Precipitants of Myocardial Ischemia

Myocardial Oxygen Demand

Myocardial oxygen demand is governed by three principal factors: heart rate, contractility, and wall tension. As the heart rate increases, the myocardial oxygen requirement increases, yet there is a concomitant decrease in diastolic filling period, which consequently decreases the available time for perfusion. As myocardial contractility increases, the requirement for oxygen and nutrients is also increased. Wall tension is the force generated by the myocardium at a given preload and afterload and may be calculated by the Laplace law ( Fig. 6.1 ). Wall tension is affected by afterload, chamber size (i.e., radius), and wall thickness. Clinically, chamber dimensions are decreased by interventions that reduce LV preload whereas afterload is largely determined by systolic blood pressure. The impact of afterload (i.e., increased systolic blood pressure) on myocardial oxygen demand is greater than the impact of preload or heart rate. As afterload increases, the radius of the ventricle may increase and further elevate the pressure required by the ventricle to propel blood from the heart. As wall tension increases, myocardial oxygen demand increases.

Assessment of these factors is essential in understanding an individual patient’s potential for developing myocardial ischemia ( Table 6.1 ). Moreover, each of these determinants of myocardial oxygen demand represents an important treatment target for reduction of ischemia (see Chapter 20 ).

Myocardial Oxygen Supply

Myocardial oxygen supply is determined by oxygen transport, oxygen delivery, and coronary arterial blood flow. Perturbations to any of these three components will decrease the ability to meet the metabolic requirements of the myocardium. Along with oxygen, the delivery of metabolic substrate to the myocardium is facilitated by normal coronary blood flow. In the normal resting state, the heart relies primarily on fatty acids, and to a lesser degree glucose, for facilitating aerobic metabolism. As supply diminishes and as demand increases—producing ischemia—the myocardium switches substrate utilization to lactate and glycogen.

Oxygen is transported in the blood bound to hemoglobin and dissociates from hemoglobin when delivered to tissues for oxidative metabolism. The transport of oxygen and the ability to deliver it to myocytes is impacted both by hemoglobin levels and factors that influence the oxygen dissociation curve ( Fig. 6.2 ). The normal oxygen dissociation curve facilitates the binding of oxygen to hemoglobin in the lungs and the dissociation within the myocardial tissue where the carbon dioxide levels are higher and pH lower. Factors that shift the curve to the left decrease oxygen release in the tissues as the hemoglobin molecule has a higher affinity for oxygen; these include hypothermia, decrease in levels of 2,3-diphosphoglycerate, increase in pH (alkalosis), decrease in CO ₂ , and increases in carbon monoxide. In addition, acquired hemoglobinopathies such as methemoglobinemia shift the curve left with a net increase in the affinity for oxygen within the affected hemoglobin molecule. Clinical states including hypothermia, acid/base disorders, anemia, hypoxemia, sepsis, and hemoglobinopathies can precipitate ischemia at lower thresholds, even in the absence of epicardial coronary artery disease (CAD). By decreasing delivery of oxygen to tissues, anemia results in reduced oxygen supply. At any level of hemoglobin, oxygen delivery is further influenced by factors that govern O ₂ dissociation from hemoglobin as previously described (see Fig. 6.2 ).

Coronary blood flow regulation is essential for the heart to adapt its metabolic requirements and to receive adequate oxygen and nutrients. Coronary circulation is mediated by perfusion pressure (aortic diastolic to LV diastolic pressure), arterial tone (autoregulation), metabolic activity, sympathetic/parasympathetic activity, and the endothelium. The regulation of coronary blood flow occurs via neural pathways, metabolic mediators, myogenic control, and extravascular compressive forces ( Table 6.2 ). Exogenous medications, including α- and β-adrenergic agonists/antagonists, adenosine, and dipyridamole, impact blood flow via coronary epicardial and resistance vessels.

Coronary autoregulation maintains a relatively constant perfusion pressure over a broad range of aortic mean pressures (40 to 130 mm Hg). The epicardial vessels do not contribute to resistance unless clinically significant stenoses are present. In the absence of coronary artery stenoses, the majority of resistance is provided by prearteriolar, arteriolar, and intramyocardial capillary vessels ( Fig. 6.3 ). At rest, the capillaries are responsible for 25% of the microvascular resistance, which increases to 75% during periods of hyperemia. In normal individuals, coronary flow can increase 3- to 5-fold under conditions of maximal hyperemia. This ability to augment coronary blood flow is termed coronary flow reserve (see Chapter 5 ). Abnormalities in coronary flow reserve occur in many pathologic states, including diabetes mellitus, hypertension, dyslipidemia, myocardial infarction, aortic stenosis, and idiopathic dilated cardiomyopathies.

Hypoxemia

Individuals frequently develop hypoxemia secondary to medical conditions such as acute or chronic pulmonary diseases or exposure to high-altitude environments including airline travel and residing or visiting high-altitude locales. In addition to the direct effects of hypoxemia on oxygen delivery, individuals who are acutely hypoxemic develop tachycardia and an increase in rate pressure product. In the absence of epicardial CAD, the coronary physiology adapts to hypoxemia by epicardial coronary vasodilation and an increase in coronary flow reserve. In the presence of epicardial coronary disease, hypoxemia-induced epicardial coronary vasodilation may not occur; when studied in individuals with greater than 50% stenoses in at least one major epicardial vessel, vasoconstriction occurred, leading to a decrease in overall myocardial blood flow. As a result, individuals with comorbidities such as hypertension may develop myocardial ischemia at a lower peak rate pressure product, which may limit their functional capacity. An understanding of the normal response to hypoxemia and the alterations that occur in patients with CAD is critical in directing patient management during critical illnesses to minimize the risk for myocardial ischemia. This should be assessed with an understanding of the impact the patient’s overall clinical condition is having on the oxygen dissociation curve as this may also adversely impact the threshold for developing ischemia.