Mechanisms of cardioprotective effects of magnesium on hypoxia-reoxygenation-induced injury

摘要

During cardiac ischemia or hypoxia, increased levels of extracellular Mg show cardioprotective effects. The mechanisms of high level Mg-induced cardioprotection were examined in Langendorff perfused rat hearts. In the control group (1.2 mM Mg during hypoxia), the recovery of the left ventricular developed pressure (LVDP) after 30 min of reoxygenation was 57.6±3.0% of the level observed before hypoxia. In the high Mg group (12 mM Mg during hypoxia), the time course of recovery was faster than in the control group; the recovery level of LVDP improved to 78.4±4.2%. This protective effect of high levels of Mg decreased to 69.0±3.6% with the application of 5-hydroxydecanoic acid (100 μM), a specific mitochondrial ATP-sensitive potassium channel (KATP) blocker. In the low Ca group (0.2 mM Ca during hypoxia), the recovery of LVDP did not reach the level observed in the high Mg group (64.7±5.9%), but with application of diazoxide, a specific mitochondrial KATP channel opener, the LVDP recovery improved to 81.8±11.1%, similar to the level observed in the high Mg group. These results suggest that cardioprotective effects of high levels of extracellular Mg during hypoxia occur not only due to energy conservation and/or by intracellular prevention of Ca²⁺ over-load, but also by opening of the mitochondrial KATP channel.