Effect of norepinephrine on coronary hemodynamics in coronary stenotic canine model

Abstract

The effect of intracoronary injection of 1μ norepinephrine was assessed in 14 open-chest dogs anesthetized with alpha chloralose. Studies were performed before and after partial coronary artery constriction by a circumferential snare. Aortic pressure, coronary pressure distal to the stenosis, and coronary flow were monitored before and after injection of norepinephrine. Calculated values were stenotic resistance and distal coronary resistance. Before coronary constriction, norepinephrine resulted in an early minimal increase in coronary flow and decrease in distal coronary resistance with prompt return to control values. In contrast with high grade coronary constriction, at 15 seconds after norepinephrine coronary flow decreased (29.8 ± 3.4 to 22.9 ± 3.6 ml./minute) (p < 0.05), coronary pressure decreased (58.8 ± 1.3 to 28.8 ± 2.6 mm. Hg) (p < 0.05), and stenotic resistance increased (2.04 ± 0.26 to 4.25 ± 2.66 mm. Hg/ml. min. −1) (p < 0.05) without change in heart rate or aortic pressure. These changes persisted over a two minute period of observation following norepinephrine. In the stenotic model the decrease in coronary pressure and coronary flow and increase in stenotic resistance were blocked by pretreatment with propranolol but not by phenoxybenzamine. Administration of isoproterenol resulted in changes similar to those induced by norepinephrine in the stenotic model. Simulation of alteration of peripheral resistance in an in vitro model demonstrated that with a high initial stenotic resistance, a decrease in peripheral resistance resulted in an increase in stenotic resistance. We conclude that the decrease in coronary pressure following norepinephrine was mediated by beta 1 or beta 2 adrenergic stimulation. We further postulate that the decreased coronary flow and increased stenotic resistance were caused by a passive decrease in radius at the stenotic site.