CVS, Cardiac energetics, cardiac biomarkers

1. CARDIAC ENERGETICAND
BIOMARKERS OFCARDIAC
INJURY
By:- Don. Siyum A.

2. Objectives
At the end of this session students able to:
• Cardiac fuels in different metabolic states
• Identify cardiac markers
• Identify specific and non specify markers of cardiac injury
by Don. Siyum A. 2
5/7/2022

3. Introduction
the metabolic demand of the heart is the largest of any organ
has minimal Energy reserves:- ATP and Creatine phosphate,
few glycogen. must be continually nourished
ATP provides energy
for contractile work, for pumping Ca2+ into the sarcoplasmic
reticulum, diastolic relaxation, for maintaining ion gradients
(e.g. Na+ and K+)
normal working conditions : 2/3 of the ATP used to fuel
contractile work, with the remaining 1/3 used for ion pumps
by Don. Siyum A. 3
5/7/2022

4. Fig. Metabolic relationships among the major human
organs. Red arrows indicate preferred routes in the well-fed
state by Don. Siyum A. 4
5/7/2022

5. Table: Energy Metabolism in Major Vertebrate
Organs by Don. Siyum A. 5
5/7/2022

6. • the heart has a relatively low ATP content (5 μmol/g wet wt) and high
rate of ATP hydrolysis (0.5μ mol · g wet wt -1 · s-1 at rest)
• complete turnover of the myocardial ATP pool every 10 s under normal
conditions
• in the healthy heart, the rate of ATP hydrolysis is matched to the
rate oxidative phosphorylation ( ATP content remains constant )
by Don. Siyum A. 6
5/7/2022

7. Sources of ATP in heart
• The primary means for ATP synthesis is oxidative phosphorylation
in the mitochondria (>98%), glycolysis (< 2%).
• post absorptive state 60–90% of the ATP comes from fatty
acids, and 10–40% comes from pyruvate (formed from lactate
and glycolysis)
by Don. Siyum A. 7
5/7/2022

8. Fig: overview of myocardial energy substrate metabolism.
by Don. Siyum A. 8
5/7/2022

9. Fig: ATP production occurs primarily through oxidative
phosphorylation
by Don. Siyum A. 9
5/7/2022

10. • There is a stoichiometric link between the rate of oxidation of carbon
fuels, NADH and FADH2 reduction, flux through the electron
transport chain, oxygen consumption, oxidative phosphorylation, ATP
hydrolysis, actin-myosin interaction, and external contractile power
produced by the heart.
• Thus an increase in contractile power results in a concomitant
increase in all of the components in the system.
by Don. Siyum A. 10
5/7/2022

11. SUBSTRATES FOR ATP SYNTHESIS
• main types of carbon substrates for myocardial ATP
synthesis: fatty acids, glucose, ketone bodies and
lactate
• myocardial metabolism is linked to arterial carbon
substrate concentration, hormone concentrations,
coronary flow, inotropic state, and the nutritional
status of the tissue
by Don. Siyum A. 11
5/7/2022

12. Fat as source of energy
• the heart readily extracts free fatty acids from the plasma and either
oxidizes them rapidly, or converts them to triglyceride stores.
• 80% of the FFA oxidized to CO2 and 20% converted to
triglyceride
• The rate of uptake dependent upon the concentration of FFA in the
plasma ( 0.2 to 0.8 mM), and the content of a specific fatty acid
transport protein in the sarcolemma membrane
by Don. Siyum A. 12
5/7/2022

13. • plasma fatty acid concentration is regulated by their net release from
triglycerides in adipocytes
• the net balance between triglyceride breakdown by
hormone-sensitive lipase and synthesis by
glycerolphosphate acyltransferase (regulated by
catecholamines and insulin)
• released from triglyceride in chylomicrons and in VLDL by lipoprotein
lipase
by Don. Siyum A. 13
5/7/2022

14. Fig. Hormonal regulation of Triacylglycerol degradation
in Adipocyte
by Don. Siyum A. 14
5/7/2022

15. • Fatty acids enter the cardiomyocyte by:
passive diffusion
protein-mediated transport (fatty acid translocase (FAT
or CD 36) or plasma membrane fatty acid binding protein
(FABP)
• FAT and FABP are associated with Fatty acylcoA synthase (FACS) =
(majority FFA activated)
by Don. Siyum A. 15
5/7/2022

16. Fig: Schematic depiction of myocardial fatty acid
metabolism
by Don. Siyum A. 16
5/7/2022

17. by Don. Siyum A. 17
5/7/2022

18. • long-chain fatty acyl-CoA, can either be esterified to
triglyceride by glycerolphosphate acyltransferase or
converted to long-chain fatty acylcarnitine by carnitine
palmitoyltransferase I (CPT-I)
• in the healthy normal heart 70–90% of the fatty acids
entering the cell are converted to acylcarnitine and
immediately oxidized, and 10–30% enter the
intracardiac triglyceride pool.
by Don. Siyum A. 18
5/7/2022

19. • The activity of CPT-I is strongly inhibited by malonylCoA, which binds to
CPT-I on the cytosolic side of the enzyme.
• Malonyl-CoA is a key regulator. role of insulin ??
• fatty acids undergo ß-oxidation. What is it ??
by Don. Siyum A. 19
5/7/2022

20. • Most patients who have impaired fatty acid β-oxidation
develop rhabdomyolysis after sustained exercise.
• Those with more severe disease may also have hypoketotic
hypoglycemia in childhood, along with liver dysfunction; those
with the most severe disease may have cardiomyopathy at
birth and die at a young age
by Don. Siyum A. 20
5/7/2022

21. Ketone as source of energy
• The heart extracts and oxidizes ketone bodies (ß- hydroxybutyrate and
acetoacetate)
• during starvation or poorly controlled diabetes, plasma ketone body
concentrations are elevated secondary to low insulin and high fatty
acids
• fatty acids, glucose and lactate uptake and oxidation are inhibited by
elevated plasma ketone bodies with the inhibitory effect mediated
through product inhibition on PDH
by Don. Siyum A. 21
5/7/2022

22. Carbohydrate as source of energy
• heart consumes glucose
• the uptake of extracellular glucose is regulated by:-
the transmembrane glucose gradient
the concentration and activity of glucose transporters in the
plasma membrane
• two isoforms from the glucose transporter identified in the myocardium,
GLUT 1 and GLUT 4, (GLUT 4 is predominant)
by Don. Siyum A. 22
5/7/2022

23. • there is a translocation of glucose transporters in
response to insulin stimulation, increased work
demand, or ischemia ( the effects of insulin and
ischemia are additive)
• translocation of GLUT-4 into the sarcolemma is also
stimulated by activation of AMP-activated protein
kinase (AMPK)
by Don. Siyum A. 23
5/7/2022

24. • an additional source of glucose 6-phosphate for the heart is intracellular
glycogen stores
• the glycogen pool in the heart is relatively small (30 μmol/g wet wt
compared with 150μmol/g wet wt in skeletal muscle)
by Don. Siyum A. 24
5/7/2022

25. Fig. The pathways and regulatory points of myocardial
substrate metabolism
by Don. Siyum A. 25
5/7/2022

26. Lactate as source of energy
• under resting conditions lactate uptake from the blood (MAT-1)
is a major source of pyruvate formation, supplying
approximately 50% of the pyruvate oxidized by the heart
• during physical exercise, lactate can become the predominant
fuel for the heart
• lactate rapidly oxidized by lactate dehydrogenase,
decarboxylated by pyruvate dehydrogenase (PDH) and
oxidized to CO2 in the Krebs cycle
by Don. Siyum A. 26
5/7/2022

27. • the healthy nonischemic heart is a net consumer of
lactate.
• The myocardium becomes a net lactate producer only when there is
accelerated glycolysis in the face of impaired oxidation of pyruvate
like ischemia or poorly controlled diabetes.
by Don. Siyum A. 27
5/7/2022

28. Inter regulation of Fatty Acid and Carbohydrate
Oxidation
• The primary physiological regulator of flux through PDH and the rate of
glucose oxidation in the heart is the rate of fatty acid oxidation
• High rates of fatty acid oxidation inhibit PDH activity
• increase in mitochondrial acetyl-CoA/free CoA and NADH/
NAD, which activates PDH kinase causing phosphorylation
and inhibition of PDH
• Conversely, inhibition of fatty acid oxidation increases glucose and
lactate uptake and oxidation
by Don. Siyum A. 28
5/7/2022

29. • Pyruvate decarboxylation is catalyzed by PDH, and is the key irreversible step
in carbohydrate oxidation
• PDH is located in the mitochondrial matrix,
• inactivatated by phosphorylation
• activated by dephosphorylation
• PDHK is the predominate form in heart, and is rapidly inducible by
starvation and diabetes
by Don. Siyum A. 29
5/7/2022

30. Regulation of pyruvate dehydrogenase (PDH) activity
by Don. Siyum A. 30
5/7/2022

31. Effects of Substrate Selection on Contractile Function and
Efficiency
• the contractile performance of the heart at a given O2 is
greater when the heart is oxidizing more glucose and lactate,
and less fatty acids
• the theoretical ATP-to-oxygen ratio for glucose or lactate are
3.17 and 3.00, respectively, while for palmitate and oleate the
values are 2.80 and 2.86, respectively
• fatty acid concentrations uncouple oxidative phosphorylation
(decrease the P/O) and cause wasting of O2 by mitochondria
•
by Don. Siyum A. 31
5/7/2022

32. This effect has been demonstrated with
1. lowering plasma free fatty acid by administering an inhibitor of
lipolysis in adipocytes
2. inhibition of CPT-I
3. inhibition of malonylCoA decarboxylase (which elevates malonyl-CoA
content and inhibits CPT-I activity)
4. direct inhibitors of fatty acid -oxidation
• it is important to note that partial inhibitors of myocardial fatty acid
oxidation have been shown to lessen ischemic dysfunction and tissue
damage in animal models of ischemia and reperfusion and have clear
benefits in clinical trials in patients with chronic stable angina
by Don. Siyum A. 32
5/7/2022

33. Metabolism during Myocardial Ischemia and Reperfusion
Myocardial energy metabolism during ischemia is very dependent
upon the duration and severity of ischemia
• Complete elimination of flow results in a rapid depletion of ATP
and Pcr, glycogen, lactate accumulation, and contractile
akinesis, → tissue necrosis and myocardial infarction
• modest reduction in flow (40–60%) causes a decrease in
myocardial oxygen consumption ( l0–50%), a transient
increased dependence on anaerobic glycolysis (glycogen
depletion and lactate production), oxidation of free fatty acids at
a reduced rate, and modest to more severe contractile
dysfunction. by Don. Siyum A. 33
5/7/2022

34. • Despite contractile dysfunction and transient lactate
production during moderate ischemia, the primary oxidative fuel is fatty
acids
Mitochondrial Metabolism in the Failing Heart
• the capacity of the mitochondria for oxygen consumption and oxidative
phosphorylation in failing heart are significantly reduced
• substrate use away from free fatty acids towards glucose
by Don. Siyum A. 34
5/7/2022

35. Biomarkers of cardiac injury

36. • A biomarker is a clinical laboratory
• useful in detecting dysfunction of an organ.
• Cardiac biomarkers
• Acute coronary syndrome resulting from myocardial
ischemia
• Congestive cardiac failure due to ventricular dysfunction
• The different markers are used to
• Detect myocardial ischemia at the earliest
• Monitor the progression of the condition
• Predict the risk in cardiac dysfunction
by Don. Siyum A. 36
5/7/2022

37. CARDIAC MUSCLE CELL
by Don. Siyum A. 37
Size and subcellular distribution of myocardial
proteins/enzymes determines time course of biomarker
appearance in the general circulation
5/7/2022

38. An ideal cardiac marker:
1. must be sensitive enough to detect a small degree of
damage
2. should be specific to the heart muscle
3. should give information regarding the severity of the infarct and the
prognosis of the disease
4. should also show the result of reperfusion therapy in AMI
(reversible and irreversible damage)
5. should help in early and late diagnosis
6. should be easy to measure, fast, cheap, and quantitate
7. should have long-term storage conditions and be stable
by Don. Siyum A. 38
5/7/2022

39. • Commonly used biomarkers for early detection of acute
myocardial infarction are:
1. Cardiac troponins, TnI and TnT
2. Creatine kinase, CK-MB
3. Of these, troponins and CK-MB are the most sensitive
and specific markers, whereas myoglobin though
sensitive, is nonspecific
• Predictors of risk in cardiac disease are of two types:
a. For predicting the onset of ischemia
b. Those which quantify the ventricular damage
by Don. Siyum A. 39
5/7/2022

40. Biochemical Changes
by Don. Siyum A. 40
BIOCHEMICAL MARKERS
release of intracellular
contents to blood
clinical manifestations
(chest pain)
ECG
changes
ischemia to myocardial muscles (with low O2 supply)
anaerobic glycolysis
increased accumulation of Lactate
decrease in pH
activate lysosomal enzymes
disintegration of myocardial proteins
cell death & necrosis
5/7/2022

41. TIME LINE OF MARKERS OF MYOCARDIAC DAMAGE &
FUNCTION
by Don. Siyum A. 41
1950 1960 1970 1980 1990 2000 2005
AST in
AMI CK in
AMI
Electrophoresis
for CK and LD
CK – MB
Myoglobin assay
RIA for
ANP
CK-MB
mass assay
cTnT assay
RIA for BNP
and proANP
cTnl assay
RIA for
proBNP
POCT for myoglobin CK-
MB, cTnI
Immuno assay for
proBNP
IMA
Genetic
Markers
Timeline history of assay methods for markers of cardiac tissue damage and myocardial function.
AST: aspartate aminotransferase ANP: atrial natriuretic peptide
CK: creatine kinase BNP: brain natriuretic peptide
LD: lactate dehyydrogenase POCT: point-of-care testing
cTn: cardiac-specific troponin IMA: ischaemia-modified albumin
Time [years]
5/7/2022

42. Aspartate aminotransferase
• The first biomarker used in the diagnosis of AMI, it is not specific to the heart
Lactate dehydrogenase
• LDH has five isoenzymes
• In myocardial infarction, total LDH activity is increased, while H4 isoenzyme is
increased 5–10 times more
• Increase in total LDH level is seen in hemolytic anemias, hepatocellular
damage, muscular dystrophy, carcinomas, leukemias, and any condition which
causes necrosis of body cells
by Don. Siyum A. 42
5/7/2022

43. Tissue distribution of LDH
Iso-enzyme Composition Present in
LDH1 ( H4) Myocardium, RBC, kidney
LDH2
(H3M1)
Myocardium, RBC,
serum, kidney
LDH3 (H2M2) Kidney, Skeletal muscle
LDH4 (H1M3) Kidney, Skeletal muscle
LDH5 (M4) Skeletal muscle, Liver
by Don. Siyum A. 43
5/7/2022

44. Characteristics of LDH Isoenzymes
by Don. Siyum A. 44
5/7/2022

45. • It increases within 6–12 hours from the onset of chest pain, peaks over
1–3 days, and returns to normal values within 8–14 days.
• LDH1:LDH2 ratio >1 is reported to be specific for AMI, but currently it is
not used in the diagnosis of AMI.(Flip pattern)
• Today, the only use of LDH is in distinguishing acute from sub-acute MI
in patients
by Don. Siyum A. 45
5/7/2022

46. Normal vs. MI
Normal
LD1:LD2 = 0.5-0.75
MI
LD1:LD2 > 1
by Don. Siyum A. 46
5/7/2022

47. Creatine kinase and CK-MB
• Three isoenzymes: CK-BB (CK1), CK-MB (CK2), and CK-MM (CK3). CK-
MM is the dominant form found in all tissue.
• 20% of CK in the myocardium is in the MB form, giving sensitivity and
specificity in the diagnosis of AMI. 5% in skeletal muscle.
• CK-MB reaches its highest point within 24 hours, starting to increase after
4–6 hours, returns to normal within 2 - 3 days
by Don. Siyum A. 47
5/7/2022

48. CK isoezymes
Serum Skeletal
Muscle
Cardiac
Muscle
Brain
0 trace BB
<6% MB
>94% MM
0 trace BB
<5% MB
95% MM
0% BB
20% MB
80% MM
97% BB
3% MB
0%MM
by Don. Siyum A. 48
5/7/2022

49. • the CK level is not increased in hemolysis or in congestive
cardiac failure; CK has an advantage over LDH.
• not used for delayed admission (more than 2 days)
Limitation of CKMB to be a specific marker of AMI
• its increasing level during trauma , Duchenne Muscular
Dystrophy, Polymyositis, Carcinomas (Colon, Lung,
Prostate, Endometrial..), Athletes (e.g. Marathon
runners)…and inflammation
by Don. Siyum A. 49
5/7/2022

50. Table: Characteristics of iso-enzymes of CK
by Don. Siyum A. 50
5/7/2022

51. Time course of elevation of CK-MB and cardiac troponins in
blood of myocardial infarction patients
by Don. Siyum A. 51
5/7/2022

52. CK-MB
by Don. Siyum A. 52
5/7/2022

53. CK-MB mass
• appears one hour earlier than CK-MB activity (more sensitive)
• So, useful for diagnosis of early cases & re-infarction
• BUT: not for diagnosis of delayed admission cases & less
specific than troponin I
CK-MB relative index
• CK-MB mass/total CK mass × 100
• If this index is 2.5% or above, CK-MB is probably of myocardial origin
by Don. Siyum A. 53
5/7/2022

54. Total CK can be elevated
• False positive (for MI) CK elevation can be seen in:
• Significant skeletal muscle injury
• Significant CNS damage (Stroke/Trauma)
• Occasionally from GI, renal, urologic disease
• Others: injection, hypothermia, exercise, intoxication and
drug abuse
by Don. Siyum A. 54
5/7/2022

55. Myoglobin in diagnosis of AMI
• Myoglobin abundantly present in the heart and skeletal muscle
• It is rapidly released (rises in the first 30 minutes) from the
myocardium during the injury and is rapidly excreted from the
kidneys within 24 hours
• It is elevated in all AMI patients within 6–10 hours and peaks at
the 12th hour. (early detection of AMI)
• It is a sensitive marker for AMI, but has no specificity
• Since it has no specificity, negative values are important in the
clinic, rather than positive values
by Don. Siyum A. 55
5/7/2022

56. Troponins
• TN-T: tropomyosin binding subunit
• TN-I: myosin ATPase inhibiting subunit
• TN-C: calcium binding subunit
by Don. Siyum A. 56
5/7/2022

57. • the most important cardiac proteins involved in the diagnosis
of AMI are TnC, TnI and TnT.
• cTnT and cTnI are different from troponins in the skeletal
muscle
• present the cytosolic pool(5%), and the contractile apparatus
(95%)
• the amount of TnC per gram of myocardium is 13–15 times
greater than the amount of CK-MB.
• cTn has higher sensitivity compared to CK-MB in the early
period by Don. Siyum A. 57
5/7/2022

58. • Cardiac troponins are elevated in different clinical conditions,
although their sensitivity and specificity are significantly higher
in detecting coronary ischemia.
• blood levels increase within 2–4 hours after
acute myocardial damage and reach peak levels in 24 hours.
• Blood cTn levels are high for 2 weeks.
by Don. Siyum A. 58
5/7/2022

59. Relative Marker increase after myocardial infraction
by Don. Siyum A. 59
5/7/2022

60. Why is release of troponin prolonged?
• Most is bound to the contractile apparatus of the cardiomyocyte
• 3% of cTnI and 6% of cTnT exist free in the cytoplasm.
• This gives the biphasic response of troponins with a rapid rise and
prolonged elevation.
• The initial elevation of cTnI or cTnT is thought to be a function of the free
cytolsolic form
• The prolonged elevation is caused by degradation of the contractile
pool
by Don. Siyum A. 60
5/7/2022

61. cTnI:
• 100 % cardiac specific
• With greater sensitivity for diagnosing minor damage of MI
• Appears in blood within 6 hours after onset of infarction
• peak: around 24 hours
• Disappears from blood after about one week (stays longer), So, useful
for diagnosis of delayed admission cases
• Prognostic marker (relation between level in blood & extent of cardiac
damage)
by Don. Siyum A. 61
5/7/2022

62. Advantages
• The existence of the cardiac –specific isoform makes them the
most specific of all biochemical markers for cardiac damage.
Highly specific markers of detecting MI
• Higher sensitivity than CK-MB
• Fewer false-positive results in the setting of trauma, surgery, and
renal failure as compared to CK-MB
• Prognostic of death from acute coronary syndrome
by Don. Siyum A. 62
5/7/2022

63. Disadvantages
• It lacks sensitivity in the early hours of AMI
• Pulmonary embolism, congestive heart failure, and myocarditis
can all lead to cardiac troponin elevation
by Don. Siyum A. 63
5/7/2022

64. Brain Natriuretic Peptide (BNP)
• The natriuretic peptide family consists of three peptides:
Atrialnatriuretic peptide (ANP), brain natriuretic peptide
(BNP), and C-type natriuretic peptide (CNP).
• ANP is produced primarily in the cardiac atria.
• BNP is present in human brain, but more in the cardiac
ventricles.
• natriuretic peptides has a strong diuretic effect, promotes
vasodilation, and facilitates cardiovascular remodeling and
response to ischemia
by Don. Siyum A. 64
5/7/2022

65. by Don. Siyum A. 65
5/7/2022

66. • Patients with congestive heart failure have high plasma
concentrations of ANP and BNP.
• The concentrations are correlated with the extent of ventricular
dysfunction.
• The best marker of ventricular dysfunction is pro-BNP.
• High concentrations of BNP predict poor long-term survival.
• Normal level of NT-proBNP is less than 400 ng/L.
• Less than 250 ng make heart failure highly unlikely
by Don. Siyum A. 66
5/7/2022

67. Ischemia-modified albumin (IMA) in diagnosis of
AMI
• A structural change in the N-terminus of albumin in patients with
myocardial ischemia was discovered, and this albumin showed lower
metal-binding capacity with cobalt on the albumin–cobalt binding test.
• IMA rise can be detected by this test 3 hours after the appearance
symptoms (sensitivity 70%, specificity 80%, positive predictive value
96%).
• However, the detection of high IMA levels in patients, with cancer,
infection, brain ischemia, liver disease, and, end-stage renal disease limits
the specificity of this test in, the diagnosis of AMI.
by Don. Siyum A. 67
5/7/2022

68. Ischemia-Modified Albumin (IMA)
by Don. Siyum A. 68
5/7/2022

69. IMA is a marker of ischemia
by Don. Siyum A. 69
5/7/2022

70. Summary
by Don. Siyum A. 70
5/7/2022

71. SPECIFICITY OF CARDIAC MARKERS
by Don. Siyum A. 71
50
60
70
80
90
100
TROPONIN-I
70%
87%
92%
99%
CK-MB TOTAL CK MYOGLOBIN
5/7/2022

72. Why do we need multiple Markers?
• No single ideal marker exists
• Complicated diseases are not likely to be associated
with single markers
• Multiple markers define disease categories
• Multi-marker panels can aid in differential diagnosis
by Don. Siyum A. 72
5/7/2022

73. MARKER TISSUE
SOURCE
PHYSIOLOGIC
FUNCTION
“DIAGNOSTIC
WINDOW”
CLINICAL
UTILITY
Creatine
Kinase (CK)
Total Activity
Skeletal
muscle
Cardiac
muscle
Skeletal
muscle
Rephosphorylation
of ADP, forming
ATP in muscle
contraction
Rise: 6-8 hr
Peak: 24-36 hr
Normal: 3-4
days
Limited
diagnostic
value since it is
increased in
various disease
states.
CK isoenzyme
analysis is
more useful for
diagnosis
by Don. Siyum A. 73
5/7/2022

74. MARKER TISSUE
SOURCE
PHYSIOLOGIC
FUNCTION
“DIAGNOSTIC
WINDOW”
CLINICAL
UTILITY
CK-MB
Isoenzyme,
Mass (amount,
not activity)
Cardiac
muscle
Skeletal
muscle to a
much
lesser extent
Same as above Rise: 4-6 hr
Peak: 12-24 hr
Normal: >48 hr
Mass assay of
CK-MB
isoenzyme,
the current
“gold
standard” for
early
diagnosis of
AMI
by Don. Siyum A. 74
5/7/2022

75. MARKER TISSUE
SOURCE
PHYSIOLOGIC
FUNCTION
“DIAGNOSTIC
WINDOW”
CLINICAL
UTILITY
CK-MB
Isoforms and
Isoforms ratio
Same as
above
Same as above Rise: 2-6 hr
Peak: 6-12 hr
Normal: 24-36
hr
Early
marker of
AMI, more
specific than
myoglobin
Myoglobin Cardiac
muscle
Skeletal
muscle
Oxygen binding
protein
Rise: 2-3 hr
Peak: 6-9 hr
Normal: 24-36
hr
Non-specific
early marker
to rule
in/rule out
AMI
by Don. Siyum A. 75
5/7/2022

76. MARKER TISSUE
SOURCE
PHYSIOLOGIC
FUNCTION
“DIAGNOSTIC
WINDOW”
CLINICAL
UTILITY
Cardiac
Troponin I
Cardiac
muscle
Muscle contraction
regulatory protein;
bound to
tropomyosin and
actin
Rise 4-8 hr
Peak: 14- 18 hr
Normal: 5-9 days
Highly specific
for myocardial
injury
Useful for
patients with
atypical
symptoms or
those who delay
seeking medical
attention
Potential to
diagnose AMI in
patients who also
have
concomitant
skeletal muscle
trauma/disease
Potential usage
to risk stratify
angina pectoris
by Don. Siyum A. 76
5/7/2022

77. MARKER TISSUE
SOURCE
PHYSIOLOGIC
FUNCTION
“DIAGNOSTIC
WINDOW”
CLINICAL
UTILITY
Cardiac
Troponin T
(cTnT)
Cardiac
muscle;
regenerating
skeletal
muscle
Same as above Rise: 4-8 hr
Peak: 14-18 hr
Normal: >14
days
As above for
cTnI
by Don. Siyum A. 77
5/7/2022

78. Reading Assignment:
OTHER FUTURE CARDIAC MARKERS
by Don. Siyum A. 78
5/7/2022

79. by Don. Siyum A. 79
5/7/2022