Antioxidant UPF1 attenuates myocardial stunning in isolated rat hearts

Oxidative stress is a crucial pathophysiological mechanism of myocardial ischaemia-reperfusion injury (IRI). We evaluated the cardioprotective effects of a novel glutathione analogue, UPF1 (4-methoxy-L-tyrosinyl-gamma-L-glutamyl-L-cysteinyl-glycine; MW 483.5), on an isolated rat heart model of thirty-minute global ischaemia followed by 90 min of reperfusion. Treatment with UPF1 (1 mg/ml) prior to ischaemia improved the recovery of post-ischaemic left ventricular end-diastolic pressure (p=0.046), developed pressure (p=0.002) and coronary flow (p=0.01). No protective effect was observed when the hearts were treated with UPF1 after ischaemia. Administration of UPF1 had no influence upon infarct size or enzyme leakage from the heart. The results suggest that glutathione analogue type of biomolecules could possess a therapeutic potential in clinical situations where myocardial IRI is presented as myocardial stunning rather than tissue infarction.