Differential effects of endothelin-1 on isolated working rat hearts before and after ischaemia and reperfusion.

Endothelin (ET) may have both detrimental (reduced coronary flow) and beneficial effects (positive inotrope, reduced arrhythmogenesis) following ischaemia. We examined the effects of ET on cardiac function during reperfusion following prolonged hypothermic cardioplegic arrest in a protocol mimicking cardiac transplantation. Isolated working rat hearts were perfused with Krebs buffer to which increasing concentrations of ET-1 or sarafotoxin S6c had been added. Identical experiments were performed after 4 h of cardioplegic arrest at 4 degrees C. Under pre-ischaemic conditions ET-1 caused a dose-dependent decrease in cardiac function compared with controls. In contrast, following ischaemia low doses of ET-1 (10(-10) M) caused a significant and beneficial increase in cardiac output (109.1% versus 81.3%), dP/dt i.e. the rate of change of pressure with time (94.7% versus 75.6%) and stroke volume (100.3% versus 77.5%) compared with controls (P<0.05). At higher doses of ET-1 there was a detrimental effect on cardiac output, dP/dt and stroke volume similar to that seen prior to ischaemia. Sarafotoxin S6c had no significant effect pre or post ischaemia on any of the parameters measured compared with controls (P=not significant). ET-1 at low concentrations during reperfusion can improve the recovery of cardiac function mediated via ET(A) receptors. ET may play an important physiological role in the recovery of cardiac function following prolonged ischaemia.

The effect of chronic L-arginine administration on vascular recovery following cold cardioplegic arrest in rats.

OBJECTIVE: Acute administration of L-arginine (LA), the physiological substrate of nitric oxide, has been used as a strategy for myocardial protection during ischemia-reperfusion. The aim of this study was to assess the effects of chronic oral LA administration on vascular functions and morphology after prolonged cold cardioplegic arrest. METHODS: Adult male Sprague-Dawley rats (600-650 g) were divided into control and LA groups, which received LA (4 mg/ml) for 6 weeks. Two experimental protocols were carried out. (1) Isolated rat heart perfusion was performed and hearts were subjected to ischemia for 4 h at 4 degrees C using cold crystalloid cardioplegia (n=8 in LA, n=7 in control). Endothelial and vascular smooth muscle functions were assessed through observations of pre- and post-ischemic coronary flow response to 5-hydroxytryptamine (5-HT) and glyceryl trinitrate (GTN) (%5-HT and %GTN, respectively). (2) Semi-quantitative assessment of tissue morphology was conducted after the same ischemia-reperfusion protocol (n=4 in each group). RESULTS: The LA group showed significantly better recovery (post-/pre-ischemic value) of %5-HT (97.0+/-65.6 versus 21.5+/-25.7%, P=0.015) and %GTN (124.5+/-117.6 versus 47.7+/-16.6%, P=0.021). The histological assessment showed no significant differences between the two groups. CONCLUSIONS: Chronic oral administration of LA significantly ameliorated the postischemic recovery of endothelial and vascular smooth muscle functions after cold cardioplegic arrest in rats.