Magnesium sulfate solution dramatically improves immediate recovery of rats from hypoxia

Abstract

This study in rats investigated the effects of 0.5 mEq/1 kg body weight of magnesium sulfate solution upon hypoxic left cardiac ventricular pressure (Part 1), optimal timing for injection of magnesium sulfate solution for successful resuscitation (Part 2) and survival benefits of magnesium sulfate after 8 or 12 min of hypoxia (Part 3) in rats resuscitated by single bolus arterial reperfusion using 2 ml of arterial blood and 6–9 μg epinephrine. A total of 153 pentobarbital anesthetized rats were subjected to 8 or 12 min 0.75% O 2:99.25% N 2 hypoxia in order to induce cardiac arrest. In Part 1, 13 rats (six control and seven injected with magnesium sulfate solution) were subjected to 12 min hypoxia and cardiac left ventricular pressure (LVP) was measured. In Part 2, 47 rats were exposed to 12 min of hypoxia. Normal saline or magnesium sulfate solution was injected prior to hypoxia, at 2 or 4 min of hypoxia, to find the optimal timing of magnesium sulfate injection for successful resuscitation by arterial reperfusion. In Part 3, 90 rats were studied to determine 7-day survival. Two control groups were injected with saline during 8 min (29 rats) or 12 min (18 rats) of hypoxia and two groups received magnesium sulfate solution during 8 min (14 rats) and 12 min (29 rats) of hypoxia. Magnesium sulfate fully reversed the hypoxic increase of LVP and improved survival after 12 min of hypoxia from approximately 15 (control) to 100% if given during the first 2.5 min of hypoxia. The main cause of the progressive resuscitation failure after 8 or 12 min control hypoxia was a progressive increase in acute cardiac failure. Although magnesium sulfate solution significantly improved immediate recovery after hypoxia (8 and 12 min), mortality due to reperfusion injury (para or tetraplegia) was observed in 62% of rats surviving longer than 1 day after 8 min and 100% after 12 min hypoxia (in control rats—50 and 100%, respectively). The overall survival after hypoxia, with or without reperfusion injury, was relatively low: 28% in control groups after 8 min and 17% after 12 min. In the magnesium sulfate groups these numbers were only slightly higher, 36 and 21%, respectively. It is concluded that in conjunction with arterial reperfusion magnesium sulfate infusion is very effective in improving acute cardiac recovery after 8–12 min of hypoxia. The likely mechanism of magnesium sulfate action is decreased incidence of ventricular fibrillation (VF) and asystole, and possibly myocardial relaxation during and after hypoxia, a property which may qualify MgSO 4 as an ischemic preconditioning agent. Poor long-term survival rates of rats exposed to hypoxia and resuscitated by intraarterial reperfusion do not support its use in resuscitation.