Cardiac Oxygen Demand Research Articles

Silent myocardial ischemia: Clinical characteristics, underlying mechanisms, and implications for treatment

A great deal of interest is being generated by the possibility that patients with coronary artery disease and typical angina pectoris may also experience periods of ischemia during activities of daily living that are not necessarily associated with angina or increased myocardial oxygen demand. It might be that the majority of ischemic episodes during daily life are not preceded by increases in myocardial oxygen demand, and are probably related to dynamic changes in coronary blood flow. Questions still remain, however, regarding the prevalence of asymptomatic ischemia in patients who present with effort angina and positive results on exercise tolerance tests. Therefore, in susceptible patients with coronary artery disease, calcium channel blockers, especially nifedipine, may be of particular benefit since they decrease myocardial oxygen demand during effort and may increase coronary blood flow, thereby aborting asymptomatic ischemia, which tends to occur at low levels of cardiac oxygen demand. It appears that a greater awareness of the total ischemic burden, i.e., the sum total of symptomatic and asymptomatic and exertional and nonexertional ischemia, may facilitate individualization of therapy for patients with coronary artery disease. Agents that both reduce myocardial oxygen demand and improve coronary blood flow, such as nifedipine, may particularly benefit individuals whose ischemia may be both asymptomatic and symptomatic, and who seem to constitute the majority of patients with coronary artery disease.

Inhibitory effects of the D(−) isomer of 3-hydroxybutyrate on cardiac non-esterified fatty acid uptake and oxygen demand induced by norepinephrine in the intact dog

The effects of ketosis on the norepinephrine-induced high rates of cardiac uptake of non-esterified fatty acids (NEFA = free fatty acids = FFA) and oxygen consumption were studied in anesthetized intact dogs. After a control infusion of norepinephrine (500 ng/kg.min into the left ventricle), the D(-) isomer or natural form of 3-hydroxybutyrate was infused intravenously as the arginine salt at rates of 20 mumol/kg.min in group A (10 dogs) and 80 mumol/kg.min in group B (10 dogs) and a second norepinephrine infusion was superimposed on the ketone treatment. At the time the effects of the second catecholamine infusion were measured, the arterial 3-hydroxybutyrate concentration averaged 1.2 +/- 0.1 mM in group A and 8.3 +/- 0.4 mM in group B, and the cardiac uptake of the ketone amounted to 17.4 +/- 0.6 and 35.8 +/- 5.3 mumol/min.100 g, respectively. Relative to the control norepinephrine infusion, the arterial NEFA concentration was reduced to 88 +/- 4% in group A and to 62 +/- 8% in group B, but the cardiac uptake of NEFA was significantly more depressed, to 65 +/- 7% in group A and to 35 +/- 8% in group B. These changes were not observed in ten non-ketotic animals under repeated norepinephrine infusion. Thus, ketosis inhibited the norepinephrine-stimulated uptake of NEFA, presumably through (1) a lowered availability of NEFA from arterial blood, attributable to a reduction of extracardiac lipolysis, and (2) competition of 3-hydroxybutyrate with NEFA for metabolism by the myocardium in the face of still high arterial NEFA concentrations, 1.7 +/- 0.1 mM in group A and 1.1 +/- 0.2 mM in group B. In both groups, the lowering of the contribution of NEFA to cardiac metabolism was associated with a reduction of the estimated oxygen demand per beat (ratio of cardiac oxygen consumption/min to the pressure-rate product), while the pressure response to norepinephrine was not modified. There was no evidence for abnormal cardiac function.

Vasodilative effect of hydralazine in awake dogs: the roles of prostaglandins and the sympathetic nervous system.

The relative roles of prostaglandins and the sympathetic nervous system in mediating the hypotensive effects of hydralazine were studied in awake dogs with and without pretreatment with indomethacin, propranolol, and phentolamine. In normal dogs, mean aortic pressure decreased 23 +/- 4 mm Hg after administration of hydralazine (cumulative dose of 0.8 mg/kg). This hypotensive effect of hydralazine was potentiated by phentolamine but was abolished by propranolol. Indomethacin caused a paradoxic pressor response (11 +/- 3 mm Hg) to hydralazine, which also was abolished by addition of phentolamine. Hydralazine produced vasodilation in the coronary, skeletal muscle (quadriceps), splanchnic, and renal circulations in normal dogs. The increase in coronary blood flow was associated with increased cardiac oxygen consumption and narrowed arteriovenous oxygen difference across the heart. Propranolol reduced the increases in cardiac oxygen consumption and coronary blood flow, but only indomethacin abolished the narrowed arteriovenous oxygen difference, suggesting that the increase in coronary blood flow was related to both the increased cardiac oxygen demand and prostaglandin-mediated active coronary vasodilation. The decrease in skeletal muscle vascular resistance after hydralazine was abolished by propranolol. Skeletal muscle vascular resistance actually increased after administration of hydralazine in dogs pretreated with both propranolol and indomethacin. These effects were blocked by the addition of phentolamine. Unlike the normal response, renal and splanchnic vascular resistances increased after administration of hydralazine in dogs pretreated with indomethacin. The splanchnic vasoconstriction was abolished by phentolamine, but the renal vascular change was affected by neither phentolamine nor propranolol. The results indicate that hydralazine does not produce uniform vasodilation in all organs and that the cardiovascular actions of hydralazine involve both prostaglandins and the sympathetic nervous system.

D(−)-3-hydroxybutyrate infusion reduces the cardiac free fatty acid uptake and oxygen demand induced by norepinephrine: J. Lammerant, T. Huynh-Thu, J. Kolanowski. Department of Physiology, School of Medicine, FNDP, B-5000 Namur, Belgium

D(−)-3-hydroxybutyrate infusion reduces the cardiac free fatty acid uptake and oxygen demand induced by norepinephrine: J. Lammerant, T. Huynh-Thu, J. Kolanowski. Department of Physiology, School of Medicine, FNDP, B-5000 Namur, Belgium

Glyceryl trinitrate ointment (percutol)

Glyceryl trinitrate (GTN), one of the mainstays of therapy for angina pectoris, dilates peripheral veins so reducing left ventricular filling pressure and size, and hence cardiac work and oxygen demand.

Cardiac Function and Hypercarbia

• In 12 patients with heart disease, hypercarbia was induced for carotid endarterectomy. Anesthesia was maintained with nitrous oxide in oxygen and methoxyflurane. In addition to intra-arterial measurements of blood pressure, cardiac output, systolic time intervals (STI), and pressure time indices (PTI) were determined in order to assess cardiovascular responses in these patients. Internal carotid stump blood pressure was measured in five patients before and after induction of hypercarbia. Mild elevation of the Paco2level affected systolic time intervals but not heart rate and blood pressure. When Paco2levels reached 56 to 65 torr, systolic but not diastolic blood pressure rose significantly, heart rate and cardiac output increased, while the shortening in the preejection period (PEP), left ventricular ejection lime (LVET), and the decrease in the PEP/LVET ratio signified increased mechanical cardiac activity. Hypercarbia caused intense sympathetic stimulation as demonstrated by twofold to threefold increases in plasma catecholamine levels. Stump blood pressure was elevated. Cardiac oxygen demand was significantly increased, while coronary filling time was shortened, as indicated by the increase in the tension time index and shortening in the diastolic time. This signified a relative myocardial underperfusion. Thus, while hypercarbia to levels of 66 to 70 torr increased internal carotid artery stump pressure, it also caused increased cardiac mechanical activity and concomitant unfavorable balance between myocardial oxygen consumption and supply. The measurement of STI and the computation of PTI provided early detection of alterations in cardiac function. (Arch Surg113:1196-1200, 1978)

Effects of the Valsalva maneuver on myocardial ischemia in patients with coronary artery disease.

The influence of the Valsalva maneuver (VM) on myocardial ischemia was evaluated in 24 patients with coronary heart disease. Clinical and hemodynamic responses to the VM were studied during acute ischemia manifested by angina pectoris with transient left ventricular (LV) dysfunction and compared with responses during nonischemic intervals. In the absence of evidence for acute ischemia (angina and increased LV end-diastolic pressure), six patients had abnormal hemodynamic responses to the VM. Five had lack of systolic pressure overshoot and in one, systolic pressure did not decline during straining. When the VM was performed during an ischemic episode, 14 patients had abnormal responses (12 with lack of overshoot in phase IV and two with lack of systolic pressure decline in phase II). In 18 patients a prompt decline in LV end-diastolic pressure occurred with the disappearance of angina during the VM. These changes uniformly occurred during the latter part of straining (VM phase II) as cardiac size and systolic pressure declined. No adverse effects occurred when a VM was performed during acute ischemia. Our observations suggest that the VM abruptly reduces determinants of cardiac oxygen demand, relieving acute ischemia without harmful effects.

Cardiac function and hypercarbia.

In 12 patients with heart disease, hypercarbia was induced for carotid endarterectomy. Anesthesia was maintained with nitrous oxide in oxygen and methoxyflurane. In addition to intra-arterial measurements of blood pressure, cardiac output, systolic time intervals (STI), and pressure time indices (PTI) were determined in order to assess cardiovascular responses in these patients. Internal carotid stump blood pressure was measured in five patients before and after induction of hypercarbia. Mild elevation of the Paco2 level affected systolic time intervals but not heart rate and blood pressure. When Paco2 levels reached 56 to 65 torr, systolic but not diastolic blood pressure rose significantly, heart rate and cardiac output increased, while the shortening in the preejection period (PEP), left ventricular ejection time (LVET), and the decrease in the PEP/LVET ratio signified increased mechanical cardiac activity. Hypercarbia caused intense sympathetic stimulation as demonstrated by twofold to threefold increases in plasma catecholamine levels. Stump blood pressure was elevated. Cardiac oxygen demand was significantly increased, while coronary filling time was shortened, as indicated by the increase in the tension time index and shortening in the diastolic time. This signified a relative myocardial underperfusion. Thus, while hypercarbia to levels of 66 to 70 torr increased internal carotid artery stump pressure, it also caused increased cardiac mechanical activity and concomitant unfavorable balance between myocardial oxygen consumption and supply. The measurement of STI and the computation of PTI provided early detection of alterations in cardiac function.

Prostaglandin-induced preservation of the ischemic myocardium.

SUMMARY The effectiveness of prostaglandin (PG) E,, E2, and F2a in altering responses to acute myocardial ischemia was studied in anesthetized, open-chest cats. Following coronary artery occlusion to induce myocardial ischemia (MI) or sham operation (sham MI), a PG (or its appropriate vehicle) was infused at 1 /*g/kg per minute for the 5-hour experimental period. Arterial blood pressure dropped significantly during PG infusion, whereas heart rate decreased only slightly. A pressure-rate index was significantly reduced in ischemic cats infused with either PGE, or PGE2. These two groups also failed to show large elevations in S-T segment which were usually observed in ischemic cats receiving PGF2a or 0.9% NaCI. Arterial blood samples (i.e., at 5 hours) showed significantly increased plasma creatine phosphokinase (CPK) specific activities in MI cats receiving PGF2a or NaCI, whereas PGE, and PGE, infusions prevented significant elevations in plasma CPK during ischemia. Myocardial tissue samples from ischemic cats receiving either PGF2a or NaCI showed significantly reduced tissue CPK in ischemic myocardial tissue. However, PGE, or PGE2 prevented decreases in myocardial CPK activity. Infusion of either Etype PG was further shown to prevent labilization of myocardial lysosomes in ischemic tissue, without significantly altering free amino-nitrogen concentrations in ischemic tissue. Thus, infusion of E-type prostaglandins significantly improved the hemodynamic status and moderated the leakage of enzymes from ischemic myocardial tissue in the cat. These prostaglandins may protect ischemic myocardial tissue by reducing cardiac oxygen demand and stabilizing cardiac lysosomal membranes.

Enflurane Depresses Myocardial Function, Perfusion, and Metabolism in the Dog

Trained dogs with chronically implanted catheters and left ventricular (LV) pressure transducers were anesthetized with 2.3 per cent (1 + MAC) and 3.6 per cent enflurane. Left ventricular function and metabolism were studied while the dogs were awake and during exposure to the two anesthetic concentrations. Enflurane depressed LV function in a dose-dependent fashion. Myocardial blood flow and oxygenation mirrored the functional changes. Myocardial oxygen extraction decreased and lactate extraction increased to the myocardium. Low concentrations of halothane in the same dogs on different days had similar effects. However, 2 MAC halothane resembled 1.6 MAC enflurane, suggesting that the cardiovascular dose-effect curve for enflurane is steeper than that for halothane. Both anesthetics produce dose-dependent negative inotropic effects in the intact dog, accompanied by equivalent decreases in cardiac oxygen demand. Contrary to previous suggestions, enflurane appears to be at least at depressant to the dog heart as halothane.