Persistence of regional left ventricular dysfunction after exercise-induced myocardial ischemia.

To determine whether regional myocardial dysfunction occurring after exercise-induced ischemic might be caused by continued abnormalities of myocardial blood flow in the post-exercise period, nine dogs were instrumented with ultrasonic microcrystals for determination of circumferential segment shortening, circumflex artery electromagnetic flow probes, and hydraulic coronary artery occluders. Dogs performed treadmill exercise during partial inflation of the coronary artery occluder. When the stenosis was maintained after exercise (persistent stenosis), subendocardial flow = 0.79 +/- 0.42 ml/min per g vs. 1.39 +/- 0.43 ml/min per g control), and this was associated with continued dysfunction in the ischemic zone (segment shortening 45.4 +/- 36.9% of resting control). When the stenosis was released immediately after exercise (temporary stenosis), however, flow was markedly increased 1 min post-exercise (mean transmural flow 4.24 +/- 1.22 ml/min per g; subendocardial flow 4.18 +/- 1.52 ml/min per g), and this was associated with a transient increase in segment shortening to 104.5 +/- 9.3% of resting control. 5 min after exercise, however, moderate reductions in ischemic segment shortening were noted after both temporary stenosis and persistent stenosis runs, and these persisted for 30 min post-exercise. It is concluded that regional left ventricular dysfunction may persist for a significant period of time after exercise-induced ischemia. Furthermore, early after exercise, dysfunction is related to persistent abnormalities of myocardial blood flow, whereas late after exercise it is independent of primary reductions in myocardial blood flow.

Recovery of transmural and subepicardial wall thickening after subendocardial infarction.

OBJECTIVES: This study tested the hypothesis that there is preferential recovery of subepicardial wall thickening after nontransmural myocardial infarction. BACKGROUND: Previous studies have demonstrated gradual recovery of mechanical function after reperfusion in acute myocardial infarction. Because myocardial necrosis is primarily subendocardial, it was hypothesized that recovery of mechanical function would occur primarily in the subepicardial layers. METHODS: Eleven mongrel dogs were instrumented with ultrasonic crystals to measure transmural and outer wall thickening. Animals performed treadmill exercise before and 8 days after nontransmural infarction produced by coronary occlusion for 90 min. RESULTS: Coronary artery occlusion reduced myocardial blood flow to inner layers more than that to outer wall layers (mean [+/- SD] 0.19 +/- 0.35 vs. 0.38 +/- 0.38 ml/g per min, p < 0.05). Infarct size (% of risk region) was also greater in subendocardial layers (33.3 +/- 24.3% inner vs. 8.3 +/- 9.7% outer). Rest transmural wall thickening was 22.4 +/- 7.5% versus 14.4 +/- 6.3% for outer wall layers. During coronary artery occlusion, transmural and outer wall thickening decreased similarly (3.2 +/- 7.7% vs. 0.2 +/- 5.9%). Eight days after reperfusion, thickening of the entire wall recovered to 7.5 +/- 4.7%; however, outer wall thickening had only recovered to 0.0 +/- 5.8%. Myocardial blood flow was abnormal during exercise 8 days after reperfusion, with markedly reduced subendocardial perfusion. However, thickening of the inner and outer layers was similar, with transmural thickening of 8.5 +/- 9.3% and outer wall thickening of 1.6 +/- 6.2%. CONCLUSIONS: Despite preferential blood flow and less necrosis, thickening of the outer layer is not preserved 8 days after subendocardial infarction. The severity of subendocardial injury appears to be the major determinant of regional function after nontransmural infarction.

Two-dimensional echocardiographic identification of complicated aortic root endocarditis: implications for surgery.

Two-dimensional echocardiography successfully displayed the location and extent of aortic root complications, annular abscess or mycotic aneurysm in nine patients with aortic valve endocarditis. Five of the nine patients had prosthetic valve endocarditis and four had native valve endocarditis. The infective process extended into the paravalvular structures, including the interventricular septum (seven patients), right ventricular outflow tract (three patients), interatrial septum (one patient) and anterior mitral valve leaflet (four patients). The amount of aorto-left ventricular discontinuity caused by these complications was quantitated in degrees of annular circumference on the parasternal short axis image and in distance on the parasternal long axis image. The echocardiographic findings were confirmed at surgery and were helpful in the preoperative anticipation of the type of surgical procedure required: aortic valve replacement or composite aortic valve and root replacement. Five patients had prosthetic valve endocarditis with calculated aorto-left ventricular discontinuity of 173 +/- 55 degrees on parasternal short axis images and 1.36 +/- 0.72 cm on parasternal long axis images. Initial surgical repair included three composite aortic root-valve prosthesis implants, one reconstructive procedure with valve replacement and one simple aortic valve replacement. During a follow-up period of 18 months (range 1 to 35), a second reparative procedure was required for only one patient to repair an aortic conduit to coronary artery venous bypass graft. Four patients had native valve endocarditis with calculated aorto-left ventricular discontinuity of 100 +/- 17 degrees on parasternal short axis images and 0.88 +/- 63 cm on parasternal long axis images. Initial surgical repair included two reconstructive procedures with valve replacement and two simple aortic valve replacements. During a follow-up period of 30 months (range 16 to 42), three of these four patients required a second reparative procedure: one each for repair of a paraprosthetic leak, a ventricular septal defect and persistent aorto-left ventricular discontinuity. Two-dimensional echocardiography accurately detected aortic annular abscess and mycotic aneurysm complicating aortic valve endocarditis and the resultant degree of aorto-left ventricular discontinuity. Circumferential aorto-left ventricular discontinuity with these complications is greater for prosthetic than native valve endocarditis and predicts a more extensive surgical repair.(ABSTRACT TRUNCATED AT 400 WORDS)

Frequent occurrence of occult pulmonary embolism from venous sheaths during endomyocardial biopsy.

To determine the frequency of occult right heart thromboembolism during endomyocardial biopsy, 51 cardiac transplant recipients undergoing routine endomyocardial biopsy were studied echocardiographically. Patients were randomized to two groups. In Group 1, the venous sheath was flushed between each biopsy attempt; in Group 2, it was flushed only at the time of initial placement. Right heart thromboemboli were identified in 18 (35%) of 51 patients. Seventeen (94%) of these 18 patients were in Group 2. Patients requiring more than six biopsy attempts had a significantly higher incidence of embolism. Other variables such as antiplatelet therapy, operator experience and total time of the procedure did not correlate with occurrence of thrombus. All right heart emboli were asymptomatic. These data demonstrate a high incidence of occult pulmonary embolism during uncomplicated routine endomyocardial biopsy. Meticulous flushing of the introducer sheath significantly reduces the incidence of thrombus formation in intravenous sheaths.

Effect of serotonin and thromboxane A2 on blood flow through moderately well developed coronary collateral vessels.

This study was performed to determine whether thromboxane A2 (as the analogue U46619) and serotonin can cause vasoconstriction of moderately well developed coronary collateral vessels. Studies were carried out in seven adult mongrel dogs 2 to 4 months after embolic occlusion of the left anterior descending coronary artery had been performed to stimulate collateral vessel growth. At the time of study this artery was cannulated to determine interarterial collateral flow from measurements of retrograde blood flow. Radioactive microspheres were administered during retrograde flow collection to determine continuing tissue flow for evaluation of microvascular collateral communications. Serotonin (50 micrograms/min) resulted in a 48 +/- 11% decrease in retrograde flow (p less than 0.01), with a 36 +/- 10% decrease in total collateral blood flow (p less than 0.02). Infusion of U46619 (0.01 microgram/kg per min) caused a 38 +/- 13% decrease in retrograde blood flow (p less than 0.01), with a 34 +/- 13% decrease in total collateral flow (p less than 0.05). Serotonin caused a significant increase in tissue flow to the subepicardium of the collateral-dependent region, whereas U46619 caused no change in tissue blood flow. These data demonstrate that both serotonin and thromboxane A2 can cause vasoconstriction of interarterial coronary collateral vessels. The findings suggest that platelet activation in coronary arteries from which collateral vessels originate has potential for causing collateral vasoconstriction, thereby compromising blood flow to the dependent myocardium.

Effects of nifedipine on coronary reactive and exercise induced hyperaemia.

The effects of nifedipine on coronary vasodilation were studied during reactive hyperaemia after a transient coronary occlusion and during active hyperaemia associated with graded treadmill exercise. Studies were performed in 10 chronically instrumented dogs in which left circumflex coronary artery flow was measured with an electromagnetic flowmeter and myocardial oxygen extraction was determined from indwelling aortic and coronary sinus catheters. Thirty minutes after administration of nifedipine (10 micrograms.kg-1 iv), when coronary blood flow, arterial pressure, and heart rate had returned to control values, the vasodilatation following a 10 s coronary occlusion was significantly blunted, so that reactive hyperaemia blood flow debt repayment (mean(SEM)) was reduced from 387(39)% during control conditions to 270(33)% after nifedipine (p less than 0.05). In contrast, nifedipine did not alter the coronary vasodilatation that occurred in response to graded treadmill exercise so that the increase in coronary blood flow during exercise was not different from the control response. Thus, although nifedipine blunted ischaemic coronary vasodilatation during reactive hyperaemia, it did not alter coronary vasodilatation during active hyperaemia resulting from physiological increases of myocardial oxygen consumption.

Echocardiographic characteristics of successful deployment of the Das AngelWings atrial septal defect closure device: initial multicenter experience in the United States.

The AngelWings device is a newer transcatheter device used for closure of secundum atrial septal defects (ASD) and patent foramen ovale (PFO), which consists of a self-centering, 2-disk system. Transesophageal echocardiography (TEE) plays a pivotal role in the deployment of the 2 disks of this device, on the appropriate sides of the atrial septum. The objective of this study is to describe the echocardiographic findings associated with successful deployment of the AngelWings device for closure of ASD and PFO. We evaluated the TEE studies of 70 patients enrolled in 4 United States centers, for closure of ASD and PFO with the AngelWings device. The TEE characteristics of successful and unsuccessful deployments were analyzed. Residual shunts across the atrial septum were assessed by TEE at the end of the procedure, 24 hours later by transthoracic echocardiography, and at 6 months by TEE. The deployment of the device was successful in 65 patients (93%). In the unsuccessful group, ASD size by TEE was larger (13.4 +/- 3.1 vs 8.9 +/- 4.7 mm, p <0.05). TEE was successful in identifying snagging of the device by intracardiac structures and prolapse of corners of the left or right atrial disk through the ASD, features that were difficult to identify by fluoroscopy. The echocardiographic characteristics outlined here are important guidelines for successful deployment of the AngelWings device.

Inhibition of adenosine-mediated coronary vasodilation exacerbates myocardial ischemia during exercise.

Persisting coronary vasoconstrictor tone that is responsive to exogenous adenosine administration has been demonstrated during myocardial ischemia. Therefore, the role and extent of endogenous adenosine-mediated coronary vasodilation in opposing coronary vasoconstriction within regions of ischemic myocardium was investigated in 10 chronically instrumented exercising dogs. Studies were performed on dogs with left circumflex coronary artery stenosis during treadmill exercise (6.5 km/h, 6% grade), while myocardial blood flow was measured with radioactive microspheres. Blood flow was measured before and again after inhibition of the effects of endogenously produced adenosine through combined inactivation of adenosine and adenosine receptor antagonism by the administration of intracoronary adenosine deaminase (ADA) (5 micrograms.kg-1 x min-1 x 10 min) plus 8-phenyltheophylline (8-PT) (5 mg/kg i.v.), respectively. Coronary perfusion pressure was held equal during both conditions at approximately 41 mmHg with a hydraulic occluder. During exercise in the presence of a coronary stenosis, blood flow was reduced in all layers of myocardium in regions supplied by the stenosed left circumflex coronary artery compared with blood flow in regions of myocardium supplied by the nonstenotic left anterior descending coronary artery. After ADA plus 8-PT, myocardial blood flow (in ml.min-1 x g-1) was further reduced in all layers of myocardium in regions supplied by the stenotic left circumflex coronary artery compared with baseline (subendocardial layer 0.44 +/- 0.09 vs. 0.67 +/- 0.13 ml.min-1 x g-1, mean transmural flow 0.92 +/- 0.13 vs. 1.25 +/- 0.2 ml.min-1 x g-1, both P < 0.05). Blood flow in regions of myocardium supplied by the nonstenotic left anterior descending coronary artery were unchanged following ADA plus 8-PT.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of urapidil on coronary blood flow during graded treadmill exercise.

We examined the effects of the alpha-adrenergic blocking agent urapidil on coronary blood flow (CBF) and myocardial O2 consumption during exercise in 11 dogs trained to run on a motor-driven treadmill. Left circumflex coronary artery (LCX) BF was measured with an electromagnetic flowmeter, and aortic and coronary sinus electromagnetic flowmeter, and aortic and coronary sinus catheters allowed determination of myocardial arteriovenous O2 extraction. During control conditions, graded treadmill exercise caused progressive increases in myocardial O2 consumption, which resulted from regular increases in CBF as well as increased O2 extraction by myocardium. Urapidil 3 mg/kg blocked the response to the selective alpha 1-adrenergic agonist phenylephrine (PE 5 micrograms/kg intravenously, i.v.), and significantly decreased arterial blood pressure (BP) at rest and during exercise. Heart rate (HR) was significantly faster than control during the lightest level of exercise after urapidil. Similarly, CBF was significantly increased during light and moderate exercise after urapidil administration. Urapidil caused a slight decrease in myocardial O2 extraction, with an increase in coronary sinus O2 tension. These data indicate that urapidil antagonized adrenergic coronary vasoconstriction, which acted to limit the increase in CBF that occurred during exercise.

Adrenergic vasoconstriction limits coronary blood flow during exercise in hypertrophied left ventricle.

This study was carried out to test the hypothesis that alpha-adrenergic vasoconstriction limits coronary blood flow (CBF) during exercise in the chronically pressure overloaded, hypertrophied left ventricle. Studies were performed in dogs in which left ventricular hypertrophy had been produced by banding the ascending aorta at 9 wk of age. Left circumflex coronary artery blood flow and myocardial O2 consumption (MVO2) were examined at rest and during treadmill exercise during control conditions, after selective alpha 1-adrenergic blockade with prazosin, and after nonselective alpha-adrenergic blockade with phentolamine. All studies were performed after beta-adrenergic blockade with propranolol. During control conditions CBF and MVO2 increased progressively during exercise, while coronary sinus O2 tension decreased. Neither prazosin nor phentolamine altered CBF at rest but, in comparison with control measurements, both agents significantly increased CBF during exercise and abolished the decrease in coronary sinus O2 tension that normally occurred during exercise. Both prazosin and phentolamine caused similar significant increases of MVO2 relative to the heart rate times systolic left ventricular pressure during exercise, indicating that the increased CBF produced by these agents enhanced MVO2. Similar findings after prazosin and phentolamine indicate that adrenergic restraint of CBF during exercise resulted principally from alpha 1-adrenergic vasoconstrictions with little additional contribution from postjunctional alpha 2-adrenergic mechanisms.

Subendocardial and subepicardial wall thickening during ischemia in exercising dogs.

To determine whether ischemia in the exercising dog is associated with preservation of subepicardial thickening relative to subendocardial thickening, 10 dogs were chronically instrumented with circumflex artery flow probes, hydraulic occluders, and pairs of ultrasonic microcrystals for determination of wall thickness in the circumflex artery distribution. One pair of crystals spanned the entire ventricular wall (transmural), and the other spanned the outer half of the ventricular wall. Inner wall thickness was computed as the difference between transmural wall thickness and outer wall thickness. Dogs performed control treadmill exercise and exercise with a coronary stenosis that reduced circumflex artery flow to resting control levels. Percent systolic thickening at rest for the transmural, inner, and outer regions was 21.3 +/- 11.8%, 35.5 +/- 20.3%, and 10.3 +/- 5.0% (mean +/- SD), respectively. During exercise without stenosis, systolic thickening increased to 143 +/- 37% of control for outer wall crystals and 137 +/- 26% of control for the inner portion of the wall. During exercise, the addition of a coronary stenosis caused a reduction in thickening to 17.7 +/- 28.5% of control for the outer wall and 40.1 +/- 32.3% of control for the inner portion of the wall; these were not significantly different. In contrast, normalized inner wall blood flow during exercise with circumflex artery stenosis (25.0 +/- 16.0%) was significantly less than for the outer portion of the wall (48.5 +/- 20.9%). Further, there was a close relation between changes in inner wall thickening and inner wall blood flow (r = 0.84), whereas there was only a very weak relation between changes in outer wall blood flow and function (r = 0.62; p = 0.04). During ischemia in the exercising dog, outer wall thickening is depressed out of proportion to reductions in outer wall blood flow and is not preserved relative to inner wall thickening.

Differences in the effects of alpha-1 adrenergic blockade with prazosin and indoramin on coronary blood flow during exercise.

This study compared the effects of two selective alpha-1 adrenergic blockers, prazosin and indoramin, on the response of coronary blood flow and myocardial oxygen consumption during treadmill exercise in chronically instrumented dogs. Left circumflex coronary artery blood flow was measured with an electromagnetic flowmeter, whereas myocardial arteriovenous oxygen difference was determined with indwelling aortic and coronary sinus catheters. During control conditions, coronary blood flow, arteriovenous oxygen extraction and myocardial oxygen consumption increased regularly with exercise. Both prazosin and indoramin decreased arterial pressure at rest and during exercise, but during heavier levels of exercise blood pressure was lower and heart rates were higher after prazosin. Prazosin did not alter myocardial oxygen consumption, whereas indoramin tended to decrease oxygen consumption; myocardial oxygen consumption was significantly less after indoramin than after prazosin during the heaviest levels of exercise. Prazosin, but not indoramin, significantly decreased coronary vascular resistance both at rest and during exercise, and blunted the decrease in coronary sinus oxygen tension which occurred during exercise. In comparison with prazosin, during heavy exercise coronary blood flow was significantly decreased, myocardial oxygen extraction significantly increased and myocardial oxygen consumption significantly decreased after indoramin.

Role of adenosine in coronary vasodilation during exercise.

This study examined the hypothesis that increases in myocardial blood flow during exercise are mediated by adenosine-induced coronary vasodilation. Active hyperemia associated with graded treadmill exercise and coronary reactive hyperemia were examined in chronically instrumented awake dogs during control conditions, after intracoronary infusion of adenosine deaminase (5 units/kg/min for 10 minutes), and after adenosine receptor blockade with 8-phenyltheophylline. Both adenosine deaminase and 8-phenyltheophylline caused a rightward shift of the dose-response curve to intracoronary adenosine; 8-phenyltheophylline was significantly more potent than adenosine deaminase. Adenosine deaminase caused a 33 +/- 7 to 39 +/- 3% decrease in reactive hyperemia blood flow following coronary occlusions of 5-20 seconds duration, respectively, while 8-phenyltheophylline produced a 40 +/- 6 to 62 +/- 8% decrease in reactive hyperemia. Increasing myocardial oxygen consumption during treadmill exercise was associated with progressive increase of coronary blood flow. Neither adenosine deaminase nor 8-phenyltheophylline attenuated the increase in coronary blood flow or the decrease of coronary vascular resistance during exercise. Neither agent altered the relation between myocardial oxygen consumption and coronary blood flow. Thus, although both adenosine deaminase and 8-phenyltheophylline antagonized coronary vasodilation in response to exogenous adenosine and blunted coronary reactive hyperemia, neither agent impaired coronary vasodilation associated with increased myocardial oxygen requirements produced by exercise. These findings fail to support a substantial role for adenosine in mediating coronary vasodilation during exercise.

Cumulative deterioration of myocardial function after repeated episodes of exercise-induced ischemia.

To determine whether progressive regional myocardial dysfunction occurs after repetitive episodes of exercise-induced ischemia, 10 dogs were instrumented with ultrasonic microcrystals for determination of regional myocardial wall thickening, circumflex artery electromagnetic flow probes, and hydraulic coronary artery occluders. Dogs performed treadmill exercise in the presence of a coronary artery stenosis, which limited coronary blood flow to control levels. Dogs performed a single 10-min exercise period one day and three identical runs separated by 1-h rest periods on the alternate day. At rest before the first exercise period, circumflex wall thickening was 18.8 +/- 6.7% and increased to 25.5 +/- 10.6% during exercise before the application of coronary stenosis. On the day that three exercise trials were performed, circumflex systolic wall thickening at rest before the third exercise period (9.7 +/- 4.0%) and during exercise without coronary stenosis (17.3 +/- 7.3%) were both significantly lower than during the first exercise period (P less than 0.0125). During exercise with stenosis, circumflex systolic wall thickening fell to 4.6 +/- 4.7% during a single run, and 5.0 +/- 2.0% during the third of three consecutive runs. Wall thickening was significantly lower 2 h after the third consecutive run (9.1 +/- 2.4%) than 2 h after a single period of exercise-induced ischemia (14.8 +/- 7.6%; P 0.0125). Transmural myocardial blood flow to circumflex myocardium during the third period of exercise-induced ischemia (0.93 +/- 0.47 ml.min-1.g-1) was not different than during the single period of exercise (0.84 +/- 0.47 ml.min-1.g-1). It is concluded that repetitive episodes of exercise-induced ischemia result in cumulative postexercise regional myocardial dysfunction.

Vasomotor activity of moderately well-developed canine coronary collateral circulation.

This study examined the ability of moderately well-developed coronary collateral vasculature to undergo vasoconstriction in response to alpha-adrenergic agonists, vasopressin and angiotensin, and vasodilation in response to nitroglycerin. Studies were performed in 20 dogs 4-16 wk after left anterior descending coronary artery occlusion had been produced by an Ameroid constrictor or hollow intravascular plug. Collateral flow was estimated from retrograde flow from the cannulated left anterior descending artery. Tissue flow was measured with microspheres. Agonists were introduced into the left main coronary artery to reach collaterals arising from the left circumflex and septal arteries. Vasopressin and angiotensin II decreased retrograde flow from 22.7 +/- 5.5 to 15.5 +/- 2.7 and from 19.2 +/- 2.8 to 14.3 +/- 1.9 ml/min, respectively (each P less than 0.05). Both agents also significantly decreased tissue flow to normally perfused and collateral dependent myocardium. Neither the selective alpha 1-adrenergic agonist phenylephrine nor the alpha 2-agonist B-HT 933 decreased retrograde flow. Nitroglycerin increased retrograde flow by 63 +/- 27% (P less than 0.01). Thus, although the moderately well-developed coronary collateral circulation is capable of vasoconstriction in response to vasopressin and angiotensin II, these data fail to support a role for alpha-adrenergic mechanisms in modulating collateral flow.

Oxygen consumption and coronary reactivity in postischemic myocardium.

Coronary vascular responses in regions of reversible postischemic myocardial contractile dysfunction (stunned myocardium) were examined in chronically instrumented, awake dogs. Left anterior descending coronary artery blood flow and oxygen extraction, aortic and left ventricular pressures, and regional myocardial segment shortening were determined. Regional myocardial blood flow was measured with microspheres. Coronary reactive hyperemia and vasodilator reserve, and regional myocardial oxygen consumption were determined. Three sequential 10-minute left anterior descending coronary artery occlusions separated by 30-minute reperfusion periods resulted in progressive postischemic dysfunction so that 1 hour after the final coronary artery occlusion, myocardial segment shortening was reduced to 37% of baseline. Despite this decrease in contractile function, left anterior descending artery flow (19.6 +/- 2.6 vs. 18.4 +/- 3.0 ml/min), myocardial blood flow and the transmural distribution of flow measured with microspheres, and regional myocardial oxygen consumption were unchanged. Although the coronary vasodilator reserve in response to adenosine was unaltered (63 +/- 9 vs. 70 +/- 15 ml/min), the reactive hyperemia response to a 10-second coronary occlusion was decreased in intensity (debt repayment ratio = 474 +/- 78% vs. 322 +/- 74%; p less than 0.05) and duration (57 +/- 9.1 vs. 35 +/- 4.5 seconds; p less than 0.05), while the peak flow response was unchanged (57 +/- 6.8 vs. 60 +/- 7.1 ml/min). Thus, in the intact awake animal postischemic myocardial contractile dysfunction was not associated with decreased myocardial oxygen consumption and did not impair the normal relation between coronary blood flow and myocardial oxygen utilization. Although coronary vessels showed a normal ability to vasodilate in response to adenosine, coronary reactive hyperemia was reduced.

Coronary vasodilator reserve in ischemic myocardium of the exercising dog.

BACKGROUND: Previous work has reported that coronary vasodilator reserve may persist in myocardium rendered ischemic by hypoperfusion. This study investigated the presence and extent of residual coronary vasomotor tone in myocardial regions made acutely ischemic by a flow-limiting coronary stenosis during exercise. METHODS AND RESULTS: Studies were done in chronically instrumented dogs undergoing treadmill exercise in the presence of a coronary stenosis that decreased distal left circumflex coronary artery perfusion pressure to approximately 40 mm Hg. Measurements of myocardial blood flow were made with radioactive microspheres during exercise (6.5 km/hr, 6% grade) before and during intracoronary infusion of the potent coronary vasodilator adenosine (40 micrograms/kg/min). Distal coronary perfusion pressure was held equal before and during intracoronary adenosine infusion (43 +/- 5 versus 42 +/- 5 mm Hg) by adjusting the hydraulic coronary occluder. During exercise in the presence of a coronary stenosis, myocardial blood flow (milliliter per minute per gram) was significantly reduced in all layers of the ischemic posterior region compared with the nonischemic anterior region. During intracoronary adenosine infusion, with no change in coronary perfusion pressure, myocardial blood flow was significantly increased compared with preadenosine flows for both the subendocardial layer flow (1.03 +/- 0.74 versus 0.66 +/- 0.50; p less than 0.05) and mean transmural flow (1.54 +/- 0.59 versus 1.16 +/- 0.36; p less than 0.05). In the presence of a coronary stenosis, regional myocardial segment shortening in the ischemic region during exercise fell significantly to 49 +/- 8% of shortening in the absence of a coronary stenosis but improved modestly during adenosine infusion (65 +/- 7 versus 49 +/- 8%; p less than 0.05). CONCLUSIONS: These results indicate that adenosine-responsive coronary vasodilator reserve persists during exercise-induced myocardial ischemia and suggest that residual microvascular vasoconstrictor tone may affect the extent of myocardial hypoperfusion occurring consequent to a flow-limiting coronary stenosis.