Direct Induction of Acute Lung and Myocardial Dysfunction by Liver Ischemia and Reperfusion

Weinbroum, Avi A.; Hochhauser, Edith; Rudick, Valery; Kluger, Yoram; Sorkine, Patrick; Karchevsky, Ela; Graf, Eran; Boher, Pnina; Flaishon, Ron; Fjodorov, Dimitri; Niv, David; Vidne, Bernardo A.

doi:10.1097/00005373-199710000-00011

Cited by 44 publications

(54 citation statements)

References 29 publications

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“…Oxygen stress may induce MOF, which is clinically significant. Data from this and previous studies [23,24,[29][30][31][32][33][34][35][36] suggest that a number of clinical features of renal dysfunction in the presence or following PNP may in fact be due to low flow/reflow situations, and thus may relate to XO-derived radical oxygen species (ROS) activity, as demonstrated herein for the C8 mmHg groups. We have previously described the toxic effects of high XO activity in the lungs [23].…”

Section: Discussionsupporting

confidence: 56%

“…We then argued that, when tissues are exposed to metabolic stress such as improper circulation or lack of oxygen-potentially occurring during PNP-tissue xanthine dehydrogenase (XDH) is converted to XO. Upon reperfusion or reoxygenation, the latter, in the presence of adequate substrates and abundant molecular oxygen influx into the post-hypoxic/ischemic tissue [36], generates oxidants such as the superoxide anion (O 2 -), hydrogen peroxide (H 2 O 2 ), and the hydroxyl radical (.OH) [34,37]. These cascades of events may start after the advent of tissue damage-here due to impediment to the vascular tree-even if followed by volume or pressure resuscitation, as demonstrated herein.…”

Section: Discussionmentioning

confidence: 99%

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Renal oxidative stress following CO2 pneumoperitoneum-like conditions

et al. 2008

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Background Physiologic renal changes associated with pneumoperitoneum (PNP) have been described and various underlying mechanisms have been suggested. We investigated the possibility that PNP-associated renal damage is pressure dependent, and that oxidative stress is thereby involved. Materials and methods Seventy Wistar rat kidneys (n = 10 per group) were isolated. They were perfused with oxygenated, warm, Krebs-Henseleit solution containing 5% albumin within an isolated environment and subjected to various CO 2 pressures (0 [control], 3,5,8,12,15, and 18 mmHg) for 60 min. Half of each group was additionally perfused for 30 min at 0 mmHg pressure.Results Renal flow decreased proportionately to the applied pressure as did urine output: both decreased (P \ 0.05) after 60 and 90 min when pressure C8 mmHg was applied. Oxygen extraction decreased (P \ 0.05) during PNP in all pressurized groups. Xanthine oxidase (XO) activity and reduced glutathione in the tissues increased (P \ 0.05) proportionately to pressures C8 mmHg. All parameters slightly reversed toward baseline values, upon the release of the intra-chamber pressure, except for the 18 mmHg group's values. Conclusions CO 2 -PNP pressure induces kidney injury, possibly reversible immediately after pressure is annulled. Pressure is associated with oxidative stress, which interferes with cellular metabolism and function, possibly via an ischemic-reperfusion-like mechanism.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Renal oxidative stress following CO2 pneumoperitoneum-like conditions

et al. 2008

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“…Hepatic ischemia has been documented to cause inflammatory lung injury. 5 In other studies, acute myocardial injury 6 and renal injury was attributed to hepatic ischemia.…”

Section: Introductionmentioning

confidence: 94%

Pretreatment with Pentoxifylline andN-Acetylcysteine in Liver Ischemia Reperfusion-Induced Renal Injury

et al. 2012

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“…Previous studies have shown that the hepatic IR injury is associated with injury to remote organs, such as the lungs (14,15) and kidneys (16,17). This may complicate the delineation of the effects of hepatic IR on the canalicular efflux transporters after in vivo administration of RH-123.…”

Section: Introductionmentioning

confidence: 99%

Effects of In Vivo Hepatic Ischemia-Reperfusion Injury on the Hepatobiliary Disposition of Rhodamine 123 and its Metabolites in Isolated Perfused Rat Livers

2012

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-Purpose.A few studies have shown that normothermic hepatic ischemia-reperfusion (IR) injury may affect the mRNA and/or protein levels of canalicular transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2). However, the effects of the injury on the functions of these canalicular transporters with respect to the biliary excretion of drugs remain largely unknown. Therefore, the purpose of this study was to investigate the effects of warm hepatic IR on the hepatobiliary disposition of rhodamine 123 (RH-123), a P-gp substrate, and its glucuronidated metabolite (RH-Glu), an Mrp2 substrate, in rats. Methods. Twenty four or 72 h following a 60-min partial ischemia or sham operation in rats, livers were isolated and perfused ex vivo with a constant concentration (~100 ng/mL) of RH-123. The concentration of RH-123 and its glucuronidated (RH-Glu) and deacylated (RH-110) metabolites were determined in the outlet perfusate, bile, and the liver tissue using HPLC, and relevant pharmacokinetic parameters were estimated. Results. Twentyfour-h IR caused a significant reduction in the hepatic extraction ratio of RH-123 (IR: 0.857 ± 0.078; Sham: 0.980 ± 0.017) and the biliary recovery of the parent drug and RH-Glu by 43% and 44%, respectively. The reductions in the biliary recovery were associated with significant reductions in the apparent biliary clearance of RH-123 and RH-Glu. Mass balance data showed that the formation of the glucuronidated or deacylated metabolite was not significantly affected by the 24-h IR injury. In contrast to the 24-h IR, the injury did not have any effect on the hepatobiliary disposition of RH-123 or its metabolites following 72 h of reperfusion. Conclusions. It is concluded that the pharmacokinetics of drugs that are subject to biliary excretion by the canalicular P-gp and Mrp2 transporters may be altered shortly after hepatic IR injury.

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Direct Induction of Acute Lung and Myocardial Dysfunction by Liver Ischemia and Reperfusion

Abstract: Ischemic and reperfused liver can directly induce myocardial and pulmonary dysfunction, presumably by oxidant-induced injury.

Cited by 44 publications

References 29 publications

Renal oxidative stress following CO2 pneumoperitoneum-like conditions

Renal oxidative stress following CO2 pneumoperitoneum-like conditions

Pretreatment with Pentoxifylline andN-Acetylcysteine in Liver Ischemia Reperfusion-Induced Renal Injury

Effects of In Vivo Hepatic Ischemia-Reperfusion Injury on the Hepatobiliary Disposition of Rhodamine 123 and its Metabolites in Isolated Perfused Rat Livers

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