CONICET | Buscador de Institutos y Recursos Humanos

The aim of this study was to determine the effects of isoespintanol (2-isopropyl-3,6-dimethoxy-5-methylphenol, ISO), isolated compound from leaves of Oxandra cf xylopioides, on ischemia-reperfusion injury. Isolated rat hearts perfused by Langendorff system were assigned to the following groups: 1. Non-ischemic control: 110 min of perfusion; 2.- Ischemic control (IC): 30 min of global ischemia (GI) and 60 min of reperfusion (R); 3.- ISO: 30 μg/ml ISO was administered during the first 10 min of R. To examine the mechanisms involved other hearts were treated with L-NAME (NOS inhibitor) or wortmannin (Akt inhibitor) or chelerythrine (PKC inhibitor) 10 min before ischemia. Infarct size was determined by TTC staining. Systolic and diastolic function was assessed by left ventricular developed pressure (LVDP) and the left ventricular end diastolic pressure (LVEDP), respectively. Coronary resistance (CR) was calculated as perfusion pressure and coronary flow ratio. The expression of phosphorylated form of endothelial NOS, Akt and PKCε was also measured. ISO significantly decreased the infarct size detected in IC group (11 ± 2 % vs. 31.0 ± 1.5%, p< 0.05) and improved post-ischemic recovery of myocardial function (LVPD: 63 ± 7 % vs. 17 ± 3%; LVEDP: 25 ± 5 vs. 52 ± 7 mmHg, p< 0.05). In IC, the level of P-eNOS, P-Akt and P-PKCε decreased approximately 45 % and after ISO treatment increased it (approximately 35 %). The increase of CR observed in IC group was significantly attenuated by ISO treatment (0.8 ± 0.2 vs. 3.3 ± 1 mmHg/ml x min-1).The administration of all the inhibitors abolished the effects detected in ISO treated hearts.The data show that acute treatment with ISO only at the onset of reperfusion decreased the infarct size and attenuated the post-ischemic myocardial contractility dysfunction and coronary resistance increase through Akt, PKCε and eNOS-dependent pathways.