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DAWN V TOMY M.Pharm., Asst.Professor, Dept. of Pharmacology, ST.JOSEPHS COLLEGE OF PHARMACY, CHERTHALA.

MYOCARDIAL INFARCTION
Myocardial infarction (MI) is the death (necrosis) of cardiac muscle due to ischemia
of the coronary artery supplying oxygen and nutrients to myocardium. Three to five days old
MI with the presence of neutrophils is known as acute myocardial infarction.
The major etiology of MI is coronary atherosclerosis. Rupture of plaque in the
coronary arteries is a primary cause in the development of AMI. The thin fibrous cap exposes
blood to plaque results in the activation, adhesion, and aggregation of platelets and the
production of thrombin, which causes thrombus formation and vessel occlusion.
The cardiac biomarker troponins released into blood by cardiac muscle as a result of
ischemia shows the extent of MI.

Risk factors: Includes hyperlipidaemia, diabetes mellitus, hypertension, tobacco use, male
gender, and family history of atherosclerotic arterial disease.
Hyperlipidaemia: Elevated levels of total cholesterol, LDL or triglycerides are
associated with an increased risk of coronary atherosclerosis and MI.
Diabetes Mellitus: Diabetes increases the rate of atherosclerotic progression and
adversely affects the lipid profile.
Hypertension: High blood pressure (BP) i.e., systolic and diastolic hypertension
increases the risk of MI.
Tobacco Use: Smoking acutely increases platelet thrombus formation.
Male Gender: The incidence of atherosclerotic vascular disease and MI is higher in
men than women in all age groups. This gender difference in MI, however, narrows
with increasing age.
Family History: Familial coronary events is multifactorial and includes genetic
components and acquired smoking and high-fat diet.

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DAWN V TOMY M.Pharm., Asst.Professor, Dept. of Pharmacology, ST.JOSEPHS COLLEGE OF PHARMACY, CHERTHALA.

AETIOLOGY:
Coronary artery stenosis (due to atherosclerosis) or coronary vasospasm limit the supply of
oxygen and nutrients to myocardium and precipitate MI.
Increased myocardial metabolic demand include extremes of physical exertion, severe
hypertension (including forms of hypertrophic obstructive cardiomyopathy), and
severe aortic valve stenosis.
Cardiac valvular pathologies and low cardiac output due to decreased mean aortic
pressure, coronary perfusion pressure results in MI.
Myocardial infarctions are also caused by a disruption in the vascular endothelium
associated with an unstable atherosclerotic plaque that stimulates the formation of an
intracoronary thrombus and results in coronary artery occlusion.
Classification:
Type 1 spontaneous MI due to plaque erosion and/or rupture, fissuring, or
dissection.
Type 2 MI secondary to ischemia due to either increased oxygen demand or
decreased supply in case of coronary artery spasm, coronary embolism, anaemia,
arrhythmias, hypertension, or hypotension.
Type 3 sudden unexpected cardiac arrest and death accompanied by ST segment
elevation in ECG, or left bundle branch block (LBBB).
Type 4 associated with coronary angioplasty or stents:
o Type 4a MI associated with Percutaneous coronary intervention (PCI)
o Type 4b MI associated with stent thrombosis.
Type 5 MI associated with Coronary Artery Bypass Graft (CABG).
Pathological types:
The types of acute myocardial infarction based on pathology are:
1. Transmural acute myocardial infarction.
2. Subendocardial acute myocardial infarction.
3. Microscopic infarcts.

Transmural infarctions involve the full thickness of the ventricle caused by


epicardial vessel occlusion due to chronic atherosclerosis and acute thrombosis.
ST segment elevations is seen in ECG and have a negative Q waves with loss of R
wave amplitude also called ST elevated MIs (STEMIs). STEMI results from
complete coronary occlusion after plaque rupture.
Subendocardial infarctions limited to the the myocardium. Subendocardial
region is affected due to hypoperfusion and hypoxia. Severe coronary artery
disease, decreases in oxygen delivery (due to hypotension, anaemia or pneumonia)
or increases in oxygen demand (due to tachycardia or hypertension) cause
subendocardial ischemic injury.
Microscopic infarcts occur in small vessel; do not show ECG variations. It occur
in vasculitis, embolization of valve or mural thrombi or vessel spasm as a result of
elevated catecholamines due endogenous (pheochromocytoma/extreme stress), or
exogenous (cocaine).

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DAWN V TOMY M.Pharm., Asst.Professor, Dept. of Pharmacology, ST.JOSEPHS COLLEGE OF PHARMACY, CHERTHALA.

PATHOGENESIS:
Coronary artery thrombosis: MIs are caused by acute coronary artery thrombosis.
Pre-existing atherosclerotic plaques serves as substrate for thrombus generation;
vascular occlusion occurs and results in subsequent transmural infarction of the
myocardium.
It can also occur due coronary artery vasospasm or embolization from thrombus or
valve vegetations.
Infarcts limited to the innermost (subendocardial) myocardium, thrombi or emboli
may be absent. Severe diffuse coronary atherosclerosis leads to marginal perfusion of
the heart and a prolonged period of increased demand (e.g., due to tachycardia or
hypertension) can lead to ischemic necrosis of the myocardium most distal to the
epicardial vessels.
Ischemia without detectable atherosclerosis or thromboembolic disease can be caused
by disorders of small intramyocardial arterioles, including vasculitis, amyloid
deposition, or stasis as in sickle cell disease.
Coronary Artery Occlusion: In MI, the sequences of events involved are:
An atheromatous plaque is suddenly disrupted by intraplaque hemorrhage or
mechanical forces, exposing subendothelial collagen and necrotic plaque contents to
the blood.
Platelets adhere, aggregate, and are activated, releasing thromboxane A2, adenosine
diphosphate (ADP), and serotonin-causing further platelet aggregation and
vasospasm.
Activation of coagulation by exposure of tissue factor and other mechanisms adds to
the growing thrombus.
Within minutes, the thrombus can completely occlude the coronary artery lumen.
Lysis of the thrombus or relaxation of spasm by thrombolysis and/or angioplasty
procedures can limit myocardial necrosis.
Plaque erosion can occur because of the actions of matrix metalloproteases and the
release of other collagenases and proteases in the plaque, which result in thinning of
the overlying fibromuscular cap. The action of proteases, in addition to hemodynamic
forces applied to the arterial segment, can lead to a disruption of the endothelium and
fissuring or rupture of the fibromuscular cap. The loss of structural stability of a
plaque often occurs at the juncture of the fibromuscular cap and the vessel wall, a site

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DAWN V TOMY M.Pharm., Asst.Professor, Dept. of Pharmacology, ST.JOSEPHS COLLEGE OF PHARMACY, CHERTHALA.

otherwise known as the shoulder region. Disruption of the endothelial surface can
cause the formation of thrombus via platelet-mediated activation of the coagulation
cascade. If a thrombus is large enough to occlude coronary blood flow, an MI can
result.
Myocardial Response to Ischemia.
1. Ischemia leads to shutting of aerobic glycolysis leads to ATP depletion switching on
lactic acid pathway leads to accumulation of lactic acid in myocytes.
2. Ischemia leads to loss of contractility of myocardium followed by myofibrillar
relaxation, glycogen depletion and cell swelling resulting in arrhythmias.
Cardiac biomarkers in MI: The cardiac biomarker troponins released into blood by cardiac
muscle as a result of ischemia shows the extent of MI. C-reactive protein (CRP) is a sensitive
marker for inflammation. CRP blood levels can predict the risk of MI, stroke and the
development of diabetes. Hyperhomocysteinemia (amino acid homocysteine in blood) in
homocysteinuria is associated with premature atherosclerosis.
Preventive Measures:
1.
2.
3.
4.

Lifestyle modifications.
Smoking cessation.
Control of alcohol and drug addiction.
Physical activity decreases risk by lowering blood pressure, lipid levels, BMI and
increasing insulin sensitivity.
5. Diet modification: Soluble fibre, vegetables, fruits and whole grains and food low
in saturated fat/cholesterol.
6. Management and control of comorbid diseases.
7. Management of Hypertension by diet modification, lifestyle changes, exercise and
medications.
8. Use of aspirin as prophylactic agent.
9. Control of diabetes.
10. Patient education.