Plasma membrane disruption is a characteristic feature of cell death induced by hypoxia or ischemia. Here, we investigated whether analysis of tissue electrical impedance allows detection of on-going cell membrane rupture and necrotic cell death in hypoxic or ischemic myocardium. Twenty-eight isolated rat hearts were submitted to 5 h of ischemia (n=8) or hypoxia (n=20). Myocardial electrical impedance and LDH release were monitored. The time-course of hypoxia-induced cell death was modified by altering pH (pH 7.4 or 6.4, 5 h), or by adding glycine 3-10 mM. Ischemia and hypoxia induced an increase in electrical impedance, followed by a plateau, and later by a reduction. During hypoxia, LDH release started after a prolonged lapse of time (80.00±8.37 min at pH 7.4 and 122.50±11.82 at pH 6.4). The onset of LDH release was followed by the onset of the late reduction in electrical impedance, and both were delayed by acidic pH (p<0.05) and by glycine (p<0.05). The time of onset of LDH release and of late electrical changes were significantly correlated (r=0.752, p<0.001). In separate experiments, induction of sarcolemmal rupture with Triton X-100 (n=6)mimicked the late effects of ischemia or hypoxia on tissue impedance. The protective effects of glycine and acidosis on membrane disruption were confirmed (propidium iodide) in energy-deprived HL-1 cardiomyocytes. These results describe for the first time a late fall in electrical impedance in myocardium submitted to prolonged oxygen deprivation, and demonstrate that this fall allows detection of on-going cell necrosis.