Differences in the calcium-handling response of isolated rat and guinea-pig cardiomyocytes to metabolic inhibition: implications for cell damage

Species differences in response to hypoxic damage have been observed in stu dies using whole hearts. The aims of this study were to determine whether ( i) species differences in response to simulated hypoxia could be detected a t the level of the single myocyte, and (ii) there were any interspecies dif ferences in the Ca2+ handling properties of the cells. Ventricular myocytes were isolated from hearts of adult rats and guinea-pigs and electrically s timulated on the stage of a fluorescence microscope. Cell length was measur ed using an edge-tracking device, and total intracellular [Ca2+] ([Ca2+](i) ) determined using indo-1. Cells were exposed to metabolic inhibition (MI) (2.5 mM NaCN and no glucose) to simulate hypoxia followed by washout of CN and re-addition of glucose ('reperfusion'). Following exposure to Mi, rat c ells underwent rigor contracture in 18.8 +/- 0.8 min (n = 80 cells), wherea s the time was longer for guinea-pig cells (32.9 +/- 1.2 min, n = 83) (P < 0.001). If cells were reperfused after 1-5 min in rigor, then rat cells sho wed improved morphological recovery compared with guinea-pig cells (P < 0.0 5); thereafter recovery decreased with increasing time spent in rigor, and was similar in both groups. In indo-1 loaded cells, [Ca2+](i) was significa ntly increased in cells from both species at the end of MI; however, the ac tual increase was much higher in guinea-pig cells. Upon reperfusion, [Ca2+] (i), recovered Fully in rat cells, but in guinea-pig cells there was no sig nificant decrease. The restoration of [Ca2+](i) to normal levels in rat cel ls following MI was associated with improved contractile recovery compared with guinea-pig cells. We conclude that rat cells are more resistant to eff ects of Mi than are guinea-pig cells; this may be related to species differ ences in Ca2+ handling during and following exposure to MI.