Myocardial pharmacokinetics of lithium in vitro

The myocardial pharmacokinetics of ionised lithium were investigated in isolated, intact rabbit hearts, which were retrogradely perfused with a modified Krebs-Henseleit solution containing lithium in a concentration of 5 mM. The rate of myocardial accumulation of lithium as a function of time was indirectly followed at constant coronary flow by means of determination of the lithium content of fractional samples of the coronary output of perfusate collected during the lithium perfusion period. The disposition rate of lithium from the myocardium was similarly determined with respect to the time lapse after the perfusion had been switched over to a lithium-free liquid. The accumulation and disposition processes were found to fit bi-exponential functions, as an expression of the myocardium behaving as a two-compartment system obeying apparently first order, linear kinetics with respect to ionised lithium. A pronounced decrease of the uncomposite elimination rate constants k10 and especially k21 was observed after continuous perfusion with 5 mM lithium perfusion liquid for about 30 min. During this perfusion period at steady state, an absolute increase of myocardial lithium accumulation obviously took place. A possible correlation of these findings to the cardiac effects of lithium is discussed.