Multiple-system organ damage resulting from prolonged hepatic inflow interruption.

Abstract

BACKGROUND: It has been reported that patients undergoing major hepatectomy tolerated 90 and 127 minutes of continuous hepatic inflow interruption with no evidence of permanent damage to the liver. We questioned the safety and feasibility of the interruption beyond 90 minutes in normothermic human beings. We also postulated that, besides injury to the liver per se, extended continuous hepatic inflow interruption would cause extrahepatic multiple-system organ damage in subjects exposed to continuous hepatic inflow interruption for 90 or 120 minutes. DESIGN: Fifty Sprague-Dawley rats were divided into three groups. Group 1 served as controls that had only laparotomy. Group 2 underwent continuous hepatic inflow interruption for 90 minutes, and group 3 was subjected to continuous hepatic inflow interruption for 120 minutes. Scanning electron microscopy and transmission electron microscopy were used to evaluate ultrastructural alterations in the liver, lung, heart, and intestine. SETTING: Lund (Sweden) University Hospital and Top Cancer Institute, Lund. INTERVENTIONS: Intraoperative and postoperative infusion and blood transfusion were given in all experimental animals. MAIN OUTCOME MEASURES: Animal survival and manifestations of multiple-system organ failure. RESULTS: In rats with continuous hepatic inflow interruption for 90 or 120 minutes, scanning electron microscopy showed a necrotic surface of the liver cells together with fibrin exudation. Hepatic sinusoids and intrahepatic nerves also had severe injury. Destruction of pulmonary structures and breakdown of microcirculation in the lung were characterized by thinned and ruptured walls of alveoli and a greatly decreased number of capillaries in the damaged alveolar wall. Transmission electron microscopy showed four types of ultrastructural changes, ie, necrosis of epithelial cells, extremely swollen mitochondria in intestinal cells, death of mucosal cells, and increased permeability of vessels in the injured intestine. The affected heart manifested highly enlarged mitochondria in myocardial cells, thickened vascular walls, and scattered necrotic lesions in myocardial tissue. CONCLUSIONS: Multiple-system organ failure resulting from ischemia-reperfusion injury and obstacle of portal hemodynamics in a subject subjected to an extended continuous hepatic inflow interruption is an unrecognized new disorder that may cause a high mortality rate. Our preliminary results indicated that animals subjected to continuous hepatic inflow interruption for 90 or 120 minutes developed various injuries to the liver, lung, heart, and gut. Therefore, we believe that continuous hepatic inflow interruption exceeding 90 minutes could also be hazardous in human beings.