Hepatic ischemia models for determining the effects of ATP-MgCl2 treatment.

Although ATP-MgCl2 treatment after global hepatic ischemia has been shown to improve cell function, a recent report has failed to confirm this in a model of regional hepatic ischemia. To determine the reason for this, rats were anesthetized and blood vessels to the left and median lobes of the liver were occluded. After 90 min of ischemia, the ligature around those vessels was removed. In Model 1, blood flow to the right lobes of the liver was then occluded whereas in Model 2, flow to those lobes was left intact. In both models the rats received intravenously 1.0 ml of saline or ATP-MgCl2 (12.5 mumole each) after ischemia. One hour after reflow, hepatic blood flow in the right and/or left lobe was measured following which mitochondria from the respective lobes were isolated and their function measured. The results indicated that although ATP-MgCl2 infusion following hepatic ischemia significantly improved hepatic blood flow and mitochondrial function in Model 1 (in which the right lobes were ligated following release of the occlusion to the left and median lobes), it failed to do so in Model 2 (in which the right lobes were not occluded after release of the occlusion to the left and median lobes). These results emphasize the importance of the rapid restoration of blood flow following hepatic ischemia. In the presence of shunts such as occur in Model 2, it is unlikely that any therapeutic agent would be effective.