Specific electromechanical responses of cardiomyocytes to individual and combined components of ischemia.

The main factors of myocardial ischemia are hypoxia, substrate deprivation, acidosis, and high extracellular potassium concentration ([K+]e), but the influence of each of these factors has not yet been evaluated in a cardiomyocyte (CM) culture system. Electromechanical responses to the individual and combined components of ischemia were studied in CM cultured from newborn rat ventricles. Action potentials (APs) were recorded using glass microelectrodes and contractions were monitored photometrically. Glucose-free hypoxia initially reduced AP duration, amplitude, and rate and altered excitation–contraction coupling, but AP upstroke velocity (max) remained unaffected. Early afterdepolarizations appeared, leading to bursts of high-rate triggered impulses before the complete arrest of electromechanical activity after 120 min. Acidosis reduced max, whereas AP amplitude and rate were moderately decreased. Combining acidosis and substrate-free hypoxia also decreased max but attenuated the effects of substrate-fr...