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.

Mitochondrial distribution within the terminal neurite of the pacinian corpuscle.

Electron-microscopic analyses of the mitochondrial organization within the neurite innervating the Pacinian corpuscle (PC) were performed to test the hypothesis that the sites of mechanotransduction are the filopodia projecting from the neurite's surface. Since high concentrations of mitochondria imply the need for metabolic energy, and since transduction mechanisms are heavily dependent on such energy, it was reasoned that the greatest concentration of mitochondria should occur near the filopodia if they are involved in mechanotransduction. The analysis that the mitochondria lie close to the terminal neurite's membrane, on average within 0.4 microns, and thus are ideally located for supplying energy for membrane mechanisms. Although they can be found in a ring-like array, as seen in cross-sections of the terminal neurite, their greatest concentration occurs where the filopodia project from the terminal neurite. A linear algebraic analysis of the data set confirmed a high probability of the joint occurrence of a filopodial base and an increased frequency (number) of mitochondria. Thus the results provide further circumstantial support for the hypothesis that transduction within the PC mechanoreceptors takes place at or near the filopodia.