Effects of vasoactive stimuli on coronary vascular resistance in isolated perfused rabbit hearts: no vasospastic response to ergonovine with or without atherogenic diet.

The mechanism of ergonovine-provoked coronary vasospasm is poorly understood. We tested the effect of ergonovine in perfused hearts from normal and cholesterol-fed (18 weeks, 2% cholesterol diet) rabbits in a constant-flow Langendorff perfusion. Aortic perfusion pressure was monitored to measure coronary vascular resistance, and left ventricular pressure was measured with an isovolumetric balloon in the left ventricle. Control coronary vascular resistance was 1.12 +/- 0.11 mm Hg/ml/min in hearts from normal rabbits and 1.53 +/- 0.16 mm Hg/ml/min in hearts from cholesterol-fed rabbits (n = 9 each, mean +/- SEM, p less than 0.05). The cholesterol content of aortae from cholesterol-fed rabbits was markedly increased (432 +/- 85 mg/g protein vs. 14.9 +/- 8.2 in controls, p less than 0.001; for coronaries: 396 +/- 136 mg/g protein vs. 125 +/- 25, p less than 0.05). In both groups, increases in coronary vascular resistance were observed with vasopressin (40 IU/l) and phenylephrine (30 microM) and decreases with adenosine (10 microM), isoprenaline (0.1 microM) and 30 sec stop-flow (all p less than 0.05). Ergonovine maleate (10 microM) and serotonin (10 microM) did not increase coronary vascular resistance. Although in whole heart perfusion small changes in the caliber of epicardial vessels may not be detectable, changes severe enough to produce measurable changes in total coronary resistance were not found. Therefore the absence in our model of an increase in coronary vascular resistance after ergonovine is not compatible with a local direct mechanism in epicardial arterial wall, even when sensitized by a high cholesterol diet.