Studies on the mechanism of beneficial effects of ATP-MgCl2 following hepatic ischemia.

Abstract

Infusion of ATP-MgCl2 following hepatic ischemia significantly improves the survival of animals. To determine the subcellular effects of infused ATP-MgCl2 and whether such effects are mediated through vasodilatation, global hepatic ischemia in rats was produced for 90 min followed by reperfusion. The rats then received iv 0.5 ml of saline, dopamine, papaverine, or ATP-MgCl2. At various intervals following reflow, hepatic mitochondria were isolated. ADP-to-O ratio and respiratory control ratio (RCR) were significantly lower 1 h following reflow, and there was a further decrease in these parameters 3 h after reflow in mitochondria from saline-treated rats. Dopamine and papaverine treatment did not improve RCR, however, ATP-MgCl2 treatment resulted in a progressive and significantly higher ADP/O and RCR following reflow. Hepatic ATP levels in saline, dopamine, and papaverine-treated rats were found to be 50% lower 3 h following reflow, however, treatment with ATP-MgCl2 resulted in significantly higher ATP levels and energy charge. Hepatic blood flow was markedly depressed 1 h following reflow in the saline-treated rats but was significantly higher in the ATP-MgCl2 group. Three hours following reflow, hepatic blood flow decreased further in the saline-treated rats, whereas in the ATP-MgCl2-treated rats there was a progressive increase in flow. Dopamine treatment resulted in an initial restoration in flow, however, this effect was not sustained. Hepatic ultrastructure deteriorated progressively following reflow in the saline-treated rats, however, it was normal in the ATP-MgCl2-treated rats 1 h as well as 20 h following reflow. These results lead us to conclude that infused ATP-MgCl2 improves mitochondrial and cellular functions either directly or by way of long-term improvement in microcirculation but not through vasodilatation.