e0028 The effect of acute activation of ALDH2 on myocardial ischaemia/reperfusion injury in rat

Background Our previous study combined several animal experiments conducted recently showed aldehyde dehydrogenase-2 (ALDH2) was correlated with myocardial ischaemia/infarction injury. But whether ALDH2 is beneficial was controversial. We speculated the way in which the ALDH2 activity was changed may be chiefly responsible for the controversy. Objective To investigate the effect of acute activation of ALDH2 on myocardial ischaemia/reperfusion injury in rat. Methods 20 male Sprague-Dawley rats were divided into five groups:sham group (n=3); control group (n=4) :occlusion of the left anterior descending coronary artery (30 min) followed by reperfusion (15 min); ethanol group (n=5):intraperitoneal injection of ethanol (0.5 g/kg) 60 min prior to ischaemia; GTN-ON group (n=3):18 h persistent nitroglycerin treatment (0.1 mg/h, delivered by a patch) combined with intraperitoneal injection of ethanol (0.5 g/kg) 60 min prior to ischaemia; GTN-OFF group (n=5):persistent nitroglycerin treatment but terminated at least 4 h before ischaemia combined with intraperitoneal injection of ethanol (0.5 g/kg). Cardiac mitochondria was isolated after reperfusion. Three parameters were measured: (1) serum CK activity before ischaemia and after reperfusion; (2) after incubation with fluorescent probe JC-1, Δψ of isolated mitochondrial was evaluated by fluorometer and fluorescent microscope; (3) ALDH2 activity was determined spectrophotometrically by monitoring the reductive reaction of NAD+ to NADH at 340 nm. Results (1) Ethanol treatment caused a 27% increase in ALDH2 activity relative to control (2.74±0.37 and 2.15±0.46, p=0.044); Treatment with persistent nitroglycerin decreased ALDH2 activity by 27% compared with ethanol treatment (2.00±0.47 and 2.74±0.37, p=0.024). There was no statistical difference in ALDH2 activity between GTN-ON and control group (2.00±0.47 and 2.15±0.46, p=0.642). (2) Δψ in cardiac myocytes in ethanol group and GTN-OFF group were 2.8 and 2.4 times higher than that in control respectively. Δψ in cardiac myocytes in GTN-ON group was reduced by 51% (119.33±10.21 and 242.20±52.18, p=0.006) and 42% (119.33±10.21 and 204.00±86.17, p=0.045) than that in ethnol and GTN-OFF group respectively. (3) Cardiac damage was reduced by 39% (0.37±0.20 and 0.61±0.12, p=0.029) and 41% (0.36±0.10 and 0.61±0.12, p=0.031) in ethnol group and GTN-OFF group compared with that in control. Conclusions Acute activation of ALDH2 reduced myocardial ischaemia/reperfusion injury possibly by preserving Δψ.