异丙酚对犬急性心肌缺血再灌注损伤左心室功能的影响

目的；研究没剂量的异丙酚对急性心肌缺血再灌注损伤左心室功能的影响。方法；杂种家犬１８只，随机分三组，ＮＳ组用量为２ｍｌ．ｋｇ＾－１，ｈ＾－１，ＨＰ组用量为１１．２ｍｇ．ｋｇ＾－１．ｈ＾－１，ＬＰ组用量为５．６ｍｇ．ｋｇ＾＝－１．ｈ＾－１。开胸阻断左冠脉前降支９０分后再灌注２００分钟，于注药前，注药后６０分钟，阻断左冠脉前降支血流９０分钟以及再灌注６０，１２０和１８０分钟时，分别测各组左心室内压峰值     

常温下阻断肝血流的麻醉处理

常温下阻断肝血流是减少肝脏手术术中出血的最有效方法.但阻断肝血流给麻醉管理带来了新问题.本文综述了肝血流阻断及开放时,机体出现的血流动力学变化及水、盐、电解质紊乱和相应处理;同时也阐述了肝血流阻断的可行时限及肝再灌注损伤与肝保护的措施.     

肝门阻断再灌注后脑钠素和心肌细胞膜Na+-K+ATPase活性的改变

目的 观察肝门阻断再灌注后血流动力学和心肌能量代谢改变.方法 大鼠气管切开机械通气.随机分为假手术对照组(A组,n=24):不作肝血流的阻断;肝血流阻断组(B组,n=24):阻断肝十二指肠韧带60 min后开放再灌注;门静脉转流下肝血流阻断组(C组,n=24):分别阻断肝左中叶及右叶肝蒂,保留尾叶血供作为门静脉血液回流通道,60 min后再灌注.每组各有8只大鼠分别于再灌注前、再灌注后1、6 h取材.血气分析研究肝门阻断期间门脉中pH值和电解质变化、ELISA检测脑钠素(BNP)水平以及比色法测定心肌细胞膜Na -K ATPase活性.结果 与A组比较,B组再灌注前pH值显著降低,K 升高幅超过1倍(P＜0.01),再灌注后开始下降,Ca2 也进行性下降;同时再灌注后B组肺动脉压(PAP)显著升高,6 h后仍不能恢复;B组BNP再灌注后高于A组(P＜0.05),但组内比较差异无统计学意义;再灌注后B组心肌Na -K ATPase活性显著降低(P＜0.01).结论 肝门阻断后再灌注可引起脑钠素和心肌细胞膜Na -K ATPase活性改变.     

热缺血再灌注损伤时肝细胞凋亡的变化

越来越多的研究表明 ,细胞凋亡在肝脏缺血再灌注损伤这一过程中发挥着重要作用。本文探讨肝脏缺血再灌注时细胞凋亡的变化。一、材料与方法1.本实验采用健康雄性Ｗｉｓｔａｒ大鼠 2 4只 ,随机分成 4组 ,每组 6只 :(1)假手术组 :只做大鼠肝脏的游离 ,目的是作为正常对照以排除手术因素对实验结果的影响 ;(2 )对照组 :阻断大鼠肝左叶和中叶的门静脉、肝动脉 6 0ｍｉｎ后 ,立即切取左叶和右叶肝组织标本检测 ;(3)实验组 1:阻断血流操作同对照组 ,恢复血流再灌注 2ｈ后 ,切取左叶和右叶肝组织标本检测 ;(4)实验组 2 :操作同实验组 1,在再灌注 2 …     

入肝血流阻断对阻塞性黄疸大鼠肝脏能量代谢的影响

目的 探讨阻塞性黄疸大鼠肝脏缺血后能量代谢变化的病理特征及其与动物耐受性的关系。方法 大鼠胆管结扎后１周,在门静脉转流入阻断入肝血流不同时程后观察动物存活率、肝细胞线粒体呼吸活性、肝组织ＡＴＰ含量及动脉血酮体比值。结果 阻断入肝血流３０、６０及９０分钟后１０天动物存活率分别为１００％、１００％及４０％;缺血后肝脏能量代谢功能明显受损,在再灌注后２４小时,阻断入肝血流３０及６０分钟两组动物肝脏能量代谢功能已有明显恢复,而阻断入肝血流９０分钟组肝脏能量代谢功能仍维持在显著低水平。结论 胆道梗阻后１周,大鼠门静脉转流下入肝血流阻断６０分钟以内肝脏能量代谢功能损害可逆,动物安全耐受;而阻断入肝血流９０分钟引起肝脏能量代谢功能不可逆性损害,动物难以安全耐受。     

影响肝缺血再灌注损伤主导因素的肌理

我们动态观察ＳＤ大鼠肝缺血４５．６０分钟复流０．１０，６０，１２０分钟，人体肝门阻断１５分钟复流５－１０分钟，４０分钟不同时限肝细胞内游离钙浓度，肝组织脂质过氧化自由基电子自旋共振信号最大幅值及脏脏超微结构病理变化，结果发现，在再灌注早期（大鼠肝血４５分钟复流１０分钟，人体肝缺血１５分钟复流５－１０分钟已可观察到（「Ｃａ＾２＋）」ｉ）增高现象，而ＲＯＯ．Ｙｍａｘ变化不显著，肝细胞超微结构仅表现为线     

人肝血流阻断对肝组织Ptio2、Ptico2、pH和T的影响

目的研究常温下入肝血流阻断对兔肝组织氧分压(Ptio2)、二氧化碳分压(Ptico2)、酸碱度(pH)和温度(T)的影响及临床意义.方法入肝血流阻断15 min后再灌注,通过组织气体分析仪持续测定兔肝组织Ptio2、Ptico2、pH和T变化.结果肝血流阻断后Ptio2下降至7.6±0.1 mmHg;Ptio2值升至163.±27 mmHg;pH值降至6.7±0.1;T下降至35.6±0.7C.再灌注15 min后,肝组织Ptio2、Ptio2、pH和T缓慢恢复.结论人肝血流阻断导致肝脏缺血/再灌注损伤,肝组织代谢异常;肝组织内Ptio2、Ptio2、pH值和T观察是监测肝缺血/再灌注损伤的一个重要方法.     

肝血流阻断方法在肝硬化患者肝肿瘤手术中的选择

目的:评价肝硬化患者行肝脏肿瘤切除术时肝血流阻断方法的选用。方法:将我院2007年6月—2012年12月63例需行肝切除的肝肿瘤伴肝硬化患者随机分为3组。A组22例,为间歇血流阻断组,采用阻断肝血流15 min,复流5 min;B组20例,为半肝血流阻断组,行同侧半肝血流持续性阻断,健侧血流正常;IP组21例,采用入肝血流阻断前先阻断5 min、复流5 min的预处理方法。比较3组术中阻断时间、肝断面单位面积出血量、3组及3组中阻断时间<30 min者术后1、3、7、14 d的ALT、AST及TB变化情况。结果:3组肝断面单位面积出血量差异有统计学意义(P<0.05)。术后B组缺血再灌注损伤最轻,IP组最重,差异有统计学意义(P<0.05)。阻断时间<30min者术后肝功比较,IP组较A组缺血再灌注损伤明显降低(P<0.05)。结论:肝血流阻断前预处理可减少肝切除术中的失血量。术前预计切除时间<30 min的患者可采用预处理减少出血量及再灌注损伤。     

肝脏低温保存肝血窦变化的实验观察

目的：探讨低温保存肝血窦超微结构的变化及其在肝微循环障碍中的作用，方法：将63只大鼠肝脏分别在低温UW液中保存0（对照组）、2、8、16、24、32和48h，然后对肝血窦进行电镜观察，结果：肝血窦内皮细胞在保存2、8h后，筛板小孔扩大，融合成许多大洞隙，16、24h细胞胞明显回缩，呈树根状，32，48h似索网状，部分内皮细胞突起，脱落，肝细胞微绒毛在保存8h后出现肿胀并形成膜浆泡从扩大的内皮小孔突入血窦；随着保存时间延长，膜浆泡增多，变大并脱落或破裂，结论：肝血窦内皮细胞的低温保存损伤和膨入血窦内的膜浆泡可引起肝微循环紊乱，导致肝血流和肝功能障碍。     

肝缺血再灌注后肝内血流动力学的变化

目的探讨肝脏缺血再灌注（I／R）后肝内分流（IHSF）和功能性肝血流（FHBF）的变化。方法健康雄性SD大鼠l2只，作右侧颈动脉、颈静脉插管；开腹后，经回结肠静脉作门静脉插管，分别用以输血、输液、给药、留样、检测等。大鼠经部分肝I／R制模后，随机分为2组（每组6只）：（1）正常对照组（对照组），术中只分离肝周围韧带，不作肝门阻断及再灌注。（2）缺血再灌注组（1／R组，实验组），进行45min的肝门阻断及60min的再灌注。然后两组均经门静脉输注D一山梨醇（10mmol／L，0．2mL／min），2min后同时取颈动脉、门静脉、肝静脉血各1mL。测定门静脉血流量（PVF）、肝动脉血流量（HAF）。计算肝脏山梨醇摄取率、FHBF和IHSF。结果两组PVF，HAF及总肝血流量（THBF）无明显统计学差异；与对照组比较，I／R组肝脏山梨醇摄取率和FHBF减少，IHSF增加（P〈0．01）。结论肝I／R后，肝内血流动力学变化表现为肝内门一体分流开放，功能性肝血流减少。     

Warm hepatic ischemia in pigs: effects of L-arginine and oligotide treatment.

Reperfusion injury represents a key event leading to graft nonfunction. Maintaining adequate nitric oxide levels and stimulating vasodilator synthesis can probably minimize endothelial damage. The aim of this study was to investigate the effect of L-arginine, a substrate of nitric oxide synthesis, and oligotide, a promoter of prostacyclin synthesis, on liver function and morphology after warm ischemia-reperfusion injury. After constructing a side-to-side portacaval shunt, ischemia was induced by clamping the hepatic hilum for 2 h above the shunt, in 19 female pigs divided into a control group (n = 7), an L-arginine treatment group (n = 6), and an oligotide treatment group (n = 6). Liver function tests and measurements of serum and red blood cell malondialdehyde and plasma nitric oxide levels were performed before reperfusion and at 1, 10, 60, and 120 min after reperfusion. Liver biopsies, taken before reperfusion and at 30 min and 7 days after reperfusion, were analyzed for tissue malondialdehyde, histological-ultrastructural features, and apoptosis evaluation. Thirty minutes after reperfusion, liver malondialdehyde, sinusoidal congestion, necrosis, and apoptosis were significantly lower in the L-arginine group than in the controls (p < .05). On postoperative day 7, tissue malondialdehyde decreased, while plasma nitric oxide and hepatocyte glycogen content were increased in the L-arginine group compared to controls (p < .05). This study demonstrates the protective effect of L-arginine on hepatic lipoperoxidation and liver morphology in a pig model of warm ischemia-reperfusion injury. The increased plasma levels of nitric oxide a week after ischemia-reperfusion injury support the hypothesis that it has a role in preventing liver damage. The same beneficial effect was not confirmed for oligotide.     

Prolonged continuous or intermittent vascular inflow occlusion during hemihepatectomy in pigs

OBJECTIVE: To assess ischemia and reperfusion (I/R) injury in a hemihepatectomy model in pigs after prolonged continuous or intermittent vascular inflow occlusion in the liver. SUMMARY BACKGROUND DATA: Massive intraoperative blood loss during liver resections can be prevented by temporary vascular inflow occlusion, consequently leading to ischemia and reperfusion injury in the remnant liver. Previously, in a pig liver resection model in which only limited I/R injury was induced during brief (90 min) vascular inflow occlusion, the authors demonstrated reduced I/R injury after continuous (CNT) occlusion, compared to intermittent (INT). This liver resection study on pigs was undertaken to assess I/R injury after prolonged (120 min) CNT or INT occlusion. METHODS: In pigs (37.0 +/- 1.5 kg), liver ischemia during 2 hours was CNT (n = 6) or INT (n = 6) (eight subsequent periods of 12 min ischemia and 3 min recirculation), followed by 6 hours of reperfusion. A left hemihepatectomy (45.5% +/- 1.4%) was performed within the first 12 minutes of ischemia. No hepatic pedicle clamping or liver resection was performed in control experiments (n = 6). Microvascular damage was assessed by hyaluronic acid (HA) uptake capacity of the liver (parameter of early sinusoidal endothelial cell damage) and restoration of intrahepatic tissue pO2 during reperfusion. Hepatocellular damage was tested by plasma concentrations of aspartate aminotransferase (AST), alanine aminotransferase, and lactate dehydrogenase (LDH). RESULTS: Hyaluronic acid uptake after 6 hours of reperfusion, compared to preischemic uptake, was unaltered in the control group, but was significantly reduced in both resection groups. However, more HA was taken up after INT occlusion, compared to CNT (60.4% +/- 5.6% and 39.5% +/- 3.7%, respectively; ANOVA: p = 0.001). Intrahepatic tissue pO2 distribution after 6 hours of reperfusion more closely returned to preischemic configuration in the INT group than in the CNT group, indicating reduced microcirculatory disturbances after INT occlusion. Release of AST and LDH after 6 hours of reperfusion was significantly increased in both CNT and INT groups. Lower AST levels, however, were found after INT occlusion than after CNT occlusion (267.0 +/- 74.7 U/l and 603.3 +/- 132.4 U/l, respectively; p = 0.06). CONCLUSIONS: Intermittent hepatic vascular inflow occlusion during prolonged liver ischemia in pigs resulted in less microcirculatory and hepatocellular injury, compared to continuous occlusion. Intermittent clamping is preferable when prolonged periods of vascular inflow occlusion are applied during liver resections.     

Warm Hepatic Ischemia in Pigs: Effects of L-Arginine and Oligotide Treatment

Reperfusion injury represents a key event leading to graft nonfunction. Maintaining adequate nitric oxide levels and stimulating vasodilator synthesis can probably minimize endothelial damage. The aim of this study was to investigate the effect of L-arginine, a substrate of nitric oxide synthesis, and oligotide, a promoter of prostacyclin synthesis, on liver function and morphology after warm ischemia-reperfusion injury. After constructing a side-to-side portacaval shunt, ischemia was induced by clamping the hepatic hilum for 2 h above the shunt, in 19 female pigs divided into a control group ( n = 7), an L-arginine treatment group ( n = 6), and an oligotide treatment group ( n = 6). Liver function tests and measurements of serum and red blood cell malondialdehyde and plasma nitric oxide levels were performed before reperfusion and at 1, 10, 60, and 120 min after reperfusion. Liver biopsies, taken before reperfusion and at 30 min and 7 days after reperfusion, were analyzed for tissue malondialdehyde, histological-ultrastructural features, and apoptosis evaluation. Thirty minutes after reperfusion, liver malondialdehyde, sinusoidal congestion, necrosis, and apoptosis were significantly lower in the L-arginine group than in the controls ( p < .05). On postoperative day 7, tissue malondialdehyde decreased, while plasma nitric oxide and hepatocyte glycogen content were increased in the L-arginine group compared to controls ( p < .05). This study demonstrates the protective effect of L-arginine on hepatic lipoperoxidation and liver morphology in a pig model of warm ischemia-reperfusion injury. The increased plasma levels of nitric oxide a week after ischemia-reperfusion injury support the hypothesis that it has a role in preventing liver damage. The same beneficial effect was not confirmed for oligotide.     

Endothelin-1 is involved in hepatic sinusoidal vasoconstriction after ischemia and reperfusion

Abstract Endothelin-1 (ET-1), a vasoactive peptide, causes a significant rise in portal vein pressure, which is most likely a result of severe vasoconstriction in the liver. In this study, the effect of ET-1 on sinusoidal vasoconstriction in the liver after ischemia and reperfusion was directly investigated using intravital microscopy. In anesthetized female Sprague Dawley rats (200–250 g) ischemia of the median and left liver lobes was induced for 90 min by temporary ligation of the left pedicle. After declamping and a 90-min reperfusion period, the livers were exposed for intravital microscopy. Using a Nikon MM-11 fluorescence microscope (545 nm, 330x), a CCD camera (Cohu FK 6990), and a SVHS video recording unit, the hepatic micro-circulation was directly investigated. Besides sham groups, two ischemia groups were studied, receiving ET-1 antiserum (anti-ET-1; 0.5 ml; Peptide Inst., Osaka, Japan) or NaCl 0.9% (0.5 ml) 5 min prior to reperfusion of the liver ( n = 6/group). Following a transient drop in the mean arterial blood pressure in the anti-ET-1-treated groups, comparable systemic hemodynamic conditions among the four groups were noted during intravital microscopic assessment at the end of the 90-min reperfusion period. Reduction in the sinusoidal diameters during postischemic reperfusion (7.7 ± 0.5 pm) was prevented by anti-ET-1 treatment (9.6 ± 0.25 pm; P < 0,01; mean ± SEM) back to control values (9.6 ± 0.32 μm), while most of other microcirculatory parameters did not show significant differences. The results supported further the role of ET-1 in dysregulation of the sinusoidal vascular tone in the liver, e.g., after ischemia and reperfusion.     

Controlled vasoregulation of postischemic liver microcirculation--a therapeutic approach.

One of the changes produced by ischemia and reperfusion is endothelin (ET)-mediated constriction of the hepatic vascular bed. This leads to microcirculatory disturbances and reduced blood flow, thereby causing local hypoxia and liver damage. Our aim was to induce stepwise changes of microvascular vessel diameters so as to define the best protective vessel width that could be produced by drug therapy and thereby to minimize ischemia/reperfusion injury. The mixed ET receptor antagonist bosentan was used in different dosages in a rat liver ischemia/reperfusion model with splenocaval shunt. In vivo microscopy was performed 30-90 min after reperfusion and local hepatic tissue pO2 was determined, together with aspartate aminotransferase/alanine aminotransferase (AST/ALT). After ischemia, sinusoidal diameters were significantly reduced to 76 +/- 7% of those in the control group. After the administration of bosentan in dosages of 0.1, 1, and 10 mg/kg body weight iv and 10 mg/kg body weight intraportally we found diameters of 83 +/- 4, 98 +/- 2, 109 +/- 6, and 137 +/- 19%, respectively. Perfusion rate and leukocyte-endothelium interactions showed dependence on sinusoidal diameters, with the best results in the group where preischemic sinusoidal vessel width had been maintained. Local tissue pO2 and transaminase levels also showed that oxygen supply was sufficient and that hepatocellular injury was most minimized in this group. Graduated blocking of ET receptors allows stepwise regulation of sinusoidal and postsinusoidal venular vessel width and offers a treatment strategy for pathophysiological situations that are associated with ET-induced vasoconstriction. The results suggest that maintenance of preischemic microvascular diameter is the best therapeutic approach.     

Inhibition of angiotensin-converting enzyme reduces rat liver reperfusion injury via bradykinin-2-receptor

BACKGROUND: Bradykinin is both a potent vasodilatator and a central inflammatory mediator. Similar to findings in myocardial reperfusion injury, bradykinin might mediate the protective effects of angiotensin-converting enzyme (ACE) inhibition after liver ischemia via increased bradykinin-2-receptor (B-2) stimulation. On the other hand, B-2-inhibition has been shown to reduce liver reperfusion injury. This study was designed to investigate the role of Bradykinin in hepatic reperfusion injury. MATERIALS AND METHODS: Twenty eight rats were allocated randomly to Sham procedure (Sham), 30-min normothermic ischemia (ischemia), ischemia with Ramiprilat (ACE-I), or ischemia with Ramiprilat and B-2-inhibitor HOE 140 (ACE-I+B-2-I). Liver microcirculation and leukocyte adherence were investigated using intravital microscopy 30 min after reperfusion (n = 7 per group). In addition, serum activities of AST and ALT were measured for 7 days (n = 28). RESULTS: Ischemia was associated with a loss of perfused sinusoids, sinusoidal vasoconstriction, and a reduction in microvascular blood flow. Permanent leukocyte adherence increased both in sinusoids and in postsinusoidal venoles. ACE-I restored sinusoidal perfusion, normalized vasoregulation, maintained sinusoidal blood flow, and inhibited leukocyte adhesion. ACE-I+B-2-I abolished the protective effects linked to ACE-I. Ischemia-induced liver cell injury after 5 h of reperfusion was ameliorated by ACE-I. In the ACE-I+B-2-I group, reduction in liver cell injury was reversed. CONCLUSION: After hepatic ischemia, ACE-I reduced reperfusion injury in a B-2-dependent manner. These results suggest a pivotal role for bradykinin in the treatment of reperfusion injury by Ramiprilat, mediating sinusoidal dilation and blunting hepatic inflammation.     

Intestinal energy metabolism during ischemia and reperfusion

BACKGROUND. In order to evaluate acute ischemic damage in the small intestine induced by superior mesenteric artery occlusion (SMAO) and subsequent reperfusion, changes in ATP, ADP, and AMP were measured by high-performance liquid chromatography, and changes in tissue blood flow were measured (from the serosal surface) by the laser doppler flow meter in a rat model. MATERIALS AND METHODS. The superior mesenteric artery of the rat was occluded for 30, 60, 90, and 120 min and then reopened. Core temperature was maintained carefully at 37 +/- 0.3 degrees C. RESULTS. All rats that underwent 90 and 120 min of SMAO died within 2 days, but those with 30 and 60 min of SMAO survived. ATP (10.39 +/- 0.90 micromol/g dry weight), ADP (3.34 +/- 0.33), and total adenine nucleotides (TAN; 14.08 +/- 0. 86) decreased with longer SMAO times. After 30 and 60 min of SMAO followed by reperfusion, recoveries of ATP and TAN were relatively good and ADP levels remained fairly steady, but little or no recovery of these levels was observed after 90 and 120 min of SMAO followed by reperfusion. There were linear correlations between the levels of ATP and TAN after 30 min of reperfusion and the time of SMAO. Tissue blood flow levels were constant during SMAO. After reperfusion, those levels were recovered along with the SMAO periods. But recovery rates compared with control values were not related with those of ATP. CONCLUSIONs. ATP and TAN levels, particularly at 30 min after reperfusion, seemed to be in good agreement with the tissue damage and the viability of the small intestine. We propose that the measurement of these levels may be useful for the evaluation of intestinal damage and viability.     

Pulmonary endothelial cell ATP depletion following intestinal ischemia.

Multiple organ failure (MOF) is known to follow systemic inflammatory mediator activation associated with intestinal ischemia-reperfusion injury. In particular, the pulmonary microvasculature appears to be susceptible to MOF-related injury. This study was designed to evaluate the hypothesis that non-cellular plasma factors associated with intestinal ischemia without reperfusion also mediate pulmonary endothelial cell injury. Male Sprague-Dawley rats had intestinal ischemia induced by microvascular clip occlusion of the superior mesenteric artery for 30, 60, 90, or 120 min. Following each period of ischemia, plasma samples were obtained from the protal vein. Time-matched sham-operated animals served as controls. Monolayers of cultured rat pulmonary artery endothelial cells were then incubated with the plasma samples and ATP levels determined using a luciferin-luciferase assay. A 51Cr-release assay using labeled endothelial cells was performed under identical conditions to assess cytotoxicity. Endothelial cell ATP levels were 1.99 +/- 0.23 x 10(-11) mole/micrograms DNA in sham preparations. After a 4-hr incubation in plasma from the 90 and 120 min ischemia groups, cellular ATP levels fell significantly to 1.07 +/- 0.23 x 10(-11) mole/micrograms DNA, respectively (P less than 0.005). No significant cytotoxic injury resulted from incubation with plasma from the 120 min group (1.0 +/- 0.4% versus 0.8 +/- 0.4% in sham group, P = NS). All animals survived 24 hr in the sham, 30, and 60 min groups. However, survival was 40 and 0% in the 90 and 120 min groups, respectively (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Piroxicam and meloxicam ameliorate hepatic oxidative stress and protein carbonylation in Kupffer and sinusoidal endothelial cells promoted by ischemia–reperfusion injury

The present study was aimed to assess the effect of protein carbonylation (PC) in hepatic cells and effects of nonsteroidal anti‐inflammatory drugs (NSAIDs) on indicators of tissue damage induced by liver ischemia–reperfusion injury (LIRI). Warm ischemia was performed by partial vascular occlusion during 90 min in Wistar rats. In serum, we determined the catalytic activity of Alanine Aminotransferase, Aspartate Aminotransferase, Lacticate Dehydrogenase, and Ornithine Carbamoyltransferase. In liver samples, we studied cellular alterations by means of histologic studies, lipid peroxidation, PC by immunohistochemistry, apoptosis and reactive oxygen species in bile by electron paramagnetic resonance. Based on PC data, sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were the first to exhibit LIRI‐associated oxidative damage and prior to parenchymal cells. Administration of piroxicam or meloxicam during the pre‐ischemic period produced a highly significant decrease in all studied injury indicators. No significant differences were revealed between the protective action of the two drugs. The data shown here suggest the potential use of NSAIDs such as piroxicam or meloxicam in minimizing ischemic event‐caused damage in liver. We also propose that PC may be employed as an adequate tool to assess tissue damage after oxidative stress.     

D-Ala2, D-Leu5] enkephalin (DADLE) protects liver against ischemia-reperfusion injury in the rat

BACKGROUND: [D-Ala(2), D-Leu(5)] enkephalin (DADLE) is a synthetic delta class of opioid and is reported to induce hibernation as well as hibernation induction trigger (HIT) in the serum of hibernating mammals. DADLE and HIT have been demonstrated to protect the heart, lung, and jejunum against ischemia-reperfusion (I-R) injury. In the present study, we examined the effect of DADLE on I-R injury of the liver in rats. METHODS: After administration of DADLE (DADLE group) or normal saline as a vehicle (Control group), partial hepatic ischemia was induced by occluding the vessels supplying 92% of the liver for 45 min, followed by declamping the vessels and resection of the non-ischemic lobe. After 120 min of reperfusion, serum glutamic-pyruvic transaminase (GPT), hyaluronic acid (HA) levels, and concentrations of malondialdehyde (MDA) of the liver tissue were measured. Additionally, bile output from the ischemic lobes was measured after reperfusion. RESULTS: GPT levels were significantly lower in the DADLE group as compared to those of the Control group (P < 0.05), but the serum levels of HA were not different between the two groups. The concentrations of MDA of the liver tissue were significantly lower in the DADLE group than in the Control group (P < 0.01). The bile output after reperfusion was not significantly different between the two groups. CONCLUSIONS: DADLE protects against I-R injury in hepatocytes, but not in the sinusoidal endothelial cells of the liver in rats. An anti-oxidative effect is suggested to be responsible for this effect.