The effects of cardiac sympathetic nerve stimulation on perfusion of stenotic coronary arteries in the dog

Abstract

The interaction of sympathetic vasoconstriction with the coronary reserve distal to stenoses and the role of α-adrenergic mechanisms in the genesis of myocardial ischemia were studied in 42 anesthetized open-chest dogs. Left cardiac sympathetic nerve stimulation was performed after bilateral cervical vagotomy: with intact coronary arteries, with an intermediate stenosis, and with a severe stenosis on the circumflex coronary artery. Stenoses were produced by a wire snare and defined as intermediate by the reduction of the reactive hyperemia repayment following a 15-second occlusion from 460 ± 100 to 140 ± 30%; a severe stenosis was defined by only 25 ± 8% reactive hyperemia repayment. Cardiac sympathetic nerve stimulation decreased the end-diastolic coronary resistance of intact coronary arteries from 0.79 ± 0.05 to 0.53 ± 0.06 mm Hg x min x 100 g/ml (P < 0.01) and the end-diastolic poststenotic resistance of the moderately stenosed arteries from 0.65 ± 0.08 to 0.50 ± 0.07 mm Hg x min x 100 g/ml (P < 0.01). Cardiac sympathetic nerve stimulation increased the end-diastolic resistance distal to severe stenoses from 0.57 ± 0.04 to 0.97 ± 0.18 mm Hg x min x 100 g/ml (P < 0.01). This stimulation resulted in net lactate production of the circumflex-perfused myocardium; 4 dogs died by ventricular fibrillation. There was a hyperbolic correlation of the cardiac sympathetic nerve stimulation-induced change in resistance to the degree of coronary hyperemic reserve (r = 0.81). Phentolamine (2 mg/kg, iv) and rauwolscine (0.2 mg/kg, iv) prevented the increase in resistance distal to severe stenoses during cardiac sympathetic nerve stimulation, whereas prazosin (1.2 mg/kg, iv) was ineffective. After β-blockade with propranolol (2 mg/kg, iv), rauwolscine still prevented the increase in poststenotic resistance during cardiac sympathetic nerve stimulation. We conclude that there is a continuous unmasking of sympathetic vasoconstriction with increasing severity of a stenosis and, thus, decreasing coronary reserve. This vasoconstriction is mediated by postjunctional α2-receptors and can induce myocardial ischemia distal to severe coronary stenoses.