Alterations in cellular calcium and magnesium during circulatory/septic shock

Hepatic cellular and mitochondrial Ca2+ and Mg2+ contents and the role of these ions in cellular dysfunction were studied in rat hemorrhagic and endotoxic models which simulate various facets of human circulatory/septic shock states. Hemorrhagic shock was induced by bleeding rats to a state of vascular decompensation at the mean arterial pressure of 40 mm Hg. Endodotoxic shock was ascertained after observing hypoglycemia, hyperlacticacidemia and hemorrhagic bowel lesions in rats injected with Salmonella enteritidis endotoxin (15-20 mg/kg). In a late stage of hemorrhagic shock, significant changes occurred in mitochondrial ion contents; Ca2+ increased and Mg2+ decreased as compared to controls. These ionic changes were correlated with depressed mitochondrial respiratory functions. Addition of 6 mM Mg2+ to shocked-rat isolated mitochondria significantly restored mitochondrial functions. In endotoxic shock, hepatic Mg2+ content was significantly lower compared to controls. Treatment of rats with the calcium antagonist, diltiazem, several minutes prior to endotoxin injections, resulted in restoration of hepatic cellular Mg2+ to control levels. Studies of hepatic intracellular Ca2+ regulation in endotoxic shock revealed (1) an elevation in free cytosolic Ca2+, (2) a blunting of catecholamine-mediated increase in cytosolic Ca2+ and (3) an inhibition of intracellular messenger-induced Ca2+ release by the endoplasmic reticulum.