Blood flow through such vessels varies approximately with the fourth power of these vessels' radii; hence, the key regulated variable for the control of coronary blood flow is the degree of constriction or dilatation of coronary arteriolar vascular smooth muscle. As with all systemic vascular beds, the degree of coronary arteriolar smooth muscle tone is normally controlled by multiple independent negative feedback loops. These mechanisms include various neural, hormonal, local non-metabolic and local metabolic regulators.
It should be noted that the local metabolic regulators of arteriolar tone are usually the most important for coronary flow regulation; these feedback systems involve oxygen demands of the local cardiac myocytes.
In general, at any one point in time, coronary blood flow is determined by integrating all the different controlling feedback loops into a single response i. It is also common to consider that some of these feedback loops are in opposition to one another. Interestingly, coronary arteriolar vasodilation from a resting state to one of intense exercise can result in an increase of mean coronary blood flow from approximately 0. As with all systemic circulatory vascular beds, the aortic or arterial pressure perfusion pressure is vital for driving blood through the coronaries, and thus needs to be considered as another important determinant of coronary flow.
More specifically, coronary blood flow varies directly with the pressure across the coronary microcirculation, which can be essentially considered as the aortic pressure, since coronary venous pressure is near zero.
However, since the coronary circulation perfuses the heart, some very unique determinants for flow through these capillary beds may also occur; during systole, myocardial extravascular compression causes coronary flow to be near zero, yet it is relatively high during diastole note that this is the opposite of all other vascular beds in the body. Oxygenated blood is pumped into the aorta from the left ventricle. This is where it enters the right and left main coronary arteries, and subsequent branching feeds the myocardial tissue of all four chambers of the heart see Figure 7.
The ascending portion of the aorta is where the origins ostia of the right and left coronaries reside; specifically, they exit the ascending aorta immediately superior to the aortic valve at the sinus of Valsalva. Blood flow into the coronary arteries is greatest during ventricular diastole when aortic pressure is highest and it is greater than in the coronaries. Typically the right coronary artery courses along the right anterior atrioventricular groove just below the right atrial appendage and along the epicardial surface adjacent to the tricuspid valve annulus.
It traverses along the tricuspid annulus until it reaches the posterior surface of the heart, where it then commonly becomes the posterior descending artery and runs toward the apex of the left ventricle.
It is difficult to tease out the role of neural control on coronary blood flow, as the metabolic effects of any change in blood pressure, heart rate and contractility dominate the subsequent response. Alpha stimulation may play a role in the distribution of blood flow within the myocardium by restricting metabolically mediated flow increase and exerting an anti-steal affect.
Parasympathetic influences are minor and weakly vasodilatory. The vasodilatory effect of acetylcholine depends on an intact endothelium. Most vasoactive hormones require an intact vascular endothelium. The peptide hormones include antidiuretic hormone, atrial natriuretic peptide, vasoactive intestinal peptide, and calcitonin gene-related peptide. Antidiuretic hormone in physiological concentration has little effect on the coronary circulation but causes vasoconstriction in stressed patients.
The other peptides cause endothelium-mediated vasodilatation. Angiotensin II causes coronary vasoconstriction independent of sympathetic innervation. It also enhances calcium influx and releases endothelin, the strongest vasoconstrictor peptide yet identified in humans.
Angiotensin-converting enzyme inactivates bradykinin, a vasodilator. The vascular endothelium is the final common pathway regulating vasomotor tone. It modulates the contractile activity of the underlying smooth muscle through synthesis and secretion of vasoactive substances in response to blood flow, circulating hormones and chemical substances. Vasorelaxants are endothelium-derived relaxing factor, nitric oxide, prostacyclin and bradykinin.
Vasoconstrictors include endothelin and thromboxane A2. The net response depends on the balance between the two opposing groups. Oxygen delivery is the product of arterial oxygen carrying capacity and myocardial blood flow. The diastolic pressure time index DPTI is a useful measure of coronary blood supply and is the product of the coronary perfusion pressure and diastolic time. Similarly, oxygen demand can be represented by the tension time index TTI , the product of systolic pressure and systolic time.
The EVR is normally 1 or more. Such a value may be reached in a patient with the following physiological data: Note that systolic time is typically fixed at ms, with diastole occupying the remaining time. The coronary circulation functions in a state of active vasodilatation. Abnormal endothelial nitric oxide production may play a role in diabetes, atherosclerosis and hypertension.
Deposits of lipids, smooth muscle proliferation and endothelial dysfunction reduce the luminal diameter. With increasing stenosis, distal arterioles dilate maximally to preserve flow up to the point where the vascular bed is maximally dilated.
Further stenosis leads to a drop in flow and flow becomes pressure dependent. Flow diverted into a dilated parallel bed proximal to a stenosis is called coronary steal and can aggravate ischemia. Flow in collaterals is also often pressure dependent. The left ventricle undergoes hypertrophy in response to raised afterload. The myofibrillar growth outstrips the capillary network, resulting in decreased capillary density. Raised intramyocardial pressure lowers the subendocardial blood flow. The pressure load increases myocardial work and oxygen demand.
There is also an impaired vasomotor response to hypoxia in hypertrophied tissue that makes it susceptible to ischaemia. Impaired ejection results in larger diastolic volumes, raised LVEDP and lower coronary perfusion pressure. Sympathetic-mediated systemic vasoconstriction may help to improve the myocardial perfusion but increases pressure load and oxygen demand. These agents act inside the lumen to prevent further reduction in the vessel diameter.
Antiplatelet drugs prevent platelet aggregation, often the initial step in the formation of an occlusive thrombus. Antithrombin agents act at various sites in the coagulation cascade to inhibit thrombin formation. Nitrates produce vasodilatation in all vascular beds, mediated by nitric oxide release.
They relieve coronary vasospasm but their main benefit is to reduce preload, afterload and to increase maximal coronary dilation. Benefits may be offset by reflex tachycardia. Compared to the non-dihydropyridines verapamil and diltiazem the dihydropyridines nifedipine produce more vasodilatation, less inhibition of the sinus and atrioventricular nodes, and less negative inotropy.
The oxygen demand is lessened because of decreases in contractility and pressure load. Angiotensin-converting enzyme inhibitors reduce conversion of angiotensin I to angiotensin II.
These drugs reduce angiotensin-mediated vasoconstriction and enhance myocardial perfusion by vasodilatation without reflex tachycardia. Over time, it also regulates fibrous tissue formation after tissue injury.
Nicorandil is a novel anti-anginal agent. In non-diseased coronary vessels, whenever cardiac activity and oxygen consumption increases there is an increase in coronary blood flow active hyperemia that is nearly proportionate to the increase in oxygen consumption. Good autoregulation between 60 and mmHg perfusion pressure helps to maintain normal coronary blood flow whenever coronary perfusion pressure changes due to changes in aortic pressure.
Adenosine is an important mediator of active hyperemia and autoregulation. It serves as a metabolic coupler between oxygen consumption and coronary blood flow. Nitric oxide is also an important regulator of coronary blood flow. Therefore, sympathetic activation to the heart results in coronary vasodilation and increased coronary flow due to increased metabolic activity increased heart rate, contractility despite direct vasoconstrictor effects of sympathetic activation on the coronaries.
This is termed "functional sympatholysis. Parasympathetic stimulation of the heart i. However, if parasympathetic activation of the heart results in a significant decrease in myocardial oxygen demand due to a reduction in heart rate, then intrinsic metabolic mechanisms will increase coronary vascular resistance by constricting the vessels. Progressive ischemic coronary artery disease results in the growth of new vessels termed angiogenesis and collateralization within the myocardium.
Collateralization increases myocardial blood supply by increasing the number of parallel vessels, thereby reducing vascular resistance within the myocardium. Extravascular compression shown to the right during systole markedly affects coronary flow; therefore, most of the coronary flow occurs during diastole.
Because of extravascular compression, the endocardium is more susceptible to ischemia especially at lower perfusion pressures.
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