Ischemic heart disease Flashcards
(44 cards)
What does the supply of oxygen to the myocardium depends on?
The supply of oxygen to the myocardium depends on the oxygen content of the blood and the rate of coronary blood flow.
What is the equation for coronary blood flow?
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
What are the factors that modulate coronary vascular resistance?
The coronary vascular resistance is modulated by (1) forces that externally compress the coronary arteries and (2) factors that alter intrinsic coronary tone.
When does the external compression of coronary artery occurs?
External compression of the coronary arteries happens during the contraction of the myocardium.
Degree of compression ∝ intramyocardial pressure.
How does the metabolic factors control the coronary tone?
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.
How does the endothelial factors control the coronary tone?
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.
How does NO regulate vascular tone? When does NO released?
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.
How does prostaglandin I2 regulate vascular tone? When does prostaglandin I2 released?
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.
How does EDHF regulate vascular tone? When does EDHF released?
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.
How does endothelin 1 regulate vascular tone? When does endothelin 1 released?
Endothelin 1 (vasoconstrictors) expression is stimulated by several factors, including thrombin, angiotensin II, adrenalin and shear stress of blood flow.
How does the Neural factors control the coronary tone?
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.
What are the main determinant of myocardial oxygen demand?
Ventricular wall stress
Heart rate
Contractility
What is wall stress? What is the equation? Talk the equation!
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.
What does the auto-regulatory mechanism do?
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.
Which part of the coronary artery is mostly subject to stenotic plaque? What does the hemodynamic significance of a coronary artery narrowing depends on?
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.
How does endothelial cell dysfunction contribute to the pathophysiology of ischemia?
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.
What are the causes of myocardial ischemia?
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.
What are the consequences of ischemia?
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
Describe stable angina!
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).
Describe unstable angina!
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.
Describe variant angina!
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.
Describe silent ischemia!
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.
Describe syndrome X!
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.
What are the clinical features of chronic stable angina! (History, quality, location, accompanying symptoms, precipitants, frequency and risk factors)
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.
