Changes in the incidence and duration of ventricular fibrillation in dependence on the extraneuronal accumulation of isoprenaline in the perfused rat heart

Summary The relationship between the accumulation of isoprenaline and the incidence and duration of ventricular fibrillation was investigated in the perfused rat heart. Isolated rat hearts were perfused with ³H-isoprenaline (1 mol/l) for 30 min at a constant flow rate of 6.5 ml/min at a temperature between 40 and 41° C. Electrocardiograms were recorded during the perfusion period and the isoprenaline content of the tissue was measured after the perfusion. The accumulation of isoprenaline was significantly increased and the duration of ventricular fibrillation was significantly prolonged by the presence of tropolone (100 mol/l). When extraneuronal uptake inhibitors such as normetanephrine (100 mol/l), 3-O-methylisoprenaline (100 mol/l) or phenoxybenzamine (1 mol/l) were added to the perfusion fluid containing ³H-isoprenaline (1 mol/l) and tropolone (100 mol/l), the accumulation of isoprenaline was sifnificantly decreased, the incidence of ventricular fibrillation was significantly reduced and the duration of ventricular fibrillation was significantly shortened. There was a significant correlation for dependence of duration of ventricular fibrillation on the isoprenaline content of rat hearts perfused with various extraneuronal uptake inhibitors in the presence of tropolone (correlation coefficient r]=0.62, P<0.001).These results indicate that the accumulation of isoprenaline in perfused rat hearts relates to the occurrence and duration of ventricular fibrillation.This study was supported in part by a Grant-in-Aid for Scientific Research (59570980) from the Ministry of Education, Science and Culture, Japan