Induction of kinetic cell death and its underlying mechanisms

Using a modified Langendorff system, we established an experimental model of kinetic cell death in the rat heart. After calcium (5.5 mM) was loaded for 20 min and 10(-7) mol isoproterenol was then delivered to the perfusion medium, the hearts developed tonic contracture. Histological examination of the myocardium revealed widespread kinetic cell death. Stimulation of alpha-adrenoceptors with phenylephrine did not induce kinetic cell death, even after calcium loading. In our kinetic cell death model in the rat, the outflow of creatine phosphokinase into the perfusion medium was increased after isoproterenol application, with a peak occurring at 45 min. The peak transient increase in the intracellular calcium ion concentration (the Ca-transient) was measured using Fura2/AM, and was found to be augmented by increasing the calcium concentration of the perfusion medium. These results suggest that in the presence of an increased intracellular calcium concentration, even slight stimulation of beta-adrenoceptors can easily induce myocardial injury.