Endothelium-derived nitric oxide reduces baseline venous tone in awake instrumented rats.

To determine whether nitric oxide, which is likely endothelium-derived relaxing factor (EDRF), modulates baseline venous tone, the effects of intravenous NG-monomethyl-L-arginine (L-NMMA) (3-25 mg/kg), an EDRF inhibitor, on mean circulatory filling pressure (MCFP) were determined in 10 awake instrumented rats. MCFP, the equilibrated systemic pressure occurring when the circulation is arrested by transient inflation of a balloon in the right atrium, is a measure of total venous capacitance. L-NMMA caused a dose-dependent increase in mean arterial pressure and a dose-dependent decrease in heart rate. MCFP rose from 6.6 +/- 0.2 to 7.6 +/- 0.2 mmHg at the highest L-NMMA dose. The effects of L-NMMA on MCFP were reversed with L-arginine. In an additional four rats, in which hexamethonium was administered to induce ganglionic blockade, L-NMMA (25 mg/kg) caused a similar increase in MCFP (4.1 +/- 0.6 to 5.0 +/- 0.7 mmHg, P = 0.22) during the ganglionic blocked state as during the control unblocked state. These findings suggest that nitric oxide, which is likely EDRF, reduces baseline venous tone.

Aging increases venous compliance in awake instrumented rats.

To determine the effects of aging on total venous compliance, mean circulatory filling pressure (MCFP) was determined at several different blood volumes in 10 young (10-mo-old) and 10 older (30-mo-old) awake instrumented male Fischer 344/Brown Norway hybrid rats. Baseline weight and mean arterial pressure were similar in the two groups; heart rate was higher in the young (426 +/- 9 beats/min) than in the older rats (376 +/- 8 beats/min). Although MCFP was similar in the two groups at baseline blood volume, MCFP rose less with transient volume expansion and fell less with transient volume depletion in the older rats. The calculated venous compliance (reciprocal of the slope of the MCFP-to-volume relation) for the older rats was 25% greater than in the younger rats (3.28 +/- 0.21 vs. 2.63 +/- 0.12 ml.kg-1.mmHg-1; P = 0.014). In this conscious instrumented rat model, baseline total venous compliance is increased in older rats.

Adenosine increases total venous capacitance in awake instrumented rats.

To determine the effect of adenosine on the venous system, mean circulatory filling pressure (MCFP) was determined during infusion of intravenous (i.v.) adenosine (66.5 to a maximum of 532 microgram.kg-1.min-1) in 9 awake instrumented rats before and during ganglionic blockade with i.v. hexamethonium, 0.6 mg.kg-1.min-1. MCFP, the equilibrated pressure (mm Hg) occurring when the circulation is arrested by transient inflation of a balloon in the right atrium, is inversely related to total venous capacitance. Both adenosine and hexamethonium caused a reduction in mean arterial pressure (MAP); heart rate (HR) decreased during adenosine infusion in the blocked, but not the unblocked, state. In the unblocked state, baseline MCFP was 6.5 +/- 0.3 mmHg; hexamethonium caused baseline MCFP to decrease to 5.3 +/- 0.3 mm Hg. In both the unblocked and the blocked state, adenosine caused a dose-related decrease in MCFP [6.5 +/- 0.3 to 5.5 +/- 0.6 mm Hg (532 microgram.kg-1.min-1 adenosine dose) unblocked state; and 5.3 +/- 0.3 to 4.3 +/- 0.3 mm Hg (400 microgram.kg-1.min-1 adenosine dose) blocked state]. This decrease in MCFP induced by adenosine was highly significant. Intravenous adenosine, in an awake instrumented rat model, increases venous capacitance, with and without ganglionic blockade.

Ischemia-induced depressed systolic thickening is transiently augmented by remote coronary occlusion.

To determine if ischemia-induced depressed myocardial thickening can be augmented by remote coronary occlusion, posterior wall function (pulsed Doppler crystal) was measured before and after left anterior descending coronary artery occlusion in the presence of reduced circumflex coronary artery flow (of sufficient severity to reduce resting function) in an anesthetized open-chest canine preparation in which the circumflex was pump-perfused with carotid arterial blood. Left anterior descending coronary occlusion elicited an immediate significant increase in posterior bed thickening fraction (TF%) (3.7 +/- 1.5 to 5.9 +/- 1.3%), but by 135 sec TF% had again deteriorated. The transient increase in thickening was not caused by increased flow to the posterior bed (microspheres, n = 3), nor was it related to a Frank-Starling mechanism (echocardiography, n = 3). Despite an ischemic-induced reduction in systolic shortening, systolic thickening can be transiently augmented by remote coronary occlusion. The etiology may be related to systolic unloading.

Intracoronary adenosine and papaverine do not increase myocardial systolic thickening.

STUDY OBJECTIVE: The aim was to determine if myocardial systolic thickening increases when coronary flow is augmented by infusing intracoronary vasodilators (adenosine and papaverine). DESIGN: Systolic thickening fraction was measured with pulsed Doppler crystals and sonomicrometer crystals before and during the intracoronary infusion of adenosine and papaverine. SUBJECTS: Sixteen anaesthetized mongrel dogs were studied. MEASUREMENTS AND MAIN RESULTS: Intracoronary adenosine did not alter systemic haemodynamics, but did induce a three- to fourfold increase in myocardial blood flow. Intracoronary papaverine caused a slight decrease in systemic arterial pressure and rise in heart rate. Neither intracoronary adenosine nor intracoronary papaverine increased systolic thickening: control thickening fraction (TF%) = 20 (SEM 1)%, adenosine TF% = 18(1)%; control TF% = 22(2)%, papaverine TF% = 20(2)%. CONCLUSIONS: These experiments do not support the hypothesis that an increase in myocardial blood flow induced by intracoronary vasodilators causes an increase in myocardial systolic function.

Effects of environmental temperature on the venodilatory response to nitroglycerin.

The venodilatory response to nitroglycerin (0.8 mg sublingually) was measured in 10 healthy young male volunteers in a cool [24.3 +/- 0.6 degrees C skin temperature (Tsk)] and a warm environment (34.7 +/- 0.2 degrees C Tsk). Nitroglycerin caused mean arterial pressure to fall and heart rate to rise in both the cool (105 +/- 2 to 96 +/- 3 mmHg; 55 +/- 3 to 62 +/- 3 beats/min) and the warm environment (87 +/- 3 to 81 +/- 3 mmHg; 66 +/- 4 to 75 +/- 3 beats/min), but the fall in pressure was greater in the cool than in the warm environment. Forearm blood flow was reduced and forearm vascular resistance elevated in the cool (117 +/- 19 units; 1.15 +/- 0.08 ml.100 cc arm-1.min-1) compared with the warm environment (15 +/- 3 units; 8.60 +/- 1.89 ml.100 cc arm-1.min-1). Nitroglycerin caused forearm vascular resistance to fall in the cool but had no effect in the warm environment. Venous distensibility (increase in venous volume per 30-mmHg increase in venous pressure) was twice as great in the warm as in the cool environment (3.90 +/- 0.27 vs. 1.88 +/- 0.23 ml/100 cc arm). However, the venodilatory effect of nitroglycerin was similar in the cool and warm environments (0.79 +/- 0.10 vs. 0.67 +/- 0.13 ml/100 cc arm, respectively). Arterioles are not dilated by nitroglycerin in the warmer environment, but the venodilatory effect of nitroglycerin is quantitatively similar in the two environments.

Relation between anterograde blood flow through a coronary artery and the size of the perfusion bed it supplies: experimental and clinical implications.

The relation between anterograde blood flow through a coronary artery and the size of the perfusion bed it supplies is not known. Accordingly, the left circumflex coronary artery was cannulated and perfused with arterial blood in 12 open chest mongrel dogs. In Group I dogs (n = 7), the goal was to correlate the size of the perfusion bed with the magnitude of anterogradely derived myocardial blood flow. The size of the perfusion bed was measured with use of two-dimensional myocardial contrast echocardiography, whereas anterograde myocardial blood flow was determined by injecting radiolabeled microspheres directly into the artery. In Group II dogs (n = 5), the goal was to study the effects of altering coronary blood flow on both anterogradely and collateral vessel-derived myocardial flow within the perfusion bed. In these dogs, microspheres were injected directly into both the coronary artery and the left atrium at each flow rate. In Group I dogs, the left circumflex perfusion bed size, as defined by myocardial contrast echocardiography, decreased at lower anterograde myocardial blood flow rates. The change in perfusion bed size occurred at the lateral zones. There was a linear relation between the normalized perfusion bed size and the normalized anterograde myocardial blood flow: y = 0.45x + 54.2 (p less than 0.001, r2 = 0.77). These results were substantiated in Group II dogs, in which the size of the perfusion bed was approximated with use of radiolabeled microspheres. The size of the perfusion bed was most affected when anterograde myocardial blood flow decreased to less than approximately 33% of normal. At the lowest flow rates, there was a linear relation between anterograde blood flow versus the fraction of the left circumflex flow derived anterogradely: y = 2.41x + 0.22 (p less than 0.001, r2 = 0.90). The lower the level of anterograde flow, the greater was the blood flow derived from remote vessels. It is concluded that the size of the area perfused by a coronary artery is significantly influenced by the magnitude of anterograde blood flow through that artery. These findings may have important implications in experimental and clinical models of myocardial ischemia.

Systolic thickening increases from subepicardium to subendocardium.

STUDY OBJECTIVE: The aim was to determine the relation between systolic function and depth below the epicardial surface, using pulsed Doppler crystals. DESIGN: Systolic excursion in mm was measured at multiple depths below the epicardial surface. Measurements were made during control conditions. SUBJECTS: Thirty four anaesthetised mongrel dogs were studied. MEASUREMENTS AND MAIN RESULTS: A total of 333 measurements of systolic excursion were made during control conditions at 1 to 3 crystal sites per dog. Two models were constructed; the model which assumed a quadratic relation between depth (d) and systolic excursion (EX) (EX = 0.498 + 0.176d + 0.006d2) fit the data better than did a model which assumed a linear relation (EX = -0.0716 + 0.254d). CONCLUSIONS: These data support the prediction from geometric models that systolic excursion increases in a non-linear fashion from subepicardium to subendocardium.

Naturally occurring cardiomyopathy in the Doberman pinscher: a possible large animal model of human cardiomyopathy?

Currently there is no large animal model of dilated cardiomyopathy. The smaller animal models of cardiomyopathy, such as the Syrian hamster, cannot be studied with echocardiography and cardiac catheterization, and the relevance of these models to human dilated cardiomyopathy is open to question. On the basis of some initial observations in Doberman pinschers, it was speculated that these dogs could have occult left ventricular dysfunction. Accordingly, studies were performed in 46 apparently healthy Doberman pinschers and in 41 mongrel dogs: two-dimensional echocardiography (30 dogs in each group), cardiac catheterization (16 Doberman pinschers and 12 mongrels) and coronary blood flow studies (13 Doberman pinschers and 6 mongrels). In the awake, unsedated dogs studied with echocardiography, left ventricular wall thickening was significantly less in the Dobermans than in the mongrels (28% versus 36%, p = 0.0003). In the anesthetized dogs undergoing cardiac catheterization, left ventricular ejection fraction was significantly lower in the Dobermans than in the mongrels (0.38 versus 0.63, p = 0.0001). Rest coronary blood flow and coronary blood flow reserve were similar in the two groups. It is concluded that apparently healthy Doberman pinschers have occult left ventricular dysfunction. These dogs may serve as a large animal model of dilated cardiomyopathy and should not be used experimentally to study normal cardiac physiology.

Effects of haemorrhage induced hypotension on coronary blood flow in an anaesthetised two vessel canine coronary stenosis-occlusion model.

STUDY OBJECTIVE: Previous experiments from our group have shown that left anterior descending coronary occlusion in the presence of hypotension caused by intravenous glyceryl trinitrate in an open chest canine model caused endocardial flow to fall in myocardium supplied by a stenosed circumflex coronary artery. The aim of the present study was to assess the effects of hypotension in a similar open chest model but without the vasodilating effect of glyceryl trinitrate on coronary vessels. DESIGN: Blood flow to and function of remote myocardium supplied by a stenosed circumflex coronary artery [gradient 27(SEM 3) mm Hg] was determined in anaesthetised dogs after haemorrhage induced hypotension [mean aortic pressure 70(3) mm Hg] and after left anterior descending coronary occlusion. Transmural blood flow was measured using microspheres and myocardial wall thickness with sonomicrometer crystals. SUBJECTS: 11 healthy mongrel dogs were used, weight 25 kg (range 19-33). MEASUREMENTS AND MAIN RESULTS: Haemorrhage induced hypotension in the setting of a circumflex stenosis reduced endocardial blood flow to the posterior myocardial bed from 0.84 (0.14) to 0.57(0.07) ml.min-1.g-1 but did not alter percent myocardial thickening. When the left anterior descending coronary artery was occluded in the presence of the circumflex stenosis and haemorrhage induced hypotension, there was no further decrease in endocardial blood flow to or thickening of the posterior myocardial bed, despite a reduction in mean coronary artery pressure from 54(3) to 43(3) mm Hg. CONCLUSIONS: These findings are in contrast to our previous findings where hypotension was induced by glyceryl trinitrate. Remote myocardial ischaemia appears to be attenuated in this two vessel stenosis-occlusion model in which hypotension is produced by haemorrhage.

Effects of nifedipine on the venodilatory response to nitroglycerin.

The venodilatory effect of nifedipine 10 mg orally and the venodilatory effect of nitroglycerin 0.8 mg spray after pretreatment with nifedipine were assessed in 15 healthy men aged 22 to 41 years. Compared to placebo, nifedipine caused arteriolar dilation but did not venodilate (control VV[30] 3.67 +/- 0.24 [mean +/- standard error of the mean], after nifedipine VV[30] 3.41 +/- 0.22 cc/100 cc arm). The venodilatory effect of nitroglycerin was not altered by pretreatment with nifedipine. VV[30] increased by 0.72 +/- 0.14 cc/100 cc arm after nitroglycerin in subjects pretreated with placebo compared to 0.70 +/- 0.09 cc/100 cc arm in subjects pretreated with nifedipine. These results suggest that, at a dose of 10 mg, nifedipine does not venodilate and the venodilatory effect of nitroglycerin is not altered by pretreatment with nifedipine.

Effects of posture on the venodilatory response to nitroglycerin.

To determine the effects of posture on the venodilatory response to nitroglycerin (TNG), the change in forearm venous volume after inflation of an upper arm cuff to 30 mmHg above cuff zero (VV[30]) was measured during control conditions and after TNG (0.8 mg spray) in 18 healthy young volunteers in the supine position and the sitting position. VV[30] was 3.24 +/- 0.98 ml/100 ml arm in the supine position and 2.46 +/- 1.32 ml/100 ml arm in the sitting position. TNG increased VV[30] by 0.56 +/- 0.19 ml/100 ml arm in supine subjects, but by only 0.38 +/- 0.17 ml/100 ml arm in sitting subjects (P = 0.013). When limb volume was measured in the forearm and calf without using a cuff to produce venous congestion, the increase in limb volume with TNG was significantly greater in the sitting than in the supine position. Because the fall in both systolic and diastolic pressure and the rise in heart rate were significantly greater after TNG was administered in the sitting position, it is suggested that a greater reflex venoconstriction occurred in this posture, which antagonized the TNG-induced increase in venous distensibility. In the seated position, the effect of gravity more than compensated for the impaired venodilatory response to TNG. These results suggest that TNG causes a greater reduction in venous return to the heart when administered in the sitting position than in the supine position.

Aging reduces venous distensibility and the venodilatory response to nitroglycerin in normal subjects.

To determine if aging alters venous tone, venous distensibility was measured during control conditions and after the administration of nitroglycerin (0.8-mg spray) to 50 subjects ranging in age from 21 to 78 years. The mean arterial pressure decreased and the heart rate increased significantly after nitroglycerin. Control venous distensibility, measured after the inflation of an upper arm cuff to 30 mm Hg above cuff zero (VV[30]) was 2.69 +/- 1.26 (standard deviation) cc/100 cc arm. The VV[30] increased to 3.06 +/- 1.43 cc/100 cc arm after the administration of nitroglycerin. There was a significant relation between age and baseline venous distensibility (r = 0.53, p less than 0.001) and between age and the change in venous distensibility after nitroglycerin (r = 0.56, p less than 0.001). Both baseline venous distensibility and the venodilatory response to nitroglycerin decreased with age. There was no significant relation between systemic arterial pressure and baseline venous distensibility or between arterial pressure and the venodilatory response to nitroglycerin. Aging appears to diminish baseline venous distensibility and attenuate the venodilatory response to nitroglycerin.

Effect of the venodilated state on sympathetic-induced venoconstriction in normal subjects.

The interaction between venoconstriction induced by application of ice to the forehead and nitroglycerin-induced venodilation was examined in 19 healthy male volunteers, ages 25 +/- 5 years (mean +/- standard deviation). Venous tone was determined by the equilibration technique. Mercury-in-silastic plethysmography was used to measure changes in forearm volume before and after ice application during control conditions, and before and after ice application in the venodilated state (nitroglycerin spray, 0.8 mg). Venous tone and arterial pressure increased significantly after the application of ice to the forehead in both the control and venodilated states, indicating that ice increased sympathetic tone. Nitroglycerin increased venous volume by 0.28 cc/100 cc arm. The venoconstrictive effect of ice after nitroglycerin (a decrease in venous volume of 0.53 cc/100 cc arm) was quantitatively similar to the venoconstrictive effect of ice during control conditions (a decrease in venous volume of 0.54 cc/100 cc arm). These results suggest that sympathetic-induced venoconstriction is not attenuated in the venodilated state.

Mechanism of remote myocardial ischaemia after coronary occlusion in open chest dogs.

To determine whether or not the fall in coronary perfusion pressure after coronary occlusion is the cause of remote myocardial ischaemia, regional myocardial blood flow was measured using radiolabelled microspheres before and after left anterior descending (LAD) occlusion in the presence of a left circumflex artery stenosis in 22 anaesthetised dogs. Aortic pressure was maintained constant at the time of left anterior descending artery occlusion in 13 dogs (group 1) and proximal left circumflex artery pressure was held constant by a servocontrolled pump in nine dogs with a carotid artery-left circumflex artery shunt (group 2). Despite the maintenance of constant mean aortic pressure in group 1, remote posterior bed mean(SEM) endocardial flow fell from 0.69(0.05) to 0.43(0.07) ml.min-1.g-1 (p less than 0.05). In the dogs in which left atrial pressure rose to less than or equal to 9 mmHg after left anterior descending artery occlusion, remote bed endocardial flow did not fall significantly (0.66(0.07) to 0.56(0.11) ml.min-1.g-1; NS). In contrast, remote bed endocardial flow fell from 0.73(0.07) to 0.28(0.06) ml.min-1.g-1 (p less than 0.0001) after left anterior descending artery occlusion in the dogs in which left atrial pressure rose to greater than 9 mmHg. The fall in remote bed endocardial flow was prevented in group 2 dogs by maintaining proximal left circumflex artery pressure constant (0.95(0.08) to 0.86(0.09) ml.min-1.g-1; NS). An important mechanism for the development of remote myocardial ischaemia appears to be the fall in proximal coronary perfusion pressure at the time of coronary occlusion.

Prognostic utility of the exercise thallium-201 test in ambulatory patients with chest pain: comparison with cardiac catheterization.

The goal of this study was to determine the prognostic utility of the exercise thallium-201 stress test in ambulatory patients with chest pain who were also referred for cardiac catheterization. Accordingly, 4 to 8 year (mean +/- 1SD, 4.6 +/- 2.6 years) follow-up data were obtained for all but one of 383 patients who underwent both exercise thallium-201 stress testing and cardiac catheterization from 1978 to 1981. Eighty-three patients had a revascularization procedure performed within 3 months of testing and were excluded from analysis. Of the remaining 299 patients, 210 had no events and 89 had events (41 deaths, nine nonfatal myocardial infarctions, and 39 revascularization procedures greater than or equal to 3 months after testing). When all clinical, exercise, thallium-201, and catheterization variables were analyzed by Cox regression analysis, the number of diseased vessels (when defined as greater than or equal to 50% luminal diameter narrowing) was the single most important predictor of future cardiac events (chi 2 = 38.1) followed by the number of segments demonstrating redistribution on delayed thallium-201 images (chi 2 = 16.3), except in the case of nonfatal myocardial infarction, for which redistribution was the most important predictor of future events. When coronary artery disease was defined as 70% or greater luminal diameter narrowing, the number of diseased vessels significantly (p less than .01) lost its power to predict events (chi 2 = 14.5). Other variables found to independently predict future events included change in heart rate from rest to exercise (chi 2 = 13.0), ST segment depression on exercise (chi 2 = 13.0), occurrence of ventricular arrhythmias on exercise (chi 2 = 5.9), and beta-blocker therapy (chi 2 = 4.3). The exclusion of myocardial revascularization procedures as an event did not change the results significantly. Although the number of diseased vessels was the single most important determinant of future events, the exercise thallium-201 stress test when considered as a whole (which included the number of segments demonstrating redistribution on delayed thallium-201 images, change in heart rate from rest to exercise, ST segment depression on the electrocardiogram, and ventricular premature beats on exercise) was equally powerful (chi 2 = 41.6). Combination of both catheterization and exercise thallium-201 data was superior to either alone (chi 2 = 57.5) for determining future events. Exercise stress test alone (without thallium-201 data) was inferior to the exercise thallium-201 stress test or cardiac catheterization for predicting future events (chi 2 = 30.6).(ABSTRACT TRUNCATED AT 400 WORDS)

Short-term infarct vessel patency with aspirin and dipyridamole started 24 to 36 hours after intravenous streptokinase.

The duration of intravenous heparin therapy required to maintain patency of the infarct-related artery after intravenous streptokinase is uncertain. Twenty-eight patients were prospectively treated with 1.5 million units of intravenous streptokinase within 4 hours of onset of chest pain. Intravenous heparin was begun after the streptokinase infusion was complete and was discontinued within 36 hours. Aspirin, 325 mg daily, and dipyridamole, 75 mg three times a day, was begun before the heparin was discontinued. Coronary angiography was performed both at 2 hours after completion of the streptokinase infusion and again at a mean of 8.7 (+/- 3.2) days after the initial catheterization. One patient died after treatment with streptokinase but before early angiography. In 21 of 27 patients (78%), Thrombolysis in Myocardial Infarction trial (TIMI) grade 2 or 3 perfusion in the infarct vessel was observed on initial angiography. Repeat angiograms were available in 17 of the 21 patients with initially patent vessels. Continued patency (TIMI grade 2 or 3) was found in 15 of the 17 patients (88%). Two of the four patients who did not undergo repeat angiography died, and the remaining two patients required coronary artery bypass grafting for unstable angina. Bleeding complications occurred in 6 of 27 patients (22%), with two (7%) requiring surgical evacuation of a groin hematoma. There were no instances of intracerebral bleeding and only two patients required transfusions. Thus, the combination of aspirin and dipyridamole following 36 hours of systemic heparinization after intravenous streptokinase infusion is associated with a reocclusion rate comparable to that which has been reported for more prolonged systemic anticoagulation with fewer hemorrhagic complications.

The safety of protamine sulfate in diabetics undergoing cardiac catheterization.

The frequency of anaphylactoid reactions to protamine sulfate was examined by reviewing the records of diabetic patients undergoing cardiac catheterization over a 5-year period, and by prospectively monitoring diabetic patients receiving NPH insulin during the infusion of protamine sulfate. No anaphylactoid reactions were noted after protamine administration (48 +/- 5 mg) in the retrospective study in either patients with prior exposure to protamine (74 catheterizations) or in diabetics with no exposure to protamine (132 catheterizations). In the prospective study, no anaphylactoid reactions were seen in the 24 NPH insulin-dependent diabetics during the infusion of protamine sulfate (45 +/- 5 mg). Five of the 42 patients (12%) from the retrospective study who underwent vascular surgery developed severe reactions to much larger doses of protamine (380 +/- 118 mg). Diabetics with prior exposure to protamine sulfate do not appear to be at increased risk of anaphylactoid reaction after the administration of protamine sulfate in the dose range of less than 50 mg at the time of cardiac catheterization.

The effect of an increase in heart rate on remote myocardial blood flow in a two vessel coronary stenosis-occlusion model.

The effect of a moderate increase in heart rate on regional blood flow (8-10 mu radiolabeled microspheres) to myocardium supplied by a stenosed left circumflex coronary artery with (n = 11) or without (n = 7) concomitant left anterior descending coronary artery occlusion was investigated in anesthetized mongrel dogs. In the presence of a left circumflex coronary artery stenosis (gradient 32 +/- 5 mmHg [x +/- SEM]) and an unstenosed left anterior descending coronary artery a pacing-induced rise in heart rate (22 +/- 1 beats/min) increased epicardial flow to the posterior wall supplied by the left circumflex coronary artery (+0.21 +/- 0.08 mL/min/g, p = 0.03). Posterior bed endocardial flow was unchanged (-0.03 +/- 0.08 mL/min/g, p = 0.76). In dogs with a left circumflex coronary artery stenosis of similar severity (gradient 34 +/- 4 mmHg), left anterior descending coronary occlusion did not significantly alter posterior bed endocardial or epicardial flow. Atrial pacing increased heart rate by 22 +/- 1 beats per minute and caused remote posterior bed endocardial flow to fall (-0.08 +/- 0.03 mL/min/g, p = 0.03). Epicardial flow to that region rose (+0.09 +/- 0.02 mL/min/g, p less than 0.0002). Thus, a moderately severe coronary stenosis prevents the expected increase in endocardial flow normally seen after an increase in heart rate. Remote bed endocardial flow actually falls when heart rate is increased in the presence of an occlusion in a second major coronary artery.