EFFECT OF THIOPENTAL ON REGIONAL BLOOD FLOWS IN THE RAT

Background: The goal of this investigation was to characterize the eff ects of thiopental on cardiac output and regional blood hows in the ra t. Blood flows influence thiopental pharmacokinetics. Acquisition of t hese data may ultimately permit evaluation of the contribution of thio pental-induced alterations in regional blood hows to the disposition a nd hypnotic effect of this drug. Methods: Chronically instrumented unr estrained 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 bur st suppression (45 mg . kg(-1)). Cardiac output and blood hows to 14 t issues 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 det ermined at all measurement times. Arterial plasma concentrations were sampled at postinfusion times. Results: No important changes in system ic cardiovascular measurements were detected after the smaller dose of thiopental. One minute after the larger dose, cardiac output decrease d from baseline (123 +/- 14 to 84 +/- 11 ml . min(-1), P < 0.01), how to muscle and fat decreased, and muscle and fat resistance increased. At 5 min, compared to baseline, no difference in cardiac output was de tected (123 +/- 14 vs. 119 +/- 11 ml . min(-1)), intestinal flows incr eased, and intestinal resistances decreased. Cardiac output was again depressed at 30, 90, and 180 min. Brain blood how decreased 25 +/- 199 6 (P < 0.01) from baseline for the duration of the study. Conclusions: Thiopental acutely decreases cardiac output, and blood hows to muscle and fat tissue. The temporary return of cardiac output to baseline ma y be related to intestinal vasodilation. These blood flow alterations may influence the pharmacokinetics of thiopental.