ATP-MgCl2 produces sustained improvement in hepatic mitochondrial function and blood flow after hepatic ischemia.

Abstract

Recent studies have shown that infusion of ATP-MgCl2 following hepatic ischemia significantly improved mitochondrial function and hepatic blood flow 1 hr after treatment. To determine if the improvement in the above parameters by ATP-MgCl2 is short-lived or whether it persists for prolonged periods of time after treatment, hepatic ischemia in rats was produced for 90 min followed by reperfusion. The rats then received iv 0.5 ml of saline or ATP-MgCl2 (12.5 mumole each). Twenty-four hours after reflow, hepatic blood flow was measured by H2 polarography following which the animals were sacrificed and hepatic mitochondria isolated. The results indicated that 24 hr after reflow, mitochondrial state 3 respiration, respiratory control ratio, adenine nucleotide translocase activity, ATP synthetic activity, and hepatic blood flow were depressed by approximately 50% in animals which were treated with saline after hepatic ischemia. In addition, there was a fourfold increase in mitochondrial free fatty acid levels of such animals. Animals which were treated with ATP-MgCl2 following hepatic ischemia showed significantly improved mitochondrial function (used as an index of cellular recovery) and hepatic blood flow. These results in conjunction with previous results suggest that infused ATP-MgCl2 improves mitochondrial function and blood flow and that these effects persist even 24 hr after administration of ATP-MgCl2. Thus, infusion of ATP-MgCl2 following severe ischemia produces sustained improvement in cellular function.