Calcium induced the damage of myocardial mitochondrial respiratory function in the early stage after severe burns

Objective: To explore the role of Ca2+ in the damage to myocardial mitochondrial respiratory function in the early stage after severe burns. Methods: An experimental model of 30%TBSA full-thickness skin scalding was reproduced in rats. Myocardial mitochondria were isolated from control and burned rats in the 1st, 3rd, 6th, 12th and 24th hour post-burn. The mitochondrial respiratory function, contents of mitochondrial calcium ([Ca2+]m), activities of mtPLA2, mtNOS, F0F1-ATPase and cytochrome c oxidase were determined. Results: (1) At the 1st hour post-burn, [Ca2+]m was increased significantly and the myocardial mitochondrial respiratory function was significantly reinforced. At the same time, mitochondrial respiratory control rate (RCR) was elevated and positively correlated with [Ca2+]m (r=0.8415, P<0.01). At the 3rd, 6th, 12th and 24th hour post-burn, [Ca2+]m increased further to a higher level, however, the mitochondrial respiratory function was decreased from the peak value at 6 h, and RCR was negatively correlated with [Ca2+]m. (2) The activities of mtNOS and mtPLA2 were higher significantly at the 3rd, 6th, 12th and 24th hour post-burn than that of the control. After severe burns, mtNOS and mtPLA2 activities were both positively correlated with [Ca2+]m (r=0.8945, P<0.05; r=0.9271, P<0.01, respectively). (3) The F0F1-ATPase synthetic activity increased at the 1st hour post-burn, but it decreased to 51.4, 44.9, 77.6 and 87.4% of that of the control at the 3rd, 6th, 12th and 24th hour post-burn respectively. The F0F1-ATPase hydrolytic activity decreased at the 1st hour post-burn and increased at the 3rd, however, it decreased again at the 6th, 12th and 24th hour post-burn. The activity of cytochrome c oxidase at the 3rd, 6th, 12th and 24th hour was low compared to the control. Conclusions: The changes of [Ca2+]m were involved in damage to or regulation of mitochondrial respiratory function after severe burns. Appropriate increase of [Ca2+]m reinforced the mitochondrial respiration at 1st hour after of burn injury, but Ca2+ severe overload impairing F0F1-ATPase and cytochrome c oxidase directly, or, indirectly by activation of mtPLA2 and mtNOS, might play an important role in damage to myocardial mitochondrial respiratory function at later stages after severe burns.