiting ionic movement
and thereby reducing myocardial energy use
• Sodium channel blockade, which arrests the heart by preventing the rapid sodium-
induced depolarization of the action potential, includes procaine and tetrodotoxin.
This class of drugs has been used successfully experimentally but is rarely used
clinically at present.

24. • Potassium channel openers induce arrest by membrane hyperpolarization, couple
the membrane potential to the cellular metabolic status, and afford
cardioprotection by a similar mechanism associated with ischemic
preconditioning.
• their clinical use remains controversial.

25. • Adenosine is an endogenous nucleoside
• Extracellular adenosine is cleared through cellular uptake, primarily by
erythrocytes and vascular endothelial cells, and has a reported half-life of less than
10 seconds in whole blood, which limits its use during a prolonged period of
surgically induced ischemia.
• Adenosine induces hyperpolarized cardiac arrest by antagonizing calcium channels
and has been shown to inhibit both the sinoatrial and the atrioventricular nodes
and atrial myocardial contraction.
• Adenosine, by its ability to antagonize the direct depressant effects on both the
sinoatrial and atrioventricular nodes and atrial tissue, results in sinus slowing and
arrest.

26. HYPOTHERMIA
• Hypothermia, whether it is mild (tepid at the room temperature range of 28° C to
32° C) or moderate (22° C to 25°C), continues to remain an indispensable adjunct
for adequate myocardial protection.
• hypothermia decreases the rate of the metabolic degradation of energy stores
during surgically induced ischemia.
• However, there is minimal advantage in reducing the myocardial temperature
below 22° C, because the MVO2 is decreased by only a minimal amount, from 0.31
mL at 22°C to 0.27 mL at 15°C per 100 g of left ventricular tissue per minute

27. BUFFERING OF THE CARDIOPLEGIC SOLUTION
• Buffering of the cardioplegic solution is necessary to combat the
unremitting intracellular acidosis associated with surgically induced
myocardial ischemia.
• Because the myocardium has the highest oxygen use of any organ in the
body related to its concentration of mitochondria, ischemia results in the
rapid accumulation of hydrogen ions and the reduction of intracellular pH
• here is clinical evidence that maintenance of the tissue pH of 6.8 or
greater is associated with adequate myocardial protection
• In addition, hypothermia assists in the neutralization of acidosis because
pH rises 0.0134 unit for each decrease in degree centigrade.
• Bicarbonate, phosphate, aminosulfonic acid,
tris(hydroxymethyl)aminomethane (THAM), and histidine buffers have all
been used as cardioplegia additives to modulate pH.

28. AVOIDANCE OF MYOCARDIAL EDEMA
• Avoidance of myocardial edema by controlling osmolarity is important to control
volume regulation of the fluid compartments of the heart because myocardial
edema is a known consequence of ischemia.
• The extent of myocardial edema has been shown to be directly modulated by
osmolarity and onconicity of cardioplegia, with decreases being directly associated
with increased myocardial edema and impaired diastolic filling.
• The extent of myocardial edema has been shown to be directly modulated by
osmolarity and onconicity of cardioplegia, with decreases being directly associated
with increased myocardial edema and impaired diastolic filling.
• In addition to cardioplegic infusions, the hemodilution from crystalloid priming of
the extracorporeal circuit, the activation of humoral and cellular mediators that
increase microvascular permeability, and the impairment of myocardial lymphatic
function may play major roles in the development of myocardial edema.
• Myocardial lymphatic function is dependent on the beating heart to transport
fluid and is significantly reduced or completely stopped during cardiac arrest.

29. CRYSTALLOID CARDIOPLEGIA
• With the advent of myocardial protection, asanguineous solutions
composed of varying electrolyte compositions, but always featuring
hyperkalemic diastolic arrest, were clinically used in Europe in the early
1970s and in the United States in the late 1970s.
• However, these solutions contained minimal amounts of dissolved oxygen,
whereas the myocardium consumes 0.33 mL of oxygen per 100 g at 15° C.
Because even a short period of ischemia results in the gradual
accumulation of oxygen debt, moderate to severe myocardial hypothermia
is necessary to prevent the rapid degradation of energy stores

30. CRYSTALLOID CARDIOPLEGIA
• Patients are first placed on CPB
• Cooled to between 28-33 °C
• Soln infused after cross-clamping aorta through cardioplegic catheter inserted into
aorta proximal to cross-clamp

31. BLOOD CARDIOPLEGIA
• In an attempt to avoid the oxygen deficits associated with crystalloid
cardioplegia, blood was introduced as a Suitable vehicle to obtain
optimum oxygenation.
• Experimentally, blood cardioplegia has been demonstrated to be superior
to oxygenated crystalloid cardioplegia.
• the physiologic advantages of blood include the buffering and reducing
capacity, the presence of colloid to avoid adverse oncotic pressure
gradients, and the presence of oxygen free radical scavengers
• The early blood cardioplegia solutions used a ratio of four parts blood to
one part crystalloid (4 : 1)
• Del Nido cardioplegia techniques The cardioplegia solution is administered
as a single dose, using dilute blood in a 1 : 4 ratio,

32. METHODOLOGIES
warm blood cardioplegia
• Warm heart surgery assumes that aerobic arrest, whereby the heart is
electromechanically arrested and continuously perfused with warm blood
cardioplegia, is the ideal statefor the performance of safe cardiac surgery.
• ADVANTAGES of this technique include
• the presumed elimination of anaerobic ischemic injury with cross-clamp times
safely extended up to 6.5 hours;
• the early resumption of a normal sinus rhythm after removal of the aortic clamp;
• the avoidance of a prolonged rewarming and reperfusion time, thus decreasing
total bypass time; and the elimination of systemic hypothermia and associated
vasoconstriction in the early postoperative period.
• PROBLEMS :
• However, difficulties in visualization of the operative field, particularly in
performing distal coronary anastomoses, mandated temporary discontinuation of
the warm cardioplegic infusion,

33. COLD BLOOD CARDIOPLEGIA
• Prepared by combining autologous blood from extracorporeal circuit (while
patient is on CPB) with a crystalloid soln of:
• citrate-phosphate-dextrose (CPD)  lowers ionic calcium
• tris-hydroxymethyl-aminomethane (tham) or bicarbonate buffersmaintains
alkaline pH of ~7.8
• potassium chloride  arrests heart at 30 mmol/L
• pH = 7.4 is physiologic, but pH is temp dependent, and optimal buffering occurs
when pKa is 7.8.

34. COLD BLOOD CARDIOPLEGIA
• Reasons to use blood for hypothermic potassium-induced cardiac arrest:
• Provides oxygenated environment
• Provides method for intermittent reoxygenation of heart during arrest
• Can limit hemodilution when large volumes of cardioplegia are used
• Has excellent buffering capacity
• Has excellent osmotic properties
• The electrolyte composition and pH are physiologic
• Contains endogenous antioxidants and free-radical scavengers
• Is less complex than other solns to prepare

35. TEPID (29°C) CARDIOPLEGIA
• introduced as a means of overcoming the deficits of warm cardioplegia, without
the adverse effects of cold cardioplegia.
• Both cold blood and warm blood solns have temperature related advantages and
disadvantages

36. METHODS OF DELIVERY
• Methods of Delivery ;
• INTERMITTENT ANTEGRADE
• ANTEGRADE VIA THE CORONARY
BYPASS GRAFTS
• CONTINUOUS ANTEGRADE
• CONTINUOUS RETROGRADE
• INTERMITTENT RETROGRADE
• ANTEGRADE FOLLOWED BY
RETROGRADE
• SIMULTANEOUS ANTEGRADE AND
RETROGRADE

37. RETROGRADE PERFUSION
• 1965 – Lillehei et al. Dis Chest.
• Reported use of retrograde perfusion to protect
heart during aortic valve surgery
• ADVANTAGE of ensuring a more homogeneous
distribution of cardioplegic soln to regions of heart
that are poorly collateralized
• Effective in setting of AR and valve surgery
• Effective in reducing risk of embolization from
SVGs that could occur during antegrade perfusion
during re-op CABG
• Effective in delivering cardioplegia in continuous
manner
• LIMITATIONS:
• Soln can be poorly distributed to the right ventricle
due to the variable venous anatomy of the heart
• Best and most continuous perfusion of the anterior
left and right ventricles is achieved using antegrade
and retrograde routes simultaneously

38. Thank you