Report Outline

Etymology
Myocardium heart muscle Infarction tissue death due to Oxygen starvation (ischemia)

Incidence Rate
WHO (2010): Leading cause of NCD deaths in 2008 were CVD Approximately 17 million deaths or 48% of all NCD deaths

Incidence Rate
DOH (2010):
Diseases of the heart ranked 1st in the list of diseases that cause death (NCD and CD) Approximately 63,000 death or 24% of all NCD and CD death

Precipitating Factors
Age Family History Sex : Male

Predisposing Factors
Hypertension High levels of LDL and low levels of HDL Smoking High in saturated fat diet

S/Sx
Sweating Varying degree of chest pain radiates to the jaw, neck, left arm, back and epigastrum; lasts 20 minutes Anxiety

S/Sx
Fainting Light-headedness Shortness of breath (Dyspnea) *Approx. of all MI patients experience warning symptoms like Angina Pectoris prior to infarction

Summary of Mechanisms Involved in the Causation of Myocardial Infarction

Development of atherosclerosis (usually polygenic)

Plaque rupture

Formation of large thrombus in a coronary artery

Ascending Aorta

Diagram : 1. occlussion of a branch of the left coronary artery 2. myocardial infarction resulting from #1 at the anterior wall of the heart

Summary of Mechanisms Involved in the Causation of Myocardial Infarction

Deprivation of blood supply (ischemia) to an area of the myocardium

Shift to anaerobic glycolysis decreased synthesis of ATP, depletion of adenine nucleotide pool

Increase of NADH due to inactive terminal electron transport chain: due to lack of oxygen

Summary of Mechanisms Involved in the Causation of Myocardial Infarction

Accumulation of lactic acid and other metabolites in myocardial muscle, causing increased cellular osmolarity and altered membrane permeability

Decrease in Ph in heart muscle cells

Increasingly inefficient contraction of heart muscle

Summary of Mechanisms Involved in the Causation of Myocardial Infarction

Cessation of contraction

Activation of membrane phospholipases, degradation of proteins by proteases, influx of Ca nucleotide pool

Death of affected area of heart muscle

Management:
Treatment with Drugs
Vasodilator gives immediate relief from pain Beta-blockers decreases the need of heart for extra metabolic Oxygen during stressful condition

Surgical Treatment
Aortic-Coronary Bypass divert or shunt the flow of blood

Surgical Treatment
Coronary Angioplasty reconstruction of damaged blood vessels

Lecture Objectives
Discuss significant enzymes in Myocardial Infarction. Enumerate and differentiate significant Isoenzymes. Discuss other protein cardiac markers.

What are the significant enzymes in diagnosis of MI? Lactate dehydrogenase (LDH) Creatine Kinase (CK)

Lactate dehydrogenase
Cytoplasmic enzyme Tetramer of 2 subunits
H (for heart) and M (for muscle)

Produce 5 isoenzyme

Isoenzyme
HHHH (LDH-1) heart and RBC 17-27% of the normal serum total. HHHM (LDH-2) heart, RBC, renal cortex 27-37% of the normal serum total. HHMM (LDH-3) variety of organs 18-25% of the normal serum total.

 HMMM (LDH-4) variety of organs

3-8% of the normal serum total.

MMMM (LDH-5) liver and skeletal muscle

0-5% of the normal serum total.

Lactate dehydrogenase
Flipped LD ratio
LDH 1 > LDH 2

rise within 12-24 hours peaks within 48-72 hours remains elevated for 10-14 days.

Creatine Kinase
transfer of energy in muscle metabolism comprised of two subunits
the B (brain) and the M (muscle)

resulting the 3 CK isoenzyme.

 CK-BB (CK-1) brain , smooth muscles CK-MB (CK-2) 35% in cardiac muscle CK-MM (CK-3) muscles, normal serum.

Creatine kinase
rise within 4-6 hours peak at 24 hours return to baseline by 48-72 hours

Enzyme

Rise

Peak

Decline

LDH

12-24 hours

48-72 hours

10 -14 days

CK

4-6 hours

24 hours

48-72 hours

Other significant protein in diagnosing Myocardial Infarction

Troponin
marker of all heart muscle damage Not present in normal serum Regulatory complex of 3 protein TnT (tropomyosin binding complex) TnI (Inhibitory subunit binds to actin) TnC (Calcium binding subunit)

Troponin T
Early and late diagnosis of AMI Rise within a few hours Peak by day 2 Elevated beyond 7 days

Troponin I
Only found in the myocardium Specific for cardiac disease Rise within 4-6 hours Peaks at 12-18 hours Elevated until 7 days

Myoglobin
Heme-containing protein Related to muscle mass and activity Lack specificity to myocardium Cleared by renal filtration

Myoglobin
2-3 hours following onset of MI, peaks about 6 hours returns to baseline after 24 hours

Therapeutic Enzymes
Outline: Enzymes that have therapeutic value to MI.
What other drugs can be used for MI?

Reperfusion Injury and its relevance to thrombolytic therapy

Therapeutic Enzymes
Thrombolytics: also known as plasminogen activators or fibrinolytic drugs

Streptokinase Urokinase Tissue Plasminogen Acivator

Thrombolytics:
Streptokinase
- Protein secreted by several species of streptococci -onset is immediate; long-acting (duration is about 12 hours, but can be as long as 24 hours)

Thrombolytics:
Urokinase
- Produced

in renal parenchymal cells - almost same function as streptokinase - onset is same with streptokinase

Thrombolytics:
Tissue Plasminogen Activator (TPA)

- Synthesized in the endothelial cells - most commonly used thrombolytic - tPA (Alteplase): onset is immediate; effects may linger up to 4 hours after infusion

Thrombolytics:

Thrombolytics:
Important To Note: - efficiency depends on the age of the clot - administration of any anticoagulant or antiplatelet drugs is contraindicated within 24-48 hours

 - thrombolytics administration is contraindicated to known surgery within 10 days, or any known case of internal bleeding

Other anti-thrombotic drugs:

Anti-platelet drugs Anticoagulant drugs

Anti-platelet drugs:
Aspirin
-Inhibits platelet cyclooxygenase - Side Effects: GI side effect (ulceration), risk for bleeding

Anti-platelet drugs:

ADP-receptor antagonist:
-Prevents ADP from attaching to receptor; platelet clumping -Ticlopidine, Clopidogrel - may cause thrombocytopenia & neutropenia (Ticlopidine)

Anti-platelet drugs:
ADP-receptor antagonist

Anti-platelet drugs:
Glycoprotein IIb/IIIa receptor inhibitor:
-Prevent cross-linking of platelets - used by specialists; not used in an outpatient setting - may cause major bleeding, thrombocytopenia - Abciximap

 Glycoprotein IIb/IIIa receptor inhibitor:

Anti-platelet drugs:

- Sites of platelet inhibitors

TXA2 Inhibitors

Anticoagulant Drugs:

- Used as blood thinner

Intravenous Heparin Oral Anticoagulant (Warfarin)

Reperfusion Injury
Refers to myocardial, vascular or electrophysiological dysfunction factors that contribute to reperfusion injury: - damage to cellular and organelle membranes, including mitocondria - myocyte hypercontracture

- free radical formation - leukocyte aggregation and inflammatory mediators - endothelium damage

Reperfusion Injury:
Clinical manifestations:
- Arrhythmias - microvascular dysfunction (No reflow phenomenon) - myocyte death

Reperfusion Injury:
Potential Therapies:
- No clear solutions yet; management - combination of techniques for rapid reperfusion, use of antioxidants, neutrophil inhibitors