Myocardial Pharmacological Preconditioning by Norepinephrine in Rabbit. A Role for Beta-3 Adrenergic Agonists?

摘要

High doses of norepinephrine abolish the infarct-limiting effect of Ischemic Preconditioning (IP) in rabbits. We wished to define the role of the beta-3 receptors in this observation. Rabbits were randomized into 5 groups of 8 animals each. In Control Group (CTRL), anaesthetized rabbits were subjected to 30 min left coronary marginal branch occlusion and 180 min reperfusion. In NEHI group, rabbits received a 10 ?g kg ¹ norepinephrine injection 10 min before coronary occlusion and reperfusion. In NELOW group, rabbits received 0.25 ?g/kg/min of norepinephrine for 5 min and then had 10 min of washout before coronary occlusion and reperfusion. In NELOWBRL group, rabbits had BRL37344 (8.3 ?g kg ¹) injection 1 min prior to a norepinephrine perfusion comparable to NELOW group, followed by ischemia and reperfusion. In BRL group, rabbits had BRL37344 (8.3 ?g kg ¹) injection 10 min before coronary occlusion and reperfusion. At termination of the experiment, Left Ventricular Volume (LVV), myocardial Volume At Risk (VAR) and Infarct Volume (IV) were determined with methylene blue and tetrazolium staining and measured using planimetry. LVV was not significantly different among groups. Myocardial VAR/LVV was not significantly different between groups (CTRL, 13.52?5.17%; NEHI, 12.11?4.23%; NELOW, 12.45?11.35%; NELOWBRL, 14.71?4.74; BRL, 8.39?4.60; p = ns). IV/VAR was significantly reduced in the NELOW group as compared with CTRL, NEHI, NELOWBRL and BRL (respectively, 16.52?5.50% vs 56.42?14.40%, 55.71?8.38%, 50.95?11.62%, 50.18?10.20, p< 0.001). There was no significant difference in IV/VAR between CTRL, NEHI, NELOWBRL and BRL. The absence of a preconditioning protective effect during a massive injection of norepinephrine could be in relation with a beta-3 stimulation that interferes with the preconditioning pathways.