Regional myocardial function is not affected by severe coronary depressurization provided coronary blood flow is maintained

It has been suggested that vasodilation distal to a stenosis may cause a profound decrease in perfusion pressure and adversely affect regional left ventricular function. This phenomenon could explain the clinical concept of reversal of regional dysfunction by coronary revascularization. To evaluate the hypothesis that regional myocardial function parallels regional coronary blood pressure in the absence of changes in coronary flow, dogs chronically instrumented with left circumflex coronary artery flow probes, cuff occluders, pressure catheters and segmental function sonomicrometers were studied. By decreasing regional coronary vascular resistance with selective intracoronary dipyridamole and controlling blood flow with a proximal coronary cuff occluder, the mean left circumflex artery pressure was reduced from 83 +/- 3 to 38 +/- 2 mm Hg while circumflex coronary blood flow was maintained constant. Regional contractile function as measured by circumflex sonomicrometers was unchanged at constant circumflex subendocardial blood flow as measured by radioactive microspheres. These findings suggest that regional contractile function is dependent on subendocardial blood flow and is independent of coronary perfusion pressure.     

Regional myocardial blood flow and left ventricular diastolic properties in pacing-induced ischemia

The relation between left ventricular diastolic abnormalities and myocardial blood flow during ischemia was studied in eight open chest dogs with critical stenoses of the proximal left anterior descending and circumflex coronary arteries. The heart was paced at 1.7 times the heart rate at rest for 3 min. In dogs with coronary stenoses, left ventricular end-diastolic pressure increased from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and 16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and end-systolic segment lengths in the ischemic regions. Left ventricular diastolic pressure-segment length relations for ischemic regions shifted upward during and after pacing tachycardia in dogs with coronary stenoses, indicating decreased regional diastolic distensibility. In dogs without coronary stenoses, the left ventricular diastolic pressure-segment length relation was unaltered. Pacing tachycardia without coronary stenoses induced an increase in anterograde coronary blood flow (assessed by flow meter) in both the left anterior descending and circumflex coronary arteries, and a decrease in regional vascular resistance. In dogs with coronary stenoses, regional vascular resistance before pacing was decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged in both the left anterior descending and circumflex coronary artery territories. During pacing tachycardia with coronary stenoses, regional coronary vascular resistance did not decrease further; subendocardial myocardial blood flow distal to the left anterior descending coronary artery stenosis decreased (from 1.03 +/- 0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Is the residual translesional pressure gradient useful to predict regional myocardial perfusion after percutaneous transluminal coronary angioplasty?

Routine assessment of the severity of a coronary artery lesion with coronary cineangiography is limited by its variability and poor correlation with blood flow and postmortem findings. In this investigation, we compared the usefulness of the final coronary artery translesional pressure gradient and the final angiographic coronary percent stenosis to assess immediate percutaneous transluminal coronary angioplasty (PTCA) success. To accomplish this, pressure gradients and percent stenoses were compared to stress thallium-201 regional myocardial perfusion before and after 56 uncomplicated PTCAs in 51 patients with single-vessel coronary artery disease. There were 39 men and 12 women; their mean age was 59 +/- 12 years. No patient had evidence of myocardial infarction. A new quantitative method to assess regional myocardial perfusion was used. Patients exercised for 433 +/- 130 seconds before PTCA and for 545 +/- 126 seconds after PTCA (p less than 0.001). Group coronary stenosis and translesional pressure gradient decreased from 77 +/- 11% and 48 +/- 5 mm Hg, respectively, before PTCA, to 25 +/- 11% and 9 +/- 5 mm Hg, respectively, after PTCA (p less than 0.001). Regional myocardial perfusion in the segment of the diseased (dilated) coronary artery increased after PTCA from 77 +/- 17% to 94 +/- 9% (p less than 0.001). Although a significant relationship was noted between regional myocardial perfusion and percent stenosis and translesional pressure gradient, a large individual scatter was present (r values lower than 0.55). We conclude that the final translesional pressure gradient during PTCA is not a better measure of immediate PTCA success than the angiographic percent stenosis.     

Exercise-induced regional dysfunction with subcritical coronary stenosis

The hypothesis was tested that regional myocardial contractile dysfunction can detect subtle regional coronary blood flow maldistribution induced by exercise. In seven dogs, left ventricular pressure (micromanometer), regional systolic wall thickening (WTh, sonomicrometry), and myocardial blood flow (MBF, microspheres) were measured when mild degrees of coronary artery stenosis were produced during treadmill exercise. During exercise without coronary stenosis, WTh increased by 21 +/- 12% (SD), and transmural MBF increased uniformly. In each dog, two levels of coronary stenosis were produced during exercise by adjusting the coronary hydraulic cuff: (1) St-Ex I, where WTh during exercise failed to increase significantly (average change 0 +/- 7%), and (2) St-Ex II, where WTh during exercise decreased moderately from the resting control value (average -20 +/- 8%). In the potentially ischemic zone coronary hyperemia occurred with each run: resting subendocardial MBF was 1.09 +/- 0.30 mg/g/min, and it was 3.04 +/- 0.83 during control exercise, 2.48 +/- 0.75 during St-Ex I, and 1.55 +/- 0.59 ml/g/min during St-Ex II (p less than .01 compared with control exercise and control area). The subendocardial-subepicardial blood flow ratio fell from 1.32 +/- 0.27 during control exercise to 1.07 +/- 0.20 (p less than .05) during St-Ex I, and to 0.64 +/- 0.15 (p less than .01) with St-Ex II. Changes in the subendocardial electrogram and reactive hyperemia occurred more consistently during St-Ex II than St-Ex I. Thus, failure of regional function to increase during exercise detected slight maldistribution of regional MBF, whereas reduction of regional function during exercise of 10% or more below the resting value was a reliable marker of a regional flow defect and was always associated with other evidence of ischemia. Therefore, regional dysfunction during exercise can detect subcritical but functionally significant coronary stenosis, which may allow regional wall motion to be used for detecting coronary artery disease at a relatively early stage.     

The effect of coronary artery lesions on the relationship between coronary perfusion pressure and myocardial blood flow during cardiopulmonary resuscitation in pigs

In subjects without coronary disease, coronary perfusion pressure generated with closed-chest cardiopulmonary resuscitation (CPR) bears a direct relationship to myocardial blood flow. The effect of coronary lesions on this relationship was studied in an experimental porcine model not requiring thoracotomy. Coronary stenoses (a 50% reduction in coronary cross-sectional area) or total coronary occlusions were created by percutaneous, transarterial catheter placement of a Teflon cylinder in the left anterior descending artery of 21 swine (30 to 60 kg). Coronary perfusion pressure, defined as the aortic diastolic pressure minus right atrial diastolic pressure, was correlated with myocardial blood flow measured with nonradioactive, colored microspheres during external chest compression CPR. Complete occlusion of the left anterior coronary artery resulted in essentially no CPR-generated blood flow to the anterior myocardium distal to the site of occlusion. Coronary perfusion pressure showed a positive correlation with myocardial blood flow above the area of occlusion (r = 0.783; p less than 0.01) but did not correlate with myocardial blood flow below the occlusion site (r = 0.239). In the presence of a patent coronary artery stenosis, coronary perfusion pressure correlated with myocardial blood flow both above (r = 0.841; p less than 0.001) and below (r = 0.508; p less than 0.05) the stenosis. During closed-chest CPR producing coronary perfusion pressures between 30 and 60 mm Hg, anterior myocardial blood flow was 109 +/- 16 ml/min/100 gm above a patent stenosis and 66 +/- 13 ml/min/100 gm below the stenosis (p less than 0.005). Over a wide range of coronary perfusion pressures, myocardial blood flow below a coronary lesion was significantly less than that above the lesion. Coronary occlusions and stenoses can substantially affect the amount of CPR-generated coronary perfusion pressure needed to produce distal myocardial blood flow.     

Effect of coronary stenosis on myocardial blood flow during exercise in the chronically pressure-overloaded hypertrophied left ventricle

This study was performed to determine if a coronary artery stenosis would result in more-severe perfusion abnormalities in hypertrophied compared with normal canine hearts during exercise. Studies were performed in eight normal control dogs and in seven adult dogs in which a 67% increase in left ventricular mass wa produced by banding the ascending aorta at 9 weeks of age. Myocardial blood flow was measured by the microsphere method during treadmill exercise in the presence of a coronary artery stenosis that decreased distal coronary perfusion pressure to 55 or 42 mm Hg. At a coronary pressure of 55 mm Hg, mean myocardial blood flow was decreased by 23 +/- 5% in normal control dogs but was decreased by 53 +/- 10% in dogs with left ventricular hypertrophy (LVH) (p less than 0.05, comparing normal vs. LVH dogs). Similarly, at a coronary pressure of 42 mm Hg, mean blood flow was decreased by 53 +/- 6% below control in normal dogs but was decreased by 76 +/- 5% below control values in dogs with LVH (p less than 0.01, comparing normal vs. LVH dogs). In both groups of dogs, the stenosis caused a gradient of hypoperfusion, worsening from epicardium to endocardium. However, for each level of stenosis, subendocardial blood flow and the ratio of subendocardial to subepicardial blood flow was less in LVH than in normal canine hearts. These findings demonstrate that the presence of LVH secondary to long-term pressure overload is associated with an increased vulnerability to myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis.     

Myocardial kinetics of technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile

To study the potential usefulness of technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-MIBI) as a cardiac perfusion imaging agent, the left circumflex coronary arteries of 12 dogs were partially occluded. Eight additional control dogs had no coronary artery stenosis. Myocardial Tc-MIBI activities in the left circumflex and left anterior descending zones were continuously monitored by miniature implantable radiation detectors for 4 hr after administration of the isotope. The dogs were then killed. Serial gamma camera images were also acquired during the study. Heart rate, arterial blood pressure, pressure distal to the stenosis, and cardiac output did not change significantly during the experiment. Microsphere-determined regional myocardial blood flow was significantly reduced in the left circumflex distribution in the 12 dogs with coronary artery stenoses. In the 12 dogs with left circumflex coronary artery stenoses, the 4 hr fractional Tc-MIBI clearances from the normal and ischemic zones were minimal and equivalent (0.15 +/- 0.05 vs 0.15 +/- 0.07). In the eight control dogs, 4 hr fractional Tc-MIBI clearances from the left anterior descending and left circumflex artery zones were minimal and equivalent (0.11 +/- 0.06 vs 0.10 +/- 0.07). Four hour fractional Tc-MIBI clearance from the blood was 0.98 +/- 0.03 for the dogs with stenosis and 0.97 +/- 0.02 for the dogs without stenosis. One additional dog had complete occlusion of the left circumflex coronary artery followed by administration of Tc-MIBI and scandium-46-labeled microspheres. This heart was immediately sectioned and counted to determine the relationship of regional blood flow to Tc-MIBI distribution (r = .92).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of exercise on the relationship between myocardial blood flow and systolic wall thickening in dogs with acute coronary stenosis

Relationships between regional myocardial perfusion and transmural function, both during treadmill exercise and at rest, were examined in conscious dogs with varying degrees of coronary stenosis produced by a hydraulic occluder. In 13 dogs we measured myocardial blood flow with microspheres (10-12 microns in diameter) and regional systolic wall thickening (%). During exercise with coronary stenosis, myocardial blood flow was characterized by nonuniform distribution, and associated with regional dysfunction. The relationships between normalized myocardial blood flow and normalized %wall thickening during exercise with coronary stenosis were linear, with significantly different slopes (mean myocardial blood flow: y = 1.23x - 0.16, r = 0.93; subendocardial myocardial blood flow: y = 1.50x - 0.02, r = 0.86; subepicardial myocardial blood flow: y = 0.83x - 0.18, r = 0.87). To fill the gap between available subendocardial and subepicardial data during exercise with coronary stenosis and control points, however, would require nonlinear components. In 10 of the dogs, coronary stenosis at rest was also produced to compare regional myocardial blood flow - %wall thickening relations at rest with those during steady state exercise. The absolute mean myocardial blood flow - %wall thickening relation during exercise with coronary stenosis (y = 11.6x - 1.9, r = 0.90) was significantly shifted rightward from the resting relation (y = 25.3x -2.1, r = 0.80). However, when changes in %wall thickening were plotted vs. myocardial blood flow per beat, the relationships at rest and exercise were nearly superimposable. Likewise, relations between normalized myocardial blood flow and changes in %wall thickening at rest and exercise were not significantly different. We conclude: %wall thickening during exercise is directly related to changes in mean myocardial blood flow but is related in nonlinear fashion to changes in subepicardial and subendocardial myocardial blood flow; %wall thickening may provide a reliable index of the relative transmural flow distribution during exercise as well as at rest; during brief bouts (5-8 minutes) of exercise with coronary stenosis, the relationship between stabilized regional contractile dysfunction and level of myocardial blood flow per beat is the same as that during coronary stenosis at rest.     

Comparative effects of nitroglycerin and nifedipine on myocardial blood flow and contraction during flow-limiting coronary stenosis in the dog

Both nifedipine and nitroglycerin are used to treat angina pectoris. The comparative effects of these agents on myocardial blood flow and contraction in the setting of flow-limiting coronary stenosis are poorly understood. Thus 24 open chest dogs underwent carotid to left anterior descending coronary arterial perfusion with coronary flow probe and perfusion pressure monitoring. Segment length was measured with ultrasonic crystals in the subendocardial ischemic and nonischemic zones. Myocardial blood flow was measured with radioactive microspheres. Partial coronary occlusion was performed to attain a diastolic perfusion pressure of 40 mm Hg. Twelve dogs received intravenous nifedipine, 3 μg/kg per min, and 12 received intravenous nitroglycerin to reduce aortic pressure by 20 mm Hg. Partial occlusion resulted in a slight but significant decrease in segment shortening in the ischemic zone. Neither nitroglycerin nor nifedipine affected shortening in the ischemic zone. After occlusion, blood flow decreased in the subendocardial ischemic zone but was unchanged in the subepicardium. Nifedipine increased subendocardial blood flow in the nonischemic zone and decreased it in the ischemic zone but caused no change in subepicardial flow in the ischemic zone. In contrast, nitroglycerin decreased subendocardial and subepicardial blood flow in both the ischemic and nonischemic zones. In the setting of coronary stenosis, different classes of vasodilators may have varying effects on myocardial blood flow, suggesting different sites and mechanisms of action. In addition, segment function may not always reflect changes in myocardial blood flow.     

Tachycardia induced reduction in coronary blood flow distal to a stenosis

Clinical and experimental data indicate that some coronary stenoses can rapidly change shape thereby influencing the hemodynamic severity of the stenosis. In 7 closed chest dogs, we examined the effects of distal coronary arteriolar vasomotor tone and myocardial oxygen demands on a coronary stenosis created by partial intraluminal occlusion, using a small balloon catheter. Myocardial blood flow (ml/g per min) was measured with 15-microns radioactive microspheres. Stenotic resistance was calculated as the mean pressure gradient across the stenosis divided by the mean blood flow through the stenosis. The mean pressure gradient was calculated as the ascending aortic pressure minus the left anterior descending coronary artery pressure distal to the stenosis. Coronary arteriolar vasodilation induced by pacing (170 beats/min) increased stenotic resistance (1.64 +/- 0.27 to 26.48 +/- 13.77 mmHg/ml per min, P less than 0.05) and decreased myocardial blood flow (endocardial 0.42 +/- 0.04 to 0.17 +/- 0.04, P less than 0.05, midcardial 0.35 +/- 0.03 to 0.13 +/- 0.04, P less than 0.05; epicardial 0.22 +/- 0.05 to 0.15 +/- 0.05). Five dogs fibrillated within 10 min of continuous tachycardia and partial arterial occlusion. The change in arteriolar vasomotor tone and decreased aortic pressure induced by pacing altered the severity of the stenosis and resulted in a reduction of blood flow to the myocardium.     

Effect of exercise intensity and duration on regional function during and after exercise-induced ischemia

BACKGROUND. Transient reversible myocardial dysfunction has been documented after episodes of exercise-induced ischemia. This study was undertaken to determine whether the duration or intensity of exercise affects the severity of postischemic dysfunction in this setting. METHODS AND RESULTS. Ten dogs were instrumented with ultrasonic microcrystals for measurement of wall thickening, with circumflex coronary artery flow probes, and with hydraulic occluders. Dogs performed low-intensity exercise, which was sufficient to increase coronary perfusion 50% above control, and high-intensity exercise, which was sufficient to double coronary blood flow. To investigate the effects of exercise intensity on postischemic dysfunction, we had dogs perform high-intensity exercise for 5 minutes in the presence of a stenosis. On the alternate day, dogs performed low-intensity exercise for 10 minutes in the presence of a stenosis. These two protocols provide equivalent coronary flow debts. Mean transmural blood flow during high-intensity exercise without stenosis (2.61 +/- 0.54 ml/min/g) was significantly higher than that during low-intensity exercise (1.74 +/- 0.61 ml/min/g, p less than 0.002). During high-intensity exercise with coronary artery stenosis, subendocardial blood flow was significantly lower than that during low-intensity exercise with stenosis (0.64 +/- 0.40 versus 1.08 +/- 0.28 ml/min/g, p less than 0.02). This difference in subendocardial perfusion was associated with greater degrees of regional dysfunction during exercise (circumflex wall thickening was 44 +/- 23% of control for high-intensity exercise versus 60 +/- 18% of control for low-intensity exercise, p less than 0.01). In addition, from 10 to 30 minutes after exercise, wall thickening in myocardium perfused by the circumflex coronary artery remained significantly lower after high-intensity exercise than that after low-intensity exercise. To assess the effects of exercise duration on the severity of postischemic dysfunction, we had dogs perform low-intensity exercise in the presence of a coronary stenosis for 10 minutes and low-intensity exercise for only 5 minutes on alternate days. Systolic wall thickening was significantly lower after low-intensity exercise for 10 minutes than after low-intensity exercise for 5 minutes. CONCLUSIONS. High-intensity exercise results in greater degrees of subendocardial hypoperfusion and greater degrees of regional dysfunction both during and after exercise-induced ischemia than does low-intensity exercise. Second, exercise duration also exerts an effect on the severity of postischemic dysfunction, although the magnitude of this effect is less important than the effect of exercise intensity.     

Subepicardial vasodilator reserve in the presence of critical coronary stenosis in dogs

Critical coronary stenosis is the term used to describe obstruction that eliminates reactive hyperemia presumably because downstream arterioles have dilated maximally to compensate for a proximal stenosis. However, evidence of distal vasomotor capacity exists despite the presence of severe constriction. Coronary blood flow in the left circumflex artery and blood pressure in the aorta and distal circumflex artery were studied in six open chest, anesthetized dogs. The circumflex artery was obstructed sufficiently to eliminate 95 to 98 percent of reactive hyperemia, but resting coronary blood flow was not reduced. The regional distribution of myocardial blood flow was studied with tracer microspheres (diameter 15 μm) before and after intracoronary injection of adenosine (5 μmoles) and after the release of a 15 to 20 second occlusion. The subendocardial to subepicardial ratio of flow in the obstructed bed was not changed by the stenosis (ratio 1.23 ± 0.10 [mean ± standard error of the mean] versus 1.28 ± 0.07, difference not significant). Administration of adenosine decreased subendocardial flow from 0.95 ± 0.07 to 0.73 ± 0.08 ml/min per g (p < 0.001) and increased subepicardial flow from 0.76 ± 0.04 to 1.31 ± 0.08 ml/min per g (p < 0.001); the subendocardial to subepicardial blood flow ratio decreased to 0.58 ± 0.06 (p < 0.001). After the release of the temporary occlusion, subendocardial flow decreased and subepicardial flow increased a comparable amount and the subendocardial to subepicardial ratio decreased to 0.55 ± 0.07 (p < 0.001). Circumflex coronary blood flow measured simultaneously with use of an electromagnetic flowmeter increased from 29 ± 2 to approximately 35 ml/min (p < 0.01). Thus, arteriolar vasodilator reserve persists in the presence of proximal critical stenosis, but the vasomotor capacity is limited primarily to the outer layers of the myocardium.     

Changes in ischemic blood flow distribution and dynamic severity of a coronary stenosis induced by beta blockade in the canine heart

The effects of equipotent beta 1-receptor-blocking doses of propranolol, metoprolol and sotalol on distal coronary pressure, stenosis resistance and regional myocardial blood flow (endo/epi) were studied in anesthetized dogs with a severe noncircumferential stenosis of the left circumflex coronary artery. No significant differences between the three beta blockers were observed for overall hemodynamics and regional myocardial blood flow. After drug treatment, subendocardial blood flow (0.47 +/- 0.05 to 0.78 +/- 0.05 ml/min/g) and endo/epi (0.67 +/-0.04 to 1.18 +/- 0.04) increased significantly (p less than 0.05) in the ischemic region. These changes were associated with a marked increase in distal coronary perfusion pressure and a decrease in heart rate. Resistance across the stenosis decreased significantly (p less than 0.05) after beta-receptor blockade (3.2 +/- 0.3 to 1.4 +/- 0.2 units). Atrial pacing to control heart rate only partially attenuated these changes. These results suggest that a favorable redistribution of ischemic blood flow after beta blockade is the result of an increase in distal diastolic pressure-time index and an autoregulation-induced increase in distal bed vascular resistance due to a decrease in myocardial oxygen demand associated with beta blockade. The latter effect also resulted in a decrease in the dynamic severity of a proximal coronary stenosis.     

Effect of intracoronary nitroglycerin administration on phasic pattern and transmural distribution of flow during coronary artery stenosis.

BACKGROUND. Nitroglycerin is effective in relieving myocardial ischemia; however, intracoronary nitroglycerin often fails to relieve angina and has been reported to have deleterious effects on subendocardial blood flow. To understand the mechanisms involved, we evaluated the direct effect of nitroglycerin on coronary circulation of the ischemic hearts. METHODS AND RESULTS. We measured the phasic pattern of intramyocardial coronary arterial flow with an 80-channel, 20-MHz pulsed Doppler ultrasound flowmeter under moderate to severe coronary artery stenosis (distal perfusion pressure approximately 45 mm Hg group 1, n = 6) and transmyocardial blood flow distribution using radioactive microspheres while maintaining coronary pressure at a low constant level (40 mm Hg, group 2, n = 6). In anesthetized open-chest dogs, the left main coronary artery was perfused directly from the right carotid or femoral artery. In this bypass circuit, pressure was controlled with an occluder or a reservoir was connected to the circuit. In group 1, the systolic and diastolic pressures distal to the stenosis decreased significantly after intracoronary administration of nitroglycerin at maximal coronary flow from 66.5 +/- 18.5 to 56.5 +/- 13.8 mm Hg (p less than 0.01) and from 36.6 +/- 14.4 to 27.5 +/- 8.9 mm Hg (p less than 0.01), respectively. The phasic pattern of the septal artery flow was predominantly diastolic and was characterized by systolic reverse flow even in the absence of stenosis. Coronary stenosis increased systolic reverse flow. Nitroglycerin increased diastolic forward flow (p less than 0.05) but augmented systolic reverse flow markedly (p less than 0.001). In group 2, nitroglycerin increased subepicardial flow (p less than 0.05) but failed to increase subendocardial flow. With the administration of nitroglycerin, the subendocardial-to-subepicardial flow ratio decreased significantly from 0.73 +/- 0.19 to 0.32 +/- 0.14 (p less than 0.01). CONCLUSIONS. The increased systolic reverse flow after intracoronary administration of nitroglycerin may be closely related to failure of subendocardial blood flow to increase with increase subepicardial flow.     

Attenuation of exercise-induced myocardial ischemia in dogs with recruitment of coronary vasodilator reserve by nifedipine

There is now evidence that under resting conditions coronary vasodilator reserve exists even in the presence of myocardial ischemia. Therefore, we tested the hypothesis that a vasodilator reserve may exist during exercise so that during exercise-induced ischemia a reduction in coronary constrictor tone can be produced that attenuates the decreases in regional myocardial blood flow and function distal to a severe coronary stenosis without changing the determinants of myocardial oxygen demand. Nine dogs were instrumented with an ameroid constrictor on the left circumflex coronary artery and were studied 2 to 3 weeks later. During a control treadmill run, heart rate increased from 119 +/- 20 to 225 +/- 20 beats/min and peak left ventricular pressure increased from 144 +/- 17 to 163 +/- 28 mm Hg. Poststenotic subendocardial blood flow (measured by a microsphere technique) fell from 1.19 +/- 0.36 to 0.51 +/- 0.30 ml/min X g and systolic wall thickening (by sonomicrometry) decreased from 24.3 +/- 5.8% to 6.0 +/- 6.1%. During an identical run after nifedipine (10 micrograms/kg iv), systemic hemodynamics were not significantly altered. However, subendocardial blood flow was increased to 0.85 +/- 0.51 ml/min X g (p less than .05) and systolic wall thickening to 11.4 +/- 7.8% (p less than .01). We conclude that in this study the amelioration of exercise-induced myocardial ischemia was due to the recruitment by nifedipine of coronary vasodilator reserve.     

Effect of tachycardia on regional function and transmural myocardial perfusion during graded coronary pressure reduction in conscious dogs

The purpose of the present study was to examine subendocardial flow and function during graded coronary pressure reduction to determine the effect of tachycardia on the lower autoregulatory pressure limit (critical coronary pressure) in unanesthetized dogs. During atrial pacing at a rate of 200 beats/min, subendocardial flow measured by radioactive microspheres averaged 1.55 +/- 0.34 ml/min/g and remained unchanged as pressure was reduced over the autoregulatory plateau from 84 +/- 10 to 59 +/- 7 mm Hg. Further reductions in coronary pressure to below a critical coronary pressure of approximately 60 mm Hg were associated with concomitant reductions in subendocardial flow and the endocardial-epicardial flow ratio during tachycardia. Although regional function remained constant over the autoregulatory plateau, there was a rightward shift of the coronary pressure-function relation during ischemia in response to a steady-state increase in rate from 100 to 200 beats/min. Reductions in regional wall thickening began when coronary pressures reached 38 +/- 7 mm Hg at a heart rate of 100 beats/min and 61 +/- 6 mm Hg at a heart rate of 200 beats/min (p less than 0.005). Similar critical coronary pressure values were obtained for subendocardial segment shortening. Relations between subendocardial flow and myocardial function measured by both transmural wall thickening and subendocardial segment shortening were linear during pacing at a heart rate of 200 beats/min with relative reductions in wall thickening related to reductions in subendocardial flow on a nearly one-to-one basis. The results of this study demonstrate that there is a shift in the lower limit of subendocardial autoregulation during tachycardia as manifest by the onset of subendocardial ischemia at a higher distal coronary artery pressure. The shift in critical coronary pressure relates to an increase in resting flow requirements due to increased demand and diminished subendocardial vasodilator reserve at any given coronary pressure secondary to a reduction in the time available for diastolic subendocardial perfusion during tachycardia.     

Measuring blood flow velocity in the coronary sinus with Doppler catheters]

Measurements of the coronary sinus blood flow velocity with Doppler catheters (Medtronic Floscan; Millar DC201) were performed to assess coronary flow reserve and significance of coronary artery stenosis. In seven patients with normal coronary angiogram coronary sinus blood flow velocity (Doppler catheters) and coronary sinus blood flow volume (thermodilution) were simultaneously recorded. Coronary flow reserve was calculated as the quotient of the peak flow velocity (peak flow volume) and resting flow velocity (resting flow volume) after infusion of 0.5 mg/kg dipyridamole intravenously. The correlation coefficient was r = 0.88. Coronary sinus blood flow velocity was measured in 31 patients at resting conditions and after injection of contrast media during coronary angiography. At resting conditions blood flow velocity was 3.6 +/- 1.5 cm/s (n = 31), 3.5 +/- 1.8 cm/s (n = 9; controls), and 3.6 +/- 1.1 cm/s (n = 9; significant stenosis of the left anterior descending; not significant). After injection of contrast media flow velocity amounted to 2.2-fold resting flow in controls and to 1.5-fold resting flow in patients with stenoses of the left anterior descending artery (p less than 0.01). Measurement of coronary sinus blood flow velocity with Doppler catheters is a valuable adjunct for determination of coronary flow reserve and for assessment of stenosis severity of the left anterior descending artery. Continuous on-line monitoring of phasic flow velocity provides important information of the myocardial perfusion, e.g., during angioplasty.     

Details of coronary stenosis morphology influence its hemodynamic severity and distal flow reserve

Differences in coronary flow reserve with anatomically similar coronary artery stenoses have been attributed to 1) nonstandard physiologic conditions, 2) inadequacies of measurements of coronary artery stenosis dimension and/or coronary blood flow, and 3) inadequate hyperemic stimulus. Our study tested the hypothesis that details of coronary artery stenosis geometry, which may or may not be apparent on coronary angiograms, also may contribute importantly to such differences. A simple and complex coronary artery stenosis, each of which reduced vessel cross-sectional area by 84%, was introduced in random order into the left anterior descending coronary artery of nine closed-chest, sedated swine. The simple stenosis had a single lumen while the complex stenosis had five small lumena whose combined area equaled that of the single lumen stenosis. Measurements of hemodynamics and regional myocardial blood flow (microspheres) were made at control and after 10 minutes of adenosine infused at 400 micrograms/min and then at 800 micrograms/min distal to each stenosis. Both heart rate and aortic mean pressure were controlled and thus did not change versus initial baseline (129 +/- 4 minutes and 120 +/- 10 mm Hg, mean +/- SD, respectively) during the study. Baseline total flow (ml/sec) distal to the stenosis was similar at each control (1.05 +/- 0.35 vs. 0.92 +/- 0.34, simple versus complex, respectively; p = NS). At maximal adenosine, total flow with the simple stenosis was 3.44 +/- 0.92 versus 2.77 +/- 0.51 for complex (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transmural variation in autoregulation of right ventricular blood flow

We examined transmurally the right coronary autoregulatory flow response to varied perfusion pressures in 11 anesthetized, open-chest dogs. Right coronary artery flow was measured electromagnetically, and its transmural distribution was defined with 15-micron radioactive microspheres. Heart rate, mean aortic blood pressure, right ventricular systolic pressure, end-diastolic pressure, and dP/dtmax were constant. At 100 mm Hg, subepicardial flow averaged 0.48 +/- 0.04 ml/min/g, and subendocardial flow averaged 0.56 +/- 0.05 ml/min/g. In contrast to the left coronary circulation, right coronary hypotension did not cause preferential subendocardial ischemia. As right coronary perfusion pressure was decreased from 100 to 40 mm Hg in five dogs, subepicardial and subendocardial flows were reduced similarly by 35-36%. As right coronary perfusion pressure was elevated from 100 to 150 mm Hg in six dogs, right ventricular subepicardial blood flow increased by 31%, whereas subendocardial blood flow increased by 70%. Right ventricular subendocardial-to-subepicardial flow ratios averaged 1.15-1.20 for perfusion pressures of 40 to 120 mm Hg, and they increased to 1.36 +/- 0.05 at 150 mm Hg. Right coronary artery autoregulatory closed-loop gain averaged 0.47 +/- 0.06 between 70 and 100 mm Hg and was greater than zero from 40 to 120 mm Hg. Between 120 and 150 mm Hg, gain fell to -0.15 +/- 0.10. Regional gain varied from 0.59 +/- 0.10 to 0.44 +/- 0.08 in subepicardium as pressure was decreased from 100 to 40 mm Hg. Subendocardial gains were similar to subepicardial gains over this pressure range.(ABSTRACT TRUNCATED AT 250 WORDS)     

No effect of coronary perfusion on regional myocardial function within the autoregulatory range in pigs. Evidence against the Gregg phenomenon

BACKGROUND. The hypothesis that increases in coronary perfusion increase ventricular performance independently from providing enhanced oxygen supply ("Gregg phenomenon") remains controversial. METHODS AND RESULTS. To study the physiological significance of changes in coronary perfusion on global and regional myocardial function in situ, the left anterior descending coronary artery of isoflurane-anesthetized swine was cannulated, and perfusion was varied. In one group of swine (n = 5), coronary arterial pressure was increased in four steps from 88 +/- 11 to 186 +/- 11 mm Hg by increasing the speed of the pump circuit providing coronary blood flow. No changes in left ventricular end-diastolic pressure, peak pressure, or maximum left ventricular dP/dt were observed. Subendocardial blood flow (by radiolabeled microspheres) increased from 0.96 +/- 0.27 to 2.04 +/- 0.73 ml/min/g without any increase in systolic wall thickening (by sonomicrometry) or myocardial oxygen consumption of the anterior myocardium. In a second group of swine (n = 8), coronary arterial pressure was kept constant and coronary blood flow was increased stepwise by intracoronary adenosine infusion. End-diastolic pressure, peak pressure, and maximum left ventricular dP/dt remained unchanged when coronary blood flow increased from 21.7 +/- 9.8 to 93.8 +/- 34.1 ml/min. Subendocardial blood flow increased from 0.89 +/- 0.26 to 3.28 +/- 1.02 ml/min/g, again without any increase in systolic wall thickening (45.6 +/- 8.6 versus 42.6 +/- 9.8%) and myocardial oxygen consumption (5.75 +/- 1.18 versus 5.87 +/- 1.67 ml/min/100 g). In a third group of swine (n = 10), coronary arterial pressure was lowered by intracoronary adenosine infusion during constant coronary inflow. Left ventricular hemodynamics remained unchanged. With a decrease in coronary arterial pressure from 130 +/- 25 to 71 +/- 14 mm Hg, no decreases in subendocardial blood flow and systolic wall thickening were observed. Only when coronary arterial pressure was further reduced to 57 +/- 13 mm Hg did systolic wall thickening fall to 25.7 +/- 9.9% (control, 31.1 +/- 11.1%), associated with a decrease in subendocardial blood flow from 1.17 +/- 0.39 to 0.87 +/- 0.52 ml/min/g. CONCLUSIONS. Thus, the Gregg phenomenon plays no significant role within or above the autoregulatory pressure-flow range normally seen in anesthetized swine in situ.