MYOCARDIAL PHARMACOKINETICS OF THIOPENTAL IN SHEEP AFTER SHORT-TERM ADMINISTRATION - RELATIONSHIP TO THIOPENTAL-INDUCED REDUCTIONS IN MYOCARDIAL-CONTRACTILITY

The myocardial kinetics and dynamics of thiopental (750 mg over 2 min) were examined in chronically instrumented sheep (five studies in four sheep). The myocardial kinetics were studied by simultaneous rapid sa mpling of arterial and coronary sinus blood for 30 min. The myocardial kinetics for four of the five studies were best described by a single flow-limited compartment with apparent volumes of between 42 and 113 mL. These volumes equated to half-lives of equilibration between blood and myocardium of between 0.49 and 1.00 min when baseline blood flow was taken into account. The remaining study was better described by a model with a slight membrane limitation (permeability/flow ratio of ap proximately 2). Myocardial contractility was studied as a measure of m yocardial pharmacodynamics and was reduced to 53% of baseline at appro ximately 2.5 min after the start of the dose. Effect compartment analy sis showed that there was hysteresis between the time course of these contractility changes and the time course of the arterial concentratio ns, with effect compartment half-lives between 0.08 and 0.87 min. Ther e was significantly less hysteresis for the coronary sinus concentrati ons. It is concluded that thiopental equilibrated rapidly with a compo nent of the myocardium, and that consequently its effects on myocardia l contractility also rapidly equilibrated with both afferent and efflu ent myocardial blood.