sodium-oxybate and Reperfusion-Injury

After cardiac surgery, transient renal dysfunction often occurs. The main reasons for impairment of renal function are intraoperative hypotension, ischemia/reperfusion injury and inflammatory response to cardiopulmonary bypass (CPB). Pentoxifylline is known to have anti-inflammatory properties. Gamma-hydroxybutyrate (GHB), an endogenous regulator of energy metabolism, showed beneficial effects on experimental intestinal ischemia/reperfusion injury and liver graft function. Both drugs may be of practical interest in diminishing renal damage during and after cardiac surgery. After approval by the ethics committee and informed consent, 45 patients for elective coronary artery bypass grafting with no clinical and laboratory impairment of renal function were randomized into 3 groups (15 patients each): group 1 received saline as control, group 2 received pentoxifylline intraoperatively (1 mg/kg/h after a priming dose of 1 mg/kg) and group 3 received GHB intraoperatively (25 mg/kg/h after a priming dose of 25 mg/kg) in a double-blinded fashion. During 3 periods (before CPB, from the beginning of CPB until the end of surgery, 24 hours postoperatively), glomerular (creatinine clearance, CCr) and tubular markers of renal function (beta-NAG, alpha 1-microglobulin) were detected in addition to clinical routine standards (creatinine, urea, fractional excretion of sodium). Changes in glomerular and in tubular function were comparable in all groups without characteristic effects of either GHB or pentoxifylline. With CPB, CCr decreased significantly until the end of operation, but showed a rise to preoperative levels on the first day after operation. Tubular function markers (beta-NAG, alpha 1-microglobulin, related to simultaneous excretion of creatinine) showed a remarkable rise after the beginning of CPB up to the postoperative period. The results of the present pilot study suggest the detection of tubular proteins and enzymes a useful addition to present routine clinical standards for recognizing early intraoperative changes in renal function. In the patients studied, there were no clinical signs of renal dysfunction. Neither GHB nor pentoxifylline--in the doses applied--was able to show a therapeutic benefit despite the theoretical advantages.

Topics: Aged; Cardiopulmonary Bypass; Coronary Artery Bypass; Female; Humans; Infusions, Intravenous; Kidney; Kidney Function Tests; Male; Middle Aged; Pentoxifylline; Postoperative Complications; Reperfusion Injury; Sodium Oxybate; Treatment Outcome

Ischemia-reperfusion (I/R) syndrome remains an important clinical consideration in hepatic surgery, hemorrhagic shock, and liver transplantation. gamma-hydroxybutyrate (GHB) has been reported to exert protective effects against ischemia-reperfusion injury to various organs. To investigate whether GHB protects the liver from warm ischemia-reperfusion injury, we performed this study in rats.. Thirty male Wistar rats were randomly divided into a sham-operation group, a control group,and three I/R groups pretreated with GHB, GHB plus naloxone or naloxone. After 30 minutes of partial ischemia, followed by 60 minutes of reperfusion in the liver, histomorphological and enzymological changes, lipid peroxidation, apoptosis, and the plasma level of endothelin-1 were observed.. I/R increased the serum levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase and the plasma level of endothelin-1 significantly (P<0.01), in addition to increase of apoptotic index (AI) from 0.28%+/-0.25% to 17.68%+/-1.91%. The levels of hepatic malondialdehyde were markedly increased, whereas the activities of superoxide dismutase were markedly decreased. GHB pretreatment prevented the liver from warm ischemia-reperfusion injury significantly, but naloxone partially blocked this effect.. GHB may significantly protect the liver from hepatic warm ischemia-reperfusion injury via several different mechanisms.

Topics: Anesthetics, Intravenous; Animals; Liver; Liver Diseases; Male; Models, Animal; Rats; Rats, Wistar; Reperfusion Injury; Sodium Oxybate

Polymorphonuclear leukocytes are thought to play a pivotal role in the generation of ischemia-reperfusion-induced mucosal injury; however, their behavior in the intestinal microvasculature following this injury has not been directly examined. In this study intravital microscopy was used to investigate the dynamics of blood flow and leukocyte behavior in the villus, serosal, and mesenteric microcirculation during ischemia-reperfusion in anesthetized hamsters. Thirty minutes of ischemia and 90 min of reperfusion resulted in almost complete microvascular stasis in the villi of control animals, whereas only a few serosal and mesenteric microvessels exhibited stasis. Following reperfusion, there was a significant increase in leukocyte accumulation in all three tissues; however, significantly fewer leukocytes adhered in the villus microvasculature than in the rest of either the mucosa, serosa, or mesentery. Treatment with gamma-hydroxybutyrate (GHB), a compound that we have previously demonstrated to be highly effective in preventing ischemia-reperfusion injury, significantly reduced both the microvascular stasis and leukocyte accumulation in all three vascular beds. This study demonstrates that there are significant differences in the response to ischemia-reperfusion in various intestinal layers and that areas most susceptible to damage are not necessarily those exhibiting the greatest leukocyte accumulation.

Topics: Animals; Cell Adhesion; Cricetinae; Intestinal Mucosa; Intestines; Jejunum; Leukocytes; Male; Mesocricetus; Microcirculation; Reperfusion Injury; Sodium Oxybate

The purpose of this study was to determine whether gamma-hydroxybutyrate provides protection against intestinal ischemia/reperfusion injury and to compare its effect with that of allopurinol and vitamin E. Thirty minutes of total regional ischemia, followed by 3 hours of reperfusion, produced intestinal damage that was completely prevented by gamma-hydroxybutyrate pretreatment. Naloxone partially blocked this protective effect. Allopurinol provided only partial protection against this injury, whereas vitamin E provided none. Treatment with gamma-hydroxybutyrate after ischemia but before reperfusion also provided significant protection. This study clearly demonstrates that gamma-hydroxybutyrate provides significant protection against intestinal ischemic injury and that it may do so via an opiate receptor-mediated mechanism.

Topics: Allopurinol; Animals; Cricetinae; Hydroxybutyrates; Intestines; Ischemia; Male; Mesocricetus; Naloxone; Reperfusion Injury; Sodium Oxybate; Vitamin E