Ischemic preconditioning before lower limb ischemia--reperfusion protects against acute lung injury

OBJECTIVE: Prolonged limb ischemia followed by reperfusion (I/R) is associated with a systemic inflammatory response syndrome and remote acute lung injury. Ischemic preconditioning (IPC), achieved with repeated brief periods of I/R before the prolonged ischemic period, has been shown to protect skeletal muscle against ischemic injury. The aim of this study was to ascertain whether IPC of the limb before I/R injury also attenuates systemic inflammation and acute lung injury in a fully resuscitated porcine model of hind limb I/R. METHODS: This prospective, randomized, controlled, experimental animal study was performed in a university-based animal research facility with 18 male Landrace pigs that weighed from 30 to 35 kg. Anesthetized ventilated swine were randomized (n = 6 per group) to three groups: sham-operated control group, I/R group (2 hours of bilateral hind limb ischemia and 2.5 hours of reperfusion), and IPC group (three cycles of 5 minutes of ischemia/5 minutes of reperfusion immediately preceding I/R). Plasma was separated and stored at -70 degrees C for later determination of plasma tumor necrosis factor-alpha and interleukin-6 with bioassay as markers of systemic inflammation. Circulating phagocytic cell priming was assessed with a whole blood chemiluminescence assay. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were markers of edema and neutrophil sequestration, respectively. The alveolar-arterial oxygen gradient and pulmonary artery pressure were indices of lung function. RESULTS: In a porcine model, bilateral hind limb (I/R) injury significantly increased plasma interleukin-6 concentrations, circulating phagocytic cell priming, and pulmonary leukosequestration, edema, and impaired gas exchange. Conversely, pigs treated with IPC before the onset of the ischemic period had significantly reduced interleukin-6 levels, circulating phagocytic cell priming, and experienced significantly less pulmonary edema, leukosequestration, and respiratory failure. CONCLUSION: Lower limb IPC protects against systemic inflammation and acute lung injury in lower limb I/R injury.     

Silent information regulator 1 protects the liver against ischemia–reperfusion injury: implications in steatotic liver ischemic preconditioning

Ischemia–reperfusion (IR) injury is an important problem in liver surgery especially when steatosis is present. Ischemic preconditioning (PC) is the only surgical strategy that has been applied in patients with steatotic livers undergoing warm ischemia. Silent information regulator 1 (SIRT1) is a histone deacetylase that regulates various cellular processes. This study evaluates the SIRT1 implication in PC in fatty livers. Homozygous (Ob) Zucker rats were subjected to IR and IR + PC. An additional group treated with sirtinol or EX527 (SIRT1 inhibitors) before PC was also realized. Liver injury and oxidative stress were evaluated. SIRT1 protein levels and activity, as well as other parameters involved in PC protective mechanisms (adenosine monophosphate protein kinase, eNOS, HSP70, MAP kinases, apoptosis), were also measured. We demonstrated that the protective effect of PC was due in part to SIRT1 induction, as SIRT1 inhibition resulted in increased liver injury and abolished the beneficial mechanisms of PC. In this study, we report for the first time that SIRT1 is involved in the protective mechanisms induced by hepatic PC in steatotic livers.     

Protection against acute porcine lung ischemia/reperfusion injury by systemic preconditioning via hind limb ischemia

Previous work on various organs and tissues has shown that ischemic preconditioning protects against reperfusion injury in these organs and also against secondary effects in the lung. In contrast, the purpose of this study was to investigate the effects of preconditioning in a remote organ (hind limb ischemia) on an ischemia/reperfusion (I/R) treatment of the lung itself. A porcine model of in situ left lung ischemia (90 min) and reperfusion (5 h) was used. Systemic preconditioning was induced by clamping the left common femoral artery (3 x 5 min). Lung injury was assessed in terms of pulmonary vascular resistance, pulmonary artery pressure, pulmonary venous and arterial pO(2), and tissue macrophage counts. The zymosan-stimulated release of reactive oxygen species (ROS) in whole blood was determined by a chemiluminometric procedure. Inflammatory cytokines (interleukin-1beta and interleukin-6) were measured in arterial plasma as indicators of a systemic inflammatory reaction. Preconditioning by hind limb ischemia completely prevented the I/R-induced functional impairment of the lung, the pulmonary hypertension and the reduced oxygenation capacity. The plasma levels of interleukin-1beta and the macrophage counts in preconditioned animals were reduced to control values, whereas the levels of interleukin-6 and the release of ROS were not affected by preconditioning. In conclusion, systemic preconditioning by repeated hind limb ischemia protects against acute I/R injury of the lung but not against all indices of reperfusion-associated systemic inflammation.     

Postconditioning protects skeletal muscle from ischemia‐reperfusion injury

Ischemia‐reperfusion (I/R) injury caused by abrupt restoration of the circulation after prolonged ischemic insult induces significant morbidity after reconstructive microsurgery. The authors investigated whether a postconditioning (post‐con) procedure attenuated skeletal muscle I/R injury and protected muscular function. Three hours of complete ischemia was induced by occluding the muscular branches of rat extensor digitorum longus (EDL) muscle. The post‐con procedure was started at the end of ischemia and involved six cycles of 15 seconds of reperfusion followed by 15 seconds of re‐occlusion (3 minutes of total intervention) prior to initiating unlimited reperfusion. EDL muscle contractilities were compared with those of normal sides (no ischemic exposure), and experimental group results were also compared with control group results (3 hours of ischemia followed by full reperfusion without post‐con) at 3 hours and 5 days postreperfusion. Muscle wet weights, myeloperoxidase (MPO) activities, and histological results were also evaluated. The muscle contractilities in the post‐con group were significantly preserved at both 3 hours and 5 days postreperfusion as compared with ischemic controls. Decreased inflammatory cell infiltration, MPO activity, and wet weight of postconditioned EDL muscle suggested that post‐con attenuated acute inflammatory reactions induced by I/R. This study demonstrates that post‐con provides effective functional protection to skeletal muscles from I/R injury. © 2010 Wiley‐Liss, Inc. Microsurgery 2010.     

Ischemic preconditioning attenuates the lipid peroxidation and remote lung injury in the rat model of unilateral lower limb ischemia reperfusion

BACKGROUND: Ischemia and reperfusion of the skeletal muscle tissue may cause remote lung injury. We aimed to evaluate the protective effect of ischemic preconditioning (IP) on the lung during unilateral lower limb ischemia reperfusion (IR). METHODS: Four groups of rats were used in this study: (i) the sham group (sham, n = 6) served as time controls, they remained anesthetized for the whole duration of the study; (ii) the ischemia and reperfusion group (IR, n = 10) underwent 4 h of left lower limb ischemia followed by 2 h of reperfusion; (iii) the ischemic preconditioning group (IP, n = 10), the left lower limbs of rats were exposed to three cycles of IP (10 min of ischemia followed by 10 min of reperfusion); and (iv) the ischemic preconditioning plus ischemia reperfusion group (IP/IR, n = 10) underwent IP followed by IR as in the IP and IR groups. Plasma and tissue samples were taken at the end of the study period for determination of lung tissue myeloperoxidase activity (MPO) and polymorphonuclear leukocyte count (PMNL), histological lung injury score and plasma thiobarbituric acid reactive substances (TBARS) level. RESULTS: PMNL count and MPO activity in the lung tissue, and plasma TBARS level were higher in the IR group compared with other groups while there were no differences between the sham and the IP and between the sham and the IP/IR groups. Histological lung injury score was higher in the IR group than in the IP/IR and sham groups. The plasma TBARS level in the IP group was significantly lower than in the IP/IR group. CONCLUSION: IP pretreatment reduces lipid peroxidation and lung injury caused by lower limb IR.     

Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice

Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.     

Ischaemic preconditioning protects against ischaemia/reperfusion injury: emerging concepts.

INTRODUCTION: Ischaemic preconditioning (IP) has emerged as a powerful method of ameliorating ischaemia/reperfusion (I/R) injury to the myocardium. This review investigates whether this phenomenon is universally applicable in modulating I/R injury to other tissues. METHODS: A Medline search was conducted to identify both animal and human studies that described IP-induced protection from I/R injury in a variety of non-cardiac organ systems. Particular emphasis was placed on elucidation of underlying physiological concepts. RESULTS AND CONCLUSIONS: IP utilises endogenous mechanisms in skeletal muscle, liver, lung, kidney, intestine and brain in animal models to convey varying degrees of protection from I/R injury. To date there are few human studies, but recent reports suggest that human liver, lung and skeletal muscle acquire similar protection after IP. Specifically, preconditioned tissues exhibit reduced energy requirements, altered energy metabolism, better electrolyte homeostasis and genetic re-organisation, giving rise to the concept of 'ischaemia tolerance'. IP also induces 'reperfusion tolerance' with less reactive oxygen species and activated neutrophils released, reduced apoptosis and better microcirculatory perfusion compared to non-preconditioned tissue. Systemic I/R injury is also diminished by preconditioning. IP is ubiquitous but more research is required to fully translate these findings to the clinical arena.     

Attenuation of acute lung injury following lower limb ischemia/reperfusion: the pharmacological approach

AIM: The purpose of this study was to examine the effects of N-acetylcysteine (NAC), calcium dobesilate (DOBE) and aprotinin on the amelioration of lung damage following ischemia/reperfusion injury in a rat hind limb model. A well known antioxidant dimethyl-sulfoxide (DMSO) was also tested for comparison. METHODS: Ischemia was induced in the lower limb for 4 h by vascular clamping and followed by 1 h of reperfusion. Lung injury was evaluated in 5 groups as a saline (control), DMSO, NAC, DOBE and aprotinin group. Plasma creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS) as well as lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. P<0.005 was considered statistically significant. RESULTS: Plasma TBARS values were found to be significantly lower in the DMSO (P<0.005), NAC (P<0.005) and aprotinin (P<0.005) groups compared to the control group. Lung TBARS values were significantly lower in the DMSO, NAC, DOBE and aprotinin groups compared to the control group (P<0.001, P<0.001, P<0.001). Also in the aprotinin group lung TBARS values were found to be significantly lower compared to DMSO (P<0.001), NAC (P<0.001) and DOBE (P<0.001) groups. Histological examination showed less prominent peribronchial leukostasis (P<0.005) and interstitial leukostasis (P<0.005) in all drug groups compared to the control group. CONCLUSION: These observations indicate that DOBE and NAC, which are known to have antioxidant properties and aprotinin, a serine proteinase inhibitor, acted effectively on the prevention of lung injury in a rat hind limb ischemia/reperfusion model. The reason why aprotinin exerts a more protective effect than the other drugs is not clear, however, its clinical use may have the dual advantage of hemostasis and lung protection in surgical practice.     

线粒体钙单向转运体在二氮嗪预处理脑保护中的作用

目的探讨线粒体钙单向转运体是否参与了二氮嗪预处理所发挥的脑保护作用方法将52只健康雄性Wistar大鼠按照完全随机方法分为4组（每组13只）：A组,假手术组;B组,脑缺血厢獾注组;C组,脑缺血,再灌注＋二氮嗪组;D组,脑缺血,再灌注＋二氮嗪＋精胺组。采用线栓法建立大鼠大脑中动脉闭塞模型,缺血2h再灌注24h后观测各组神经行为变化,缺血侧脑组织线粒体钙含量及超氧化物歧化酶（superoxide dismutase,SOD）活性、丙二醛（malondialdehyde,MDA）含量、一氧化氮（nitric oxide,NO）含量和谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-Px）活性。结果与B组比较,C组二氮嗪预处理可以改善大鼠脑缺血／再灌注引起的神经行为障碍（13．1±0．8,P〈0．01）,降低缺血侧脑线粒体钙含量（293±7）nmol／mgprot,（P〈0．05）,提高SOD（143±18）U／mgprot及GSH-Px（84±8）U／mgprot活性、降低MDA（0．799±0．092）nmol／mgprot,及NO（0．216±0．138）nmol／mgprot,含量（脚．05）。与c组比较,D组精胺可减弱二氮嗪预处理改善神经行为障碍（8．0±0．7,P〈0．01）、降低脑线粒体钙含量（322±10）nmol／mgprot,提高SOD（128±7）U／mgprot和GSH-Px（731-6）U／mgprot活性以及降低MDA（0．955±0．141）nmo]]mgprot,和NO（0．575±0．292）nmol／mgprot,含量的效应（P〈0．05）。结论二氮嗪预处理对抗大鼠脑缺血/再灌注损伤所发挥的脑保护效应,可能与其再灌注时减少线粒体钙单向转运体的活动以减少线粒体内钙含量及过氧化损伤有关。     

Carvedilol protects tubular epithelial cells from ischemia–reperfusion injury by inhibiting oxidative stress

Objectives: Renal ischemia–reperfusion injury (IRI), leading to acute kidney injury, is a frequent complication with renal transplantation and it is associated with graft function. Its pathogenesis involves ischemia, vascular congestion and reactive oxygen metabolites. Carvedilol is an antihypertensive drug with potent anti‐oxidant properties. In this study we investigated the protective effects of carvedilol in a rat renal IRI model. Methods: Twenty‐four rats were randomized into sham, untreated control and carvedilol (2 mg/kg 30 min before surgery and 12 hr after reperfusion) treatment groups and were subjected to 60 min of left renal ischemia followed by reperfusion at 24, 48, 96 and 168 hr. Results: Treatment with carvedilol significantly decreased plasma creatinine levels after IRI (up to 168 hr) compared to controls (P < 0.001), suggesting an improvement in renal function. Histopathological analysis revealed decreased IRI‐induced damage in kidneys from carvedilol‐treated rats. A significant increase in the expression levels of Cu/Zn superoxide dismutase and reduction of 8‐hydroxydeoxyguanosine and apoptosis levels (P < 0.005) suggested a protective effect after treatment with carvedilol. Conclusions: Our findings suggest that carvedilol ameliorates IRI resulting in improved renal function.     

Chlorogenic acid protects mice against lipopolysaccharide-induced acute lung injury

Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in human diet. Our previous in vitro study demonstrates that CGA presents anti-inflammatory activities in RAW 264.7 cells. Here we show that CGA protects mice against lipopolysaccharide (LPS)-induced acute lung injury (ALI). We treated mice with CGA (5, 20 and 50 mg/kg body weight) 30 min or 3 h after intratracheal administration of LPS. The histological results showed that CGA, at dose of 50 mg/kg, protected mice from LPS-induced ALI which displayed by edema, haemorrhage, blood vessel and alveolar structural damage. CGA inhibited LPS-increased pulmonary MPO activity and migration of polymorphonuclear neutrophils (PMNs) into bronchoalveolar lavage fluid (BALF). Furthermore, CGA markedly decreased the activity of inducible nitric oxide synthase (iNOS) in lung tissues and thus prevented nitric oxide (NO) release in response to LPS challenge. In conclusion, these results indicated that CGA was greatly effective in inhibiting ALI and might act as a potential therapeutic reagent for treating ALI in the future.     

Curcumin protects against sepsis-induced acute lung injury in rats

The present study aimed to investigate the effect of curcumin on sepsis-induced acute lung injury (ALI) in rats, and explore its possible mechanisms. Male Sprague-Dawley rats were randomly divided into the following five experimental groups (n = 20 per group): animals undergoing a sham cecal ligature puncture (CLP) (sham group); animals undergoing CLP (control group); or animals undergoing CLP and treated with vehicle (vehicle group), curcumin at 50 mg/kg (low-dose curcumin [L-Cur] group), or curcumin at 200 mg/kg (high-dose curcumin [H-Cur] group).At 6, 12, 24 h after CLP, blood, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level, and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathologic changes in lungs. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, as well as superoxidase dismutase (SOD) activity were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interluekin-8 (IL-8), and macrophage migration inhibitory factor (MIF) were determined in the BALF. Survival rates were recorded at 72 h in the five groups in another experiment. Treatment with curcumin significantly attenuated the CLP-induced pulmonary edema and inflammation, as it significantly decreased lung W/D ratio, protein concentration, and the accumulation of the inflammatory cells in the BALF, as well as pulmonary MPO activity. This was supported by the histopathologic examination, which revealed marked attenuation of CLP-induced ALI in curcumin treated rats. In addition, curcumin significantly increased SOD activity with significant decrease in MDA content in the lung. Also, curcumin caused down-regulation of the inflammatory cytokines TNF-α, IL-8, and MIF levels in the lung. Importantly, curcumin improved the survival rate of rats by 40%-50% with CLP-induced ALI. Taken together, these results demonstrate the protective effects of curcumin against the CLP-induced ALI. This effect can be attributed to curcumin ability to counteract the inflammatory cells infiltration and, hence, ROS generation and regulate cytokine effects.     

雷帕霉素预处理对大鼠肢体缺血-再灌注诱发肺损伤的影响

目的探讨雷帕霉素预处理对大鼠肢体缺血-再灌注诱发肺损伤的影响及相关机制。方法健康雄性SD大鼠60只,4~5月龄,体重250~300g,采用随机数字表法分为五组:假手术组(S组)、肢体缺血-再灌注组(IR组)、雷帕霉素1、5、10mg/kg预处理组(R1、R5和R10组),每组12只。采用肢体缺血2h再灌注3h的方法制备肢体缺血-再灌注损伤模型。检测各组血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)、IL-1β、IL-6和TNF-α的浓度;取肺组织,光镜下观察肺组织病理学结果,并测定肺组织湿干比重(W/D)。结果 IR、R1和R5组SOD活性明显低于S组(P0.05);R1、R5和R10组SOD活性明显高于IR组,且R5和R10组明显高于R1组,R10组明显高于R5组(P0.05)。IR、R1和R5组血清MDA、IL-1β、IL-6、TNF-α浓度和肺W/D明显升高(P0.05);R1、R5和R10组血清MDA、IL-1β、IL-6、TNF-α浓度和肺W/D明显降低,且R5和R10组明显低于R1组,R10组明显低于R5组(P0.05)。与S组比较,IR组肺组织病理学损伤加重;与IR组比较,R1、R5和R10组肺组织病理学损伤逐渐减轻。结论雷帕霉素预处理可减轻大鼠肢体缺血-再灌注诱发的肺损伤,并且呈剂量依赖性,剂量越大,其减轻肢体缺血-再灌注诱发肺损伤的作用越强,其机制可能与抗氧化应激和抗炎反应有关。     

KATP在异氟烷预处理减轻低温心肌缺血再灌注损伤中的作用

目的 研究异氟烷预处理(ISOP)对离体大鼠心脏17℃低温缺血常温再灌注心肌损伤的影响及膜K_(ATP)(sK_(ATP))和线粒体K_(ATP)(mK_(ATP))通道在其中的作用。方法 应用Langendorff灌注系统,建立离体大鼠17℃低温全心心肌缺血150min常温再灌注60min损伤模型。将32个心脏随机分为四组(n均=8):对照组(CON),异氟烷预处理组(ISOP),ISOP+GLB(Glibenclamide,格力苯脲)组,ISOP+5-HD(5-hvdroxydecanoate)组。检测心肌功能、冠脉流量、心肌梗死面积及CK释放量。结果 心脏低温缺血开始到LVP快速上升的开始时间(STIME)和达到拐点的时间CTIME)与梗死面积之间有负性相关关系(n=32;r=-0.638,P<0.01;r=0.396,P<0.05)。与CON组相比,ISOP组STIME、CTIME明显延迟(P<0.05);再灌注期间LVDP及LVDP×HR明显改善(P<0.05);梗死面积显著减少(P<0.05)。ISOP+GLB组和ISOP+5-HD组,心肌梗死面积明显高于ISOP组(P<0.05),STIME和CTIME明显短于ISOP组(P<0.05);复灌45min时ISOP+GLB及ISOP+5-HD组LVDP明显低于ISOP组(P<0.05),而ISOP+GLB组HR×LVDP明显低于ISOP组(P<0.05);复灌60min时显示只有ISOP+GLB组HR×LVDP明显低于ISOP组(P<0.05)。结论 ISOP能减轻中度低温心肌缺血再灌注损伤。     

S-nitroso-n-acetylcysteine protects skeletal muscle against reperfusion injury

The effects of a nitric oxide (NO) donor on microcirculation and contractile function of reperfused skeletal muscle were studied. Rat cremaster muscles underwent 5 hours of ischemia and 90 minutes of reperfusion and were divided into two groups systemically infused with S-nitroso-N-acetylcysteine (SNAC, 100 nmol/ min) and phosphate-buffered saline (PBS), respectively. The results showed that the vessels in the SNAC group had more rapid and complete recovery than that in controls. A significant difference was found from 10 to 40 minutes and at 90 minutes in 10–20-μm arterioles, from 10 to 90 minutes in 20–40-μm arterioles, and at 10 and 90 minutes in 40–70-μm arteries. When compared to controls, SNAC-treated muscles showed larger fluorescein filling areas at 15, 30, 60, and 90 minutes and greater isometric tetanic contractile forces in response to stimulation frequencies of 40, 70, 100, and 120 Hz. The data indicate that supplementation of exogenous NO could effectively improve microcirculation and contractile function of skeletal muscle during early reperfusion. © 1998 Wiley-Liss, Inc. MICROSURGERY 18:299–305, 1998     

缺血预处理对大鼠肝脏缺血再灌注损伤的保护机制

目的验证缺血预处理(IPC)对大鼠肝脏缺血再灌注损伤(I/R)的保护作用,探讨一氧化氮(NO)与蛋白激酶C(PKC)在IPC过程中的作用.方法在原位灌流的大鼠肝脏缺血再灌注模型上,观察IPC的保护作用.同时经肠系膜上静脉注射NO前体L-精氨酸和蛋白激酶C特异性激动剂1,2-二辛酸甘油(DOG)以及两者的特异性阻滞剂N-硝基-L-精氨酸甲酯(NAME)和多粘菌素B,来检测NO和PKC在IPC中的关系.结果预处理可阻止血清谷丙转氨酶(ALT)[(200.86±40.30)U/Lvs.(257.65±20.18)U/L],谷草转氨酶(AST)[(211.06±13.59)U/Lvs.(309.17±24.79)U/L],乳酸脱氢酶(LDH)[(824.73±127.11)U/Lvs.(1118.60±82.21)U/L]及脂质过氧化物(LPO)[(0.414±0.069)mmol/mgvs.(0.531±0.054)mmol/mg]水平升高(P＜0.05),而使组织超氧化歧化酶(SOD)保持在较高水平[(10.33±0.88)U/mgvs.(6.01±0.91)U/mg],(P＜0.05).NO与PKC均可模拟预处理的保护效应.结论缺血预处理对大鼠肝脏I/R有明确的保护作用,NO与PKC发挥IPC保护作用的途径不同.     

Ischaemic preconditioning protects the rat kidney from reperfusion injury.

OBJECTIVE: To examine the possible role of ischaemic preconditioning (IPC), an adaptive pathophysiological phenomenon that increases tolerance to ischaemia-reperfusion (I-R) injury, in renal protection when rats are presented with an I-R challenge. MATERIALS AND METHODS: Female Wistar rats (n=36) were divided randomly into four groups: (A) sham-operated controls; (B) IPC only; (C) renal ischaemia (RI) only; and (D) IPC+RI. The left kidney in groups B and D was preconditioned with four cycles of renal artery occlusion lasting 4 min, each occlusion separated by 11 min of reperfusion. The ischaemic insult, applied in groups C and D, comprised 40 min of sustained left renal artery occlusion. In Group D, the IPC cycle was completed 5 min before the start of the ischaemic insult. Differential left renal function was calculated by 99mTc-labelled dimercaptosuccinic acid scintigraphy at 0, 2 and 9 days after treatment, and expressed as a percentage of the total renal uptake. RESULTS: The mean (sem) maximum decrease in left renal function, to 14.5 (4.3)% of the total, occurred on day 2 in Group C. The equivalent value in Group D showed relative preservation of function, at 36.0 (3.5)% (P=0.001 compared with Group C). The mean left renal function improved by day 9, to 39.6 (6.7)% (Group C) and 48.6 (1.5)% (Group D). The mean left renal function in Group B (50.5-53.9%) did not differ from that in controls (49.4-51.4%). CONCLUSION: An IPC regimen applied 5 min before RI in the rat significantly protects it from the functional impairment associated with ischaemia and reperfusion.     

缺血预处理减轻骨骼肌缺血再灌注损伤

目的 观察缺血预处理对骨骼肌缺血再灌注损伤的保护作用。方法 选择２４只健康兔,随机等分为实验组和对照组。实验组先进行缺血预处理,再持续阻断后肢血流４ｈ;对照组直接阻断后肢血流４ｈ,制作骨骼肌缺血再灌注损伤模型。测定再灌注期血清中肌酸磷酸激酶（ＣＰＫ）和天门冬氨酸氨基转移酶（ＡＳＴ）,镜下观察骨骼肌变化。结果 实验组血清中ＣＰＫ和ＡＳＴ的含量均明显低于对照组（Ｐ〈０．０５）。实验组骨骼肌线粒体空泡变     

Sevoflurane anesthetic preconditioning protects the lung endothelial glycocalyx from ischemia reperfusion injury in an experimental lung autotransplant model

Purpose

The glycocalyx is a glycoprotein-polysaccaride layer covering the endothelium luminal surface, and plays a key regulatory role in several endothelial functions. Lung ischemia reperfusion (IR) is a clinical entity that occurs in everyday thoracic surgery and causes glycocalix destruction and a florid local and systemic immune response. Moreover, sevoflurane is able to modulate the inflammatory response triggered by IR lung injury. In this study, we evaluated the protective effects of sevoflurane on the pulmonary endothelial glycocalyx in an in-vivo lung autotransplant model in pigs.

Methods

Sixteen Large White pigs underwent pneumonectomy plus lung autotransplant. They were divided into two groups depending on the hypnotic agent received (propofol or anesthetic preconditioning with sevoflurane). Glycocalyx components (syndecan-1 and heparan sulphate), cathepsin B, chemokines (MCP-1, MIP-1, and MIP-2) and adhesion molecules (VCAM and ICAM-1) were measured at four different timepoints using porcine-specific enzyme-linked immunosorbent assay (ELISA) kits.

Results

There were no differences between groups in weight or in surgical and one-lung ventilation time. Greater glycocalyx destruction and higher chemokine and adhesion molecule expression were observed in the group that did not receive sevoflurane. Heparan sulphate and serum syndecan levels were higher in the propofol group (P < 0.0001) after reperfusion, as was cathepsin B activity (P < 0.015). MCP-1, MIP-1, MIP-2, VCAM, and ICAM-1 levels were also higher in the propofol group (P < 0.006).

Conclusion

Sevoflurane preconditioning protects pulmonary glycocalyx and reduces expression of leukocyte chemokines in an in-vivo model of pulmonary IR.