Factors predisposing to rupture of atherosclerotic plaques:
Vulnerable or high risk plaque (Instrinsic instability): Large lipid core, thin fibrous caps, high density of macrophages and T lymphocytes, relative paucity of smooth muscle cells and increase in plaque neovascularity and intraplaque hemmorhage
Physical stresses on atherosclerotic lesion: blood pressure, heart rate and force of ventricular contraction (exercise or emotional stress)
ii. Loss of normal antithrombotic properties
C) Non-atherosclerotic causes of ischemia:
i. Decreased coronary perfusion pressure: Hypotension (shock)
ii. Decreased blood oxygen content: Severe anemia, Pulmonary diseases
iii. Significant increase in myocardial oxygen demand: tachycardias, acute hypertension, severe aortic stenosis
Severe transient coronary spasm: Primary, Cocaine-induced
Congenital abnormalities, trauma, radiation or aneurysm
Risk Factors of Ischemic Heart Disease
A. Modifiable
Smoking
Cholesterol:
elevated LDL
low HDL (<40 mg/dl)
Arterial hypertension
Diabetes mellitus
Physical inactivity
Dietary factors:
PUFA deficient diets
Low Vitamin C and E
Obesity (BMI ≥30 kg/m2)
Stress factors
Fibrinogen and factor VII
B. Non-modifiable
Family history of premature CAD
<55 yrs for male
<65 yrs for female
Age and gender:
Male ≥ 45 years
Female ≥ 55 years
Genetic factors: operate in hyperlipidemia, plasma fibrinogen concentration and other coagulation factors, some of which are modifiable by lifestyle changes
C. Non-conventional
Apolipoprotein B and Altered lipoprotein (a)
C-reactive protein (CRP)
Hyperhomocysteinemia
Pain Mechanism in Ischemic Heart Disease
Pathophysiology of Silent Myocardial Infarction (SMI)
1. Cardiac autonomic neuropathy (CAN):
Damage of afferent autonomic nerves – seen in Diabetes
Associated with postural hypotension
2. Gating mechanisms:
Afferent signals converge onto gates, situated at the dorsal horn of the spinal cord and in the thalamus, and compete with other incoming impulses for interpretation by pain centres in the thalamus.
Higher brain centres are responsible for prioritisation of these messages by delivering an equal descending inhibitory stimulus that suppresses incoming signals that are not perceived as acutely beneficial.
An imbalance in this equilibrium is set to reveal the perception of pain.
This theory suggests that pain centres may focus on another aspect of sensory mechanisms during SMI such as dyspnoea.
3. Individual pain threshold:
Increased pain threshold in some individuals
Higher post-exercise beta-endorphins level in some individuals
4. Personality type:
Typical type A personality are likely to have silent MI, while depressed patients are likely to have angina
Mechanism of chest pain/discomfort: Metabolic products such as lactate, serotonin and adenosine accumulate locally and may activate peripheral pain receptors in the C7 to T4 distribution.
Spectrum of Myocardial Dysfunction Following Ischemia
1. Rapid and full recovery: after a brief episode of angina
2. Prolonged contractile dysfunction without myocyte necrosis with potential recovery of normal function:
Stunned myocardium: Delayed recovery of systolic function despite recovery of adequate perfusion
Due to myocyte calcium overload and accumulation of oxygen-derived free radicals during ischemia
Hibernating myocardium: Chronic ventricular contractile dysfunction in response to a persistently reduced blood supply (multivessel CAD)
↑ Extracellular K → Alteration in transmembrane potential → Electrical instability and susceptibility to arrhythmias
↑ Intracellular Ca → Activation of degradative lipases and proteases → Tissue necrosis
Acute inflammatory response with neutrophil infiltration and further tissue damage
B) Late changes in MI (days to weeks):
Resorption of irreversibly injured/dead myocytes by macrophages:
Structural weakness of ventricular wall → Susceptibility to myocardial rupture
Fibrosis and scarring
Ventricular remodeling:
Infarct expansion – thinning and dilation of necrotic tissue without additional necrosis
Increased ventricular wall stress
Further impairment in systolic contractile function
Increased likelihood of aneurysm formation
Remodeling of non-infarcted ventricle:
Dilation due to overwork in response to increased wall stress (when reaches beyond limits of Frank-Starling’s law → heart failure and predisposition to arrhythmias)
Pathophysiology of Complications of Myocardial Infarction
Involvement of conduction pathway → Conduction defects and bradycardias
Right coronary artery occlusion → Infarction of AV node and conduction system above bundle of His OR increased vagal tone → Sinus bradycardia, first degree heart block and type 1 second degree heart block
Anterior infarcts → Infarction and necrosis of bundle branches in septum → Complete heart block\
Defects in conduction system below bundle of His → type 2 second degree heart block
Transmural necrosis of interventricular septum → VSD