CARDIAC PROTEINS

Myoglobin

Small heme protein found in skeletal and cardiac muscles;

Transports and stores oxygen from hemoglobin to intracellular respiratory enzymes of contractile cells

2%

Myoglobin is approximately how much of total muscle protein?

18 kDa

Myoglobin molecular weight

Nephrotoxin

Myoglobin is a potential what?

Immunoassay

Method for myoglobin

>100 ug/L

Serum AMI value of myoglobin

Positive reaction

Urine myoglobin dipstick reaction for occult blood due to pseudoperoxidase activity

Ischemic muscle cells

Myoglobin is one of the protein markers to diffuse out of what?

Chest pain (angina);

Acute myocardial infarction (AMI)

Myoglobin is a marker for what and early detection of what?

1-3 hours

In AMI, myoglobin onset is in how many hours?

5-12 hours

In AMI, myoglobin peak level is in how many hours?

18-30 hours

In AMI, myoglobin plasma level normalizes in how many hours?

Reperfusion

Myoglobin is a useful marker for monitoring the success or failure of what?

AMI

Angina

Acute myositis

Rhabdomyolysis

Muscle trauma

Strenous excercise

Intramascular injection

Acute renal failure

Increased level of myoglobin

Troponin

Regulatory complex of 3 proteins that bind to the thin filaments of striated muscles

Myosin and actin

Troponin is the regulators of what?

Cardiac troponin T (cTnT) and cardiac troponin I (cTnI)

Two types of cardiac troponin

Calcium-meditated regulation

Troponin is vital for what that helps regulate skeletal and cardiac muscle contraction?

Troponin C

Does not have cardiac specificity since its cardiac isoform is shared by slow-twitch skeletal muscles

Troponin t (TnT/tropomyosin-binding subunit)

Valuable tool in the diagnosis of AMI;

Useful for assessment of early and late AMI

Unstable angina

Troponin T is a sensitive marker for the diagnosis of what?

Thrombolytic therapy

Troponin T is useful in monitoring the effectiveness of what in AMI patients?

Fetal skeletal muscle

Troponin T is also detected in what skeletal muscle?

3-4 hours

In AMI, troponin T onset is how many hours?

10-24 hours

In AMI, troponin T peak level is in how many hours?

7 days

In AMI, troponin T returns to normal in how many hours?

TNNT1

TnT gene for slow skeletal muscle

TNNT2

TnT gene only located in the cardiac muscle

TNNT3

TnT gene for fast skeletal muscle

0-0.1 ng/mL

Reference range of troponin T

<15 ng/L

Male reference range for troponin T

<10 ng/L

Female reference range for troponin T

Troponin I (inhibitory subunit or actin binding unit/TnI)

Highly specific and sensitive marker for acute myocardial infarction

Myocardium

Troponin I is the only troponin isotope present in where and is not expressed during any developmental stage in skeletal muscle?

No

Is TnI elevated with renal failure?

Yes

Is TnT elevated in renal failure?

Cardiac necrosis

TnI is a very senstive indicator of even minor amount of what?

3-6 hours

In AMI, TnI onset rise in how many hours?

12-18 hours

In AMI, TnI peak rise in how many hours?

5 to 10 days

In AMI, TnI return to normal in how many days?

TNNI1 and TNNI2

TnI gene found in skeletal muscles

TNNI3

TnI gene found only in the cardiac muscles

0-0.4 ng/mL

Reference range of troponin I

TnC, TnT, TnI

Subunits of troponin

Calcium ions

Troponin C is an 18 ku proteint that binds what?

Tropomyosin

Troponin t is a 37 ku protein that binds to what thereby attaching the troponin complex to the thin filament?

Skeletal muscle disease

Troponin T is elevated in what?

Actin

Troponin I is a 24 ku protein that binds to what?

Calcium

Troponin I decreases troponin C affinity for what?

Actin-myosin interaction

TnI inhibits what interaction?

Cardiac troponins

Preferred biomarkers in acute coronory syndrome

Immunoassay

Method for troponin subunits

Heparinized plasma

Sample used for troponin subunits

Biotin

Negative interference of troponin subunit

>1.5 ng/mL

Suggestive level of troponin subunit of AMI

Type 1 SMF (slow-twitch oxidative)

Type 2 SMF

Types of skeletal muscle fibers

Type IIa: fast twitch oxidative

Type IIb: fast twitch glycolytic

2 types of type 2 SMF

Atherosclerotic plaque disruption with thrombosis

Myocardial injury related to acute myocardial ischemia

Reduced myocardial perfusion

Increased myocardial demand

Myocardial injury related to acute myocardial ischemia because of oxygen supply/demand imbalance

Myofilaments

Majority of cardiac troponins is bound to what?

Myocardial injury

Any elevated result for cTn, defined as result above the 99th percentile of a reference population

Acute myocardial injury

Requires a rise/or fall in the mentioned biomarker values, with persistanly elevated cTn levels then it is chronic myocardial injury

Chronic myocardial injury

If the clinical presentation of myocardial injury is without the concomitant rise and/or fall in the mentioned biomarker values, with persistently elevated cTn levels then it is what type of myocardial injury?

Cardiac procedural myocardial injury

Marked isolated elevation of cTn values within the 48-hour post operative period, even in the abscence of ECG/angiographic or other imaging evidence of MI, indicates prognostically significant what?

Myocardial ischemia

Happens when the heart has insufficient blood supply due to heart block caused by, for instance, atherosclerosis

Cardiac troponins

Help determine who has acute MI

Myocardial ischemia

Diagnosis of MI begins with what?

ECG and patient’s history

Myocardial ischemia is determined through what?

Myocardial infarction

Defined pathologically as myocardial cell death due to prolonged ischemia

Diminished cellular glycogen

Relaxed myofibrils

Sarcolemmal disruption

Myocardial infarction first ultrastructural change

10-15 minutes

The first ultrastructural changes of myocardial infarction are observed as early as how many minutes after the onset of ischemia?

10 minutes

Mitochondrial abnormalities are observed as early as how many minutes after coronary occlusion by electron microscopy and are progreesive?

Type 1 MI

Caused by acute coronary atherothrombotic myocardial injury with either plaque rupture or erosion

Type 2 MI

Caused by acute myocardial ischemia without acute coronary atherothrombotic injury but with oxygen supply-demand imbalance

Type 3 MI

Caused by typical presentation of myocardial ischemia/infarction with presumed new ischemic ECG changes or ventricular fibrillation

Type 4a MI

Caused by percutaneous coronary intervention

Type 4b MI

Caused by stent/scaffold thrombosis associated with percutaneous coronary intervention

Type 4c MI

Caused by restenosis associated with percutaneous coronary intervention

Type 5 MI

Caused by coronary artery bypass grafting

Atherosclerosis and thrombosis

Type 1 MI is characterized by what symptoms?

One value above

Type 1 MI detects a rise and/or fall of cTn values at least how many value above the 99th percentile URL

Coronary artery disease

Reduced myocardial perfusion

Increased myocardial demand

Type 2 MI is characterized by what?

Oxygen supply-demand imbalance

Type 2 MI has an imbalance of what?

cTnI and cTnT

Preferred biomarkers for the evaluation of myocardial injury

hs-cTn assays

Recommended for routine clinical use

10-30 ng/L

Reference range for hs-cTn

<20 ng/L

Reference range for male for hs-TnI

<15 ng/L

Reference range for female for hs-TnI

<23 ng/L

Reference range for male for hs-TnT

<15 ng/L

Reference range for female for hs-TnT

<0.01 ng/mL

Fourth generation study of MI reference value of hs-cTn

Carbonic anhydrase

Found in the kidneys, pancreas, liver and RBCs and a “negative predictor for AMI” since it is not significantly found in the human heart

Glycogen phosphorylase BB (GPBB)

Sensitivity and specificity is greater than CK-MB and myoglobin in patients of AMI within 4 hours after the onset of chest pain and can be used as an additional biomarker for the early diagnosis of AMI

GPBB

Most sensitive biomarker for early diagnosis of AMI

Myoglobin

2nd most sensitive biomarker for early diagnosis of AMI

CK-MB

3rd most sensitive biomarker for early diagnosis of AMI

Cardiac myosin-binding protein C (cMyC)

Serum concentration is associated with myocardial hypertrophy fibrosis and an increased risk of mortality in aortic stenosis and is the first cardiac-restricted protein to be analyzed as a diagnositc test for AMI since cTn and discrimination for myocardial infarction

Copeptin

Secreted in the hypothalamus and a precursor of arginine vasopressin (AVP)

Serum CRP

This inflammatory marker is increased in AMI