This study was carried out to test the hypothesis that alpha 1-adrenergic activation during exercise causes preferential vasoconstriction of subepicardial coronary resistance vessels, thereby augmenting blood flow to the subendocardium. Studies were performed in 7 dogs in which left ventricular hypertrophy was produced by banding the ascending aorta at 6-9 weeks of age. Animals were studied at approximately 1 year of age when the left ventricular/body weight ratio was 7.7 +/- 0.3 g/kg (mean +/- SE). Left anterior descending (LAD) coronary artery flow was measured with a Doppler velocity flow probe at rest and during a three-stage graded treadmill exercise protocol. The transmural distribution of myocardial blood flow was assessed with radioactive microspheres. Coronary blood flow increased progressively as a function of heart rate and rate-pressure product in response to exercise. In contrast to normal dogs which maintain preferential blood flow to the subendocardium (ENDO) relative to the subepicardium (EPI) during exercise, the ENDO/EPI flow ratio in the hypertrophied left ventricles was 0.88 +/- 0.10 during exercise. Selective alpha 1-adrenergic blockade by infusion of prazosin (10 micrograms/kg) into the LAD decreased mean aortic pressure during exercise from 86 +/- 6 to 76 +/- 4 mmHg (p < 0.05), but did not change coronary pressure, heart rate, left ventricular systolic or enddiastolic pressures, or LVdP/dtmax. Coronary blood flow was not significantly altered by prazosin at rest, but was progressively increased during increasing levels of exercise levels. During the heaviest level of exercise prazosin caused a 22 +/- 3% increase in mean myocardial blood flow which was similar in all transmural layers, with no change in the transmural distribution of perfusion (ENDO/EPI = 0.85 +/- 0.09). These findings demonstrate that alpha 1-adrenergic vasoconstrictor tone limits blood flow during exercise in the hypertrophied left ventricle, but do not support the concept that alpha 1-adrenergic activation augments perfusion of the subendocardium during exercise.

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PubMedDate not supplied

Effect of nifedipine on the myocardial and vascular response to myocardial ischemia.

Nifedipine reduces reactive hyperemia following brief coronary artery occlusions. To determine whether this is related to improvement in collateral blood flow to ischemic myocardium or alterations in myocardial oxygen consumption, ten chloralose anesthetized dogs were instrumented with coronary sinus catheters, circumflex artery flowmeters, and ultrasonic microcrystals for measurement of myocardial segment shortening. Myocardial oxygen consumption and circumflex coronary artery flow were determined at rest and during incremental infusions of isoproterenol. Myocardial blood flow measured with microspheres and segmental function were assessed during and following 30- and 60-second coronary artery occlusions. Thirty minutes after the intravenous administration of nifedipine, 10 micrograms/kg iv, all measurements were repeated. Nifedipine did not alter myocardial oxygen consumption or the relationship between oxygen consumption and circumflex coronary artery flow either at rest or during isoproterenol infusion. Following 60-second coronary occlusions, nifedipine reduced peak circumflex coronary artery flow (176 +/- 99 vs. 128 +/- 68 cc/min) and reactive hyperemia debt repayment (221 +/- 84 vs. 158 +/- 66%; p less than 0.01). Nifedipine did not alter flow to ischemic segments during coronary artery occlusions (0.16 +/- 0.10 vs. 0.19 +/- 0.13 ml/min/g mean transmural flow). Furthermore, nifedipine did not affect the severity of ischemic segment dysfunction, nor the rate of recovery of ischemic segment function following release of coronary artery occlusion. We conclude that the reduction in reactive hyperemia induced by nifedipine was not related to alterations in the severity of hypoperfusion in ischemic areas, or alterations in myocardial oxygen consumption. Reductions in reactive hyperemia produced by nifedipine did not impair recovery of mechanical function in postischemic myocardium.

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PubMedDate not supplied

Reactive hyperemia following total and subtotal coronary occlusion in the awake dog.

This study examined the reactive hyperemia following total and subtotal coronary artery occlusions. Studies were carried out in awake dogs with electromagnetic flowmeters and hydraulic occluders on the left circumflex coronary artery; the regional distribution of perfusion was examined with radionuclide-labeled microspheres. Reactive hyperemia following total and subtotal occlusions resulted in similar mean blood flow debt repayments of 451 +/- 34% and 492 +/- 51%, respectively. However, the distribution of perfusion was markedly different, with the ratio of subendocardial to subepicardial blood flow being 1.77 +/- 0.22 after total occlusion and 4.14 +/- 0.73 after subtotal occlusion (p less than 0.01). Further examination of the pattern of perfusion during reactive hyperemia demonstrated a direct relationship between the local blood flow debt and blood flow during the subsequent reactive hyperemia. These data demonstrate that coronary reactive hyperemia does not occur uniformly throughout the distribution of the vascular bed served by the previously occluded artery, but rather is coupled to the degree of hypoperfusion during the preceding occlusion.

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