Threshold level of NF-kB activation in small bowel ischemic preconditioning procedure

Ischemic preconditioning (IPC), which is obtained by exposure to brief periods of vascular occlusion, improves organ tolerance to prolonged ischemia. The aim of this study was to evaluate the threshold level of NF-kB activation in small intestine during an IPC procedure. Various intestinal IPC were performed on 20 Wistar rats in seven groups: group I (GI, nonpreconditioned); group II (GII, 1-minute ischemia and 1-minute reperfusion); group III (GIII, two cycles of 1-minute ischemia and 1-minute reperfusion); group IV (GIV, 2-minutes ischemia and 2-minutes reperfusion); group V (GV, two cycles of 2-minute ischemia and 2-minute reperfusion); group VI (GVI, 5-minute ischemia and 10-minute reperfusion); group VII (GVII, two cycles of 5-minute ischemia and 10-minute reperfusion). Bowel biopsies were collected after laparotomy (control) as well as at 30, 60, and 120 minutes following IPC. We determined the cytoplasmic and nuclear NF-kB by a chemiluminescence-based ELISA method. Our results showed low, constant NF-kB levels in GI. In the preconditioned groups (GII-GVII), NF-kB was significantly elevated at 30 minutes following IPC (P < .05 vs control). After 1 hour, NF-kB activity decreased to the control level. However, 2 hours after IPC both forms of NF-kB were elevated significantly again, which was independent of the number of IPC cycles (P < .05 vs control). Our experiments revealed that one cycle of 1-minute ischemia and 1-minute reperfusion is a critical threshold level for NF-kB activation during small bowel IPC. Longer and more IPC cycles did not result in further elevation of NF-kB activation.     

The role of ischemic preconditioning in rat liver graft

OBJECTIVE: The objective of this study was to investigate the protective effects of different modes of ischemic preconditioning (IPC) on an ischemia/reperfusion (I/R) injury in rat liver graft. METHODS: A total of 192 Wistar rats were randomly allocated into 4 groups, each including 48 rats: control group (C), experimental group 1 (E(1)), experimental group 2 (E(2)), and experimental group 3 (E(3)). IPC was not performed in group C. Among the animals in the experimental groups, IPC was performed by blocking blood flow by the portal vein and the hepatic artery followed by reperfusion by removal of the clamp before donor liver resection: Group E(1), 5-minute ischemia and 10-minute reperfusion; Group E(2), 5-minute ischemia and 5-minute reperfusion and immediately the same procedure; and Group E(3), 10-minute ischemia and 15-minute reperfusion. Liver transplantations were performed 4 hours after IPC. At 0.5 hour, 2 hours, 6 hours, and 24 hours after portal vein reperfusion recipient blood and graft samples were obtained to determine the levels of ALT, AST, TNF-alpha, and apoptosis index (AI). RESULTS: At 0.5 hour and 2 hours after portal vein reperfusion, serum tumor necrosis factor (TNF)-alpha in the experimental groups (E(1), E(2), and E(3)) was significantly lower than in the control group (P < .05). The values in group E(2) were significantly lower than those in groups E(1) and E(3) (P < .05). At 24 hours serum TNF-alpha in group E(2) was significantly lower than groups C, E(1), and E(3) (P < .05). At 2 hours and 6 hours, AI values in experimental groups (E(1), E(2), and E(3)) were significantly lower than in group C (P < .05). AI in group E(2) was significantly lower than that in groups E(1) and E(3) (P < .05). At 24 hours, AI values among experimental groups (E(1), E(2), and E(3)) were significantly lower than that in the control group (P < .05). CONCLUSION: IPC may attenuate liver graft injury by decreasing apoptosis of hepatocytes and production of TNF-alpha. The method of IPC with 5-minute ischemia and 5-minute reperfusion followed immediately by another cycle of the same procedure was a better way to protect a liver graft from I/R injury.     

缺血预处理对大鼠肝脏缺血再灌注损伤保护作用机制的研究

目的　探讨缺血预处理 (IPC)保护作用的发生机制。方法　建立大鼠部分肝脏热缺血再灌注模型。IPC采用肝脏缺血 10min ,再灌注 10min。结果　IPC后肝组织中腺苷和NO水平明显升高 ,与对照组相比差异显著 (P <0 0 1) ,但IPC前应用腺苷A2 受体拮抗剂后NO的升高被抑制 (P<0 0 1)。缺血再灌注 (I/R) 2h后血清中TNF α、AST、ALT、LDH及W/D水平和假手术组相比明显增加 ,而IL 10含量降低 (P <0 0 1) ;IPC、I/R前加入腺苷、IPC前应用腺苷A1受体拮抗剂显著地降低TNF α释放和AST、ALT、LDH及W /D水平 ,提高IL 10含量 ,与I/R组相比差异显著 (P <0 0 1) ;但IPC前应用腺苷A2 受体拮抗剂 (IPC +A2 antag)和NO合成酶抑制剂NAME并没有能像IPC组那样有效降低TNF α、AST、ALT、LDH及W /D的水平 ,提高IL 10的含量 (P <0 0 1) ;而IPC前给IPC+A2 antag组提供NO前体精氨酸又获得和IPC组同样的结果 (P >0 0 5 )。结论　IPC引起细胞外腺苷水平升高 ,腺苷A2 受体活化 ,介导了NO合成增加 ,最终通过抑制效应器TNF α的释放、增加IL 10的合成来实现对缺血组织的保护作用。     

Effect of ischemic preconditioning on hepatic microcirculation and function in a rat model of ischemia reperfusion injury

Ischemic preconditioning (IPC) may protect the liver from ischemia reperfusion injury by nitric oxide formation. This study has investigated the effect of ischemic preconditioning on hepatic microcirculation (HM), and the relationship between nitric oxide metabolism and HM in preconditioning. Rats were allocated to 5 groups: 1. sham laparotomy; 2. 45 minutes lobar ischemia followed by 2-hour reperfusion (IR); 3. IPC with 5 minutes ischemia and 10 minutes reperfusion before IR; 4. L-arginine before IR; and 5. L-NAME + IPC before IR. HM was monitored by laser Doppler flowmeter. Liver transaminases, adenosine triphosphate, nitrites + nitrates, and guanosine 3'5'-cyclic monophosphate (cGMP) were measured. Nitric oxide synthase (NOS) distribution was studied using nicotinamide adeninine dinucleotide phosphate (NADPH) diaphorase histochemistry. At the end of reperfusion phase, in the IR group, flow in the HM recovered partially to 25.8% of baseline (P < .05 versus sham), whereas IPC improved HM to 49.5% of baseline (P < .01 versus IR). With L-arginine treatment, HM was 31.6% of baseline (NS versus IR), showing no attenuation of liver injury. In the preconditioned group treated with L-NAME, HM declined to 10.2% of baseline, suggesting not only a blockade of the preconditioning effect, but also an exacerbated liver injury. Hepatocellular injury was reduced by IPC, and L-arginine and was increased by NO inhibition with L-NAME. IPC also increased nitrate + nitrate (NOx) and cGMP concentrations. NOS detected by NADPH diaphorase staining was associated with hepatocytes and vascular endothelium, and was induced by IPC. IPC induced NOS and attenuated HM impairment and hepatocellular injury. These data strongly suggest a role for nitric oxide in IPC. (Liver Transpl 2002;8:1182-1191.)     

缺血预处理对肢体缺血再灌注损伤的影响

目的　观察缺血预处理 (IPC)对肢体缺血再灌注损伤的影响。方法　选择 2 0例需充气止血带止血进行手术的患者 ,随机分为对照组 (n =10 )和IPC组 (n =10 )。IPC组患者术前应用 3次 5min循环缺血 ,间隔 5min再灌注预处理后在止血带下进行手术 ;对照组直接在止血带下进行手术。在肢体缺血前和再灌注 30min、90min、180min分别取静脉血检测血清肌酸磷酸激酶 (CPK)、谷草转氨酶(AST)、乳酸脱氢酶 (LDH)、丙二醛 (MDA)和过氧化物歧化酶 (SOD)水平。结果　随着肢体缺血再灌注时间的延长 ,血中CPK、AST、LDH、MDA含量逐渐升高 ,而SOD活性逐渐降低。IPC组在缺血前及再灌注同时间 ,血中CPK、AST、LDH、MDA含量低于对照组 (P <0 0 5 ,P <0 0 1) ;而SOD活性高于对照组 (P <0 0 5 ,P <0 0 1)。结论　IPC能有效地减轻肢体缺血再灌注损伤程度 ,减轻脂质过氧化反应 ,提高肢体缺血耐受性     

Near-infrared monitoring of myocardial oxygenation during ischemic preconditioning

Background. Ischemic preconditioning has been advocated as a method of cardioprotection for minimally invasive direct coronary artery bypass. This study was performed to estimate the cardioprotective effect of ischemic preconditioning before ischemia by examining the changes in myocardial tissue oxygenation and also to examine whether adenosine triphosphate-sensitive potassium channel opener enhances the cardioprotective effect of ischemic preconditioning.

Methods. Myocardial ischemia was induced in three groups of 6 dogs by temporary occlusion of the left anterior descending coronary artery. Group 1 dogs received a 30-minute coronary occlusion and subsequent 3-hour reperfusion. Groups 2 and 3 dogs underwent three periods of 5-minute coronary occlusion and 5-minute reperfusion and then received 30-minute sustained ischemia and 3-hour reperfusion. In group 3, nicorandil was administered during the procedure. Myocardial oxygenation was measured using three-wavelength near-infrared spectroscopy. Myocardial blood flow was measured by the colored microsphere method.

Results. During ischemic preconditioning the myocardial tissue oxygen saturation decreased rapidly at coronary occlusion and increased at reperfusion. It was increased stepwise at the second and third coronary occlusion. Myocardial oxygen saturation during 30-minute sustained ischemia was significantly higher in groups 2 and 3 than in group 1 (p < 0.05). The myocardial tissue hemoglobin concentration showed similar changes to myocardial oxygen saturation. During 30-minute sustained ischemia, it was significantly higher in group 2 than in group 1 (p < 0.001), and it was significantly higher in group 3 than in groups 1 and 2 (p < 0.05). Regional myocardial blood flow showed no difference after 30 minutes of sustained ischemia among the three groups. Troponin-T levels were significantly lower in groups 2 and 3 than in group 1 (p < 0.01).

Conclusions. Ischemic preconditioning had beneficial effects on myocardial oxygenation during sustained ischemia, and the protected state of the myocardium could be monitored with the use of near-infrared spectroscopy. Ischemic preconditioning coupled with nicorandil administration might provide protection for minimally invasive direct coronary bypass.     

Preconditioning protects against ischemia/reperfusion injury of the liver

Ischemic preconditioning (IPC) of an organ may induce protection against the injury caused by longer duration of ischemia and subsequent reperfusion. In a standardized model of such injury in the rat liver, we used the following protocol to investigate whether adenosine played a role in IPC by preventing its enzymatic degradation by dipyridamole pretreatment according to the following protocol: group 1, non-ischemic control rats; group 2, ischemic control rats subjected to 60 minutes of ischemia by clamping of the common hepatic artery followed by 60 minutes of reperfusion; group 3, IPC with 10 minutes of ischemia followed by 15 minutes of reperfusion, prior to the ischemia/reperfusion period as in group 2; group 4, pharmacologic preconditioning with administration of dipyridamole prior to the ischemia/reperfusion period as in group 2. Peripheral liver blood flow was significantly reduced during clamping (groups 2 to 4). After unclamping, blood flow was still reduced in the ischemic rats (group 2) but had returned to preclamp values in the animals that had been subjected to ischemic (group 3) or pharmacologic (group 4) preconditioning. Liver cell injury was significantly increased in the ischemia group (group 2) only. In our experimental model of ischemia/reperfusion injury in the rat liver, we found an equally beneficial effect with ischemic and pharmacologic preconditioning. Adenosine appears to be a crucial factor in IPC.     

Delayed energy protection of ischemic preconditioning on hepatic ischemia/reperfusion injury in rats

BACKGROUND: Hepatic ischemia/reperfusion (IR) injuries associated with hepatic resections are unresolved problems in the clinical practice. The aim of this study is to elucidate the effect of ischemic preconditioning (IPC) on the energy charge (EC) and related mechanisms at the late phase of hepatic IR injury. METHODS: 30 Wistar rats were randomly divided into sham, IR and IPC groups. The model of partial hepatic IR was used. The rats were subjected to 60 min hepatic ischemia, pretreated by IPC (10/15 min) or not. After 24 h of reperfusion, serum alanine aminotransferase (ALT), nitrite/nitrate (NOx), malondialdehyde (MDA), hepatic tissue arginase activity, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and EC of the liver were measured. RESULTS: Liver injury reduced by IPC is measured by liver tissue arginase activity and serum ALT. Tissue NOx levels in rats pretreated with IPC were significantly higher than levels in the IR group (p < 0.001). Tissue levels of MDA in the liver of the IPC group were found to be significantly lower than the levels in the IR group (p < 0.001). ATP and EC levels 24 h after hepatic ischemia in rats pretreated with IPC were higher than the levels in the IR (p < 0.05). All groups had similar ADP and AMP levels in the liver tissues. The IPC procedure significantly reduced the hepatic necrosis (p < 0.001). CONCLUSION: The results of this study demonstrated that pretreatment with IPC improved tissue ATP, EC, and hepatic necrosis at late stages of ischemia reperfusion injury of the liver. Increased nitric oxide, reduced MDA and arginase activity seemed to play a regulatory role in this delayed protective effect of IPC.     

Is ischemic preconditioning of the kidney clinically relevant?

BACKGROUND: Renal ischemic preconditioning (IPC) is a phenomenon whereby a brief period of ischemia and reperfusion (I/R) provides tolerance to subsequent periods of ischemia. IPC has been demonstrated to protect rodent kidneys during I/R. The applicability to large mammals, including human beings, is unclear. The objective of this study was to determine if renal IPC has a beneficial effect in a large animal model of warm I/R and hypothermic preservation injury, which occurs with renal allografting. METHODS: Renal ischemia (45 minutes) and reperfusion was studied in untreated dogs and in dogs receiving IPC (10-minute/10-minute I/R). IPC was administered immediately before I/R (early IPC) or 24 hours before I/R (delayed IPC). In another group of dogs, pharmacologically induced IPC was attempted with local intra-arterial administration of dipyridamole (2.4 mg/kg/min) to increase local adenosine concentrations. Finally, IPC was induced in kidneys before harvest, cold stored for 24 hours in University of Wisconsin flush solution, and subsequently reperfused for 4 hours in allogeneic recipients. Renal functional parameters, including vascular resistance, glomerular filtration rate, urine production, oxygen consumption, and proximal tubular fluid reabsorption, were monitored during the reperfusion period and were compared with the control ischemic group. RESULTS: Renal function significantly declined during I/R, relative to the nonischemic contralateral kidney but was not different with any form of IPC, relative to the ischemic control group not treated with IPC. IPC pretreatment also did not affect the preservation injury observed in cold-stored kidneys reperfused after transplantation. CONCLUSIONS: It is concluded that IPC has no significantly measurable effects in warm or hypothermic renal I/R injury in large animals. The clinical usefulness of IPC in human renal ischemic conditions remains uncertain.     

The liver protective effect of ischemic preconditioning may be mediated by adenosine

Abstract We investigated the involvement of adenosine in ischemic preconditioning (IPC) by the unspecific antagonist, 8‐phenyltheophylline (8‐PT). Anesthetized Wistar rats were treated as follows: 1. nonischemic controls, 2. ischemic controls: 60 min of clamping of the common hepatic artery followed by 60 min reperfusion, 3. IPC: 10 min ischemia followed by 15 min reperfusion, prior to the identical ischemia‐reperfusion (IR) period as in group 2, 4. 8‐PT + IPC: 8‐PT 10 mg/kg i. v. was given 10 min prior to the identical procedure as in group 3. The peripheral liver blood flow was monitored by laser‐Doppler flowmetry. Blood alanine aminotransferase (ALT) was analyzed once every 60 min. IPC significantly reduced impairment of liver blood flow, as well as ALT increase during reperfusion. This effect was abolished by pretreatment with 8‐PT. Adenosine appears to be a crucial effector in IPC. Clinical studies need to be undertaken to explore a possible effect of IPC in liver transplantation.     

Ischemic preconditioning reduces neurologic injury in a rat model of spinal cord ischemia.

BACKGROUND: Ischemic preconditioning (IPC) is an endogenous cellular protective mechanism whereby brief, noninjurious periods of ischemia render a tissue more resistant to a subsequent, more prolonged ischemic insult. We hypothesized that IPC of the spinal cord would reduce neurologic injury after experimental aortic occlusion in rats and that this improved neurologic benefit could be induced acutely after a short reperfusion interval separating the IPC and the ischemic insult. METHODS: Forty male Sprague-Dawley rats under general anesthesia were randomly assigned to one of two groups. The IPC group (n = 20) had 3 minutes of aortic occlusion to induce spinal cord ischemia 30 minutes of reperfusion, and 12 minutes of ischemia, whereas the controls (n = 20) had only 12 minutes of ischemia. Neurologic function was evaluated 24 and 48 hours later. Some animals from these groups were perfusion-fixed for hematoxylin and eosin staining of the spinal cord for histologic evaluation. RESULTS: Survival was significantly better at 48 hours in the IPC group. Sensory and motor neurologic function were significantly different between groups at 24 and 48 hours. Histologic evaluation at 48 hours showed severe neurologic damage in rats with poor neurologic test scores. CONCLUSIONS: Ischemic preconditioning reduces neurologic injury and improves survival in a rat model of spinal cord ischemia. The protective benefit of IPC is acutely invoked after a 30-minute reperfusion interval between the preconditioning and the ischemic event.     

缺血后处理对大鼠肝缺血再灌注损伤早期的保护作用

目的 探讨缺血后处理（IPC）对大鼠肝脏缺血再灌注损伤早期的保护作用机理。方法 建立大鼠肝脏缺血再灌注模型，54只健康雄性SD大鼠随机分为假手术组（SO组）、对照组（IR组）和缺血后处理组（IPC组）。后处理组于完全再灌注前，给予多次短暂复灌复停作为缺血后处理。分别于再灌注后1h、3h及6h抽血进行血清ALT、AST活性及TNF-α表达测定，免疫组化测定肝脏NF-kB活性及ICAM-1的表达。结果 与SO组比较，IR组及IPC组再灌注后大鼠血清ALT、AST活性明显增高，肝脏NF-kB活性明显增强，TNF-α和ICAM-1表达也随之增加；同IR组相比，IPC组的血清ALT、AST活性明显降低，NF-kB活性及TNF-α和ICAM-1表达亦明显降低，差异均具有统计学意义（P〈0．01）。结论 缺血后处理能够减轻肝脏缺血再灌注损伤。其保护作用可能与通过抑制再灌注早期NF-kB的活性，降低了TNF-α和ICAM-1等炎性细胞因子水平有关。     

缺血预处理对家兔脑缺血保护效应的实验研究

目的 探讨缺血预处理脑保护效应,以及神经细胞凋亡与缺血性脑损害的关系。方法 家兔１５只,随机分为３组,对照组,缺血组,缺血预处理组。Ａ组只做手术操作,Ｂ组采用二血管夹闭全脑缺血１０分钟,Ｃ组在缺血前增加缺血预处理２分钟再灌注３０分钟。对比观察缺血后３天海马ＣＡ１区神经元密度和缺血细胞数,同时使用ＴＵＮＥＬ原位标记法,检测缺血３天后海马区的凋亡细胞。     

缺血预处理对家兔肢体缺血再灌注后肺抗氧化系统的影响

目的：观察肢体缺血预处理对家兔肢体缺血再灌注后肺损伤时肺抗氧化系统的影响并探讨其机制。方法：健康家兔30只，随机分为假手术对照组（SC）、缺血再灌注组（IR）和缺血预处理组（IPC），每组10只。实验结束时，取肺组织测定超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）、黄嘌呤氧化酶（XOD）活性和丙二醛（MDA）、一氧化氮（N0）含量，同时计算肺系数及进行肺病理学检查。结果：肢体缺血再灌注后肺组织SOD、GSH-PX活性和NO含量显著下降，XOD活性和MDA含量明显增高，肺系数升高，肺组织病变明显，肢体缺血预处理可明显缓解上述变化。结论：家兔肢体缺血再灌注后，肺抗氧化功能下降参与肺脏的损伤过程，肢体缺血预处理对这种肺损伤有明显的保护作用。     

不同时限缺血预处理对硬化肝脏保护作用的实验研究

目的: 探讨缺血预处理对硬化肝脏缺血再灌注的作用,并寻找一种有效缺血预处理的时间窗和理想方案. 方法: 将64只雄性、肝硬化SD大鼠随机分为八组,每组八只:假手术组(SO组);缺血再灌注组(I/R组);缺血预处理1、2、3、4、5和6组(IPC1、IPC2、IPC3、IPC4、IPC5和IPC6).以肝组织ATP、ADP、AMP及EC(用高效液相色谱法测定),血清ALT、AST、LDH(用全自动生化仪测定)和肝脏胆汁分泌量来评价肝功能. 结果: 再灌注末,IPC3组、IPC4组、IPC5组ATP含量均明显高于I/R组(P分别为0.01、0.07和0.000);同样,测定EC时发现,IPC3组、IPC4组和IPC5组均明显高于I/R组(P=0.000).与I/R组比较,IPC4组和IPC5组的血清ALT差异有显著性(P分别为0.013和0.000);其血清LDH差异亦有显著性(P=0.023,P=0.000),而血清AST却只有IPC5组显著低于I/R组(P=0.001).IPC3组、IPC4组和IPC5组肝脏的胆汁分泌量明显高于I/R组(P=0.028,P=0.023,P=0.008). 结论: 5~10min予一次或两次缺血预处理,能启动IPC对肝硬化大鼠肝脏I/R损伤的保护作用;10 min的缺血预处理,对肝硬化大鼠肝脏I/R损伤的保护作用最强.     

肾脏缺血预适应及细胞间黏附分子1的作用

目的建立肾脏缺血预适应大鼠模型,探讨缺血预适应对细胞间黏附分子(ICAM)-1mRNA表达的影响。方法摘除右肾后,对左肾采用2min缺血 5min再灌注,4个循环后再缺血45min,建立大鼠肾脏缺血预适应模型。RT-PCR检测肾脏ICAM-1mRNA表达。结果缺血预适应使肾缺血后Scr的升高幅度值减少,肾小管损伤减轻,髓质ICAM-1mRNA表达降低。结论肾脏缺血预适应可从组织学和功能上减轻肾脏的急性缺血性损伤,这可能与肾组织ICAM-1表达降低及局部炎症减轻有关。     

Cardioprotective effect of ischemic preconditioning on global myocardial ischemia in a sheep right heart bypass model

OBJECTIVES: Ischemic preconditioning has been used to induce the myocardium to adapt to ischemic stress preceded by short periods of ischemia and reperfusion. We used a sheep right heart bypass model with a conductance catheter to assess the cardioprotective effect of ischemic preconditioning on 30-minute normothermic global myocardial ischemia. METHODS: Ischemic preconditioning was conducted in 6 sheep in 35-minute aortic cross-clampings interspersed with 5 minutes of reperfusion during cardiopulmonary bypass, with 6 sheep as time-matched controls. Global myocardial ischemia was subsequently achieved in 30-minute aortic cross-clamping with left ventricular unloading during normothermic cardiopulmonary bypass. Weaning from cardiopulmonary bypass was conducted 40 minutes after reperfusion. Before ischemia and 40, 70, and 100 minutes after reperfusion, left ventricular pressure-volume loops were measured using a conductance catheter during right heart bypass preparation. Left ventricular contractility, diastolic function, and mechanical efficiency were then evaluated. Right heart bypass was instituted to control the preload and to decompress the right ventricle completely, thereby eliminating parallel conductance variation. RESULTS: No differences in the studied parameters were seen between ischemic-preconditioning and control groups before ischemia. Left ventricular contractility, diastolic function, and mechanical efficiency in the ischemic-preconditioning group were significantly superior to those in the control group after reperfusion. CONCLUSIONS: Ischemic preconditioning attenuates postischemic myocardial dysfunction in a sheep model using 30-minute unloaded normothermic global myocardial ischemia. Ischemic preconditioning would thus be clinically significant when the ischemic damage is severe.     

Effects of ischemic preconditioning on regenerative capacity of hepatocyte in the ischemically damaged rat livers

BACKGROUND: Liver regeneration after partial hepatectomy is regulated by several factors that activate or inhibit hepatocyte proliferation. A short period of ischemia-reperfusion (IR), called ischemic preconditioning (IPC), protects the liver against subsequent sustained ischemic insults. The present study investigated the effects of IPC on liver regeneration after partial hepatectomy under IR in rats. MATERIALS AND METHODS: Male Wistar rats were subjected to 45 min of total hepatic ischemia, and 70% hepatectomy was performed just before reperfusion. Animals were pre-treated with either IPC (10/15 min) (IPC + PHx group) or not (ischemia + PHx). The survival rate, serum transaminases, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 levels, hepatocyte proliferation and histological change of the remnant liver were measured in both groups and compared with non-ischemic controls subjected to 70% hepatectomy alone (PHx group). RESULTS: The survival rate was significantly better in the IPC + PHx group than in the ischemia + PHx group. Furthermore, IPC reduced liver injury determined by liver histology and serum transaminases. There was an early rise in serum TNF-alpha and IL-6 levels in the ischemia + PHx group. Compared with non-ischemic controls, IPC significantly decreased TNF-alpha, but not IL-6 during the late (24 and 48 h) phases of reperfusion. Rats subjected to 70% hepatectomy and 45 min of hepatic ischemia showed significantly reduced hepatocyte proliferation (mitotic index, proliferating cell nuclear antigen, and relative liver weight) when compared with animals subjected to hepatectomy alone. However, hepatocyte proliferation was markedly increased in rats pretreatment with IPC when compared with ischemic controls. CONCLUSION: These results suggest that ischemic pre-conditioning ameliorates the hepatic injury associated with ischemia-reperfusion and has a stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective modality. Il-6 appears to be key mediator in promoting regeneration after combined ischemia and hepatic resection.     

Does adenosine administration during the early reperfusion period affect ischemic preconditioning?

We hypothesized that the adenosine administration during the early reperfusion period might affect ischemic preconditioning (IPC) and might reduce infarct size and enhance post-ischemic functional recovery. Twenty-four anesthetized rabbits underwent 30 min. normothermic global ischemia with 120 min. reperfusion in a buffer-perfused isolated, paced heart model and divided into four groups. Global ischemic hearts (GI, n = 6) were subjected to 30 min. global ischemia without intervention. Control hearts (n=6) were subjected to perfusion without ischemia. Ischemic preconditioned hearts (IPC, n=6) were subjected to one cycle of 5 min. global ischemia and 5 min. reperfusion prior to global ischemia. IPC + Ado hearts (n=6) received IPC and adenosine administration (100 m mol/L) during 3 min. early reperfusion period. Post-ischemic functional recovery was better in IPC + Ado hearts as compared to GI and IPC hearts, but the effect of post-ischemic functional recovery in IPC + Ado hearts became weaker during 120 min. reperfusion after prolong ischemic insult. Infarct size wre 1.0 ± 0.3% in Control hearts, 32.9 ± 5.1% in GI hearts, 13.8 ± 1.3% in IPC hearts and 8.1 ± 0.9% in IPC + Ado hearts. Infarct size in IPC hearts was significantly decreased (p<0.01) as compared to GI hearts. The reduction rate against myocardial necrosis in IPC + Ado hearts versus GI hearts was higher as compared to IPC hearts versus GI hearts (p<0.001, IPC+Ado hearts vs GI hearts; p<0.01, IPC hearts vs GI hearts; p = ns, IPC + Ado hearts vs Control hearts). These data suggest that adenosine administration during the early reperfusion period reinforce IPC effect and reduce myocardial reperfusion injury. Cardiomyoprotective effects of IPC and exogenous adenosine are exerted during early reperfusion after coronary occlusion in the isolated perfused rabbit hearts.     

缺血预处理对大鼠小体积供肝的保护作用及机制

目的探讨缺血预处理（IPC）对大鼠小体积供肝的保护作用及其机制。方法120只SD大鼠随机分为3组（每组20对）：无热缺血组（NWI）、缺血再灌注组（WI）和缺血预处理组（IPC）。用双袖套法建立大鼠小体积肝移植模型。各组10只受体大鼠于术前1d、术后1、2、3、5d取血，用自动生化分析仪检测AST和ALT。NWI组于供肝灌注前及植入后0．5、1、2、3h，WI组于热缺血前及植入后0．5、1、2、3h，IPC组于IPC前、IPC后及植入后0．5、1、2、3h取肝组织，用硝酸还原法检测其NO浓度。结果IPC可降低大鼠小体积肝移植术后血清AST和ALT浓度，提高再灌注早期肝脏组织NO的浓度，降低再灌注晚期肝脏组织NO的浓度（P〈0．05）。结论NO在大鼠肝脏的缺血再灌注损伤中可能具有双重作用。IPC对大鼠小体积供肝的缺血再灌注损伤有保护作用。其机制可能是通过促进供肝再灌注后早期NO合成，改善肝脏微循环，同时抑制供肝再灌注后晚期NO合成，减轻过量NO的损伤作用，从而保护移植肝脏功能。