Background: Although purported to be a cardiotoxin, the medical literature contains contradictory accounts of lithium's effects on the heart. Objective: To evaluate the effects of several concentrations of lithium (Li) on cardiac function in the isolated, spontaneously beating rat heart. Methods: Male Sprague-Dawley rats (300-350g, n=4) were anticoagulated with heparin (2500 IU, ip) and anesthetized with Nembutal (50 mg, ip). Hearts were harvested and coronary arteries perfused on a Langendorff apparatus via retrograde perfusion of the aorta. Coronary flow was maintained at 10 ml/min. Spontaneously beating hearts were perfused with Krebs-Henseleit-Bicarbonate (KHB) solution, aerated with 95% 02/ 5% CO2 at 37¡C. Left ventricular pressure was measured via a balloon-tipped catheter positioned in the left ventricle via the mitral valve. Left ventricular end diastolic pressure and coronary artery perfusion pressure were used as indices of ventricular compliance and coronary vascular resistance, respectively. Following a stabilization period, hearts were then perfused with KHB containing 0.1, 1, 10, and 100 mM ionized lithium chloride (LiCl) in an antecedent dose-response protocol and perfused for 10 minutes at each dose. Concentrations ranged from those thought to represent subtherapeutic amounts of Li (0.1 mM) to those which greatly exceed levels occurring in most overdose scenarios (10mM). Results: LiCl did not have any effect on left ventricular peak systolic pressure (95 mmHg), left ventricular end diastolic pressure (4.7 mmHg), heart rate (303 bpm) and coronary hemodynamics at concentrations from 0.1 to 10 mM. At 100 mM LiCl, left ventricular peak systolic pressure decreased from 95 mmHg to 78 mmHg. Heart rate decreased from 303 bpm to 178 bpm, while left ventricular end diastolic and coronary artery perfusion pressures were unaffected. Conclusions: These data demonstrate that cardiac function, hemodynamics and heart rate are not affected directly by LiCl at concentrations of 0.1 to 10 mM. Only at 100 mM LiCl, a concentration beyond that seen in even most large overdoses, were there negative inotropic and chronotropic effects.