Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis

Koti, Rahul; Yang, Wenxuan; Glantzounis, Georgios K.; Quaglia, Alberto; Davidson, Brian R; Seifalian, Alexander M.

doi:10.1042/cs20040130

Cited by 30 publications

(32 citation statements)

References 52 publications

(59 reference statements)

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“…Two studies with rat models of IR-induced liver injury have shown that IPC has some protective effect against IR injury in fatty livers, possibly by reducing necrosis and improving hepatic circulation (4,131). In a subgroup analysis of patients undergoing major liver resection with or without IPC, obese patients with fatty livers seem to benefit the most from IPC (102).…”

Section: From Those Of Normal Livers?mentioning

confidence: 97%

Hepatic Ischemia-Reperfusion Injury: Roles of Ca2+ and Other Intracellular Mediators of Impaired Bile Flow and Hepatocyte Damage

et al. 2006

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Liver resection and liver transplantation have been successful in the treatment of liver tumors and end-stage liver disease. This success has led to an expansion in the pool of patients potentially treatable by liver surgery and, in the case of transplantation, to a shortage of liver donors. At present, there are significant numbers of potential candidates for liver resection and liver donation who have fatty livers, are aged, or have livers damaged by chemotherapy. All of these are at high risk for ischemic reperfusion (IR) injury. The aims of this review are to assess current knowledge of the clinical effectiveness of ischemic preconditioning and intermittent ischemia in reducing IR damage in liver surgery; to evaluate the use of bile flow as a sensitive indicator of IR liver damage; and to analyze the molecular mechanisms, especially intracellular Ca2+, involved in IR injury and ischemic preconditioning. It is concluded that bile flow is a sensitive indicator of IR injury. Together with reactive oxygen species (ROS) and other extracellular and intracellular signaling molecules, intracellular Ca2+ in hepatocytes plays a key role in the normal regulation of bile flow and in IR-induced injury and cell death. Ischemic preconditioning is an effective strategy to reduce IR injury but there is considerable scope for improvement, especially in patients with fatty and aged livers. The development of effective new strategies to reduce IR injury will depend on improved understanding of the molecular mechanisms involved, especially by gaining a better perspective of the relative importance of the various intrahepatocyte signaling pathways involved.

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Section: From Those Of Normal Livers?mentioning

confidence: 97%

Hepatic Ischemia-Reperfusion Injury: Roles of Ca2+ and Other Intracellular Mediators of Impaired Bile Flow and Hepatocyte Damage

et al. 2006

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“…7,8 There is some evidence in isolated hepatocytes and experimental models of perfused liver that mitogen-activated protein kinases (MAPKs) are involved in the protective mechanisms of ischemic preconditioning. 9,10 Signaling pathways involved in HSP induction include MAPKs.…”

Section: 4mentioning

confidence: 99%

Heat Shock Proteins and Mitogen-activated Protein Kinases in Steatotic Livers Undergoing Ischemia-Reperfusion: Some Answers

Massip-Salcedo

Casillas-Ramírez

Franco-Gou

et al. 2006

The American Journal of Pathology

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Ischemic preconditioning protects steatotic livers against ischemia-reperfusion (I/R) injury, but just how this is achieved is poorly understood. Here, I/R or preconditioning plus I/R was induced in steatotic and nonsteatotic livers followed by investigating the effect of pharmacological treatments that modulate heat shock proteins (HSPs) and mitogen-activated protein kinases (MAPKs). MAPKs, HSPs, protein kinase C, and transaminase levels were measured after reperfusion. We report that preconditioning increased HSP72 and heme-oxygenase-1 (HO-1) at 6 and 24 hours of reperfusion, respectively. Unlike nonsteatotic livers, steatotic livers benefited from HSP72 activators (geranylgeranylacetone) throughout reperfusion. This protection seemed attributable to HO-1 induction. In steatotic livers, preconditioning and geranylgeranylacetone treatment (which are responsible for HO-1 induction) increased protein kinase C activity. HO-1 activators (cobalt(III) protoporphyrin IX) protected both liver types. Preconditioning reduced p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in HSP72 induction though HO-1 remained unmodified. Like HSP72, both p38 and JNK appeared not to be crucial in preconditioning, and inhibitors of p38 (SB203580) and JNK (SP600125) were less effective against hepatic injury than HO-1 activators. These results provide new data regarding the mechanisms of preconditioning and may pave the way to the development of new pharmacological strategies in liver surgery.

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“…Choukér et al, 28 in a randomized clinical trial involving 68 patients, demonstrated that IP attenuated the hemodynamic effect of liver infl ow occlusion and reduced the need for intraoperative vasopressor therapy. The same authors, evaluating α-glutathione S-transferase as an early marker of hepatic I/R injury after liver resection, postulated that postoperative liver dysfunction could be 19 2005 Fatty rat liver 5I+10R 40 ↓ AST levels Selzner 20 2007 Older mouse 60 IP not protective against I/R injury in older mice Schiesser 21 2008 Older rat 10I+10R, 5I+10R 45 IP less effective than intermittent clamping against I/R injury IP, ischemic preconditioning; I, ischemia; R, reperfusion; ↑, increase; ↓, reduction; TNF-α, tumor necrosis factor alpha; LDH, lactate dehydrogenase; IL-6, interleukin-6; AST, aspartate aminotransferase; I/R, ischemia/reperfusion injury prevented by IP. 29 Nuzzo et al, 30 in a prospective randomized clinical trial of 42 patients, also confi rmed the hepatoprotective role of IP.…”

Section: Mechanical Preconditioningmentioning

confidence: 96%

Ischemia/reperfusion injury in liver resection: A review of preconditioning methods

et al. 2011

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Ischemic preconditioning is one of the therapeutic interventions aiming at preventing ischemia/reperfusion-related injury. Numerous experimental studies and a few clinical series have shown that during liver resections, ischemic preconditioning is a promising strategy for optimizing the postoperative outcome. Moreover, various types of pharmacological intervention as well as different types of preconditioning, such as remote preconditioning, the use of heat shock, and hyperbaric oxygen, have been developed to attenuate the functional impairment accompanying ischemia/reperfusion injury. This review summarizes the various forms of preconditioning, thus suggesting that close cooperation between surgeons and anesthesiologists paves the way to apply novel strategies to improve the outcome of liver resection.

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Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis

Cited by 30 publications

References 52 publications

Hepatic Ischemia-Reperfusion Injury: Roles of Ca2+ and Other Intracellular Mediators of Impaired Bile Flow and Hepatocyte Damage

Hepatic Ischemia-Reperfusion Injury: Roles of Ca2+ and Other Intracellular Mediators of Impaired Bile Flow and Hepatocyte Damage

Heat Shock Proteins and Mitogen-activated Protein Kinases in Steatotic Livers Undergoing Ischemia-Reperfusion: Some Answers

Ischemia/reperfusion injury in liver resection: A review of preconditioning methods

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