Effect of multiorgan abdominal ischemic preconditioning on experimental kidney transplantation.

Remote Ischemic Preconditioning: Is the Groove in the Heart?

Interleukin-6 is a key mediator of the hepatoprotective and pro-proliferative effects of ischaemic preconditioning in mice

Ischemia-reperfusion (I/R) injury is a serious condition that can affect the success rate of microsurgical reconstructions of ischemic amputated limbs and complex tissue defects requiring free tissue transfers. The purpose of this study was to evaluate the effects of ischemic preconditioning (IPC) and C1 esterase inhibitor (C1-Inh) intravenous administration following I/R injury in a rat skin flap model. Superficial caudal epigastric skin flaps (3 cm × 7 cm) were performed on 50 Wistar rats that were randomly divided into five groups. Ischemia was not induced in the control group. All other flaps underwent 8 hours of ischemia prior to revascularization: I/R control group (8-hour ischemia), IPC group (preconditioning protocol + 8-hour ischemia), C1-Inh group (8-hour ischemia + C1-Inh), and IPC + C1-Inh group (preconditioning protocol + 8-hour ischemia + C1-Inh). Survival areas were macroscopically assessed after 1 week of surgery, and histopathological and biochemical evaluations were also measured. There were no significant differences in flap survival between the treatment groups that were suffering 8 hours of ischemia and the control group. A significant increase in neovascularization and lower edema formation were observed in the IPC group compared with that in the I/R group. Biochemical parameters did not show any significant differences. Intravenous administration of C1-Inh did not significantly modulate I/R-related damage in this experimental model, but further research is needed. On the other hand, IPC reduces tissue damage and improves neovascularization, confirming its potential protective effects in skin flaps following I/R injury.

Evaluation of preservation solutions by ESR-spectroscopy: Superior effects of University of Wisconsin over Histidine–Tryptophan–Ketoglutarate in reducing renal reactive oxygen species

Experimental study on prophylactic effects of vardenafil in ischemia–reperfusion model with intestinal volvulus injury in rats

Continuity of research outcomes: The correlation of bench toxicity mechanisms to clinical outcomes—are they dependable?

We previously showed that activation of the A1 adenosine receptor protected the kidney against ischemia-reperfusion injury by induction and phosphorylation of heat shock protein 27 (HSP27). Here, we used mice that overexpress human HSP27 (huHSP27) to determine if kidneys from these mice were protected against injury. Proximal tubule cells cultured from the transgenic mice had increased resistance to peroxide-induced necrosis compared to cells from wild-type mice. However, after renal ischemic injury, HSP27 transgenic mice had decreased renal function compared to wild-type mice, along with increased renal expression of mRNAs of pro-inflammatory cytokines (TNF-alpha, ICAM-1, MCP-1) and increased plasma and kidney keratinocyte-derived cytokine. Following ischemic injury, neutrophils infiltrated the kidneys earlier in the transgenic mice. Flow cytometric analysis of lymphocyte subsets showed that those isolated from the kidneys of transgenic mice had increased CD3(+), CD4(+), CD8(+), and NK1.1(+) cells 3 h after injury. When splenocytes or NK1.1(+) cells were isolated from transgenic mice and adoptively transferred into wild-type mice there was increased renal injury. Further, depletion of lymphocytes by splenectomy or neutralization of NK1.1(+) cells resulted in improved renal function in the transgenic mice following reperfusion. Our study shows that induction of HSP27 in renal tubular cells protects against necrosis in vitro, but its systemic increase counteracts this protection by exacerbating renal and systemic inflammation in vivo.

Objective To investigate the effect of ischemic preconditioning (IPC) on Akt surviv-al signal pathways in rat reduced-size liver graft and its significance. Methods Thirty-six adult male SD rats were randomly divided into two groups:50% sized liver transplantation group (control group) and IPC group. The expression of protein of Akt signaling pathway including total and phospho-Akt, phospho-Bad and phospho-GSK3β was assessed by Western blot. The change and significance of Akt survival signaling pathway was analyzed in rat reduced-size liver graft in combination with hepatic function and histopatholog-ical analysis. Results Compared with control group, serum ALT levels were significantly lower at 6th and 24th h after reperfusion in IPC group (6 h: 1064.49±126.53 vs 802.90±82.39,24 h: 1401.13±172.73 vs 943.80±116.25 P<0.01). Histopathological analysis showed disruption of lobular architecture, apparent hepatocelluar degeneration accompanied by focal necrosis;significant edema, congestion and inflammatory cell infiltration in periportal area at the 24th h after reperfusion in control group,whereas minimal damage was observed in IPC group. Western blot revealed that p-Akt,p-Bad and p-GSK3β expression levels were significantly up-regulated at the 2nd, 6th, and 24th h after reperfusion in IPC group compared to control group. Conclusion IPC could ameliorate early reperfusion injury in reduced-siz liver grafts, and the pro-tective mechanisms might be mediated in part by activation of Akt survival signal pathway. Key words: Liver transplantation; Reperfasion injury; Ischemic preconditioning; Akt signal pathway

ABSTRACTBackground: In previous studies, it has been demonstrated that Nigella Sativa (NS) has protective effects against ischemia reperfusion injury on various organs. However, its protective effects on intestinal tissue against ischemia reperfusion injury are unclear. We aimed to determine whether NS prevents intestinal ischemia- reperfusion injury in rats. Materials and Methods: Thirty rats were divided into three groups as sham (group 1), control (group 2), and NS-treatment group (group 3). All rats underwent intestinal ischemia for 60 min followed by a 60-min period of reperfusion. Rats were intraperitoneally infused only 0.9%% saline solutions in group 2. Rats in the group 3 received NS (0,2 mL/kg) intraperitoneally, before ischemia and before reperfusion. Total antioxidant capacity (TAC), catalase (CAT), total oxidative status (TOS), oxidative stress index (OSI), and myeloperoxidase (MPO) in ileum tissue were measured. Also, ileum tissue histopathology was evaluated by a light microscope. Results: The levels of liver enzymes in group 3 were significantly lower than those in group 2 (p <.01). TAC and CAT activity levels in ileum tissue were significantly higher in group 3 than in group 2. TOS, OSI, and MPO in ileum tissue were significantly lower in group 3 than group 2 (p <.05 for TOS and MPO; p < .01 for OSI). Histological tissue damage was milder in the NS treatment group than in the control group. Conclusion: Our results suggest that NS treatment protected the rat's intestinal tissue against intestinal ischemia- reperfusion injury.

To determine whether Nigella sativa prevents hepatic ischemia-reperfusion injury to the liver. Thirty rats were divided into three groups as sham (Group 1), control (Group 2), and Nigella sativa (NS) treatment group (Group 3). All rats underwent hepatic ischemia for 45 min followed by 60 min period of reperfusion. Rats were intraperitoneally infused with only 0.9% saline solution in group 2. Rats in group 3 received NS (0.2 mL/kg) intraperitoneally, before ischemia and before reperfusion. Blood samples and liver tissues were harvested from the rats, and then the rats were sacrificed. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were determined. Total antioxidant capacity (TAC), catalase (CAT), total oxidative status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) in hepatic tissue were measured. Also liver tissue histopathology was evaluated by light microscopy. The levels of liver enzymes in group 3 were significantly lower than those in the group 2. TAC in liver tissue was significantly higher in group 3 than in group 2. TOS, OSI and MPO in hepatic tissue were significantly lower in group 3 than the group 2. Histological tissue damage was milder in the NS treatment group than that in the control group. Our results suggest that Nigella sativa treatment protects the rat liver against to hepatic ischemia-reperfusion injury.

Acute kidney injury (AKI) is a complex clinical condition associated with significant morbidity and mortality and lacking effective management. Ischemia-reperfusion injury (IRI) remains one of the leading causes of AKI in native and transplanted kidneys. The aim of this study was to evaluate the efficacy of adipose-derived mesenchymal stem cells (ADSCs) in the prevention of renal IRI in rats. The study was conducted on male Sprague-Dawley rats (n=72) weighing 250–300 g. Rats were randomly assigned to three main groups: i) Sham-operated control group (n=24); ii) positive control group, in which rats were subjected to IRI and were administered culture media following 4 h of IRI (n=24); and iii) ADSC group (n=24), in which rats were administered 1×106 ADSCs via the tail vein following 4 h of IRI. Each main group was further divided according to the timing after IRI into four equal-sized subgroups. Renal function was tested via the measurement of serum creatinine levels and creatinine clearance. In addition, malondialdehyde (MDA) levels were determined in serum and renal tissue homogenate as an indicator of oxidative stress. Histopathological changes were analyzed in different regions of the kidney, namely the cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM) and inner medulla. In each region, the scoring system considered active injury changes, regenerative changes and chronic changes. The ADSCs were assessed and their differentiation capability was verified. IRI resulted in a significant increase in serum creatinine, serum and tissue MDA levels and a significant reduction in creatinine clearance compared with those in sham-operated rats,. These changes were attenuated by the use of ADSCs. The prominent histopathological changes in the cortex, ISOM and OSOM were reflected in the injury score, which was significantly evident in the positive control group. The use of ADSCs was associated with significantly lowered injury scores at days 1 and 3; however, no significant effect was observed on day 7. These results indicate that the use of ADSCs ameliorates renal injury and dysfunction associated with IRI in rats.

Investigation of dose-dependent effects of berberine against renal ischemia/reperfusion injury in experimental diabetic rats

Investigation of dose-dependent effects of berberine against renal ischemia/reperfusion injury in experimental diabetic rats

Preconditioning describes the phenomenon by which a traumatic or stressful stimulus confers protection against subsequent injury. Originally recognized in dog heart subjected to ischemic challenges, preconditioning has been demonstrated in multiple species, can be induced by various stimuli, and is applicable in different organ systems. Tremendous progress has been made elucidating the signal transduction cascade of preconditioning. Preconditioning represents a potent tissue-protective condition, and mechanistic understanding may allow safe clinical application. This review recalls the history of preconditioning and how it relates to the history of the investigation of endogenous adaptation; summarizes the current mechanistic understanding of acute preconditioning; outlines the signal transduction cascade leading to the development of delayed preconditioning; discusses preconditioning in noncardiac tissue; and explores the potential of using preconditioning clinically.

Ischemic preconditioning1 has been shown to reliably reduce ischemic myocardial cell necrosis in a host of animal models.2 Although preconditioning is one of the most powerful and reproducible phenomena in cardioprotection, it has not readily translated to routine clinical use. One issue is that the timing of the long duration of ischemia must be known in advance and the treatment must be applied before the long duration of ischemia. Thus, although evidence suggests that preinfarction ischemia (angina) before an ST-segment elevation myocardial infarction is associated with smaller infarct size and better clinical outcome,3 there is no reliable way to predict when a myocardial infarction will occur and hence no way to either induce ischemic preconditioning or apply a preconditioning mimetic agent just before the infarction. There are, of course, situations in which myocardial ischemia is planned, eg, during coronary artery balloon angioplasty, during coronary artery bypass surgery, during excision and transportation of a donor heart, and before exercise in a patient with known demand-induced ischemia. Preconditioning has been applied to some of these situations. For example, multiple brief balloon inflations and deflations in the coronary artery reduce the severity of chest pain, ST-segment elevation, and lactate production on subsequent balloon inflations compared with an initial balloon inflation without necessarily recruiting blood flow.4 Intermittent aortic cross clamping before coronary artery bypass surgery has been observed to preserve cardiac high-energy phosphate levels.2 These examples of ischemic preconditioning require an invasive procedure to induce ischemia within the heart and the possibility of showering atherosclerotic emboli either down the coronaries or into the aorta as a coronary angioplasty balloon is repeatedly inflated or deflated or the aortic cross clamp is repeatedly clamped and unclamped. Article p 820 Another approach exists that has the potential to be entirely noninvasive: remote …