Effects of Thiopental on Regional Blood Flows in the Rat

Abstract

The goal of this investigation was to characterize the effects of thiopental on cardia output and regional blood flows in the rat. Blood flows influence thiopental pharmacokinetics. Acquisition of these data may ultimately permit evaluation of the contribution of thiopental-induced alterations in regional blood flows to the disposition and hypnotic effect of this drug. Chronically instrumented unrestrained Wistar rats (n=20) aged 3-4 months received either a dose of thiopental sufficient to induce a brief period of unconsciousness (20 mg.kg(-1)) or a larger dose achieving electroencephalographic burst suppression (45 mg.kg(-1)). Cardiac output and blood flows to 14 tissues were determined at 4 times in each rat for a period of 420 min using injections of radioactive microspheres (expressed as mean +/- SD). Mean arterial pressure, heart rate, and blood gas tensions were determined at all measurement times. Arterial plasma concentrations were sampled at postinfusion times. No important changes in systemic cardiovascular measurements were detected after the smaller dose of thiopental. One minute after the larger dose, cardiac output decreased from baseline (123 +/- 14 to 84 +/- ml.min (-1), P< 0.01), flow to muscle and fat decreased, and muscle and fat resistance increased. At 5 min, compared to baseline, no difference in cardiac output was detected (123 +/- vs. 119 +/- ml.min (-1)), intestinal flows increased and intestinal resistances decreased. Cardiac output was again depressed at 30, 90, and 180 min. Brain blood flow decreased 25 +/- 19 % (P< 0.01) from baseline for the duration of the study. Thiopental acutely decreases cardiac output, and blood flows to muscle and fat tissue. The temporary return of cardiac output to baseline may be related to intestinal vasodilation. These blood flow alterations may influence the pharmacokinetics of thiopental.