TACHYCARDIA ALONE FAILS TO CHANGE THE MYOCARDIAL PHARMACOKINETICS ANDDYNAMICS OF LIDOCAINE, THIOPENTAL, AND VERAPAMIL AFTER INTRAVENOUS BOLUS ADMINISTRATION IN SHEEP

Previous reports have suggested that tachycardia alone can increase th e rate of myocardial uptake of some drugs. As part of a systematic stu dy of the determinants of the myocardial uptake and effects of drugs i n critical illness, the effect of tachycardia induced by intracardiac pacing on the myocardial disposition and effects of lidocaine, verapam il, and thiopental were studied in chronically instrumented sheep. For each drug, seven sheep received either 100 mg of lidocaine, 10 mg of verapamil, or 750 mg of thiopental over 2 min in unpaced and paced (14 0 beats/min) states on separate occasions and in random order. Arteria l and coronary sinus (effluent from the heart) blood samples were take n at regular intervals for 30 min, and the maximum late of change of l eft ventricular pressure (LV dP/df(max)) was measured as an index of m yocardial contractility. There were no differences between unpaced and paced studies in the time courses of arterial and coronary sinus conc entrations, or the time-courses of myocardial contractility and blood flow, after bolus iv injections of these drugs. Tachycardia alone does not appear to influence the myocardial kinetics or dynamics of lipoph ilic drugs that can rapidly diffuse into the heart.