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

To determine if lithium exerts direct cardiac toxicity, using an isolated, perfused rat heart model, paced and unpaced beating rat hearts were perfused with Krebs-Henseleit bicarbonate solution and left ventricular pressures were measured via a balloon-tipped catheter positioned in the left ventricle via the mitral valve. Following a stabilization period, hearts were then perfused with Krebs-Henseleit bicarbonate solution containing 1, 10, and 100 mM ionized lithium chloride or lithium carbonate in an antecedent dose-response protocol and perfused for 10 min. at each dose. To control for the possibility of osmotic effects from the high dose of lithium, an additional group was studied in which hearts were perfused with Krebs-Henseleit bicarbonate solution for an initial stabilization period, then perfused for an additional 20 min. with Krebs-Henseleit bicarbonate solution alone, and finally with Krebs-Henseleit bicarbonate solution containing mannitol (200 mOsm/l) for 10 min. Lithium did not have any effect on left ventricular peak systolic pressure, left ventricular end diastolic pressure, heart rate or coronary haemodynamics at concentrations of 1 or 10 mM. At 100 mM LiCl and Li2CO3, left ventricular peak systolic pressure decreased transiently during the first minute of lithium infusion, but recovered significant function by 10 min. Heart rate decreased significantly by 10 min. of infusion. These effects 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.