Systolic Pressure Product Research Articles

Activité anti-ischémique comparée de l'aténolol et du diltiazem: Étude randomisée simple aveugle croisée par épreuve d'effort informatisée

The anti-ischaemic activities of atenolol (200 mg) and diltiazem (240 mg) were compared in 23 patients undergoing retraining 4 weeks after a limited postero-inferior or anterior primary myocardial infarction. The patients, who had signs of residual ischaemia during stress with or without angina, were subjected to 3 exercise tests on a bicycle ergometer; a computer was used to analyze the results (Case-Marquette). The first test was performed under placebo, the second after randomized treatment with one of the two drugs and the third test after taking the other drug. The parameters evaluated were: total duration of the test, time of occurrence of a 1 mm ST-segment depression, maximal work load and total work performed, heart rate, systolic arterial pressure, heart rate X systolic arterial pressure product at rest and at submaximal and maximal stress, and ST depression at submaximal and maximal stress. The results showed that exertion was improved to the same degree by the two drugs, but atenolol had greater anti-ischaemic activity than diltiazem.

Plasma epinephrine concentration in healthy men: Correlation with systolic pressure and rate-pressure product

Relations among plasma epinephrine, norepinephrine and renin activity and systolic pressure, diastolic pressure, heart rate and the product of heart rate and systolic pressure (rate-pressure product) were evaluated in 31 healthy men whose arterial pressure spanned the range from normal to mildly elevated. Measurements were made during 60 minutes with the patient in the supine position and during 10 minutes of quiet standing. In the supine position, highly significant regressions were found between systolic pressure or rate-pressure product and plasma epinephrine, but not between these variables and norepinephrine or renin activity. A weakly significant correlation was also found between heart rate and norepinephrine. On standing, norepinephrine and epinephrine increased significantly. In this position, rate-pressure product was significantly related by regression analysis only with plasma epinephrine. Weakly significant correlations between systolic pressure and epinephrine and between heart rate and norepinephrine and epinephrine were also found. Plasma renin activity was not significantly correlated with arterial pressure, heart rate or rate-pressure product in either position. These results suggest that plasma epinephrine is a determinant of systolic pressure when postural reflexes are minimized and that epinephrine may participate in control of cardiac work load, as reflected by rate-pressure product in the absence of exercise or definable stress.

Improved recovery of myocardial segment function following a short coronary occlusion in dogs by nicorandil, a potential new antianginal agent, and nifedipine.

The effects of nicorandil [SG-75, 2-nicotinamidoethyl nitrate (ester)] and nifedipine on the recovery of myocardial segment shortening were compared to a vehicle-treated group following a short occlusion (15 min) of the left anterior descending coronary artery (LAD) and reperfusion (5 h). The relationship between myocardial blood flow and myocardial segment shortening was examined by means of the radioactive microsphere technique and sonomicrometry. Nicorandil (100 micrograms/kg followed by 25 micrograms/kg/min, i.v.) or nifedipine (3 micrograms/kg followed by 1 microgram/kg/min, i.v.) was administered 10 min prior to and throughout the occlusion period. Both drugs produced similar decreases in mean arterial pressure (approximately 25 mm Hg) during LAD occlusion. Similar degrees of ischemia (flow deprivation) were produced in the vehicle, nicorandil, and nifedipine groups; however, nicorandil produced a significantly greater decrease in the heart rate-left ventricular systolic pressure product during coronary occlusion. During reperfusion of the LAD there was no difference in the hemodynamics of the vehicle, nicorandil, or nifedipine groups. Neither drug altered myocardial blood flow to the ischemic region during the occlusion or reperfusion period when compared to the vehicle-treated group; however, both nicorandil and nifedipine pretreatment significantly improved recovery of percentage of segment shortening of the ischemic region. Nicorandil improved the recovery of function (percentage of segment shortening) to a greater extent than did nifedipine throughout the reperfusion period, most likely because of the greater decrease in afterload produced by nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS)

Low extracellular Ca2+ and enzyme release in the perfused rabbit heart.

Previous studies have shown that the well-oxygenated perfused rabbit heart releases creatine kinase when treated with the calcium antagonist drug verapamil (VER) in a dose-related manner. It is possible that this effect is related to Ca2+ ion deprivation of the sarcolemma. This possibility was explored by perfusing hearts with low Ca2+ (0.5, 0.23, 0.15, and 0 mM) versus a control group (1.27 mM Ca2+) for 60 min. Low Ca2+ perfusion was associated with reduction in the heart rate--left ventricular systolic pressure product and O2 consumption, tendency for the coronary sinus flow to increase, electromechanical dissociation, prolongation of atrioventricular conduction and QT interval, and decrease in myocardial glycogen. Lower total adenosine nucleotides were found only in the 0 mM Ca2+ group. As the Ca2+ concentration was reduced, the hearts lost increasing amounts of creatine kinase, aspartate aminotransferase, and lactate dehydrogenase. These results confirm the importance of Ca2+ ions in contractile and electrical cardiac functions and show that decreased availability of this cation leads to increasing enzyme leakage resembling that seen in VER-treated hearts.

Systemic circulatory adjustments to acute hypoxia and reoxygenation in unanesthetized sheep. Role of renin, angiotensin II, and catecholamine interactions.

The hemodynamic consequences of the hypoxic inhibition of angiotensin-converting enzyme activity were studied in chronically instrumented unanesthetized sheep (n = 8) breathing a hypoxic gas mixture for 60 min (PaO2 = 31 mm Hg) followed by reoxygenation with room air. Changes in cardiac output, vascular pressures, blood flow distribution, arterial pH, PaCO2, PaO2, and arterial levels of plasma renin activity, angiotensin II, bradykinin, and catecholamines were measured at selected time points. Seven additional sheep underwent the same protocol but received saralasin, an angiotensin II receptor blocker beginning at 55 min of hypoxia and extending into the reoxygenation period. During hypoxia, both groups developed identical hemodynamic patterns including a rise in cardiac output (25%), blood pressure (15%), and preferential blood flow distribution to the heart, brain, adrenals, diaphragm, and skeletal muscle, as well as a decrease in the fraction of cardiac output to the kidneys and most of the gut. This was associated with a decrease in angiotensin II concentrations (from 35 to 17 pg/ml) in spite of a doubling in plasma renin activity and catecholamines. Bradykinin levels did not change. Upon reoxygenation, bolus production of angiotensin II (from 17 to 1,819 pg/ml) occurred in spite of a constant level of plasma renin activity. Concurrently, different hemodynamic patterns between control and saralasin groups emerged upon reoxygenation, including an elevation from base line in blood pressure and systemic vascular resistance in the control group. Cardiac work (heart-rate systolic pressure product) in the control group remained elevated upon reoxygenation while coronary blood flow returned to base-line values. Saralasin reduced cardiac work upon reoxygenation and restored the match between coronary blood flow and work. We conclude that plasma renin activity and oxygen tension together govern angiotensin II levels for an optimal level of systemic vasomotor tone during hypoxia. However, upon reoxygenation, bolus production of angiotensin II may result in pathophysiologic circulatory patterns, such as impairment in oxygen delivery to the myocardium proportional to persistently elevated cardiac work in the immediate postresuscitation period.

Comparison of coronary hemodynamic effects of nitroprusside and sublingual nitroglycerin with anterior descending coronary arterial occlusion

This study compares the coronary hemodynamic effects of an infusion of nitroprusside and of sublingual nitroglycerin in the same patients. The coronary hemodynamic responses of the anterior left ventricular (LV) region to both drugs were studied in 9 patients whose anterior descending branch of the left coronary artery was filled by collaterals. Before and during administration of each drug (given in doses designed to produce similar changes in LV diastolic pressure), heart rate, LV and aortic pressure, and anterior regional flow, oxygen delivery and lactate metabolism were measured. Given in this manner, as expected, both drugs decreased the double product of heart rate and systolic pressure. Concomitant with these changes, anterior regional blood flow increased or decreased modest amounts or did not change with either drug. Similar directional flow changes or no change occurred in 6 patients and directionally different changes in the other 3 patients. The ratio of mean aortic pressure or of the double product to anterior regional flow consistently decreased during the administration of both drugs. Additionally, anterior regional myocardial oxygen uptake remained similar during both drug periods compared with control values. Anterior region lactate extraction was abnormal (< 10%) in 4 of the 9 patients during the initial control period. Lactate extraction was usually normal during both the nitroprusside and the nitroglycerin periods. In general, coronary hemodynamic values were remarkably similar during both of these periods. Thus, although relative differences in systemic arterial and venous dilation were obtained with nitroprusside and nitroglycerin, similar and beneficial coronary hemodynamic changes generally occurred.

The effect of intracellular oxygen concentration on lactate release, pyridine nucleotide reduction, and respiration rate in the rat cardiac tissue.

By measuring the absorbance change due to myoglobin oxygenation in hemoglobin-free isolated perfused rat hearts, we analyzed effects of perfusion pressure and heart rate upon the intracellular oxygen concentration. With Langendorff perfusion, the cardiac tissue was kept normoxic (above 50 microM O2) at aortic pressure above 50 cm H2O, but became hypoxic (8 microM O2) at 30 cm H2O. The increase in cardiac work, expressed as the product of peak systolic pressure and heart rate, increased oxygen consumption at aortic pressure of 50-200 cm H2O. The heart was kept normoxic under these conditions. Lactate release, oxygen consumption, and the oxidation-reduction state of pyridine nucleotide were measured as a function of myoglobin oxygenation under various normoxic and anoxic conditions. Pyridine nucleotide fluorescence and lactate release started to increase as the intracellular oxygen concentration decreased to 6 and 10 microM, respectively. Oxygen consumption was kept constant until the oxygen concentration decreased to 10 microM and slowed down below it. A close relationship between oxygen consumption and lactate release was observed. Infusions of epinephrine and norepinephrine under normoxic perfusion conditions increased cardiac work, oxygen consumption, and lactate release. More than 50% of myoglobin was then deoxygenated even under normoxic perfusion conditions. The increase in lactate release was ascribable to the increase in glycolytic flux caused by hypoxia. The change of pyridine nucleotide fluorescence by epinephrine was also explained by hypoxia in cardiac tissue.

Cold pressor thallium-201 myocardial scintigraphy in the diagnosis of coronary artery disease

Thallium-201 myocardial scintigraphy was performed during cold pressor stimulation in 36 patients aged 37 to 69 years. Thirty-one patients had coronary artery disease and 5 patients did not, as confirmed by coronary cineangiography. Thallium-201 (1.5 to 2 mCi) was injected at 30 seconds of the cold pressor stimulation. The product of systolic pressure × heart rate increased from a baseline of 77.4 ± 16 (standard deviation [SD]) to 103.6 ± 17 at 30 seconds of the cold pressor test (p < 0.0005). Transient perfusion deficits developed in 24 of 31 patients with coronary artery disease (sensitivity 77%), and all 5 patients without coronary artery disease had normal scintigrams. The sensitivity in detecting coronary artery disease was 40% in patients with 1 vessel disease, 91% in patients with 2 vessel disease, and 100% in patients with 3 vessel disease. Exercise electrocardiograms (available in 29 of 36 patients) were positive for ischemia in 18 of 24 patients with coronary artery disease and in 1 of 5 patients without coronary artery disease (sensitivity 75% and specificity <80%). Exercise thallium-201 scintigrams, obtained in 16 patients, were positive in 11 patients with coronary artery disease and positive cold pressor thallium-201 scintigrams. Five patients without coronary artery disease and with normal cold pressor thallium-201 scintigrams had normal exercise thallium-201 scintigrams. Coronary cineangiography performed during cold pressor stimulation in 6 patients who had positive cold pressor and exercise thallium-201 scintigrams did not show coronary spasm. Our data indicate that cold pressor thallium-201 scintigraphy offers promise as a noninvasive test in the diagnosis of coronary artery disease and may be used in patients in whom exercise testing is not feasible.

Use of Propranolol to Control Rate-Pressure Product during Cardiac Anesthesia

The use of propranolol to control heart rate (HR), systolic pressure, and rate-pressure product (RPP) during laryngoscopy and sternotomy was studied in 21 patients, New York Heart Association functional Classes 1 and 2, scheduled for coronary artery bypass graft surgery. All patients were anesthetized in an identical fashion, but the treatment group (N = 13) received propranolol, 0.5 to 1 mg IV, 4 minutes before laryngoscopy and again, in most cases, before skin incision. Patients not given propranolol (N = 8) showed a clinically and statistically significant increase in HR and RPP, whereas HR and RPP remained essentially unchanged from the preanesthetic period in patients given propranolol.

Changes in R wave amplitude during aerobic exercise stress testing in hypertensive adolescents

The change in R wave amplitude during progressive aerobic exercise was studied in hypertensive adolescent boys. A comparable control group consisted of normotensive adolescent boys matched for age, body size and race. Twenty-four normotensive and 22 hypertensive subjects exercised to exhaustion on a treadmill utilizing the Bruce protocol. Blood pressure and heart rate were monitored during exercise and recovery. The change in R wave amplitude in a lead V 5 electrocardiogram was determined at each level of exercise. The normotensive group demonstrated a progressive increase in systolic pressure, heart rate and rate-pressure product (heart rate × systolic pressure) during exercise and a progressive decrease in R wave amplitude with a significant correlation of R wave change versus the cardiac response variable (p < 0.001). Hypertensive subjects manifested a greater increase in systolic pressure, heart rate and rate-pressure product during exercise with no decrease in R wave amplitude until the exercise end point. The difference in R wave response to progressive exercise in the two groups was significant (p < 0.01). A variation in myocardial function in hypertensive adolescents as demonstrated by a difference in R wave response to exercise may reflect a level of peripheral vascular resistance greater than that of normotensive control subjects.

Effect of peroral administration of sotalol on the hemodynamics of the baboon.

We investigated the effect of oral administration of sotalol on coronary and renal blood flow and other hemodynamic parameters of the baboon. Measurements were made in anesthetized baboons under basal conditions and during the intravenous infusion of isoproterenol at rates of 0.5, 1.0, 2.0 microgram. min-1 in an experimental (n = 20) and a control (n = 6) group. Subsequently, sotalol (dose 1-4 mg.kg-1, mean 2.25 mg.kg-1) or placebo was administered. After 2 h the procedure was repeated. Measurements included renal (RBF) and coronary (COR BF) blood flow, cardiac output (CO), heart rate (HR), stroke volume (SV), left ventricular systolic pressure (LVSP), maximum positive dP/dt (dP/dt max), aortic diastolic (APD) and mean (APM) pressures, heart rate-left ventricular systolic pressure product (RPP), and left ventricular stroke work index (LVSWI). RBF and COR BF were determined indirectly from the rate of 133 Xe clearance. In the control group, changes before and after the administration of placebo did not differ significantly for all parameters. In the experimental group, changes after sotalol administration were significantly lower for COR BF, CO, HR, LVSP, dP/dt max, APD, APM and RPP, but were not significantly different for RBF, SV and LVSWI. Beta-blockade had no effect on RBF. The reduction in COR BF was associated with a reduction in RPP (myocardial oxygen consumption). However, the oxygen supply-demand relationship was maintained. Decrease in CO was largely due to reduction in HR since SV (and LVSWI) were unaffected by Beta-blockade.

Direct effects of carbon monoxide on cardiac function.

The direct effects of carbon monoxide (CO) on cardiac function were investigated in hemoglobin-free living rabbits treated with perfluorochemical blood substitutes. After exchange transfusion with a perfluorochemical emulsion, the erythrocyte count was below 10 X 10(4)/mm3 in each animal. Gas mixtures of oxygen with 5%, 10%, and 20% of CO or nitrogen were administered via a respirator. The results showed that the cardiac effects of CO and nitrogen were significantly different as regards changes in arterial pressure, pulse pressure, heart rate, and the product of heart rate and systolic arterial pressure in spite of the same oxygen tension in the inhaled gases. It was concluded that there was a direct effect of CO not mediated by hemoglobin.

Subjective assessment and cardiovascular response to ischemic pain in young, healthy women users and non-users of oral contraceptives

Experimental pain was introduced in women volunteers, some of whom were taking oral contraceptives. Pain perception and tolerance were the same, regardless of oral contraceptive use. All responded to the introduction of pain with increasing heart rate (HR), blood pressure (BP) and the product of systolic pressure, HR and the left ventricular ejection time (LVET). The users had a more consistent response pattern, and their reported levels of pain were positively and highly correlated with the changes in pre-ejection period (PEP) and the ratio PEP/LVET. Non-users had more variable systolic time interval (STI) responses.

Metabolism of the perfused rabbit heart. IV. Effects of β-adrenergic blockade on enzyme release and late energy stores during postanoxic reoxygenation

The effects of 80 microM dl-propranolol on left ventricular (LV) performance, energy stores, and creatine kinase (CK) release were studied in a modified Langendorff rabbit heart preparation during 75 min of aerobic perfusion and postanoxic reoxygenation. The data showed that this concentration of propranolol, which blocked the effects of beta-adrenergic stimulation without affecting LV performance, coronary sinus flow (CSF), or oxygen consumption (MV O2), was associated with greater stores of glycogen and adenine nucleotides at the end of aerobic perfusion. Similar effects were observed during postanoxic reoxygenation, when recoveries of left ventricular systolic pressure, heart rate, heart rate--left ventricular systolic pressure product, CSF, and MV O2 remained unchanged during propranolol administration, but myocardial concentrations of glycogen, creatine phosphate, and ATP were greater and the ATP:AMP ratio and the energy charge were higher than in untreated hearts. In addition, the rate of CK loss was lower in the blocked postanoxic hearts than in the unblocked group. These results indicate that propranolol had a beneficial effect on cardiac metabolism during postanoxic recovery tending to normalize energy stores and to reduce enzyme loss during reoxygenation or perfused rabbit hearts without affecting mechanical performance, coronary flow, or O2 metabolism.

Comparison of Myocardial Oxygen Consumption Indices in Man

Hemodynamic indices of myocardial oxygen consumption (MVO2) were examined in 13 patients with coronary heart disease. The specific aim of this study was to investigate whether clinical results agree with experimental findings in animals. During hemodynamic and respiratory steady-state conditions at rest, the MVO2 (7.6-14.2 ml/min/100 g) was measured directly by myocardial blood flow (argon method) and arterio-coronary venous oxygen content difference. MVO2 was compared with five indirect indices of MVO2. A complex additive parameter consisting of five components of MVO2 had the highest correlation with MVO2 (r = 0.97), as was also demonstrated in a recent experimental study at maximum changes in hemodynamics and MVO2. More easily measurable predictors of MVO2 such as tension-time index (r = 0.923), product of mean systolic aortic pressure and square root of heart rate (r = 0.928), pressure rate product (r = 0.915), and triple product (r = 0.941) were less closely correlated with MVO2. The lower correlations of the readily obtainable indices of MVO2 are probably related to their failure to incorporate factors such as contractility and ventricular dimensions, which are known to exert an important influence on MVO2. The excellent correlation of the hemodynamic additive parameter with MVO2 supports the theoretical concept and the implications of the experimental study. The accurate prediction of MVO2 is based on adequate measurement of MVO2 for the velocity of tension development and maintenance of tension during systolic ejection period, both of which are integrated in the additive index.

Metabolism of the isolated perfused rabbit heart. III. Energy stores and creatine kinase release during prolonged reoxygenation and atrial pacing.

When the perfused rabbit heart is reoxygenated for 75 min after 25 min of anoxic perfusion, left ventricle performance stabilizes at 50% of control levels, but the rate of creatine kinase (CK) release is high (1.9 U/min) and ATP stores are low (5 μmol/g dry weight). These results suggest that the preparation is on the verge of severe failure. This possibility was investigated by following the recovery for an extra 60 min of reoxygenation and by stressing the hearts with atrial pacing.The data show that no deterioration occurred during the extra recovery period; on the contrary, mechanical performance remained stable, while the rate of CK release fell to 1.1 U/min, and ATP stores increased by 204%. In aerobic hearts, pacing increased the product of left ventricular systolic pressure (LVSP) and heart rate, myocardial uptake of oxygen [Formula: see text], coronary sinus flow, and O2 extraction, but LVSP and [Formula: see text] per beat fell. Similar responses were seen in postanoxic hearts, but LVSP improved during pacing while the rate of CK loss declined and ATP stores increased. These metabolic changes were inversely related to the rate of contraction. It is concluded that the preparation was not deteriorating at 75 min of reoxygenation, and that its metabolism was improved by cardiac pacing.

Rest and exercise hemodynamic studies in patients with isolated aortic stenosis.

Hemodynamic data obtained during rest and exercise in 22 patients with aortic stenosis were analyzed. Mean aortic valve gradient for the group did not change significantly during exercise but there was large individual variability. Aortic valve flow increased during exercise in all but 2 patients. There was no correlation between change in gradient and change in flow during exercise. Although the mean calculated aortic valve area for the group did not change significantly during exercise, the calculated area was larger during exercise in most patients. Change in the calculated valve area correlated best with changes in aortic valve flow, left ventricular stroke work index, and the product of left ventricular systolic pressure and stroke volume. This suggests that in some patients there may be a dynamic component to aortic valve obstruction that may vary with changing hemodynamics.

Effects of alpha adrenergic blockade upon coronary hemodynamics.

The effect of alpha adrenergic block-ade on coronary blood flow regulation at rest was studied in 11 normally innervated patients and 8 cardiac allograft recipients by measuring arterial pressure and coronary sinus blood flow by thermodilution before and after alpha adrenergic blockade with phentolamine. Coronary vascular resistance was calculated by using coronary sinus blood flow and mean arterial pressure, and metabolic demand was estimated by the product of systolic arterial pressure and heart rate. In addition, the coronary sinus blood flow response to tachycardia was examined in 9 innervated patients and 12 denervated patients, with measurements repeated after phentolamine in 8 of the 9 innvervated patients and 6 of the 12 denervated patients. There was a 7.3+/-4.4% increase in coronary sinus blood flow in the innervated patients in response to alpha blockade, whereas the transplanted patients had an 8.2+/-1.8% fall in coronary sinus blood flow, despite equivalent changes in rate pressure product. The innervated patients also demonstrated a significantly greater increase in coronary sinus blood flow than did the transplanted patients during the first 5 s of an abrupt increase in heart rate (26+/-4 vs. 8+/-2.5 ml/min, P <0.001). This early response was blunted after alpha adrenergic blockade. We conclude that there is basal alpha adrenergic tone present on the coronary vasculature in man that is withdrawn by a sudden increase in heart rate.

Evaluation of Myocardial Damage in Patients Undergoing Coronary-Artery Bypass Procedures with Halothane-N2O Anesthesia and Adjuvants

During a 6-month period in 1975, 102 patients undergoing scheduled coronary-artery bypass grafting were studied by both conventional ECG and heart-specific enzymatic methods to evaluate the incidence and estimate the extent of myocardial damage associated with an anesthetic management protocol using halothane as a primary agent with adjuvant agents. Anesthetic interventions were made to maintain heart rate and systolic pressure at resting levels or below the heart rate systolic pressure product documented during exercise-induced angina. These interventions included adjustment of halothane concentration in all patients, the use of adjuvant agents in 88.2 percent, vasodilators in 26.5 percent, and the precardiopulmonary bypass use of vasoconstrictor or cardiostimulants in 9.8 percent. There were 2 early postoperative deaths. ECG evidence of infarction was observed in 4 surviving patients. Sustained release of heart-specific CPK-MB isoenzyme occurred in 78 percent of surviving patients. Isoenzyme activity was detected in only 1 patients prior to cardiopulmonary bypass (CPB), in 1 patient during CPB, and in all others after termination of CPB. The extent of myocardial damage as estimated by integrating CPK-MB values over time was directly related to number of vessels grafted and to aortic cross-clamp and CPB times. The ECG and enzymatic data both document a low level of myocardial damage associated with this anesthetic management protocol.

Halothane-induced Decrease in Experimental Myocardial Ischemia in the Non-failing Canine Heart

The effect of halothane on net myocardial oxygen balance of ischemic myocardium was studied in the non-failing canine heart. Myocardial ischemia was produced by repeated reversible occlusions of a coronary artery; the severity of ischemia was estimated by summating ST-segment elevations (sigma ST) obtained by epicardial ECG mapping at 15 to 18 sites. Control measurements were obtained before and after administration of halothane (0.75 per cent) to six dogs with chloralose-urethane basal anesthesia. Halothane was associated with significant decreases of systemic arterial pressure (P less than .001), heart rate (P less than .01), and the product of systolic arterial pressure X heart rate (P less than .01), an indirect index of myocardial oxygen consumption, while left atrial pressure remained unchanged at normal levels. sigmaST during occlusion was less (P less .001) during halothane (26.5 +/- 7.4 (SD) mv) than before (36.6 +/- 5.4 mv) or after (34.4 +/- 8.2 mv) its administration. Thus, halothane decreased the severity of experimentally-induced myocardial ischemia in the non-failing canine heart. The data suggest that, in the absence of ventricular failure, halothane influences the relationship between myocardial oxygen supply and demand in a favorable direction when coronary blood flow is limited.