Curcumin Treatment Protects Against Renal Ischemia and Reperfusion Injury–Induced Cardiac Dysfunction and Myocardial Injury

ObjectivesRenal ischemia and reperfusion (I/R) injury frequently leads to acute renal failure (ARF) and multiple-organ injury with a substantial morbidity rate. The primary cause of ARF-associated death is, however, cardiac failure instead of renal failure itself, and the pathogenesis of renal I/R-induced cardiac injury is still poorly understood. We evaluated the efficacy of curcumin pretreatment on cardioprotection.MethodsThirty Sprague-Dawley rats were evenly divided into 3 groups of sham-operated control, renal I/R injury, and a curcumin pretreatment group. Renal ischemia was conducted by bilateral occlusions of pedicles for 45 minutes, followed by 3 hours of reperfusion. The cardiac function was assessed by the left ventricular end-systolic-pressure-volume-relation (ESPVR), systolic pressure (SP), ejection fraction (EF), and stroke volume (SV). Myocardial injury was assessed based on creatine kinase muscle brain fraction (CK-MB) and Troponin I (cTnI), and kidney injury was assessed based on blood urea nitrogen (BUN) and creatinine. We also assessed the levels of tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) in the heart tissues.ResultsSV, EF, and SP reduced moderately during the ischemic phase with no major change in ESPVR. During reperfusion, SV, SP, and ESPVR initially increased, and then steadily decreased. Myocardial and kidney injury were marked by the increases in serum CK-MB and cTnI, and creatinine and BUN level. Curcumin pretreatment ameliorated ESPVR and attenuated injuries of both the heart and kidney resulting from I/R insult.ConclusionsCurcumin pretreatment improved cardiac contractility and attenuated myocardial and renal injury through reducing inflammatory response in the kidney and heart and oxidative stress in the myocardium.     

lncRNA-MALAT1/miRNA-145在舒芬太尼预处理减轻大鼠心肌缺血-再灌注损伤中的作用

目的探讨长链非编码RNA(lncRNA)肺腺癌转录子1(MALAT1)在舒芬太尼预处理减轻大鼠心肌缺血-再灌注损伤(MIRI)中的作用。方法 SPF级大鼠36只,体重180~200 g,随机分为三组:假手术组(Sham组),缺血-再灌注损伤组(IR组),缺血-再灌注损伤+舒芬太尼组(SUF组),每组12只。IR组和SUF组建立大鼠心肌缺血-再灌注损伤模型,SUF组于再灌注前10 min尾静脉注射舒芬太尼1μg/kg,Sham组和IR组注射等体积生理盐水。再灌注后2 h检测大鼠血清中肌酸激酶同工酶MB(CK-MB)、心肌肌钙蛋白T(cTnT)和乳酸脱氢酶(LDH)活性,同时检测大鼠心肌梗死面积;检测心肌细胞凋亡相关蛋白Bcl-2、Bax、Cleaved-caspase-3和Caspase-3含量;检测大鼠心肌组织中lncRNA-MALAT1和miRNA-145的相对表达量。结果与Sham组比较,IR组和SUF组CK-MB和cTnT浓度明显升高,LDH活性明显增强,心肌梗死面积明显增大,心肌组织中Bax/Bcl-2比值明显降低,Cleaved-caspase-3蛋白含量明显升高,lncRNA-MALAT1相对表达量明显升高,而miRNA-145相对表达量明显降低(P<0.05)。与IR组比较,SUF组CK-MB和cTnT浓度明显降低,LDH活性明显减弱,心肌梗死面积明显减小,Bax/Bcl-2比值明显升高,Cleaved-caspase-3蛋白含量明显降低,lncRNA-MALAT1相对表达量明显降低,miRNA-145相对表达量明显增加(P<0.05)。结论舒芬太尼预处理能减轻大鼠心肌缺血-再灌注损伤程度,其机制可能与抑制lncRNA-MALAT1、升高miRNA-145表达有关。     

左旋精氨酸对心内直视手术期间血清心肌肌钙蛋白T的影响

目的 探讨左旋精氨酸(L-Arg)对心肺转流期间心肌缺血-再灌注损伤的保护作用.方法 拟行心内直视手术的先天性心脏病患者30例,随机均分为L-Arg组(L组)和对照组(C组).L组于主动脉开放后给予L-Arg 200 mg/kg.分别于主动脉插管时、主动脉开放后30 min、2、6 h检测心肌肌钙蛋白T(cTnT)、乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活力.结果 主动脉开放后两组cTnT比主动脉插管时显著升高(P＜0.01),L组cTnT在主动脉开放后2、6 h显著低于C组(P＜0.05).与C组比较,L组主动脉开放后2 h血浆cTnT、LDH、CK-MB和MDA的上升幅度显著降低(P＜0.05或P＜0.01),SOD活性显著升高(P＜0.05).结论 L-Arg对心内直视手术期间心肌有良好的保护作用.     

N-acetylcysteine Improves Cardiac Contractility and Ameliorates Myocardial Injury in a Rat Model of Lung Ischemia and Reperfusion Injury

ObjectivesLung ischemia and reperfusion (I/R) injury is the major complication subsequent to cardiopulmonary bypass surgery and lung transplantation. Lung I/R injury frequently induces cardiac dysfunction leading to significant mortality. So far, the literature on therapeutic interventions in cardiac dysfunction and myocardial injury is still scarce. In this study, we examined the efficacy of N-acetylcysteine (NAC) administration against lung I/R injury–induced cardiac dysfunction.MethodsLung ischemia was established by occluding the left lung hilum for 60 minutes, followed by 2 hours of reperfusion. Studies were performed in 3 groups: sham-operated (same surgical procedure except vessel occlusion; N = 8), lung I/R injury (N = 12), and NAC-administered group (N = 12). The cardiac function was assessed using simultaneous left ventricular (LV) pressure and volume measured via a high-fidelity pressure-volume catheter. Myocardial injury was assessed based on serum creatine kinase muscle brain fraction (CK-MB) and troponin I (cTnI) level, and lung injury based on the degree of protein concentration in lung lavage. We also examined the degrees of myocardial lipid peroxidation and hydroxyl radical production with and without NAC.ResultsDuring lung ischemia, LV stiffness increased with relative intact contractility. After 2 hours of reperfusion, LV contractility decreased with dilated and stiffened ventricle, along with apparent myocardial and lung injury. NAC administration effectively attenuated heart and lung injury, and ameliorated impaired LV contractility and stiffening resulting from lung I/R injury.ConclusionsNAC administration reduced lung I/R-induced increases in myocardial hydroxyl radical production and lipid peroxidation, and ameliorated LV contractility and stiffening.     

地氟烷在二尖瓣置换手术中对缺血再灌注心肌的保护作用

在心脏外科手术中心肌缺血再灌注(ischemia-reperfusion,I-R)损伤的防治是急需解决的问题。缺血预处理(ischemic preconditioning,IPC)具有心肌保护作用[1,2]。研究显示挥发性麻醉药也具有类似IPC的麻醉药预处理(anesthetic-induced preconditioning,APC)作用[3,4],能减轻I-R后     

Troponin must be measured before and after PCI to diagnose procedure-related myocardial injury

OBJECTIVE: To evaluate troponin I >99th percentile of normal as a criterion for myocardial injury after percutaneous coronary intervention (PCI). DESIGN: Troponin I and creatine kinase monobasic (CK-MB) were measured in 327 patients before and after percutaneous transluminal coronary angioplasty (PTCA) with stent implantation. RESULTS: Troponin I was elevated before PCI in 100 of a total of 222 patients with acute coronary syndrome (ACS). In 91 of these 100 patients, troponin I was elevated also after PCI but actual increases in troponin I concentrations from before to after PCI were found in only 32 patients. The increase of troponin I correlated with post-procedural CK-MB whereas post-procedural troponin I levels did not correlate. In the 122 patients with ACS but normal/normalized troponin I before PCI and in 105 patients with stable coronary artery disease post-procedural troponin I appeared to be a reliable indicator of myocardial infarction (MI), however more sensitive than CK-MB. CONCLUSION: Troponin I after PCI is sensitive to pre-procedural concentrations. To avoid false positive MI diagnoses we thus suggest that troponin I should be measured before as well as after the procedures and only actual increases should be regarded as indicating procedure-related MI.     

Ligustrazine attenuates acute myocardium injury after thermal trauma

This study was designed to investigate the effects of ligustrazine on burn-induced myocardiac injury as well as TNF-alpha levels in severely burned rats. Sprague-Dawley rats were divided into four groups: (1) sham group, rats who underwent sham burn; (2) fluid-resuscitated sham group (FRsham), rats who underwent sham burn, and lactated Ringer's solution for resuscitation; (3) control group, rats given third-degree burns over 30% total body surface area (TBSA) and lactated Ringer's solution for resuscitation; (4) ligustrazine group, rats given burn and lactated Ringer's solution with ligustrazine inside for resuscitation. Myocardial injury was assessed at 6h after burn by detecting serum levels of creatine kinase MB fraction (CK-MB) and lactate dehydrogenase (LDH), as well as water content, histological score, and ultrastructure change of cardiac tissue. In addition, myocardium ATP content was analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to examine cardiac tumor necrosis factor-alpha (TNF-alpha) levels. The results showed that burn trauma resulted in the increasing serum LDH and CK-MB, elevated myocardial water content, aggravated myocardial histological and ultrastructural lesions, increased myocardium ATP, and serum TNF-alpha. Ligustrazine 10mg/kg iv markedly inhibited increases in serum CK-MB and LDH, reduced myocardial water content from 76.91+/-0.19% in control group to 75.40+/-0.57%, significantly decreased the histologic scores of myocardium, and mollified the ultrastructural damage in cardiac myocytes. Ligustrazine significantly attenuated elevations in serum TNF-alpha level and myocardial ATP quantity. Therefore, our results demonstrate that ligustrazine exhibits significant protective effects on burn-induced myocardial injury via inhibiting the release of TNF-alpha and improving utilization of ATP.     

Protective Effect of Citric Acid Against Hepatic Ischemia Reperfusion Injury in Sprague-Dawley Rats

ObjectiveHepatic ischemia reperfusion (I/R) injury is regarded as a serious concern in clinical practice. Citric acid reduces oxidative stress and inflammation during hypoxia and reoxygenation. Our objective was to investigate the protective effect of citric acid against hepatic I/R injury in rats.MethodsWe fed Sprague-Dawley rats either citric acid (100 mg/kg/d) or saline. One week later, ischemia was induced by clamping the rats’ common hepatic artery and portal vein for 30 minutes. The rats were randomly divided into 3 major groups that were treated as follows: 1. the sham operated group; 2. the I/R group; and 3. the I/R-citric acid group.ResultsCompared to the sham group, the I/R group had higher expression of aspartate aminotransferase and alanine aminotransferase and lower expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, nitric oxide, and albumin. Compared to the I/R group, the I/R-citric acid group had higher expression of catalase, superoxide dismutase, antioxidants, and nitric oxide, and lower expression of aspartate aminotransferase and alanine aminotransferase.ConclusionsThese results suggest that citric acid therapy has significant therapeutic potential in ischemic liver injury.     

Cardiac performance during reperfusion improved by pretreatment with oxygen free-radical scavengers

We studied the effects of oxygen free radicals on cardiac performance during reperfusion of ischemic myocardium. The pig heart, isolated in situ, was subjected to 60 minutes of regional ischemia at normothermia by occlusion of the left anterior descending coronary artery followed by 60 minutes of hypothermic cardioplegic arrest and 60 minutes of normothermic reperfusion. The oxygen free-radical scavengers, superoxide dismutase and catalase, were administered before occlusion of the left anterior descending coronary artery in the experimental group. The generation of free radicals in the untreated group, estimated by the measurement of malondialdehyde in the perfusate, was significant during reperfusion and was associated with a corresponding increase in creatine kinase. Superoxide dismutase and catalase significantly slowed the appearance of malondialdehyde and the release of creatine kinase during reperfusion. Superoxide dismutase and catalase did not alter coronary flow and myocardial oxygen extraction or consumption during occlusion of the left anterior descending coronary artery; however, coronary flow and oxygen consumption were significantly higher (p less than 0.05) during reperfusion in hearts treated with antioxidants. Left ventricular developed pressure and its maximum first derivative were measured under isovolumic conditions. In the untreated group, left ventricular developed pressure and its maximum first derivative declined to 61.1% and 57.1% of baseline values, respectively, after 60 minutes' occlusion of the left anterior descending, and to 45% of baseline values after 15 minutes of reperfusion. The decline in left ventricular developed pressure and its maximum first derivative during reperfusion was significantly (p less than 0.05) inhibited by superoxide dismutase and catalase, but left ventricular end-diastolic pressure was not significantly altered. These results implicate oxygen-derived free radicals in the injury resulting from reperfusion of ischemic myocardium and suggest that oxygen free-radical scavengers effectively protect against such injury.     

On-pump beating heart versus off-pump coronary artery bypass surgery—evidence of pump-induced myocardial injury

Objective: By maintaining native coronary blood flow in on-pump beating heart surgery (OnP-BH) and comparing with OPCAB strategy pump-related effects on myocardial injury and cardiac dysfunction could be specifically differentiated from ischemia/reperfusion-related consequences of surgical coronary revascularization. Methods: In a randomized-prospective design, 40 elective patients with normal EF and three vessels coronary artery disease (left main disease excluded) were assigned to OPCAB or OnP-BH surgery. Before coronary occlusion and 1, 30, 60, and 90 min after reperfusion with the LIMA graft, coronary sinus (CS) blood was sampled to determine intraoperative myocardial ischemia (pH, lactate, pO₂) and oxidative stress (malondialdehyde, MDA). Additionally to CS blood arterial blood was analyzed 4, 12, and 24 h postoperatively to determine myocardial necrosis (CK-MB, cardiac troponin I), myocardial dysfunction (NT-proBNP) and inflammation (C-reactive protein). Results: Groups were identical with regards to age and gender (OPCAB 63.0±6.0 versus OnP-BH 65.3±3.9 y, 20% female patients). Number of grafts were 3.0±0.5 in OPCAB versus 2.9±0.3 in OnP-BH (n.s.) with 44 versus 34% bilateral IMAs and 56 versus 50% complete arterial revascularization. Regarding ischemia, intraoperatively only lactate values increased significantly in the OnP-BH group. Significantly higher CK-MB and troponin I levels were found from LIMA-LAD flow release onwards to 4 h postoperatively in the OnP-BH group. NT-proBNP levels were significantly higher in the OnP-BH group during the entire study period. CRP levels were higher in the OnP-BH group 12 and 24 h postoperatively. Conclusions: In this randomized study on routine coronary patients with normal ventricular function, OPCAB revealed less myocardial injury than OnP-BH. These findings implicate that CPB slightly affects the myocardium.     

异丙酚预先给药对糖尿病大鼠心肌缺血再灌注损伤的影响

目的 探讨异丙酚预先给药对糖尿病大鼠心肌缺血再灌注损伤的影响.方法 健康雄性SD大鼠84只,体重230～280 g,随机分为7组(n=12),假手术组(Ⅰ组);Ⅱ组采用结扎左冠状动脉前降支30 min,再灌注120 min制备心肌缺血再灌注模型;糖尿病大鼠假手术组(Ⅲ组)采用腹腔注射链脲左菌素(STZ)55 mg/kg制备糖尿病模型;糖尿病大鼠心肌缺血再灌注组(Ⅳ组)腹腔注射STZ 3周后制备心肌缺血再灌注模型;Ⅴ组、Ⅵ组和Ⅶ组糖尿病大鼠分别于缺血前10 min至再灌注120 min时静脉输注异丙酚3、6、12 mg·kg-1·h-1.记录再灌注120 min时心率(HR)、左心室收缩峰压、左心室舒张末压(LVDEP)及左心室内压上升,下降最大速率(±dp/dtmax),计算左心室发展压(LVDP);测定血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)活性、心肌组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、心肌线粒体肿胀度、总ATP酶和谷胱苷肽过氧化物酶(GSH-Px)活性;透射电镜观察心肌组织超微结构.结果 与Ⅲ组比较,Ⅳ组HR、LVDP和±dp/dtmax、心肌组织SOD活性、线粒体总ATP酶及GSH-Px活性降低,LVEDP、血清LDH、CK-MB活性、心肌组织MDA含量及线粒体肿胀度升高(P<0.05或0.01);与Ⅳ组比较,Ⅵ组和Ⅶ组HR、LVDP和±dp/dtmax、心肌组织SOD活性、线粒体总ATP酶及GSH-Px活性升高,LVEDP、血清LDH、CK-MB活性、心肌组织MDA含量和线粒体肿胀度降低,Ⅴ组+dp/dtmax及线粒体总ATP酶活性升高,血清CK-MB活性降低(P<0.05).Ⅵ组和Ⅷ组心肌组织超微结构损伤减轻.结论 异丙酚6、12 mg·kg-1·h-1预先给药可减轻糖尿病大鼠心肌缺血再灌注损伤,可能与其抑制心肌组织脂质过氧化反应,改善心肌细胞线粒体膜通透性有关.     

Intermittent cardiac troponin-I screening is an effective means of surveillance for a perioperative myocardial infarction

OBJECTIVE: Several studies suggest that cardiac troponin-I (cTn-I) is a more sensitive indicator of cardiac injury compared with other biochemical markers of injury, but the strategy with the highest diagnostic yield (true positive and true negative) for perioperative surveillance is unknown. The authors undertook a prospective evaluation of the perioperative incidence of myocardial infarction (MI) and evaluated surveillance strategies for the diagnosis of MI. DESIGN: Prospective, cohort study. SETTING: Two university hospitals. PARTICIPANTS: Four hundred sixty-seven high-risk patients requiring noncardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The diagnosis of myocardial injury was determined by cardiac protein markers combined with either postoperative changes on 12-lead electrocardiography or 1 of 3 clinical symptoms consistent with MI (chest pain, dyspnea, requirement for hemodynamic support). A receiver operating characteristic curve evaluating troponin in the diagnosis of MI revealed a value of 2.6 ng/mL as having the highest sensitivity and specificity. The sensitivity and specificity of cTn-I value > or =2.6 ng/mL, troponin > or =1.5 ng/mL, total creatine kinase (CK) > or =170 IU/L with MB > or =5%, and CK-MB > or =8 ng/mL were compared. Surveillance strategies were determined on a subset of patients (n = 257). The incidence of MI was 9.0% by cTn-I > or =2.6 ng/mL criteria, 19% by cTn-I > or =1.5 ng/mL, 13% by CK-MB mass, and 2.8% by CK-MB%. The specificity of cTn-I > or =2.6 ng/mL as an indicator of MI was 98%, and its positive predictive value (PPV) was 85%. Cardiac troponin-I > or =2.6 ng/mL had equal specificity but greater PPV than the cTn-I > or =1.5 ng/mL (specificity 98% and PPV 79%). If surveillance of cTn-I > or =2.6 ng/mL was used to detect MI, then the strategy with the highest diagnostic yield was surveillance on postoperative days 1, 2, and 3. CONCLUSIONS: Perioperative cardiac injury continues to occur frequently after noncardiac surgery, as detected by cTn-I. Serial monitoring of cardiac troponin-I on postoperative days 1, 2, and 3 provides the strategy with the highest diagnostic yield for surveillance of MI.     

Anti-TNF-α单克隆抗体对急性梗阻性黄疸大鼠心肌的保护作用

目的:探讨抗肿瘤坏死因子α单克隆抗体(anti-TNF-α)对急性梗阻性黄疸大鼠心肌损伤的保护作用.方法:24只雄性SD大鼠随机均分为模型组(行胆总管结扎),治疗组(行胆总管结扎+anti-TNF-α治疗),假手术组.治疗组于胆总管结扎后第3天开始经尾静脉注射anti-TNF-α(1 mg/kg),连用5d;模型组和假手术组以同样方法注射等体积的生理盐水.术后7d,分别检测各组大鼠血清肌酸激酶同工酶( CK-MB)和TNF-α水平,以及大鼠心肌组织中丙二醛(MDA)和超氧化物歧化酶( SOD)含量,并观察心肌组织形态学改变.结果:除假手术组外,模型组和治疗组大鼠术后3d开始均出现黄疸,并逐渐加重.与假手术组比较,模型组和治疗组大鼠术后7d血清CK-MB,TNF-α水平及心肌组织中MDA含量明显升高,SOD活性明显降低(均P＜0.01),但治疗组以上指标的改变不如模型组明显,差异均有统计学意义(均P＜0.01).光镜下可见假手术组心肌无明显病理改变,模型组心肌纤维稀疏、变细、坏死,心肌细胞浊肿,治疗组比模型组心肌损伤减轻.结论:TNF-α可能是急性梗阻性黄疸后大鼠心肌损伤的重要介导因子,anti-TNF-α可以通过拮抗TNF-α而减轻急性梗阻性黄疸时大鼠的心肌损伤.     

Adrenomedullin attenuates aortic cross-clamping–induced myocardial injury in rats

Background

In this study we investigate the effects of adrenomedullin on myocardial injury after ischemia-reperfusion (I/R) after abdominal aortic surgery.

Methods

Thirty-two Wistar rats were randomized into 4 groups (n = 8) as follows: control group (sham laparotomy), the aortic I/R group, aortic I/R plus adrenomedullin group (underwent aortic I/R periods, and received a bolus intravenous injection of .05 μg/kg/min adrenomedullin), and the control plus adrenomedullin group.

Results

Biochemical analysis showed that aortic I/R significantly increased (P < .05) the plasma levels of troponin-I and tumor necrosis factor-α, and the myocardial tissue levels of malondialdehyde, superoxide dismutase, catalase, and angiotensin II, whereas aortic I/R plus adrenomedullin significantly decreased these same factors (P < .05). Aortic I/R significantly increased (P < .05) myocardial tissue levels of nitric oxide whereas aortic I/R plus adrenomedullin significantly increased the same factor (P < .05).

Conclusions

These results indicate that adrenomedullin has protective effects against myocardial injury induced by abdominal aortic I/R in rats.     

Hesperidin Shows Protective Effects on Renal Function in Ischemia-induced Acute Kidney Injury (Sprague-Dawley Rats)

ObjectiveHesperidin is a well-known flavanone glycoside copiously found in sweet orange and lemon, which was recently reported to possess significant anti-inflammatory, analgesic, antifungal, antiviral, antioxidant, and anticancer activities. Ischemia-reperfusion (I/R) injury is a major problem after renal transplantation. Furthermore, inflammatory responses to I/R exacerbate the resultant renal injury. In the present study, we investigated whether hesperidin exhibits renoprotective effects against I/R-induced acute kidney injury in a rat model.MethodsWe fed Sprague-Dawley rats either hesperidin (100 mg/kg/d) or saline. One week later, ischemia was induced by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion. The rats were randomly divided into 3 groups, which were treated as follows: 1. the sham operated group; 2. the I/R group; 3. the I/R-hesperidin groupResultsCompared to the sham group, the I/R group had higher expression of blood urea nitrogen and serum creatinine and lower expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidants, and nitric oxide. Compared to the I/R group, the I/R-hesperidin group had higher expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, and nitric oxide and lower expression of blood urea nitrogen and serum creatinine.ConclusionsHesperidin improved acute renal I/R injury through its antioxidant effects. These findings suggest that hesperidin is a potential therapeutic agent for acute ischemia-induced renal damage.     

Hesperidin Ameliorates Hepatic Ischemia-Reperfusion Injury in Sprague-Dawley Rats

ObjectiveHepatic ischemia and reperfusion (I/R) is a destructive event associated with high rates of liver failure after liver transplantation. Hesperidin significantly contributes to the antioxidant defense system and has been reported to act as a powerful agent against superoxide and hydroxyl radicals. Our objective was to investigate the protective effect of hesperidin against hepatic IR injury in a rat model.MethodsWe fed Sprague-Dawley rats either hesperidin (100 mg/kg/d) or saline. One week later, ischemia was induced by clamping the rats’ common hepatic artery and portal vein for 30 minutes. The rats were divided into 3 groups: 1. the sham operated group; 2. the I/R group; and 3. the I/R-hesperidin group.ResultsCompared to the sham group, the I/R group had higher expression of serum aspartate aminotransferase and serum alanine aminotransferase and lower expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, nitric oxide, and albumin. Compared to the I/R group, the I/R-hesperidin group had higher expression of catalase, superoxide dismutase, antioxidant and nitric oxide and lower expression of serum aspartate aminotransferase and serum alanine aminotransferase.ConclusionsOur findings suggest that hesperidin is a potential therapeutic agent for hepatic I/R injury.     

星状神经节阻滞对大鼠急性心肌梗死后室性心律失常的影响

目的探讨星状神经节阻滞(stellate ganglion blockade, SGB)对大鼠急性心肌梗死(myocardial infarction, MI)后室性心律失常(ventricular arrhythmia, VA)的影响。方法雄性SPF级SD大鼠45只,体重200～250 g,随机数字表法分为三组:假手术组(S组)、MI组和SGB组,每组15只。结扎冠状动脉制备MI模型。记录VA诱发率、室颤阈值和有效不应期,以及血浆超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。采用ELISA法测定血浆儿茶酚胺抑素(catestatin, CST)浓度。结果造模后1周,S组、MI组和SGB组分别有2只、1只和1只大鼠死亡。与S组比较,MI组VA诱发率明显升高(P0.05),MI组和SGB组室颤阈值和有效不应期明显减小(P0.05)。与MI组比较,SGB组VA诱发率明显降低,室颤阈值和有效不应期明显增加(P0.05)。与S组比较,MI组血浆CST浓度和MDA含量明显升高,SOD活性明显降低(P0.05)。与MI组比较,SGB组CST浓度和MDA含量明显降低,SOD活性明显升高(P0.05)。结论星状神经节阻滞可抑制心肌梗死后室性心律失常的发生,其机制可能与降低交感流出和抗氧化损伤有关。     

Relationship between perioperative troponin elevation and other indicators of myocardial injury in vascular surgery patients

Background. In 2000 the European Society of Cardiology and theAmerican College of Cardiology published a consensus documentrevising the definition of myocardial infarction. The usefulnessof this revised definition has been challenged. It has beensuggested that, rather than any release of cardiac troponinbeing potentially diagnostic of myocardial infarction, a diagnosticthreshold consistent with significant myocardial injury shouldbe defined. Methods. We studied 65 patients undergoing elective major vascularsurgery to examine the relationship between the magnitude ofcardiac troponin I (cTnI) and creatine kinase MB fraction (CK-MB)release and clinical signs or symptoms of myocardial injury.cTnI and CK-MB concentrations were measured preoperatively andon the first 4 postoperative days using the ACCESS® assay(Beckmann). Patients were considered to have suffered a perioperativemyocardial infarction if they had either symptoms or ECG changesconsistent with this diagnosis, together with cTnI release. Results. Peak postoperative cTnI concentrations above the lowerdetection limit of the ACCESS® assay (0.06 µg litre^–1)occurred in 26 patients. Eight of these patients displayed symptomsor ECG changes consistent with myocardial injury. A cTnI levelgreater than 0.68 µg litre^–1 was found to be consistentwith the clinical diagnosis of myocardial infarction. The optimalcut-off for the diagnosis of MI using CK-MB was 40.4 µglitre^–1. Conclusions. These data suggest that further studies are requiredto define the optimal cardiac troponin diagnostic thresholdfor the diagnosis of myocardial infarction in the non-cardiacsurgery population.      

Toll-like receptor 4 mediates ischemia/reperfusion injury of the heart

BACKGROUND: Restoration of blood flow to the ischemic heart may paradoxically exacerbate tissue injury (ischemia/reperfusion injury). Toll-like receptor 4, expressed on several cell types, including cardiomyocytes, is a mediator of the host inflammatory response to infection. Because ischemia/reperfusion injury is characterized by an acute inflammatory reaction, we investigated toll-like receptor 4 activation in a murine model of regional myocardial ischemia/reperfusion injury. We used C3H/HeJ mice, which express a nonfunctional toll-like receptor 4, to assess the pertinence of this receptor to tissue injury after reperfusion of ischemic myocardium. METHODS: Wild-type mice (C3H/HeN) or toll-like receptor 4 mutant mice (C3H/HeJ) were subjected to 60 minutes of regional myocardial ischemia followed by 2 hours of reperfusion. At the end of reperfusion, the area at risk and the myocardial infarct size were measured as the end point of myocardial ischemia/reperfusion injury. Myocardial mitogen-activated protein kinase activation was measured by Western blotting, and nuclear translocation of nuclear factor-kappaB and activator protein-1 was determined by electrophoretic mobility shift assay. Ischemia/reperfusion-injured myocardium was also assessed by ribonuclease protection assay for expression of inflammatory mediators (tumor necrosis factor-alpha, interleukin-1beta, monocyte chemotactic factor-1, and interleukin-6). RESULTS: The area at risk was similar for all groups after myocardial ischemia/reperfusion injury. There was a 40% reduction in infarct size (as a percentage of the area at risk) in C3H/HeJ mice compared with C3H/HeN mice (P =.001). Within the myocardium, significant activation of c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase was observed in both strains after ischemia and during reperfusion as compared with an absence of mitogen-activated protein kinase activation during sham operations; however, c-Jun N-terminal kinase activity, but not p38 or extracellular signal-regulated kinase activity, was significantly reduced in C3H/HeJ mice (P <.05). In both groups, nuclear factor-kappaB and activator protein-1 nuclear translocation occurred in the myocardium during myocardial ischemia/reperfusion injury, but, by densitometric analysis, nuclear translocation of nuclear factor-kappaB and activator protein-1 was significantly decreased in C3H/HeJ mice compared with C3H/HeN mice. Interleukin-1beta, monocyte chemotactic factor-1, and interleukin-6 were detectable in reperfused ischemic myocardium but were not detected in sham-operated myocardium; the expression of each of these mediators was significantly decreased in the myocardial tissue of C3H/HeJ mice when compared with expression in the control C3H/HeN mouse strain. CONCLUSIONS: Our data suggest that toll-like receptor 4 may mediate, at least in part, myocardial ischemia/reperfusion injury. Inhibition of toll-like receptor 4 activation may be a potential therapeutic target to attenuate ischemia/reperfusion-induced tissue damage in the clinical setting.     

Pathogenesis of early cardiac myocyte damage after severe burns

BACKGROUND: The importance of early cardiac myocyte damage during postburn trauma has been emphasized in recent years. However, its pathogenesis, prevention, and treatment have not been fully clarified. The aim of this study is to define its pathogenesis. METHODS: Rats with 30% third-degree burns were used. Cardiac biochemical markers reflecting cardiac myocyte damage including troponin T, cardiac myosin light chain 1, creatinine kinase and its cardiac-specific isoenzyme compound, as well as inflammatory mediators such as tumor necrosis factor, endothelin/nitric oxide ratio, malondialdehyde, and superoxide dismutase, were determined. RESULTS: Cardiac biochemical markers reflecting cardiac myocyte damage, including troponin T, cardiac myosin light chain 1, cardiac-specific isoenzyme compound, were all significantly elevated between 3 hours and 24 hours after burn. Changes in tumor necrosis factor, endothelin/nitric oxide ratio, and malondialdehyde were similar to those of cardiac biochemical markers. In contrast, levels of superoxide dismutase declined markedly after burn. CONCLUSION: The findings of this study showed that considerable amounts of myocardial constructive protein degradation and release due to destruction of cardiac myocytes occurred early after severe burns. The inflammatory mediators released after burn injury may be involved in the pathogenesis of myocardial destruction.