Species differences in vulnerability to injury by oxidant stress: a possible link with calcium handling?

Abstract

The aim was to exploit species- and age dependent differences in calcium handling to assess the role of calcium as a mediator of oxidant stress induced injury in the mammalian heart. Hearts from immature and mature rats and rabbits were perfused aerobically with buffer containing rose bengal which was photoactivated by illumination--a process that generates singlet oxygen and superoxide. This oxidant stress rapidly leads to electrocardiographic abnormalities, ultrastructural injury, and a redistribution of calcium. Isolated perfused hearts from mature (60-90 d old) and immature (4-6 d old) rats, and mature (60-90 d old) and immature (7-10 d old) rabbits. In hearts (n = 6 per group) from mature rats, aerobic perfusion and photoactivation for 5 min with buffer containing rose bengal (250 and 1000 nmol.litre-1) had no significant effect upon heart rate (until the onset of arrhythmias) but did result in a dose dependent transient increase in coronary flow. ECG abnormalities appeared within less than 30 s and these deteriorated to ventricular premature beats (VPB) and ventricular tachycardia (VT) in most hearts. By contrast, in identical studies with comparable sized hearts from young rabbits, ECG changes and arrhythmias occurred later, and the incidence of VT and the mean number of VPB were lower. Although arrhythmias were less severe in rabbit hearts, photoactivation of rose bengal caused both coronary flow and heart rate to fall in a dose dependent manner. Increasing the concentration of rose bengal to a value (2500 nmol.litre-1), which would be highly toxic in the rat heart, increased the severity of injury in the rabbit heart, the nature of which differed from that in the rat heart. To assess whether developmental state, as opposed to species, was a factor determining the differences in vulnerability to injury, hearts from immature rats and adult rabbits were perfused with various concentrations of rose bengal (250-2500 nmol.litre-1) with the intensity of illumination (1400-6600 Lux) adjusted to account for the size of the heart. Under these conditions rabbit hearts were found to be less vulnerable to injury and arrhythmias than rat hearts, and hearts from immature rats were found to be less vulnerable than those from adult rats. The results of this and other studies suggest that species and developmental differences in calcium handling (sarcolemmal v sarcoplasmic reticulum control) might explain the differences in vulnerability to arrhythmias.