D Wang1, K Dou, Z Song, Z Liu. 1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changlexi Street, Xi'an, Shaanxi Province, PR China. wangdesh@163.com
Abstract
BACKGROUND: Na+/H+ exchanger (NHE) is one of the major mechanisms for restoring pH after ischemia-induced intracellular acidosis. However, activation of NHE during ischemia and reperfusion (I/R) is also involved in the paradoxical induction of cell injury. This study was designed to evaluate the effects of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), an NHE inhibitor, on hepatic I/R injury. METHODS: Partial hepatic ischemia was induced in male Wistar rats by cross-clamping the hepatic arterial and portal venous branches to the left lateral and median lobes of the liver for 120 minutes. The caudate and right lateral lobes were removed immediately after reperfusion. The concentrations of serum enzymes and ATP levels and energy charge in the live tissue were examined after 1-hour reperfusion. RESULT: EIPA afforded considerable protection against I/R injury, as demonstrated by decreased transaminase release and reduced histologic hepatocyte damage and increased energy charge. The 7-day survival rate was significantly improved from 15.4% to 55.6% (P <.05). CONCLUSIONS: This study shows for the first time that NHE may play an important role in the hepatic I/R injury and that EIPA should be considered as a new therapeutic approach to prevent hepatic I/R injury.
BACKGROUND: Na+/H+ exchanger (NHE) is one of the major mechanisms for restoring pH after ischemia-induced intracellular acidosis. However, activation of NHE during ischemia and reperfusion (I/R) is also involved in the paradoxical induction of cell injury. This study was designed to evaluate the effects of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), an NHE inhibitor, on hepatic I/R injury. METHODS: Partial hepatic ischemia was induced in male Wistar rats by cross-clamping the hepatic arterial and portal venous branches to the left lateral and median lobes of the liver for 120 minutes. The caudate and right lateral lobes were removed immediately after reperfusion. The concentrations of serum enzymes and ATP levels and energy charge in the live tissue were examined after 1-hour reperfusion. RESULT: EIPA afforded considerable protection against I/R injury, as demonstrated by decreased transaminase release and reduced histologic hepatocyte damage and increased energy charge. The 7-day survival rate was significantly improved from 15.4% to 55.6% (P <.05). CONCLUSIONS: This study shows for the first time that NHE may play an important role in the hepatic I/R injury and that EIPA should be considered as a new therapeutic approach to prevent hepatic I/R injury.
Authors: Karen S Uray; Shinil K Shah; Ravi S Radhakrishnan; Fernando Jimenez; Peter A Walker; Randolph H Stewart; Glen A Laine; Charles S Cox Journal: Surgery Date: 2011-01 Impact factor: 3.982