Beneficial effect of the addition of nitroglycerin to the cardioplegic solution on lipid peroxidation during coronary artery bypass surgery

The effects of the addition of a nitric oxide (NO) donor to the cardioplegic solution on reperfusion injury and lipid peroxidation (LPO) in coronary artery bypass grafting (CABG) are not known. Therefore, this work was conducted to determine the possible effects of nitroglycerin on LPO and reperfusion injury as a result of CABG. A prospective double-blind, placebo-controlled study was conducted in 30 consecutive patients with coronary artery disease who underwent CABG with cardiopulmonary bypass. The patients were randomly assigned to receive 3 microg/kg of nitroglycerin added to the cardioplegic solution (NTG group) or 3 microg/kg of placebo added to the cardioplegic solution (placebo group). MDA increased significantly in the placebo group compared to the NTG group during the ischemic (P < 0.01) and reperfusion periods (P < 0.01). The level of troponin I decreased significantly in the NTG group compared to the placebo group during the ischemic and reperfusion periods (P < 0.001). The level of NO increased significantly in the NTG group compared to the placebo group during the ischemic and reperfusion periods (P < 0.01). LPO was increased in response to CPB during CABG, together with simultaneous decreases in serum nitric oxide levels, whereas LPO was significantly decreased in response to CPB with nitroglycerin, together with simultaneous increases in the levels of serum nitric oxide.     

Isoflurane pre-treatment before cardiopulmonary bypass alleviates neutrophil accumulation in dog lungs

Objective

This study investigated the effect of isoflurane pre-treatment on cardiopulmonary bypass (CPB)-related lung injury.

Methods

Twelve dogs were randomly divided into two groups of six each. In one group, 1.0 minimum alveolar concentration (MAC) of isoflurane was administered for 30 min before CPB, while the control group received no anaesthetic. Both groups then underwent 100 min of mild hypothermic CPB with 60-min aortic cross clamping. Haemodynamic parameters, respiratory mechanics and alveolar arterial oxygen difference (AaDO₂) were measured during the experiment. One hundred and fifty minutes after CPB, lung tissue samples from the non-dependent and dependent portions of the left and right lungs were harvested for polymorphonulear leukocyte (PMNs) counts.

Results

Following CPB, within the control group, pulmonary vascular resistance (PVR) was significantly increased at 60, 120 and 180 min after declamping, AaDO2 deteriorated at 180 min post-declamping, and dynamic lung compliance (DLC) was reduced dramatically after declamping. Isoflurane pre-treatment before CPB significantly reduced PVR compared to the controls. AaDO₂ was impaired at 180 min after declamping and DLC was decreased after declamping within the isoflurane group. No differences in AaDO₂ and DLC were found between the isoflurane and control groups. At 180 min after declamping, the PMN count in both the non-dependent and dependent regions of the isoflurane pre-treated lungs was significantly lower than that of the controls.

Conclusions

Our results suggest that 30-min pre-treatment with 1.0 MAC isoflurane before CPB caused a reduction in PMN accumulation in the dog lungs, inhibition of increases in PVR, and it did not affect AaDO2 in the early post-CPB stage.     

Activated protein C and inflammation in human myocardium after heart surgery

To assess possible interactions between inflammation and activation of the anticoagulant protein C system during post-ischemic reperfusion protein C, APC, neutrophil L-selectin expression and myocardial myeloperoxidase activity (MPO) were measured in 19 patients undergoing cardiopulmonary bypass. After reperfusion for 10 min, APC to protein C ratio (APC/PC) increased from pre-reperfusion value 1.43 +/- 0.12 (mean +/- SEM) to 2.25 +/- 0.29, p = 0.015. Negative correlations were observed between APC/PC and MPO activity (Spearman r -0.64, p = 0.007) and APC/PC and neutrophil L-selectin expression (r = -0.7, p = 0.007, demonstrating that post-ishemic protein C activation was associated with decreased neutrophil tissue sequestration. Thus, physiological protein C activation may be involved in regulation of the inflammatory injury during reperfusion of human ischemic coronary circulation.     

Progressive loss of myocardial contractile function despite unimpaired coronary blood flow after cardiac surgery

Objective Mild to moderate transient contractile dysfunction is frequently observed after cardiac surgery on cardiopulmonary bypass (CPB) but may also lead to low–cardiac–output (LCO) failure especially in patients with unstable angina, and is often referred to represent myocardial stunning. Whether time course of contractile dysfunction after cardiac surgery is similar to that of myocardial stunning was investigated in pigs. Methods After baseline measurements of systemic hemodynamics (micromanometry), myocardial contractile function (sonomicrometry), cardiac output and coronary flow (ultrasonic probe), CPB was instituted. Control animals (n = 7) were weaned after 3 h from CPB. In LCO animals (n = 8), global ischemia was induced for 10 min by aortic crossclamping, followed by 1 h of cardioplegic cardiac arrest. After declamping and reperfusion, CPB was terminated after a total of 3 h. Measurements were repeated at 15 min, 4 h and 8 h after CPB. Systemic TNF–plasma concentrations were measured (ELISA) and left ventricular biopsies were analyzed with respect to myocardial TNF (immunohistochemistry) and irreversible cellular damage (light/electron microscopy). Results Contractile function decreased in LCO (75 ± 12%) and control (83 ± 17%) at 15 min compared to baseline (p < 0.05). Thereafter, contractile function remained unchanged in control, but progressively decreased in LCO (52 ± 12% at 4 h; 36 ± 5% at 8 h; p < 0.05). Coronary flow remained unchanged in both groups. Cardiac output progressively decreased to 2.8 ± 0.9 l/min at 8 h in the LCO group compared to baseline (5.9 ± 1.1 l/min, p < 0.05) and control (5.7 ± 1.4 l/min, p < 0.05). There was no evidence for myocardial infarction. TNF–plasma concentrations and myocardial TNF–staining were increased at 8 h after CPB in the LCO group compared to baseline and control (p < 0.05). Conclusions The progressive pattern of myocardial dysfunction apart from ongoing ischemia after cardiac surgery suggested underlying mechanisms at least partially different from those of myocardial stunning.     

乌司他丁在婴幼儿体外循环手术期间的心肌保护作用

目的探讨乌司他丁在婴幼儿体外循环手术中对心肌缺血/再灌注损伤的保护作用。方法选择38例诊断为室间隔缺损的婴幼儿患者,随机分为试验组(n=18):1.2万U/kg乌司他丁;对照组(n=20):以等量生理盐水代替。记录阻断和转流时间,血管活性药物使用和心脏复跳情况。于转流前,主动脉开放即刻,开放30min,停机后4h、24h检测CK、CK-MB和cTnI,并观察心肌超微结构。结果①两组CK-MB、CK和cTnI转流前差异均无统计学意义,CPB后明显升高(P<0.05);试验组停机后4h、24h,CK、CK-MB较对照组低(P<0.05),cTnI主动脉开放30min,停机后4h、24h低于对照组(P<0.05)。②实验组多巴胺/多巴酚丁胺平均使用剂量少于对照组(P<0.05),心脏自动复跳率明显高于对照组(P<0.01),术后心肌组织超微结构显示心肌细胞损害较对照组轻。结论乌司他丁能降低CK、CK-MB、cTnI的释放,减轻婴幼儿体外循环手术中心肌损害,对心肌缺血/再灌注损伤有保护作用。     

成人瓣膜手术体外循环中应用不同利尿剂对电解质的影响

目的:观察托拉塞米与呋噻米用于成人瓣膜手术体外循环(cardiopulmonary bypass,CPB)中对电解质的影响。方法:随机选取择期CPB下行瓣膜置换术患者60例,分为托拉塞米组(A组)30例,呋噻米组(B组)30例,分别在CPB前、升主动脉阻断后15min、升主动脉开放15min、CPB停机时和术后2h抽取静脉血进行血气分析,记录K+、Na+、Mg++及Ca++离子浓度。同时记录2组患者转机中尿量及自动复跳率。结果:2组患者转机前、阻断升主动脉后15minK+、Na+、Mg++及Ca++离子浓度差异无统计学意义(P>0.05);A组患者开放升主动脉后15min血K+明显高于B组,差异有显著性统计学意义(P<0.01),Mg++、Ca++差异无统计学意义(P>0.05);停机时及术后2h,2组患者血K+、Na+、Mg++及Ca++差异无统计学意义(P>0.05)。2组患者转中尿量及自动复跳率差异无统计学意义。结论:托拉塞米可以用作CPB下瓣膜置换术的利尿剂,但要注意防止复跳时的高钾。     

Continuous tepid blood cardioplegia can preserve coronary endothelium and ameliorate the occurrence of cardiomyocyte apoptosis

OBJECTIVE: In modern cardiac surgery, crystalloid or blood cardioplegic solutions have been used widely for myocardial protection; however, ischemia does occur during protection with intermittent infusion of cold crystalloid or blood cardioplegic solutions. The present study was designed to evaluate the effect of different cardioplegic methods on myocardial apoptosis and coronary endothelial injury after global ischemia, cardiopulmonary bypass (CPB), and reperfusion in anesthetized open-chest dogs. METHODS: The dogs were classified into five groups to identify the injury of myocardium and coronary endothelium: group 1, normothermic CPB without cardiac arrest; group 2, hypothermic CPB with continuous tepid blood cardioplegia, and with cardiac arrest; group 3, hypothermic CPB with intermittent cold blood cardioplegia, and with cardiac arrest; group 4, hypothermic CPB with intermittent cold crystalloid cardioplegia, and with cardiac arrest; and group 5, sham-operated control group. During CPB, cardiac arrest was achieved with different cardioplegia solutions for 60 min, followed by reperfusion for 4 h before the myocardium and coronary arteries were harvested. Coronary arteries were harvested immediately and analyzed by scanning electron microscopy. Cardiomyocytic apoptosis was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling, Western blot, and DNA ladder methods. RESULTS: Regardless of the detection method used, significantly higher percentages of apoptotic cardiomyocytes were found in group 3 and group 4 than in other groups. Expression of caspase-3 correlated with increased apoptosis. Scanning electron microscopy revealed severe endothelial injury of coronary arteries in group 3 and group 4. CONCLUSION: These results point to an important explanation for the difference in cardiac recovery after hypothermic ischemia and arrest with various cardioplegic solutions.     

The effect of nitecapone, a new antioxidant, on myocardial function after aortic cross-clamping in experimental heart ischemia

During aortic cross-clamping, the myocardium suffers from global ischemia, which is followed by reperfusion after declamping. The generation of free oxygen radicals increases during reperfusion, resulting in arrhythmias and impaired cardiac function. This study was conducted to evaluate the effect of a novel antioxidant nitecapone (NC) on cardiac reperfusion injuryin vivo. Twelve pigs were anesthetized and after sternotomy the aorta and the right atrium were cannulated for cardiopulmonary bypass. The heart was arrested with either +4°C crystalloid cardioplegia alone in the control group (n=6) or cardioplegia with NC (50 µM) added in the NC group (n=6). Cardioplegia was added every 20 minutes. After 1 hour of aortic crossclamping, blood samples for oxidative stress analysis were taken, and hemodynamic profile surveillance continued for 90 minutes. Heart rate (p=0.04) and left ventricular end diastolic pressure (LVEDP) (p=0.04) were significantly lower in the NC group than in the C group after aortic declamping. Cardiac output and myocardial contractility (dP/dt_max) were also enhanced in the group receiving NC, but the difference was not statistically significant. At 30 minutes after reperfusion, the coronary production (coronary sinus-aorta) of thiobarbituric acid reactive substances correlated inversely with cardiac output (r=–0.90,p=0.001) and stroke volume (r=–0.82,p=0.007). The effect of NC on lipid peroxidation seems to be modest and therefore the target of NC is unclear. NC would appear, however, to be a beneficial additive in the crystalloid cardioplegia in terms of functional recovery.     

Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model

We wanted to test the hypothesis that NO generation by L-arginine (LA) infusion will be beneficial in increasing blood flow to all organs to counteract the process of global ischemia during cardiopulmonary bypass (CPB) and to reduce platelet emboli by platelet inhibition. The effect of LA infusion on NO formation, vasodilation, and reduction of thromboembolic burden in organs and tissues after CPB was quantified with In-111-labeled autologous platelets in two major groups: 180 minutes CPB (CPB) and 90 minutes CPB plus 90 minutes reperfusion (RP). Platelets labeled with In-111 tropolone (650–780 Ci) were administered 24 hours before CPB and LA infusion (bolus, 10 mg/kg and infusion at 2 mg/kg/min, 21 pigs for 180 minutes CPB) in 8 groups of 30 Yorkshire pigs (30–35 kg, 6 pigs; LA 2 mg/kg/min, 3 pigs; sham-thoracotomy control, 6 pigs; unoperated control, 6 pigs). Two groups of 9 pigs (control CPB, 6 pigs; LA 2 mg/ kg/min, 3 pigs) underwent 90 minutes of CPB and 90 minutes of reperfusion. All pigs were heparinized (ACT >400 seconds); CPB was instituted with a roller pump, an oxygenator (OX: Bentley Univox, 1.8 m²), and an arterial filter (AF: 0.25 m², Bentley) at a blood flow of 2.5–3.5 1/min. Radioactive thrombi in OX and AF and emboli in viscera, brain, and connective tissues were imaged with a gamma camera and were finally measured with an ion chamber and a gamma counter. The percent of injected platelets (mean ± SD) in the organs and tissues of all pigs was calculated. Cerebral emboli were mapped in 25 regions of both hemispheres of pig brain. Flow cytometry with antibodies to CD61 (GPIIIa) and CD62P (GMP-140: control) of porcine platelets was carried out with blood samples taken before, during, and after CPB. Coronary bypass with LA infusion decreased the amount of adherent thrombi in OX and AF (p < 0.07). The embolic burden in brain and lung also decreased. Regional cerebral mapping of In-111 platelets showed reduced emboli in almost all regions, including the medulla, hippocampus, and posterior cerebral cortex in both LA-treated groups. Flow cytometry of blood samples demonstrated the shift of equilibria from single platelet to platelet-aggregate-microparticle during CPB and steady-state level after the first 5–10 minutes of initiation of CPB. The L-arginine infusion reduced thrombi and emboli during CPB in the pig model.     

Effect of thoracotomy and cardiopulmonary bypass on activated platelet and neutrophil dynamics and platelet emboli in a pig model

The effects of thoracotomy and components of extracorporeal circuits on dynamics of platelets and neutrophils were quantified with autologous In-111-labeled platelets (INPLT) and neutrophils (INN) during cardiopulmonary bypass (CPB) operations in Yorkshire pigs. Cardiopulmonary bypass was carried out with a hollow-fiber oxygenator and an arterial filter in 48 pigs (30–35 kg); 12 unoperated controls for platelets and neutrophils; 12 sham operated controls; 12 with 180 minutes of CPB with platelets and neutrophils; 12 with 90 minutes of CPB and 90 minutes of reperfusion at 2.5–3.5 one/min. Platelets and neutrophils were labeled with In-111 tropolone and were injected intravenously: platelets at 24 hours and neutrophils at 15 minutes before CPB. All pigs were systemically heparinized [activated coagulation time (ACT) > 400 seconds]; CPB was instituted with a roller pump, oxygenator (OX; Bentley Univox, 1.8 m²), and arterial filter (AF; 0.025 m²) for durations of 180 minutes and 90 minutes of bypass, followed by 90 minutes of reperfusion. The kinetics and pooling of platelets and neutrophils were monitored by a Geiger probe. The adherent thrombi and neutrophils in the OX, AF, viscera, and brain were imaged with a gamma camera and were measured with an ion chamber and a gamma counter. The percentile distribution of labeled platelets and neutrophils expressed as the mean ± standard deviation of injected dose in eight groups was calculated and statistical analyses were performed (ANOVA and paired t-test). Sham operation alone increased platelet retention in the lung, heart, and brain significantly (p < 0.001) over that of unoperated pigs. Neutrophil margination to lung immediately after injection was high; CPB and reperfusion altered the distribution in blood, viscera, and connective tissues. During CPB, an equilibrium among single platelets, platelet thrombi, and emboli was reached in the blood, oxygenator, arterial filter, perfused organs, and tissues. After CPB, the pulmonary neutrophil retention increased significantly (p < 0.001). Reperfusion of 90 minutes following 90 minutes of CPB decreased the level of neutrophils and increased the level of platelets in the lung. Only a small amount of platelets and neutrophils was retained in the oxygenator and arterial filter. Neutrophil retention in the OX and AF was higher than that of platelets. The small amount of retained neutrophils in the heart, kidneys, and brain suggested that cytokines, rather than marginated neutrophils alone, may play a major role in inflammatory insult to these organs during and after CPB. OX thrombi increased with the time of CPB; AF thrombus in both groups was almost similar. During CPB, AF functioned minimally as a thrombus trap with a small percent of retained thrombi; reperfusion post-CPB did not change the amount. Thoracotomy alone has a significant effect on platelet and neutrophil kinetics, and on the subsequent effect of thrombus formation, embolization, and neutrophil margination in organs during the CPB procedure.     

High mobility group box 1 levels in on and off-pump cardiac surgery patients

High mobility group box 1 (HMGB1), which has properties similar to those of proinflammatory cytokines, is released from activated immune cells and necrotic cells. It is known that cardiopulmonary bypass (CPB) induces systemic inflammation and aortic cross-clamping induces myocardial ischemia. This study was conducted to clarify whether HMGB1 is released in CPB-supported cardiac surgery in comparison to off-pump coronary artery bypass grafting (OPCAB) where CPB is not used.Nineteen adult patients undergoing cardiac surgery involving CPB (CPB group) and 5 OPCAB patients (OPCAB group) were included in this study. Plasma concentrations of proinflammatory cytokines including HMGB1 were measured before, during, and after cardiac surgery. The plasma HMGB1 level was significantly increased at one hour after aortic declamping in the CPB group and at 30 minutes after revascularization in the OPCAB group. The peak HMGB1 level was slightly higher in the CPB group than that in the OPCAB group. These values decreased toward baseline value after surgery in both groups. TNF-α and IL-1β were not detectable throughout the study period in either group. IL-6 and IL-10 increased after aortic declamping in the CPB group and after coronary revascularizations in the OPCAB group.Based on these results, we conclude that the major factor involved in the increase in HMGB1 level might be myocardial ischemia/reperfusion during cardiac surgery. Activation of immune cells, altered tissue perfusion, and pulmonary ischemia and reperfusion could be additional factors that increase the HMGB1 level in CPB-supported cardiac surgery.     

Levocarnitine Decreases Intradialytic Hypotension Episodes: A Randomized Controlled Trial

Intradialytic hypotension is common complication in stage 5 chronic kidney disease patients on hemodialysis. Incidence ranges from 15 to 30%. These patients have levocarnitine deficiency. A randomized, placebo‐controlled quadruple‐blinded trial was designed to demonstrate the levocarnitine efficiency on intradialytic hypotension prevention. Patients were randomized into four groups, to receive levocarnitine or placebo. During the intervention period, levocarnitine and placebo was administered 0 and 30 min before each hemodialysis session, respectively. During the trial, 33 patients received 1188 hemodialysis sessions. We identified 239 (21.3%) intradialytic hypotension episodes. The intradialytic hypotension episodes were less frequent in the levocarnitine group (9.3%, 60 IH events) (P < 0.001). Hemodialysis is frequently perplexed by intradialytic hypotension episodes. Levocarnitine supplementation before each hemodialysis session efficiently diminishes the intradialytic hypotension episodes. This is a new application method that must be considered and explored.     

Protection from postconditioning depends on the number of short ischemic insults in anesthetized pigs

Abstract Postconditioning in the early reperfusion period confers protection to the heart after a potentially lethal episode of prolonged ischemia. Protection from this novel intervention has been documented in rat, rabbit and canine hearts, but one group has reported that it is ineffective in pigs, a large-animal species that should be most relevant to humans. We hypothesized that this negative result was related to an inappropriate postconditioning protocol rather than the species. The present study, therefore, tested whether an effective postconditioning protocol could be identified that limits infarct size in anesthetized pigs. Domestic Landrace pigs weighing 25–29 kg were anesthetized, and after a mid-sternal thoracotomy and pericardiotomy the left anterior descending coronary artery was ligated for 60 min followed by 3 h of reperfusion. Three groups were studied: control group (n = 5) with no other intervention, 4–30 PostC group (n = 5) with 4 cycles of 30-s reperfusion/30-s ischemia, and 8–30 PostC group (n = 6) with 8 cycles of 30-s reperfusion/30-s ischemia. The two postconditioning protocols started immediately after termination of the 60-min coronary occlusion. Region at risk and infarct size were delineated with the aid of pre-mortem monastral blue injection and postmortem staining with triphenyltetrazolium chloride, respectively. In control hearts 33.5 ± 7.6% of the risk zone infarcted and 36.7 ± 3.7% in the 4–30 PostC group (P = NS). But there was only 10.5 ± 0.5% infarction in the 8–30 PostC group (P < 0.01 vs. the other two groups). Postconditioning confers protection in pigs but requires more than 4 ischemia/reperfusion cycles. Postconditioning may protect by inhibiting mitochondrial permeability transition pore formation by keeping the heart acidotic as it is reoxygenated. If true, then it would be difficult to employ too many occlusion cycles.     

红花黄色素对体外循环肺再灌注损伤的保护作用

目的:探索红花黄色素(SY)对体外循环(cardiopulmonary bypass,CPB)后肺再灌注损伤的保护作用。方法:将24只小型猪随机分为四组,每组6只。假手术组(A组);CPB对照组(B组);红花黄色素0.26 g/kg组(C组);红花黄色素0.37 g/kg组(D组)。CPB前、肺再灌注30、60、120和240min采集相应的动脉血(或肺静脉血),检测丙二醛(MDA)含量、肿瘤坏死因子(TNF-α)、中性粒细胞和单核细胞,再灌注240min后,取右肺下叶相同部位肺组织,测定湿干质量比值。结果:与A组比较,B组的MDA和TNF-α再灌注后显著增高(P0.05),中性粒细胞和单核细胞也明显升高(P0.05);与B组比较,C,D组的MDA和TNF-α有所降低,尤其在肺再灌注240min(P0.01),单核细胞显著降低(P0.05);D组与B组相比较,中性粒细胞显著降低(P0.05),湿干重质量比值明显减少(P0.05);与C组比D组的TNF-α降低明显(P0.05)。结论:红花黄色素对CPB肺损伤具有缓解作用,高剂量组较低剂量组效果更加明显。     

Centrifugal and roller pumps — are there differences in coagulation and fibrinolysis during and after cardiopulmonary bypass?

Summary A number of hemostatic parameters reflecting the activation of coagulation and fibrinolysis were investigated in a prospective study of 24 patients undergoing cardiopulmonary bypass (CPB) during heart surgery. The patients were randomized to a group in which either a roller (group 1) or a centrifugal pump (group 2) was used. Blood samples were taken preoperatively, at the onset of and every 20min during CPB, after the administration of protamine, and 4, 20, 44, and 68 h postoperatively. The groups did not differ significantly in hematocrit, fibrinogen, factor XIII, and antithrombin III. Significant differences in favor of group 2 during and after CPB were found in prothrombin fragment F1+2, plasmin-antiplasmin complex (PAP), thrombin-antithrombin complex (TAT), and D-dimer (F1+2P < 0.01 after 80-min CPB, PAPP < 0.005 after 40-min CPB, TAT and D-dimerP < 0.05 after 100-min CPB, D-dimer and PAPP < 0.05 after protamine administration, TAT and F1+2 4h after CPB).These findings indicate the activation of fibrinolysis preceding thrombin generation during cardiopulmonary bypass. In addition, we conclude that centrifugal blood pumping is beneficial in avoiding excessive activation of both coagulation and fibrinolysis.     

体外循环肺缺血再灌注损伤的实验研究

研究兔体外循环中肺的缺血再灌注损伤并探讨其可能机制。采用兔体外循环模型 ,测定肺组织的丙二醛 (MDA) ,髓过氧化物酶 (MPO) ,一氧化氮 (NO)含量、肺血管通透性 (EB值 )及肺组织湿干比 (W /D值 )。CPB组肺组织MDA含量 (139 4± 17.0 )mmol/ g明显高于对照组 (2 7.6± 1.8)mmol/ g ,P <0 .0 1;MPO含量 (9.4± 0 .6 )u/ g明显高于对照组 (1.9± 0 .7)u/ g ,P <0 .0 1;NO含量 (8.4± 3.8) μmol/ g明显低于对照组(2 0 .9± 1.7) μmol/ g ,P <0 .0 1;W /D值 (8.5± 2 .1)明显高于对照组 (4 .5± 0 .9)P <0 .0 1;EB值 (3.2 33±0 .0 7)明显高于对照组 (1.394± 0 .0 6 ) ,P <0 .0 1。动物实验提示CPB中肺的缺血再灌注是肺损伤的重要原因 ,内源性NO减少是肺损伤的重要环节     

Protective Effects of Caffeic Acid Phenethyl Ester on Intestinal Ischemia-Reperfusion Injury

Aim Intestinal ischemia reperfusion (IR) causes tissue injury in two ways, starting a pro-inflammatory cascade and oxidative stress. The aim of this study was to investigate the possible protective effects of caffeic acid phenethyl ester (CAPE), which has antioxidant and anti-inflammatory properties, against intestinal IR injury in rats. Materials and Methods Forty male Wistar-Albino rats were divided into five groups: Sham, IR, IR plus ethanol (vehicle), IR plus 10 mg/kg (IR + 10CAPE), and 30 mg/kg CAPE (IR + 30CAPE) at the 30-min ischemic period. Intestines were exteriorized and the superior mesenteric artery was occluded for 45-min ischemia and then the clamp was removed for 120-min reperfusion. After the experiment, the intestines were removed for biochemical and light microscopic examinations. Additionally, blood samples were taken for plasma TNF-α measurement. Results The TBARS levels of the IR and IR + Ethanol groups were higher than the Sham group (P < 0.05). Both CAPE treatments decreased TBARS levels in comparison with the IR group (P < 0.05). In both CAPE-treated groups, while the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were increased compared to all other groups, which was similarly the case for the CAT activity compared to the Sham and IR + Ethanol groups (P < 0.05). There were no significant differences between GSH levels of all study groups. The TNF-α levels of the IR and IR + Ethanol groups were non-significantly increased compared to the Sham group (P > 0.05). The TNF-α levels of 10 and 30 mg/kg CAPE groups were non-significantly decreased compared to the IR group (P > 0.05). The tissue MPO activities of the IR and IR + Ethanol groups were higher than the Sham group (P < 0.05). The MPO activities of the IR + 10CAPE and IR + 30CAPE groups were not significantly different from the Sham group (P > 0.05). There was necrosis of mucosa in the IR and IR + Ethanol groups in light microscopic evaluations. Those changes were significantly reversed by 30 mg/kg CAPE treatment. Conclusion The intestinal IR injury may be reversed by anti-inflammatory and antioxidant actions of the CAPE. However, 30 mg/kg CAPE treatment may be more efficient in preventing intestinal IR injury in rats.     

添加紫外线照射充氧血预充液对体外循环手术红细胞膜ATP酶的保护作用

目的 探讨体外循环心内直视手术中使用添加紫外线照射充氧血（UBIO）预充液对患者红细胞膜ATP酶的作用.方法 体外循环心脏瓣膜置换手术患者44例,随机分为治疗组和对照组（每组各22例）.治疗组于全身血液肝素化后通过锁骨下静脉按10 ml/kg体重放血或使用库血行紫外线照射并充氧后加入预充液,对照组使用等量生理盐水,其他处理两组相同.两组均在麻醉诱导后（T1）,转机30 min（T2）,开放主动脉30 min（T3）、2 h（T4）及术后第1天（T5）抽取动脉血测定Na＋-K＋-ATPase、Ca2＋-Mg2＋-ATPase活性.结果 体外循环开始后,两组T2～T4时点红细胞膜Na＋-K＋-ATPase、Ca2＋-Mg2＋-ATPase活性水平均明显下降（P〈0.05）;对照组T2～T4时点活性水平较治疗组下降更明显（P〈0.05）.结论 UBIO通过减轻体外循环手术患者红细胞脂质过氧化作用,对体外循环手术红细胞膜ATP酶有一定的保护作用.     

Differential-display polymerase chain reaction identifies nicotinamide adenine dinucleotide-ubiquinone oxidoreductase as an ischemia/reperfusion-regulated gene in cardiomyocytes

OBJECTIVE: Cardiac ischemia/reperfusion-induced oxidative damage often occurs in mitochondria. We identified differentially expressed genes in the canine heart after global cardiac ischemia/reperfusion injury was induced during cardiopulmonary bypass (CPB). METHODS: Differential-display polymerase chain reaction (ddPCR) was performed on cardiac tissue from canine hearts with or without global cardiac ischemia/reperfusion injury induced during CPB. Ischemia/reperfusion-associated mitochondrial injury was investigated at the protein level using various cardioplegic solutions and Western blot analysis. RESULTS: A mitochondrial protein nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase gene was identified on ddPCR. The NADH:ubiquinone oxidoreductase gene was up-regulated in canine hearts after 60 min of global cardiac ischemia/reperfusion injury during CPB. Western blot analysis revealed that, after manipulation with different cardioplegic solutions, increased Bcl-2 expression and decreased cytochrome c expression were associated with cardiomyocytic apoptosis. CONCLUSIONS: The NADH:ubiquinone oxidoreductase gene is up-regulated during global cardiac ischemia/reperfusion injury during CPB in canines. To our knowledge, involvement of this gene in global cardiac ischemia/reperfusion injury during CPB has not been described previously. The NADH:ubiquinone oxidoreductase gene may have a role in the regulation of molecular changes during the global cardiac ischemia/reperfusion injury during CPB, such as the up-regulation of Bcl-2, which might block release of cytochrome c from the mitochondria and prevent cardiomyocytic apoptosis.