Age-dependent vulnerability to ischemia-reperfusion injury of cyanotic myocardium in a chronic hypoxic rat model

This study evaluated the effects of chronic hypoxia from birth on the resistance of rat hearts to global ischemia, with special emphasis on the duration of hypoxia. Male Wistar rats were housed from birth for 4 weeks or 8 weeks either in a hypoxic environment (FiO₂ = 0.12) or in ambient air (8 animals for each group). Isolated rat hearts were perfused for 40 min with oxygenated Krebs-Henseleit buffer, subjected to 20 min global no-flow ischemia at 37°C, and then underwent 40 min of reperfusion. A non-elastic balloon was inserted into the left ventricle and inflated until the pre-ischemic LVEDP rose to 8mmHg. Cardiac function was measured before and after ischemia. The post-ischemic percent recovery of LVDP in hypoxic hearts was worse than in normoxic hearts (4 weeks: 55 ± 7 vs. 96 ± 3%, p< 0.01; 8 weeks: 40 ±5 vs. 92 ± 4%, p<0.01), and was worst in the 8-week-hypoxic hearts. Similarly, the percent recovery of +dP/dt in the hypoxic hearts was lower than in the normoxic hearts (4 weeks: 51 ± 5 vs. 96 ± 7%, p<0.01; 8 weeks: 31 ± 6 vs. 92 ± 7%, p<0.01, and was lowest in the 8-week-hypoxic hearts. In conclusion, cyanotic myocardium revealed an age-dependent vulnerability to isch-emia-reperfusion injury in a chronic hypoxic rat model.