Effects of altered site of electrical activation on myocardial performance during inotropic stimulation

The effects of altering the site of electrical activation on responses to isoproterenol (ISO) and treadmill exercise were examined in mongrel dogs instrumented for long-term measurement of left ventricular pressure, left ventricular dP/dt, coronary blood flow, cardiac output, left ventricular diameters, and mean arterial pressure and O2 content in the coronary sinus and aorta. During spontaneous rhythm, 0.2 micrograms/kg/min ISO increased heart rate by 90 +/- 7 beats/min, left ventricular dP/dt by 2479 +/- 301 mm Hg/sec, cardiac output by 3.5 +/- 0.9 liters/min, coronary blood flow by 30.4 +/- 3.9 ml/min, and myocardial oxygen consumption (MVO2) by 3.91 +/- 0.84 ml/min. During right atrial pacing at 193 +/- 7 beats/min, the effects of ISO were not different from the effects during spontaneous rhythm, with the exception of a lesser increase in coronary blood flow and lesser reductions in coronary resistance and left ventricular end-diastolic diameter and pressure. During right ventricular pacing at an identical rate, ISO increased left ventricular dP/dt (1140 +/- 158 mm Hg/sec) and cardiac output (2.2 +/- 0.5 liters/min) significantly less (p less than .025) than during either sinus rhythm or right atrial pacing, while MVO2 rose to a higher value. During right ventricular pacing the changes in mean arterial pressure and left ventricular end-diastolic diameters with ISO were not significantly different from those during right atrial pacing. Treadmill exercise induced significantly smaller (p less than .025) increases in left ventricular dP/dt during right ventricular pacing as compared with during either right atrial pacing or sinus rhythm, while MVO2 rose to a higher value.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodynamic effects of atenolol in patients with coronary artery disease.

The haemodynamic effects of atenolol, a new cardioselective beta-blocking agent, have been studied at rest in 8 patients with coronary artery disease. The drug was administered intravenously in cumulative doses of 0.03, 0.06, and 0.12 mg/kg body weight. A significant decrease in heart rate was associated with a fall in cardiac output. However, this cardiac output fall was not entiely rate dependent, since stroke volume fell significantly both during spontaneous sinus rhythm and when heart rate was maintained constant by atrial pacing. A dose related and significant reduction occurred in left ventricular dP/dt max without significant change in left ventricular filling pressure or mean aortic pressure. Total peripheral resistance at rest rose after atenolol. The haemodynamic findings more closely resemble those which follow intravenous propranolol than those after intravenous practolol in a similar group of patients. These actions of atenolol suggest that it may be a useful agent in the treatment of patients with angina pectoris.     

Haemodynamic effects of atenolol in patients with coronary artery disease.

The haemodynamic effects of atenolol, a new cardioselective beta-blocking agent, have been studied at rest in 8 patients with coronary artery disease. The drug was administered intravenously in cumulative doses of 0.03, 0.06, and 0.12 mg/kg body weight. A significant decrease in heart rate was associated with a fall in cardiac output. However, this cardiac output fall was not entiely rate dependent, since stroke volume fell significantly both during spontaneous sinus rhythm and when heart rate was maintained constant by atrial pacing. A dose related and significant reduction occurred in left ventricular dP/dt max without significant change in left ventricular filling pressure or mean aortic pressure. Total peripheral resistance at rest rose after atenolol. The haemodynamic findings more closely resemble those which follow intravenous propranolol than those after intravenous practolol in a similar group of patients. These actions of atenolol suggest that it may be a useful agent in the treatment of patients with angina pectoris.     

Effects of diltiazem on cardiac and coronary circulation, at rest and during rapid auricular electric stimulation

The effects on cardiac performance and systemic and coronary blood flow of rapid atrial pacing alone and associated with an intravenous infusion of a slow calcium channel inhibitor, diltiazem, at a dose of 20 mg/kg were studied in 20 patients with chronic coronary artery disease. Atrial pacing increased coronary flow and myocardial oxygen consumption: it decreased coronary arterial resistance and the coronary arteriovenous difference in lactates. Left ventricular end diastolic pressure rose significantly compared to the basal state in the period following pacing. The administration of diltiazem was associated with a significant fall of femoral arterial pressure, of coronary arteriovenous difference and myocardial consumption of oxygen, and an increase in the coronary arteriovenous difference in lactate. Left ventricular end diastolic pressure did not differ significantly from the basal values recorded after terminating atrial pacing. Left ventricular end diastolic volume decreased. Diltiazem opposed or cancelled the undesirable effects of rapid atrial pacing with respect to coronary arteriovenous difference in lactate content. The beneficial action of diltiazem does not seem to be closely related to its hemodynamic effects. It could be related to a reduction in myocardial oxygen demands due to a decrease in systolic ventricular strain and the specific metabolic effects of the drug, and also to an increase in myocardial oxygen supply due to the reduction in left ventricular end diastolic stress and the coronary vasodilation caused by the drug.     

Short-term effects of right atrial, right ventricular apical, and atrioventricular sequential pacing on myocardial oxygen consumption and cardiac efficiency in patients with coronary artery disease.

OBJECTIVE--To investigate the short-term effects of atrial, atrioventricular, and ventricular pacing on myocardial oxygen consumption, myocardial blood flow, and cardiac efficiency in patients with coronary artery disease. DESIGN--Prospective study that started at the end of diagnostic coronary angiography in 13 patients and was performed during atrial, atrioventricular, and ventricular pacing for 5 min, in random order, at 20 beats/min more than the heart rate of the patient's positive exercise test. A Baim thermodilution catheter in the coronary sinus was used to measure myocardial blood flow and oxygen consumption and a pacing electrode at the right ventricular apex and a catheter in the pulmonary artery were used to estimate cardiac output. SETTING--Referral cardiology centre. PATIENTS--13 patients with coronary artery disease (mean (SD) age 53(5) years). All the patients had a positive exercise test and most of them (77%) had left anterior descending coronary artery disease. RESULTS--Mean (SD) cardiac output increased by 0.5(1.6) l/min during atrial pacing, increased by 0.1(1) l/min during atrioventricular pacing, and decreased by 0.8(1.2) l/min during ventricular pacing (P = 0.01 v atrial pacing, P = 0.03 v atrioventricular pacing). Diastolic pulmonary pressure increased by 6(4) mm Hg during atrial pacing, by 8.6(4) mm Hg during ventricular pacing (P = 0.02 v atrial pacing), and by 7.5(4.7) mm Hg during atrioventricular pacing. Changes in myocardial oxygen consumption and cardiac efficiency during the different pacing modes were similar. CONCLUSION--Atrial, atrioventricular, and ventricular pacing had similar short-term effects on myocardial oxygen consumption, myocardial blood flow, and cardiac efficiency in patients with coronary artery disease. Ventricular pacing, however, did not increase cardiac output.     

Effect of aortocoronary bypass surgery on coronary circulation and myocardial metabolism during atrial pacing

Summary Eleven patients with coronary heart disease, in whom at least one of several bypass grafts to the left coronary artery was patent, were selected for the study. The hemodynamics, coronary sinus blood flow, myocardial oxygen consumption, and myocardial lactate metabolism were evaluated at rest and during atrial pacing stress test before and after surgery.There were no significant improvements in the cardiac index, pulmonary arterial end-diastolic pressure, and left ventricular ejection fraction after aortocoronary bypass surgery. However, significant improvement of coronary sinus blood flow, myocardial oxygen consumption, and myocardial lactate extraction and consumption were found during postoperative atrial pacing compared with the preoperative findings.These results suggest that successful bypass grafting may improve myocardial lactate metabolism in ischemic lesions and contribute to the postoperative relief of angina.     

Effect of graded reductions of coronary pressure and flow on myocardial metabolism and performance: a model of "hibernating" myocardium

The term "hibernating" myocardium has been applied to chronic left ventricular dysfunction without angina or ischemic electrocardiographic changes in patients with coronary artery disease that is reversed by therapy that increases myocardial blood flow. To investigate the relation between coronary blood flow and ventricular function experimentally, graded reductions in coronary artery pressure were produced in isolated perfused rat hearts as contractile performance (peak systolic pressure and its first derivative [dP/dt]) and metabolic variables were measured using phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy. As coronary pressure and flow were reduced, significant reductions in myocardial oxygen consumption and contractile performance were observed, which returned to control levels when coronary artery pressure and flow were restored to baseline values. Two phases of metabolic abnormality were observed. With modest reductions in coronary perfusion, proportionate reductions in myocardial oxygen consumption and contractile behavior were accompanied by a slight reduction in creatine phosphate but no significant lactate production. With greater reductions in coronary artery pressure and flow, creatine phosphate decreased more, adenosine triphosphate levels and myocardial pH decreased significantly and myocardial lactate production increased. The balanced reductions in myocardial contractility and oxygen consumption without metabolic abnormalities traditionally associated with "ischemia" observed in the first phase provides evidence in normal hearts for resetting of the myocardial contractile behavior and oxygen consumption in the presence of reduced coronary flow (that is, hibernating myocardium). The data suggest that reductions in adenosine diphosphate and the index of the reduced form of nicotinamide adenine dinucleotide (NADH) (lactate formation) do not explain the coupling between coronary artery pressure and flow and myocardial oxygen consumption as contractile performance decreases.     

Effect of digoxin on coronary blood flow and myocardial oxygen consumption in patients with chronic coronary artery disease

In 10 patients with chronic coronary artery disease and without clinical evidence of congestive heart failure, the effects of 1.0 mg of digoxin intravenously on systemic hemodynamics, coronary blood flow, myocardial oxygen consumption and myocardial lactate extraction were studied both at rest and during atrial pacing. Atrial stimulation at a rate just below the threshold for angina led to a significant decrease in left ventricular enddiastolic pressure, from 10.6 ± 1.6 to 7.1 ± 0.8 mm Hg, associated with a significant decrease in left ventricular stroke work index per beat, from 76.7 ± 5.11 to 40.3 ± 4.01 g-m/m². After digoxin, nearly identical results in stroke work index could be observed at rest and during stimulation (75.2 ± 6.74 and 44.1 ± 5.92, respectively). However, left ventricular enddiastolic pressure decreased significantly before and during atrial stimulation (8.1 ± 1.29 and 4.7 ± 1.09 mm Hg, respectively). Cardiac index decreased from 3.08 ± 0.20 to 2.73 ±0.17 liters/min per m² at rest but during pacing it no longer differed before and after digoxin (3.17 ± 0.22 and 3.10 ± 0.20 liters/min per m², respectively). Myocardial oxygen consumption and lactate extraction remained unchanged after digoxin both at rest and during atrial pacing.It is concluded that some deficiency in left ventricular function is present in patients with chronic coronary artery disease even without clinical evidence of congestive heart failure. Digoxin improves left ventricular performance at rest and during stress conditions. An expected increase in myocardial oxygen consumption due to enhanced contractility is completely counterbalanced, probably by a decrease in left ventricular volume after digoxin.     

Systemic and coronary hemodynamic effects of pinacidil in awake normotensive and hypertensive dogs

We studied the systemic and coronary hemodynamic effects of a new antihypertensive agent, pinacidil, in nine morphine-sedated chronically instrumented dogs with one-kidney renal hypertension and eight similarly treated sham-operated normotensive dogs. The renal hypertensive dogs exhibited higher mean aortic blood pressure, total peripheral vascular resistance, and plasma renin activity before pinacidil administration than the sham-operated animals. The renal hypertensive dogs also had a lower left ventricular norepinephrine content, but the two groups did not differ significantly in plasma norepinephrine levels, cardiac output, or heart rate. Pinacidil decreased mean aortic pressure and total peripheral vascular resistance and increased cardiac output and heart rate in both groups. The changes in aortic pressure, total peripheral vascular resistance, and cardiac output were similar between the two groups, but the increase in heart rate was attenuated in renal hypertension. The peak rate of rise of left ventricular pressure (dP/dt), the ratio of left ventricular dP/dt and the developed pressure during isovolumic contraction (dP/dt/P), myocardial oxygen consumption, and plasma norepinephrine levels increased after pinacidil administration in the sham-operated dogs, but did not change in the renal hypertension group. The two groups did not differ in their responses of left ventricular dP/dt to intravenous isoproterenol. Pinacidil also caused coronary vasodilation in both groups, as evidenced by an increase in coronary blood flow and decreases in coronary vascular resistance and myocardial oxygen extraction. The decrease in myocardial oxygen extraction was similar in the two groups, but the increase in coronary blood flow was significantly less (p less than 0.05), probably because of the absence of an increase in myocardial oxygen consumption in the renal hypertensive dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved myocardial contractility with glucose-insulin-potassium infusion during pacing in coronary artery disease

The metabolic and mechanical effects of a solution of glucose-insulin-potassium (G-I-K) were investigated in 18 patients who underwent diagnostic cardiac catheterization for coronary artery disease. All patients were paced at a rate of approximately 140 beats/min before and after infusion of G-I-K. Basal and paced left ventricular (LV) end-diastolic pressure, dP/dt, arterial substrate levels and osmolarity were measured in all 18 patients. In 13 patients cardiac index was also measured. In 5 patients arterial-coronary sinus measurements of oxygen, carbon dioxide, glucose, free fatty acids, lactate, alanine, glutamate, glutamine, ammonia and urea were made, in addition to coronary sinus blood flow. G-I-K increased the blood sugar level to approximately 200 mg/dl and raised the serum osmolarity 9 mosmol. Pacing alone raised the cardiac index 4% and pacing with G-I-K increased the cardiac index 6% (p less than 0.05). Pacing before G-I-K augmented dP/dt (21%) and pacing with G-I-K increased it (30%) (p less than 0.01). The metabolic changes noted included a shift in the respiratory quotient from 0.77 to 0.96 with G-I-K infusion (p less than 0.05). During G-I-K infusion the myocardial oxygen consumption at rest increased from 17.1 to 21.8 ml/min (23%, p less than 0.05). Myocardial oxygen consumption during pacing was similar before and after G-I-K infusion. Before G-I-K infusion nitrogen balance was slightly positive; after G-I-K infusion it was negative with regard to the nitrogen-containing compounds measured.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of ouabain effect on pacing-induced myocardial ischemia in patients with coronary artery disease

Sixteen patients with significant two and three vessel coronary artery disease but without clinical congestive heart failure were studied during rapid atrial pacing before and after infusion of 0.015 mg/kg of ouabain. Seven patients with a decreased (less than 50 percent) election fraction and nine patients with a normal election fraction had a significant (P < 0.05) increase in resting arterial systolic pressure after the administration of ouabain. However, resting values for coronary sinus flow, coronary vascular resistance, myocardial oxygen consumption and myocardial lactate extraction did not change significantly in either group. During pacing, patients with a decreased ejection fraction demonstrated more ischemia than patients with a normal ejection fraction; however, the administration of ouabain did not significantly alter pacing-related changes in coronary sinus flow, myocardial oxygen consumption, myocardial lactate extraction, ischemic electrocardiographic changes or onset of chest pain in either group. The administration of ouabain has a negligible effect on coronary hemodynamics, myocardial metabolism or clinical signs of ischemia in patients with coronary artery disease with normal or abnormal left ventricular function.     

Effects of oral dipyridamole on coronary dynamics and myocardial metabolism at rest and during pacing-induced angina in patients with coronary artery disease

The effects of oral dipyridamole administration (150 mg) on coronary hemodynamics, myocardial metabolism, and pacing threshold were studied in 10 patients with significant coronary artery disease (CAD). Following dipyridamole through 120 minutes, there was no significant change in resting heart rate, arterial pressure, coronary venous flow, coronary resistance, myocardial lactate extraction, or myocardial oxygen consumption. Rapid atrial pacing performed before and at 60, 90, and 120 minutes after dipyridamole failed to demonstrate any significant reduction in pacing threshold or evidence of increased ischemia after dipyridamole. Blood dipyridamole levels showed variable and slow absorption which probably explains the difference between intravenous and oral dipyridamole on coronary dynamics and myocardial response to pacing.     

Acute haemodynamic effects of felodipine during beta blockade in patients with coronary artery disease

The acute effects of felodipine on left ventricular function and haemodynamics were studied in 11 patients with coronary artery disease. To block reflex sympathetic activation due to peripheral vasodilatation and to avoid effects secondary to changes in heart rate all patients received a standard regimen of beta adrenoceptor blockade and all measurements were made during sinus rhythm and right atrial pacing. At 30 minutes after an oral dose (0.075 mg/kg in solution) felodipine plasma concentration were 16.4 (3.5) nmol/l. A significant fall in systemic vascular resistance (30%) and increase in cardiac index (30%) occurred, whereas pulmonary vascular resistance was unchanged. Felodipine increased left ventricular ejection fraction and mean velocity of circumferential fibre shortening but had no effect on derivates of left ventricular pressure (dP/dt or dP/dt P-1) during sinus rhythm or pacing. Thus at the dosage used felodipine was a potent dilator of systemic arterioles but had no direct effect on left ventricular function.     

Acute haemodynamic effects of felodipine during beta blockade in patients with coronary artery disease.

The acute effects of felodipine on left ventricular function and haemodynamics were studied in 11 patients with coronary artery disease. To block reflex sympathetic activation due to peripheral vasodilatation and to avoid effects secondary to changes in heart rate all patients received a standard regimen of beta adrenoceptor blockade and all measurements were made during sinus rhythm and right atrial pacing. At 30 minutes after an oral dose (0.075 mg/kg in solution) felodipine plasma concentration were 16.4 (3.5) nmol/l. A significant fall in systemic vascular resistance (30%) and increase in cardiac index (30%) occurred, whereas pulmonary vascular resistance was unchanged. Felodipine increased left ventricular ejection fraction and mean velocity of circumferential fibre shortening but had no effect on derivates of left ventricular pressure (dP/dt or dP/dt P-1) during sinus rhythm or pacing. Thus at the dosage used felodipine was a potent dilator of systemic arterioles but had no direct effect on left ventricular function.     

Comparison of hemodynamic and coronary effects of 2 antianginal vasodilator drugs: nifedipine and trinitrine]

Twenty patients with coronary insufficiency had measurements taken while they were in normal rhythm (NR) and during atrial pacemaking (AP) before and after taking nifedipine (n: 12) or after intravenous perfusion of trinitrin (n: 8): measurements were taken of pulmonary capillary pressure (PCP), arterial femoral pressure (AFP), cardiac output (QC) and coronary sinus flow (QCS), coronary arterio-venous oxygen difference (DaVO2), myocardial oxygen consumption (MVO2) and the myocardial coefficient of extraction of lactates (K).--Under nifedipine in NR and AP, AFP was decreased and QC increased. QSC was increased in NR, but was not changed under AP. DaVO2 was shortened under both sets of conditions. MVO2 decreased only during AP. Nifedipine brought back to normal the lowering of K which occurred with pacemaking.--Under trinitrin, both in NR and under AP, AFP, PCP, QC, QSC and MVO2 were lowered. K and DaVO2 were unchanged.--A plethysmographic study in 13 patients showed that these haemodynamic effects could be explained by the arterial vasodilator action of nifedipine which occurred without changing the venous tone, and the mixed action of trinitrin.     

Effects of pharmacologically-induced hypertension on myocardial ischemia and coronary hemodynamics in patients with fixed coronary obstruction

Twenty patients with fixed coronary artery obstruction were studied during rapid atrial pacing and methoxamine infusion. During pacing to heart rates of 142 +/- 4 (mean +/- SEM) beats per minute coronary sinus flow increased from 108 +/- 8 to 187 +/- 15 cc/min and myocardial oxygen consumption increased by + 80 +/- 11%. During methoxamine infusion that raised arterial systolic pressure to 196 +/- 5 mm Hg, similar increases in coronary sinus flow (to 179 +/- 13 cc/min) and myocardial oxygen consumption (+ 77 +/- 12%) occurred. Chest pain and ischemic ST segment changes developed in 17 and 14 patients respectively during atrial pacing, an incidence significantly greater (P less than 0.05) than during infusion of methoxamine (6 and 3 patients). Myocardial lactate extraction which averaged 26 +/- 4% during control was decreased to 10 +/- 8% during pacing and to 24 +/- 7% during methoxamine; the difference between decreases was not significant. The data show that at similar increases in myocardial oxygen consumption stress of increased heart rate results in more myocardial ischemia than stress of increased afterload.     

Effects of intravenous trinitrin infusion on systemic and coronary circulations during atrial electric stimulation]

Intravenous infusion of trinitrin (0.38 +/- 0.25 mg/hour) during rapid atrial pacing reduced pulmonary capillary pressures, cardiac output, coronary blood flow and myocardial oxygen consumption. At these dosages trinitrin allows patients with ischaemic heart disease to undergo atrial pacing in the best conditions by maintaining the pulmonary capillary and systemic arterial pressures and myocardial lactate production within limits close to the basal values. The beneficial effects last during the recovery period after the termination of pacing and of the intravenous infusion.     

Coronary haemodynamic effects of nifedipine. Comparison with glyceryl trinitrate.

The coronary haemodynamic effects of nifedipine and glyceryl trinitrate were compared in 22 patients undergoing investigations for suspected coronary artery disease. Myocardial blood flow was estimated by the coronary sinus thermodilution technique. In sinus rhythm nifedipine increased mean coronary sinus flow from 135 ml/min to 152 ml/min, and reduced arterio-coronary sinus oxygen difference from 12.4 to 10.96 ml/100 ml without causing a significant change in coronary vascular resistance or in myocardial oxygen consumption. Glyceryl trinitrate reduced mean coronary sinus flow from 165 to 111 ml/min, myocardial oxygen consumption from 19.2 to 11.9 ml/min, and arterio-coronary sinus oxygen difference from 11.7 to 10.9 ml/100 ml. There was a rise in coronary vascular resistance from 54 355 to 74 364 dynes s cm-5. During atrial pacing nifedipine reduced the arterio-coronary sinus oxygen difference from 11.99 to 11.0 ml/100 ml but had no significant effect on the other variables measured. Glyceryl trinitrate caused a fall in mean coronary sinus flow from 207 ml/min to 168 ml/min; myocardial oxygen consumption fell from 24 ml/min to 18 ml/min, while coronary vascular resistance rose from 41 714 to 51 234 dynes s cm-5. Direct comparison of the two drugs showed a significant difference in effects on coronary sinus flow and coronary vascular resistance in sinus rhythm. Both drugs appeared effective in relieving ischaemia as judged by a reduction of the incidence of pacing induced angina and an improvement in lactate status.     

Changes in contractility parameters, coronary flow and myocardial oxygen consumption following intravenous diltiazem in patients with coronary heart disease

In 11 patients (9 men, 2 women) with angiographically confirmed coronary heart disease, hemodynamics, myocardial blood flow, oxygen consumption and lactate extraction were measured at rest before and after administration of 0.3 mg diltiazem per kg body weight. There was a prompt and sustained drop in mean systolic arterial pressure from 141 mm Hg to 127 mm Hg along with a reduction in total peripheral resistance. The filling pressure of the left ventricle remained constant following a post-injection rise lasting up to 5 minutes. A marked sustained drop in heart rate from 82/min to 73/min was registered. Concomitantly, stroke volume index rose from 39 to 49 ml/m2. Due to the decrease in load and frequency, contractility parameters dP/dt and dP/dt/P dropped slightly. Myocardial blood flow did not change. On the other hand, a decrease in the difference between arterial and coronary venous oxygen content indicated a coronary dilatory effect. Fifteen minutes after injection, myocardial oxygen consumption had dropped from 11.6 to 10 ml O2/min and 100 g of tissue. There was no substantial change in lactate extraction. Through a drop in peripheral arterial resistance and heart rate, diltiazem leads to a measurable decrease in myocardial oxygen consumption while the patient is still at rest. At the same time, there are indications of a coronary dilatory effect.     

Influence of frequency of atrial contraction on coronary blood flow and ventricular performance in the conscious dog with myocardial infarction.

The effects of alterations in the frequency of contraction on coronary blood flow and ventricular performance were studied in 12 conscious, unsedated dogs with established myocardial infarction. Total and regional coronary blood flow was measured using radioactive microspheres. The peak increase in flow to the right ventricle was 71% to the infarcted area of the left ventricle was 72% to the non-infarcted area of the left ventricle was 90% and to the ventricular septum was 104%. Despite the generalized increases in regional myocardial blood flow, flow tended to decrease to the subendocardial portion of the infarcted area of the left ventricle. The peak increases in coronary flow and the reduction in flow to the subendocardial portion of the infarcted area occurred at a heart rate of approximately 200/min provided by atrial pacing. Myocardial contractility, as evidenced by peak increases of 16% in maximum LV dP/dt and 12% in dP/dtP, was only enhanced with abrupt incremental changes in heart rate and not with continuous atrial pacing over 15-min periods. Despite the generalized increases in coronary perfusion coronary sinus oxygen content decreased with a widening of the coronary arteriovenous oxygen difference indicating increased myocardial oxygen usage. Thus increasing frequency of contraction in myocardial infarction results in a slight initial but not sustained inotropic effect, a moderate and generalized increase in regional myocardial blood flow, increased myocardial oxygen consumption, and the potential for subendocardial extension of the area of myocardial damage within the infarcted area.