Impact of hyperthermic preconditioning on postischemic hepatic microcirculatory disturbances in an isolated perfusion model of the rat liver

Abstract

Sublethal hyperthermia and the following recovery from this heat exposure, referred to as hyperthermic preconditioning, elicits a transient state of tolerance to oxidative insults through an intracellular protective response: stress response. The impact of hyperthermic preconditioning on hepatic microcirculatory disturbance, which is one of the determinants of ischemia/reperfusion-induced injury of the liver, was investigated by using intravital fluorescence microscopy. Thirty minutes of ischemia and a subsequent 120 minutes of reperfusion was induced in an in situ isolated perfusion model of Sprague-Dawley rats. Heat stress was given by whole-body hyperthermia, and a subsequent recovery was allowed for 18 or 48 hours, respectively. Postischemic decrease in sinusoidal perfusion rate and sinusoidal diameter, leukocyte stagnation in sinusoids, and leukocyte adhesion in postsinusoidal venules were significantly attenuated in both hyperthermia-pretreated groups. A recovery of bile production, a reduction of liver enzyme release, and an attenuation of tissue edema and histological damage were also observed. A marked expression of heat shock protein (HSP) 70 and heme oxygenase (HO-1)/HSP32 was correlatively observed in the liver tissue coincident with the induction of these protective effects. Hyperthermic preconditioning provides a continuous long-term and constant inhibitory effect (up to 48 hours after heat exposure) on postischemic injury of the liver through the attenuation of microcirculatory disturbances. These beneficial effects might be associated with a concomitant increase in HSP70 and HO-1/HSP32 expression. (HEPATOLOGY 2000;31:407-415.)Ischemia/reperfusion-induced injury is one of the major perioperative complications in liver surgery and liver transplantation. The administration of specific protective agents has been attempted to reduce postischemic hepatic injury. [1][2][3] To the contrary, preconditioning therapies based on an endogenous protection response against stressful events, referred to as heat stress response, have been studied as another therapeutic strategy. Hyperthermic preconditioning, the exposure to a transient sublethal hyperthermia, and the following appropriate recovery develops protection not only to subsequent thermal stress, but also to oxidative stress such as ischemia/reperfusion. [4][5][6][7][8] Heat stress response has been reported to be associated with the induction of specific heat shock proteins (HSPs). In particular, HSP70 is generally considered to contribute to the protective mechanism of hyperthermic preconditioning, based on the finding that overexpression of HSP70 in a transgenic mouse increases the resistance of the heart to ischemic injury. 9,10 Heme oxygenase (HO)-1/HSP32 is another HSP playing a role in the modulation of the inflammatory response. HO catabolizes intracellular heme to biliverdin, which is converted to bilirubin by bilirubin reductase. During this degradation process, carbon monoxide (CO) is released. 11 HO consists of HO-1 (inducible isoenzyme) and ...

Beneficial effects of rutin andl-arginine coadministration in a rat model of liver ischemia-reperfusion injury

“…I/R injury is a common consequence of hepatic surgery, particularly following hepatectomies and liver transplantation, and is complicated by microcirculatory failure, followed by necrosis and cell death (23,39). In this context, oxidative damage is thought to play an important role, including the outcome of organ transplantation.…”

Ischemic preconditioning of the liver: A few perspectives from the bench to bedside translation

“…Preconditioning strategies effective in the laboratory include ischemic preconditioning (IPC), anesthetic preconditioning, hyperthermic or heat-shock preconditioning, and pharmacological preconditioning. [1][2][3][4][5][6][7] In the past decade, serious efforts have commenced to translate some of the robust benefits of preconditioning against ischemia reperfusion (RP) to the clinical arena. Although all of the preconditioning methods offer potential clinical benefits, much of the initial translational effort has focused on IPC, probably due to its extensive and consistently beneficial laboratory experience.…”

Prevention of Kidney Ischemia/Reperfusion-induced Functional Injury, MAPK and MAPK Kinase Activation, and Inflammation by Remote Transient Ureteral Obstruction

“…In the kidney, the effect of the heat shock response and HSPs to protect against ischemic injury remain controversial (9,14,15). Recently, it has been suggested that prior heat shock reduces the inflammatory reaction (16), which is one of the major mediators of ischemia/reperfusion injury (17,18), and attenuates a postischemic microcirculatory disturbance (19,20). Prior heat shock suppresses cytokine-induced interleukin-8 and tumor necrosis factor-␣ expression and the translocation of the p65 subunit of NF-B (18).…”