Ischemic heart disease

Question 1

What does the supply of oxygen to the myocardium depends on?

Answer 1

The supply of oxygen to the myocardium depends on the oxygen content of the blood and the rate of coronary blood flow.

Question 2

What is the equation for coronary blood flow?

Answer 2

Coronary artery flow (Q) is directly proportional to the vessel’s perfusion pressure (P) and is inversely proportional to coronary vascular resistance (R)

Q ∝P/R

Question 3

What are the factors that modulate coronary vascular resistance?

Answer 3

The coronary vascular resistance is modulated by (1) forces that externally compress the coronary arteries and (2) factors that alter intrinsic coronary tone.

Question 4

When does the external compression of coronary artery occurs?

Answer 4

External compression of the coronary arteries happens during the contraction of the myocardium.
Degree of compression ∝ intramyocardial pressure.

Question 5

How does the metabolic factors control the coronary tone?

Answer 5

During hypoxemia, the production of ATP decreases, and the ADP and AMP accumulate are degraded to adenosine. Adenosine is a potent vasodilator that bind to the receptor on vascular smooth muscle and decreases calcium entry into cells, which leads to relaxation, vasodilation, and increased coronary blood flow. Other metabolites include lactate, hydrogen ions, and carbon dioxide.

Question 6

How does the endothelial factors control the coronary tone?

Answer 6

Vasodilators produce by the endothelium include nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor (EDHF). Endothelin 1 is a vasoconstrictor produced by the endothelium.

Question 7

How does NO regulate vascular tone? When does NO released?

Answer 7

NO regulates vascular tone by diffusing into and then relaxing neighbouring arterial smooth muscle by a cGMP-dependent mechanism. NO is release when endothelium is exposed to acetylcholine (ACh), thrombin, products of aggregating platelets (e.g., serotonin and ADP), or even the shear stress of blood flow.

Question 8

How does prostaglandin I2 regulate vascular tone? When does prostaglandin I2 released?

Answer 8

Prostacyclin (vasodilators) is released from endothelial cells in response to many stimuli, including hypoxia, shear stress, Ach, and platelet products (e.g., serotonin) It cause relaxation of vascular smooth muscle by a cyclic AMP-dependent mechanism.

Question 9

How does EDHF regulate vascular tone? When does EDHF released?

Answer 9

EDHF (vasodilators) is a diffusible substance released by the endothelium that hyperpolarized neighbouring vascular smooth muscle cells. It is released by Ach and normal pulsatile blood flow.

Question 10

How does endothelin 1 regulate vascular tone? When does endothelin 1 released?

Answer 10

Endothelin 1 (vasoconstrictors) expression is stimulated by several factors, including thrombin, angiotensin II, adrenalin and shear stress of blood flow.

Question 11

How does the Neural factors control the coronary tone?

Answer 11

Coronary vessels contain α-adrenergic and β2-adrenergic receptors. Stimulation of α-adrenergic receptors results in vasoconstriction, whereas β2-adrenergic receptors promote vasodilatation.

Catecholamine stimulation of the heart may initially cause coronary vasoconstriction via the α-adrenergic receptor neural effect. However, catecholamine stimulation also increases myocardial oxygen consumption through increased heart rate and contractility (β1-adrenergic effect), and the resulting increased production of local metabolites induces net coronary dilatation instead.

Question 12

What are the main determinant of myocardial oxygen demand?

Answer 12

Ventricular wall stress
Heart rate
Contractility

Question 13

What is wall stress? What is the equation? Talk the equation!

Answer 13

The major determinants of myocardial oxygen demand are ventricular wall stress, heart rate and contractility.

Ventricular wall stress is the force acting on the myocardial fibers, tending to pull them apart, and energy is expended in opposing that force. Wall stress is related to intraventricular pressure (p), the radius of the ventricle (r), and ventricular wall thickness (h):

σ=(Pxr)/2h

Circumstance that increase pressure in the left ventricle, such as aortic stenosis or hypertension, increases wall stress and myocardial oxygen consumption. Conditions that decrease ventricular pressure, such as antihypertensive therapy, reduce myocardial oxygen consumption.
Because wall stress is directly proportional to the radius, conditions that increase left ventricular filling also increases wall stress and oxygen consumption. The opposite is true!

Wall stress is inversely proportional to ventricular wall thickness because the force is spreading over a greater muscle mass. Hypertrophied heart has lower wall stress and oxygen consumption per gram of tissue than a thinner-wall heart.

Question 14

What does the auto-regulatory mechanism do?

Answer 14

Auto-regulatory mechanism adjust coronary tone to match myocardial oxygen supply with oxygen requirements, as long as the aortic perfusion pressure is 60 mm Hg or greater.

Question 15

Which part of the coronary artery is mostly subject to stenotic plaque? What does the hemodynamic significance of a coronary artery narrowing depends on?

Answer 15

The proximal vessels of coronary arteries are subjected to atherosclerosis that results in stenotic plaques. The distal vessels are usually free of flow-limiting plaques and can adjust their vasomotor tone in response to metabolic needs. The hemodynamic significance of a coronary artery narrowing depends on both the degree of stenosis of the epicardia portion of the vessel and the amount of compensatory vasodilation the distal resistance vessels are able to achieve. If the stenosis narrows the diameter by more that 70%, resting blood flow is normal, but maximal blood flow is reduced even with full dilation of the resistance vessels. When the diameter is narrowed to 90%, blood flow is inadequate to meet requirements and ischemia can develop at rest.

Question 16

How does endothelial cell dysfunction contribute to the pathophysiology of ischemia?

Answer 16

Abnormal endothelial cell function can contribute to the pathophysiology of ischemia by:

Inappropriate vasoconstriction
- During physical exercise, the increased blood flow and shear stress stimulate the release of endothelial-derived vasodilators, such as NO. The relaxation of NO outweighs the direct α-adrenergic constrictor effect of catecholamines on arterial smooth muscle, such that vasodilatation results. However, dysfunctional endothelium release less endothelial vasodilators.

Loss of normal antithrombotic properties
- Less factors are released from endothelial cells (include NO and prostaglandin I2), which normally exert antithrombotic properties by interfering with platelet aggregation.

Question 17

What are the causes of myocardial ischemia?

Answer 17

Common causes of decreased myocardial oxygen supply include (1) decreased perfusion pressure due to hypotension and (2) severely decreased blood oxygen content. Profound increase in myocardial oxygen demand can cause ischemia even in the absence of coronary atherosclerosis. This can occur with rapid tachycardia, acute hypertension, or severe aortic stenosis.

Question 18

What are the consequences of ischemia?

Answer 18

The reduced generation of ATP impairs the interaction of the contractile proteins and results in a transient reduction of both ventricular systolic contraction and diastolic relation (both are energy-dependent processes). The consequent elevation of left ventricular diastolic pressure is transmitted to the pulmonary capillaries and can precipitate pulmonary congestion and the symptom of shortness of breath.
Ischemic insults can result in a period of prolonged contractile dysfunction without myocytes necrosis, and recovery of normal function may follow.
Ischemic syndromes

Question 19

Describe stable angina!

Answer 19

Chronic pattern of transient angina pectoris, precipitated by physical activity or emotional upset, relieved by rest within a few minutes, episodes often associated with temporary depression of the ST segment, by permanent myocardial damages doesn’t result.
Some patient may have fixed-threshold angina or variable-threshold angina (patient can exert without chest discomfort, but on another day, the same degree of myocardial oxygen demand does produce symptoms).

Question 20

Describe unstable angina!

Answer 20

Patten of increased frequency and duration of angina episodes produced by less exertion or at rest. Unstable angina and MI are also known as acute coronary syndromes and result from rupture of an unstable atherosclerotic plaque with subsequent platelet aggregation and thrombosis.

Question 21

Describe variant angina!

Answer 21

Typical angina discomfort, usually at rest, which develops because of coronary artery spasm rather than an increase of myocardial oxygen demand; episodes often associated with ST segment, usually ST elevation. The mechanism may involve increased sympathetic activity in combination with endothelial dysfunction.

Question 22

Describe silent ischemia!

Answer 22

Asymptomatic episode of myocardial ischemia. It is detected by laboratory techniques such as continuous ambulatory EKG or it can be elicited by exercise stress testing.

Question 23

Describe syndrome X!

Answer 23

Refers to patients with typical symptoms of angina pectoris who have no evidence of significant atherosclerotic coronary stenosis on coronary angiograms. The pathogenesis of ischemia is related to inadequate vasodilator reserves of the coronary resistance vessels. It is thought that the resistance vessels may no dilate during period of increased myocardial oxygen demand. Microvascular dysfunction, vasospasm, and hyper- sensitive pain perception may each contribute to this syndrome.

Question 24

What are the clinical features of chronic stable angina! (History, quality, location, accompanying symptoms, precipitants, frequency and risk factors)

Answer 24

History – Interview and examine a patient during an actual episode of angina.

Quality – angina described as pressure, discomfort, tightness, burning or heaviness in the chest. It is rare that the sensation is described as “pain”. Anginal discomfort is neither sharp or stabbing, and it does not vary significantly with inspiration or movement of the chest wall.

Location – the discomfort is diffuse usually located in the retrosternal area, back, arms, necks, lower face, or upper abdomen.

Accompanying symptoms – during an acute anginal attack, generalized sympathetic and parasympathetic stimulation may result in tachycardia, diaphoresis, and nausea.

Precipitants – Angina, when not caused by pure vasospasm, is caused by physical effort, anger, and other emotional excitement. Angina is relieved within minutes after the cessation of the activity that caused it and more quickly by sublingual nitroglycerin.

Frequency – it depends on the activities that normally cause it.

Risk factors – cigarette smoking, dyslipidemia, hypertension, diabetes, and genetics.

Question 25

What the physical feature of myocardial ischemia?

Answer 25

An increased heart rate and blood pressure are common because of the augmented sympathetic response. Myocardial ischemia may lead to papillary muscle dysfunction and therefore mitral regurgitation. Ischemia decrease ventricular compliance, producing a stiffened ventricle and therefore an S4 gallop on physical examination during atrial contraction.

Question 26

What are the signs of atherosclerotic disease?

Answer 26

Sings of atherosclerotic diseases include: carotid bruits (abnormal sound-reflect turbulent blood flow) may indicate the presence of cerebrovascular disease. While femoral bruits may mean peripheral arterial disease.

Question 27

What are the EKG changes in myocardial ischemia?

Answer 27

EKG – During myocardial ischemia, ST segment and T wave changes commonly appear.

• Acute ischemia usually results in transient horizontal or downsloping ST segment depressions and T wave flattening or inversions.
• ST segment elevations means a more severe transmural myocardial ischemia and can also be observed during the intense vasospasm of variant angina.

Question 28

How is standard exercise testing done? When is the test considered positive?

Answer 28

The heart rate, EKG and blood pressure are checked at regular intervals. The test is continued until angina develops (or patient becomes too fatigued to continue), signs of myocardial ischemia appear on the EKG, a target heart rate is achieved (85% of maximal predicted heart rate; 220 beats/min – the patient age).
The test is considered positive if (1) ischemic EKG changes develop in the first 3 minutes of exercise and after it has stopped; (2) the magnitude of the ST segment depressions is >2 mm; (3) the systolic blood pressure abnormally falls during exercise; (4) high-grade ventricular arrhythmias develop; or (5) the patient can’t exercise for at least 2 minutes because of cardiopulmonary limitations.

Question 29

How does nuclear imaging studies used to detect infarct?

Answer 29

The standard exercise test is less useful in patients with baseline abnormalities of the ST segment. In such situations, radionuclide imaging can be combined with exercise testing to overcome these limitations and to increase the sensitivity and specificity of the study.
During myocardial perfusion imaging, a radionuclide is injected intravenously at peak exercise, after which imaging is performed. The radionuclide accumulates in proportion to the degree of perfusion of viable myocardial cells. Therefore, areas of poor perfusion during exercise and irreversibly infarcted areas do not accumulate radionuclide and appear as “cold spots” on the image. To differentiated between transient ischemia and infarcted tissue, imaging is also performed at rest. If the cold spot fills in, a region of transient ischemia has been identified.

Question 30

How does pharmacologic stress test works? Which agents are used?

Answer 30

For patient that can’t exercise. Pharmacologic stress testing can be performed using various agent, including the inotrope dobutamine [which increases myocardial oxygen demand by stimulating (β1 receptors of the sympathetic nervous system) the heart rate and force of contraction. Dobutamine is predominantly a β1-agonist, with weak β2 activity and α1 antagonist.] or the vasodilators dipyridamole (blocks the cellular uptake and destruction of adenosine and thereby increases adenosine’s circulating concentration) or adenosine. Adenosine binds to its vascular receptor, coronary vasodilation results. These pharmacologic interventions are coupled with nuclear imaging or echocardiography to revel regions of impaired myocardial perfusion.

Question 31

What are the predicators of mortality in myocardial infarcts?

Answer 31

The location, extent of coronary stenosis and other critical that include (1) the extent of impaired left ventricle contractile function, (2) poor exercise capacity, and (3) the magnitude of clinical anginal symptoms.

Question 32

What is medical treatment of acute episode of angina?

Answer 32

When experiencing acute angina, the patient should stop physical activity. Sublingual nitroglycerin is the drug of choice in this situation. Nitrate relieve ischemia primarily through vascular smooth muscle relaxation (vasodilation). When coronary vasospasm plays a role in the development of ischemia, nitrate-induced coronary vasodilation may be partially beneficial.

Question 33

What are the treatment to prevent recurrent ischemic episodes?

Answer 33

These include pharmacologic agent to decrease the workload and to increase myocardial perfusion. These include:
Organic nitrates
B-blockers
Calcium channel blockers

Question 34

How does organic nitrates has its affect on myocardial infarction? What are the side effects?

Answer 34

Sublingual nitroglycerin are used in the treatment of an acute attacks because of their rapid onset of action. Long-acting anginal prevention can be achieved though nitrate preparation, including oral tablets of isosorbide dinitrate or a transdermal nitroglycerin patch. To avoid drug tolerance, the patient be provided a nitrate-free interval for several hours each day, usually while the patient sleeps.

Side effects : headache, hypotension and reflex trachycardia

Question 35

How dose B-blockers works as a treatment for MI? What are their side effects? Why are they not suppose to be used?

Answer 35

• β blocker – they reduce the myocardial oxygen demand. Β-adrenergic antagonists decrease the force of ventricular contraction and heart rate, thereby relieving ischemia by reducing myocardial oxygen demand. Β blocks also decrease the rate of recurrent infarction and mortality following an acute MI. They even reduce the likelihood of an initial MI in patients with hypertension. β-blockers don’t decrease the myocardial blood perfusion by blocking the vasodilating β2-adrenergic receptor on the coronary arteries due to the autoregulation effect.
• Side effects include: may precipitate bronchospasm by antagonizing β2-receptors in the bronchial tree. They can cause fatigue and sexual dysfunction.
• β-blockers are not used in patient with acutely decompensated LV dysfunction because they could intensify heart failure symptoms by reducing inotropy.
• They should be used with caution in insulin-treated diabetic patients because they can mask tachycardia and other catecholamine-mediated responses that can warn of hypoglycaemia.

Question 36

How does calcium channel blockers treatment myocardial infarct? Any side effects?

Answer 36

• The dihydropyridines are potent vasodilators. They relieve myocardial ischemia by (1) decreasing oxygen demand (venodilation reduce the ventricle filling and size, arterial dilation reduces the resistance against which the ventricle contracts, and both action decrease wall stress) and (2) increasing myocardial oxygen supply via coronary dilation. They are potent agent for relief of coronary artery vasospasm.
• Nondihydropyridine calcium channel blocker – they are more potent cardiac depressant actions: they reduce the force of ventricle contraction and slow the heart rate (also decrease oxygen demand).
• Short-acting calcium channel blockers drug have been associated with an increased incidence of MI and mortality.

Side effects: headache, flushing, lowers contraction, marked bradycardia, edema, constipation

Question 37

Why can’t patients take B-blocker with non-dihydropyridine?

Answer 37

Because the additive negative chronotropic effect can cause excessive bradycardia and the combined negative inotropic effect could precipitate heart failure in patient with LV contractile dysfunction.

Question 38

How does Ranolazine work as a treatment of myocardial infarct? Side effects ?

Answer 38

Ranolazine – which decrease the frequency of anginal episodes and improve exercise capacity in patients with chronic CAD but differs from other anti-ischemic drugs that that it doesn’t affect the heart rate and blood pressure. It inhibits the late phase of the action potential’s inward sodium current in ventricular myocytes. The late phase tends to be abnormally enhanced in ischemic myocardium, and the associated increased sodium influx results in higher-than-normal intracellular calcium.

Side effects: dizziness and constipation, and nausea

Question 39

What are the medical treatment to prevent acute cardiac events?

Answer 39

Anti-platelet therapy
Lipid regulating therapy
Angiotensin-converting enzymes

Question 40

How does anti-platelet therapy work? Which medication are used?

Answer 40

Antiplatelet therapy reduces the risk of these acute coronary syndromes in patients with chronic angina. Aspirin has antithrombotic actions through inhibition of platelet aggregation as well as anti-inflammatory properties that may be important in stabilizing atheromatous plaque. Clopidogrel, a thienopyridine, is one of a group of novel antiplatelet agents that block the platelets P2Y12 ADP receptor, thereby preventing platelet activation and aggregation. The combination of aspirin and clopidogrel is superior to aspirin alone in reducing death and ischemic complications in patient with acute coronary syndromes.

Question 41

How does lipid regulating therapy work? Which medication are used?

Answer 41

HMG-CoA (such as statin) reductase inhibitors lower MI and death rates in patient with coronary disease and those in risk of CAD. Statin also decrease vascular inflammation and improve endothelial dysfunction and thus may help stabilizing atherosclerotic plaque.

Question 42

When are ACE used?

Answer 42

They are used in treatment of hypertension, heart failure, and following MI.

Question 43

When is revascularization pursued?

Answer 43

Coronary revascularization is pursued if (1) the patient’s symptoms of angina don’t responds adequately to antianginal drug therapy, (2) unacceptable side effects of medication occurs, or (3) the patient is found to have high risk coronary disease.

Question 44

What are the two mechanisms of revascularization?

Answer 44

PCI include percutaneous transluminal coronary angioplasty (PTCA), the procedure is performed under fluoroscopy in which a balloon-tipped catheter is inserted through a peripheral artery (femoral, brachial, or radial) and maneuvered into the stenotic segment of a coronary vessel.
To reduce the rate of restenosis, a coronary stent is used. Because stents are thrombogenic, a combination of oral antiplatelet agents is crucial after stent implantation. However, the reintimal proliferation remains an important cause of in-stent restenosis and recurrent anginal symptom. Drug-eluting stents are polymer coat that incorporates an antiproliferative medication such as sirolimus (an immunosuppressive agent that inhibits T-cells activation) or paclitaxel (which interferes with cellular microtubule function).

CABG surgery entails grafting portions of a patient’s native blood vessels to bypass obstructed coronary arteries. Two methods are used:
Employs native vein (saphenous vein) this is sutured from the base of the aorta to a coronary segment downstream form the region of stenosis.
Usage of arterial grafts (internal mammary artery) that can be directly anastomosed distal to a stenotic coronary site. These are more resistant to atherosclerosis that vein grafts.