Coronary Physiology and Pathophysiology

Determinants of Myocardial Oxygen Consumption

The working myocardium requires a coronary blood flow of 70 to 90 mL/100 g of myocardium per minute to provide for an oxygen consumption of 8 to 15 mL/100 g of tissue per minute at rest for contraction and relaxation. This figure rapidly increases fivefold to sixfold with exercise or sympathetic arousal. At rest, the heart consumes most of the oxygen contained in its blood supply. Therefore any increase in oxygen demand must be met by an increase in coronary blood flow.

With each beat, developed muscle tension requires oxygen; total tension developed in unit time is directly proportional to the oxygen needs of the working myocardium. The frequency of developed tension (heart rate) is also quantitatively important with regard to oxygen consumption, whereas stroke volume (muscle shortening) has a smaller impact on the needs for oxygen delivery. Excitation–contraction coupling and changes in calcium flux influence contractility, which impacts the demands for oxygen delivery and myocardial blood flow.

At the level of the intact heart, myocardial oxygen demand and myocardial blood flow are determined by developed systolic wall tension, heart rate, and contractility. In the absence of coronary vascular disease or dysfunction, myocardial blood supply is determined by metabolic demands, autoregulation, blood oxygen-carrying capacity, diastolic time, neurohumoral factors, and extravascular compressive forces ( Fig. 6.1 ). The following sections discuss the dominating controlling influences of metabolic regulation and autoregulation.

Vessel Wall and Local Control of Coronary Blood Flow

The coronary vasculature is subject to neural innervation and the effects of circulating mediators, such as serotonin, adenosine diphosphate, epinephrine, and vasopressin. These are in addition to the local mechanisms that respond to the oxygen and metabolic needs of the heart (discussed earlier). The local microvascular endothelium transduces many of these physiologic signals, including local shear force, pulse pressure, sympathetic stimulation, and blood flow itself. It responds by exerting its own local control on vascular smooth muscle cells by governing constriction and relaxation. Vascular endothelial cells possess membrane-associated channels sensitive to many circulating and local regulators, such as shear forces, flow, serotonin, and thrombin. The endothelium is also sensitive to α-adrenergic sympathetic stimulation and aggregating platelets. These signals can cause the endothelium to release vasodilators locally, such as nitric oxide, endothelium-dependent hyperpolarizing factor (EDHF), and prostacyclin or vasoconstrictors such as endothelin-1 and thromboxane. The sum total of these local mediators provides precise control of blood flow in each segment of the coronary microcirculation.

Healthy coronary arteries maintain the ability to control local vasomotion, maintain an anticoagulant surface, and present a biologic barrier that prevents infiltration and proliferation ( Fig. 6.2 ). These key defensive mechanisms are important in maintaining health; a clear understanding of them is important to understand the effects of diseases such as atherosclerosis.

Coronary Arterial System

The coronary arterial system is composed of three compartments that have different functions ( Fig. 6.3 ). The large epicardial coronary arteries (diameter ~500 µm to ~5 mm) visualized on coronary angiography have a capacitance function and offer little resistance to blood flow. During systole, epicardial coronary arteries dilate and accumulate elastic energy as they increase their blood content by about 25%. This elastic energy is transformed into blood kinetic energy at the beginning of diastole and contributes to the prompt reopening of intramyocardial vessels that had been compressed closed by systole. Prearterioles (diameter ~100 to 500 µm) represent the intermediate compartment and are characterized by a measurable pressure drop along their length. Their specific function is to maintain pressure at the origin of the next compartment within a narrow range in response to changes in coronary perfusion pressure and/or flow; proximal prearterioles are most responsive to changes in flow, whereas distal prearterioles are most responsive to changes in pressure. Finally, the distal compartment is composed of arterioles (diameter <100 µm), which are characterized by a very large pressure drop along their length. Arterioles are the site of metabolic regulation of myocardial blood flow because their tone is influenced by substances (such as hydrogen peroxide and adenosine) produced during myocardial metabolism. The specific function of arterioles is the matching of myocardial blood supply and oxygen demand. Notably, each compartment is governed by distinct regulatory mechanisms. In contrast to the epicardial arteries, both prearterioles and arterioles are below the resolution of current angiographic systems and, therefore, cannot be visualized using angiography. The importance of coronary microcirculation for the maintenance of appropriate myocardial perfusion has been recognized by physiologists since the 1950s; evidence has accrued over the past 30 years indicating that functional and structural abnormalities of this section of the circulation can be responsible for impairment of myocardial perfusion and ischemia, a condition often referred to as coronary microvascular dysfunction (CMD). CMD has a high prevalence in both men (51%) and women (54%) with suspected CAD and is associated with adverse outcomes in both stable CAD and acute MI.