Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1α expression

Abstract

Hypoxia-inducible factor-1α (HIF-1α) is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each): sham-operated (group S), hindlimb ischemia-reperfusion (group IR), and ischemic postconditioning (group IPO). Each group was divided into subgroups (n=6) according to reperfusion time: immediate (0 h, T0), 1 h (T1), 3 h (T3), 6 h (T6), 12 h (T12), and 24 h (T24). In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T0-T24), serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01). In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01), and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury-triggered inflammatory response.

The Value of Postconditioning in Plastic and Reconstructive Surgery: A Systematic Review

“…As reported in these studies, the post-con had positive impact on muscle wet content, 19,20,27,29,33 cellular redox state, 20,26,27,33 local inflammation, [18][19][20][28][29][30] contractility, 19 mitochondrial function, 18,26 muscular gene expression patterns, 20,26,28,30 as well as on histological muscle damage. [18][19][20][28][29][30]33 Two studies 18,33 showed that mechanical post-con reduced MPO, which is a marker of systemic inflammatory response. However, no statistical difference in MPO between the mechanical post-con and control groups was revealed in another study.…”

“…Based on the results of the published articles (►Tables 1-4), rats and mice 9,10,17,[19][20][21][23][24][25][26][27][28][29][30][31][32] are the common animal models used for the study of post-con. There are also several other animal models undertaken as flap models, which were not widely used in experimental studies, including pigs 18 and rabbits.…”

Isometric Exercise Training for Managing Vascular Risk Factors in Mild Cognitive Impairment and Alzheimer’s Disease

“…The production of a number of metabolites such as beta endorphins, prostaglandins and hypoxia-inducible factor-1 α (HIF 1 α) are postulated to result from ischemia induced by full or partial restriction of the brachial artery during IHG exercises (Stiller-Moldovan et al, 2012; Wong and Wright, 2014; Wong et al, 2015). These metabolites play a number of roles including, supporting the immune system, managing inflammation (Cabot et al, 1997; Pedersen and Hoffman-Goetz, 2000), vasodilation and vasoconstriction (Davidge, 2001), stimulating angiogenesis, and tissue repair and regeneration (Wang et al, 2014). It may be that the intensity of the hand grip contraction employed during IHG exercise determines the existence or absence of reactive hyperemia; intuitively, even at intensities less than 55% of MVC partial occlusion of blood flow is likely.…”

Recovery of Skeletal Striated Muscle Tissue in a Model of Reversible Injury

“…Also, controlling bleeding due to accidents occurring in distant places and treatments for joint diseases or contractures requires a tourniquet. The use of the tourniquet entails reversible injury triggered by ischemic conditions during determined periods of time [1][2][3]. Arthroscopic procedures, for instance, are performed during 15 to 60 minutes, while to transport an injured person from far places to the nearest health institution, can require two to three hours.…”

“…However, since the last 20 years, the evidence has pointed out that ischemic conditions less than three hours caused by an acute compartmental syndrome, tourniquet or artery clamp, for example, lead to necrosis [3,13]. The stem cells of the skeletal striated muscle tissue, called satellite cells, are postnatal myogenic precursors that can regenerate the myocytes [14].…”