ABSTRACT
We tested the hypothesis that the selective kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) improves recovery from myocardial stunning. Ten dogs were chronically instrumented for measurement of heart rate, left atrial, aortic and left ventricular pressure (LVP), and the maximum rate of LVP increase (LV dP/dt(max)) and decrease (LV dP/dt(max)), coronary blood flow velocity and myocardial wall-thickening fraction. Regional myocardial blood flow was determined with fluorescent microspheres. Catecholamine plasma levels were measured by high-performance liquid chromatography, and beta-endorphin and dynorphin plasma levels by radioimmunoassay. An occluder around the left anterior descending artery (LAD) allowed induction of a reversible LAD-ischemia. Animals underwent two experiments in a randomized crossover fashion on separate days: (a) 10 min LAD-occlusion (control experiment), (b) second ischemic episode 24 h after nor-BNI (2.5 mg/kg IV) (intervention). Dogs receiving nor-BNI showed an increase in wall-thickening fraction, LV dP/dt(max) and LV dP/dt(min) before ischemia and during the whole reperfusion (P < 0.05 versus control experiment). After nor-BNI pretreatment, dynorphin levels increased after induction of ischemia to a peak level of 15.1 +/- 3.6 pg/mL (P < 0.05 versus control experiment). The increase in plasma beta-endorphin during ischemia and early reperfusion was attenuated after nor-BNI. Compared with the control experiment, nor-BNI left global hemodynamics, regional myocardial blood flow, and catecholamine levels unchanged. In conclusion, nor-BNI improves recovery from myocardial stunning after regional myocardial ischemia in chronically instrumented dogs.
Subject(s)
Myocardial Stunning/drug therapy , Naltrexone/analogs & derivatives , Narcotic Antagonists/pharmacology , Receptors, Opioid, kappa/antagonists & inhibitors , Animals , Blood Pressure/drug effects , Coronary Circulation/drug effects , Dogs , Dynorphins/blood , Epinephrine/blood , Female , Heart Rate/drug effects , Male , Myocardial Stunning/physiopathology , Naltrexone/pharmacology , Norepinephrine/blood , Radioimmunoassay , Ventricular Function, Left/drug effects , beta-Endorphin/bloodABSTRACT
In this study we tested the hypothesis that inhalational administration of xenon improves recovery from myocardial stunning. Ten dogs were chronically instrumented for measurement of heart rate; left atrial, aortic, and left ventricular pressure; coronary blood-flow velocity; and myocardial wall-thickening fraction. Regional myocardial blood flow was determined with fluorescent microspheres. Catecholamine plasma levels were measured by high-performance liquid chromatography. An occluder around the left anterior descending artery (LAD) allowed the induction of a reversible LAD ischemia. Animals underwent 2 experimental conditions in a randomized crossover fashion on separate days: (a) 10 min of LAD occlusion under fentanyl (25 microg. kg(-1). h(-1)) and midazolam (0.6 mg. kg(-1). h(-1)) (control) and (b) a second ischemic episode under the same basal anesthesia with concomitant inhalational administration of 75 +/- 1 vol% xenon (intervention). Anesthesia was induced 35 min before LAD occlusion and was discontinued after 20 min of reperfusion. Dogs receiving xenon showed a significantly better recovery of wall-thickening fraction up to 12 h after ischemia. The increase in plasma epinephrine during emergence from anesthesia and in the early reperfusion period was significantly attenuated in the xenon group. There were no differences between groups concerning global hemodynamics, blood-flow velocity, or regional myocardial blood flow. In conclusion, inhalational administration of 75 vol% xenon improves recovery from myocardial stunning in chronically instrumented dogs under fentanyl/midazolam anesthesia.
