Lithium has no direct effect on cardiac function in the isolated, perfusedrat heart

To determine if lithium exerts direct cardiac toxicity, using an isolated, perfused rat heart model, paced and unpaced beating rat hearts were perfuse d with Krebs-Henseleit bicarbonate solution and left ventricular pressures were measured via a balloon-tipped catheter positioned in the left ventricl e via the mitral valve. Following a stabilization period, hearts were then perfused with Krebs-Henseleit bicarbonate solution containing 1, 10, and 10 0 mM ionized lithium chloride or lithium carbonate in an antecedent dose-re sponse protocol and perfused for 10 min. at each dose. To control for the p ossibility of osmotic effects from the high dose of lithium, an additional group was studied in which hearts were perfused with Krebs-Henseleit bicarb onate solution for an initial stabilization period, then perfused for an ad ditional 20 min. with Krebs-Henseleit bicarbonate solution alone, and final ly with Krebs-Henseleit bicarbonate solution containing mannitol (200 mOsm/ l) for 10 min. Lithium did not have any effect on left ventricular peak sys tolic pressure, left ventricular end diastolic pressure, heart rate or coro nary haemodynamics at concentrations of 1 or 10 mM. At 100 mM LiCl and Li2C O3, left ventricular peak systolic pressure decreased transiently during th e first minute of lithium infusion, but recovered significant function by 1 0 min. Heart rate decreased significantly by 10 min, of infusion. These eff ects were also seen in the osmotic controls and thus do not appear to be a direct effect of lithium. At the doses tested, lithium had no direct effect on cardiac function which could not be explained by an osmotic effect.