Inhibition of nitric oxide synthesis in ischemia/reperfusion of the rat liver is followed by impairment of hepatic microvascular blood flow

Koeppel, Thomas A.; Thies, Jochen; Schemmer, Peter; Trauner, Michael; Gebhard, Martha-Maria; Otto, Gerd; Post, Stefan

doi:10.1016/s0168-8278(97)80297-8

Cited by 74 publications

(49 citation statements)

References 19 publications

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“…Our data are compatible with recent evidence for some dependence of hepatic microvascular blood¯ow on nitric oxide after hepatic warm ischaemia and reperfusion injury (Kobayashi et al, 1995;Koeppel et al, 1997), with possible sites of action the endothelial and/or stellate (Ito) cells (Moncada et al, 1991;Rockey et al, 1995). Injury to these cells, like that to the vascular endothelium and Kuper cells, has been shown to increase progressively with the duration of ischaemia Ohno et al, 1994).…”

Section: Discussionsupporting

confidence: 92%

Evidence that S‐adenosyl‐L‐methionine diastereoisomers may reduce ischaemia‐reperfusion injury by interacting with purinoceptors in isolated rat liver

Dunne¹,

Berndt²,

Williams³

et al. 1998

British J Pharmacology

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Mechanisms underlying the haemodynamic activity of diastereoisomers of S‐adenosyl‐L‐methionine (SAM) were investigated using inhibitors of purinoceptors and nitric oxide (NO) synthase in perfused rat livers damaged by sequential 24 h cold and 20 min rewarming ischaemia+reperfusion. Stored livers were flushed with 10 ml saline alone (control) or with added (R,S) or (S,S) SAM (100 μM) and reperfused in the absence (control) or presence of 10 μM 8‐phenyltheophylline (8‐PT) or 100 μM L‐N‐monomethylarginine (L‐NMMA). Both SAM diastereoisomers rapidly increased blood flow and bile production versus controls (P<0.001) but the (R,S) isomer induced greater increases in blood flow and the (S,S) isomer greater increases in bile production: 625 versus 596 versus 518 ml blood flow and 100 versus 119 versus 56 mg bile production per g liver over 3 h in (R,S), (S,S) and control, respectively. 8‐PT prevented the enhancement of blood flow by (S,S) SAM (529 versus 596 ml g −1liver over 3 h for (S,S) SAM alone, P<0.001), but was without effect in control livers. 8‐PT also reduced SAM‐enhanced bile production: 51 versus 119 mg g −1liver over 3 h, P<0.001. L‐NMMA reduced blood flow and bile production similarly in the absence or presence of (S,S) SAM. Thus, SAM may improve liver perfusion after ischaemia‐reperfusion injury via stimulation of P1 (A2) purinoceptors at which SAM shows activity. The choleretic activity of (S,S) SAM is disproportionately greater than enhanced blood flow and may occur independently of a NO‐dependent component of bile production. British Journal of Pharmacology (1998) 125, 225–233; doi:10.1038/sj.bjp.0702043

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Section: Discussionsupporting

confidence: 92%

Evidence that S‐adenosyl‐L‐methionine diastereoisomers may reduce ischaemia‐reperfusion injury by interacting with purinoceptors in isolated rat liver

Dunne¹,

Berndt²,

Williams³

et al. 1998

British J Pharmacology

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“…Accordingly, Yu et al suggested that miR-223 is a more sensitive indicator of hepatic I/R injury than traditional liver function tests (ALT and AST). [26] Moreover, previous studies confirmed that propofol has a hepatoprotective effect through its role in reduction of free radical generation and free radical scavenging, dumping of inflammatory reactions. [32,33] It has inhibitory effects on calcium channels and diminution of intracellular calcium overload , improved microcirculation through reported induced nitric oxide (NO) and vasodilatory prostanoid production.…”

Section: Discussionmentioning

confidence: 95%

“…[25] As regard plasma miR-223; it functions as an important modulator of cellular differentiation, including dendritic cells and macrophage activation. [26] Furthermore, miR-223 influences the inflammatory response through activation of neutrophils and the secretion of inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs versus traditional biomarkers in predicting reperfusion injury in Hepatitis C Patients after major surgery

Demerdash

Arida

Zanaty

et al. 2018

APALM

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Background: Exposure to anesthesia in patients with chronic hepatitis C (CHC) may induce hepatic ischemia / reperfusion (I/R) with subsequent biochemical changes, provoked by alteration in molecular processes. This study explored miR-122 and miR-223 expression changes induced by anesthesia in CHC patients and their role in predicting hepatic I/R injury. Methods:This study included two hundered ASA II -III adult patients, scheduled for major surgery under general anesthesia. Patients were divided into 2 main groups; CHC patients group and non-hepatitis patients group. Each group was further divided into 2 equal subgroups (50 patients each) according to type of anesthesia received either Sevoflurane SC /S or Propofol PC/P ). Blood samples were analyzed for liver enzymes, prothrombin time, and serum lactate at several intervals; preoperative, 12 and 48 hours postoperative. Also, plasma miR-122 and miR-223 were estimated by Reverse Transcription PCR preoperative and 12 hours postoperative.Results: CHC groups showed significantly increased preoperative expression of both miR-122 and miR-223 compared to non-hepatitis groups (P<0.05). Moreover, postoperative samples revealed more exaggerated expression miR-122 and miR-223. Receiver operating characteristic curve (ROC) results revealed;values for area under the ROC for miR-122, miR-223, ALT and serum Lactate were 0.991, 0.965, 0.746 and 0.732 respectively. Based on the ROC finding, for prediction IR in CHC patients receiving anesthesia miR-122 had best Accuracy, sensitivity, and specificity. Conclusion:Our results suggested that both miR-122 and miR-223 could be regarded as more sensitive and specific biomarkers for predicting hepatic I/R injury than traditional biomarkers particularly in CHC patients undergoing major surgery.

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“…The beneficial effects of nitric oxide (NO) in the circulation and microcirculation have been widely documented [3,24,26,32,37]. Reports demonstrate its vasodilatory properties and its role in maintaining and regulating blood flow in healthy tissues [18,19].…”

Section: Introductionmentioning

confidence: 99%

Early iNOS impairment and late eNOS enhancement during reperfusion following 2.49 MHz continuous ultrasound exposure after ischemia

Hightower

Intaglietta

2009

Ultrasonics Sonochemistry

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Objective-Ischemia reperfusion (IR) injury, occurring during heart attacks, hemorrhagic shock, and bypass and transplant surgeries, impairs microcirculatory function and nitric oxide (NO) synthesis. We report the regulation of endothelial and inducible NO synthase (eNOS and iNOS) proteins as a consequence of the application of continuous mode diagnostic frequency ultrasound application following IR injury.Methods-Animals were assigned to one of 5 groups for microcirculatory assessment or western blot analysis (WB) as follows: 1) IR+iNOS inhibition (1400W); and 2) IR+1400W+ultrasound for microcirculatory assessment, 3) Control; 4) IR; and 5) IR+ultrasound for WB. Functional capillary density and microvascular diameter, flow velocity, and flow were monitored for microcirculatory assessment. Skin tissue samples were harvested for WB. 2.49 MHz continuous ultrasound was used for irradiation.Results-Both the inhibition of iNOS alone and iNOS inhibition with ultrasound irradiation positively influenced the microcirculation of observed animals relative to baseline values. Ultrasound exposure resulted in a significant production of eNOS protein in skin tissue harvested 24 h into reperfusion (p < 0.01). iNOS levels from the same tissue of irradiated animals were found to be significantly decrease 0.5 h into reperfusion (p < 0.05).Conclusion-Protection from lasting IR injury effects in the microcirculation, with continuous mode diagnostic frequency ultrasound, results from augmented eNOS levels during late reperfusion. Ultrasound inhibited iNOS production during early reperfusion may also confer protection from IR injury.

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Inhibition of nitric oxide synthesis in ischemia/reperfusion of the rat liver is followed by impairment of hepatic microvascular blood flow

Cited by 74 publications

References 19 publications

Evidence that S‐adenosyl‐L‐methionine diastereoisomers may reduce ischaemia‐reperfusion injury by interacting with purinoceptors in isolated rat liver

Evidence that S‐adenosyl‐L‐methionine diastereoisomers may reduce ischaemia‐reperfusion injury by interacting with purinoceptors in isolated rat liver

MicroRNAs versus traditional biomarkers in predicting reperfusion injury in Hepatitis C Patients after major surgery

Early iNOS impairment and late eNOS enhancement during reperfusion following 2.49 MHz continuous ultrasound exposure after ischemia

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