Alpha 1-adrenergic tone does not influence the transmural distribution of myocardial blood flow during exercise in dogs with pressure overload left ventricular hypertrophy.

Abstract

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.