等容血液稀释和川芎嗪在兔心肌缺血再灌注损伤中的抗氧化作用

目的：研究6％羟乙基淀粉（6％hydroxyethyl starch,6%HES)急性等容血液稀释和川芎嗪注射液对兔心肌缺血再灌注损伤的保护作用。方法：32只家兔随机分为四组，每组8只，I组为对照组；Ⅱ组为稀释组；Ⅲ组为川芎嗪组；Ⅳ组为稀释加川芎嗪组。观察在急性心肌缺血45min及再灌180min状态下血浆过氧化物歧化酶（SOD）活性、丙二醛（MDA）含量的变化及心肌超微结构改变。结果：缺血后，I组血浆SOD活性明显降低（P＜0．05）；Ⅱ，Ⅲ，Ⅳ组血浆SOD活性亦降低，但差异无显著性。再灌后，I组血浆SOD活性进一步降低（P＜0．05）。I组MDA含量在缺血后及再灌后升高（P＜0．05），Ⅱ，Ⅲ，Ⅳ组升高程度较I组轻。心肌细胞超微结构可见I组结构破坏严重，Ⅱ，Ⅲ组结构破坏均较轻，Ⅳ组结构基本接近正常。结论：6％HES等容血液稀释和川芎嗪对心肌缺血再灌注损伤均有保护作用，两者合用保护作用更为显著。     

羟乙基淀粉行急性等容血液稀释对兔脊髓缺血-再灌注损伤的保护作用

目的 探讨用羟乙基淀粉(HES130/0.4)急性等容血液稀释(ANH)对兔脊髓缺血-再灌注损伤的保护作用.方法 24只新西兰雄性大白兔,随机均分成三组:HES组,生理盐水组(NS组),对照组(C组).HES组和NS组分别用HES130/0.4和生理盐水行ANH,使红细胞压积(Hct)达30%.ANH的方法为:15 min内经股动脉恒速放出计算的血量,同时利用微量输液泵经静脉输注与放血量等量的液体(HES组)或输注3倍于放血量的液体(NS组),放血和输液速度相等,维持术中大白兔的血压和心率恒定.稳定15 min后,行肾下腹主动脉(IRA)阻闭建立脊髓缺血-再灌注损伤模型.分别于稀释前、稀释后和腹主动脉开放后采集动脉血进行血气分析.评估再灌注后4、8、12、24及48 h后肢运动功能,并于48 h处死动物取脊髓(L5)制标本行病理组织学观察.结果 再灌注后48 h.HES组和NS组动物的后肢运动功能比C组明显改善(P＜0.05或P＜0.01);HES组和NS组动物脊髓前角正常运动神经元计数比C组显著增加(P＜0.05或P＜0.01),但两组间差异无统计学意义.结论 HES130/0.4行适度ANH对脊髓缺血-再灌注损伤具有显著地保护作用.     

血液稀释联合潘通预防肢体缺血再灌注损伤

目的探讨静脉血液稀释疗法和潘通对肢体缺血再灌注损伤（I／R）预防作用。方法复制家兔左下肢缺血／再灌注损伤模型,分别在阻断左下肢前、阻断4h灌注1h和再灌注24h采集假手术组、I／R组、潘通组、血液稀释组和联合治疗组静脉血,测定血浆丙二醛（malondialdehyde,MDA）、超氧化物歧化酶（erythrocuprein,SOD）、血栓素B2（TXB2）含量,应用SAS8．1对实验数据进行均数问双因素方差分析,两两比较用SNK-q检验。结果潘通组、血液稀释组和联合治疗组血浆MDA、TXB2含量较I／R组显著降低,SOD显著升高,而联合治疗组与潘通组、血液稀释组相比也有显著性差异（P值均〈0．05）。结论静脉血液稀释和潘通可有效缓解肢体缺血再灌注损伤,而联用静脉血液稀释和潘通可取得更好的效果,两者具有良好的协同效应。     

KATP通道在参附注射液减轻大鼠心肌缺血再灌注损伤中的作用

目的研究KATP通道在参附注射液（SFI）减轻大鼠心肌缺血再灌注损伤中的作用。方法24只SD大鼠,雌雄不拘,体重240～320 g,随机分为4组（n=6）：对照组（C组）、缺血再灌注组（I/ R组）、SFI组和SFI＋KATP通道阻滞剂格列苯脲组（SG组）。C组仅穿线不结扎左冠状动脉前降支,穿线后静脉输注生理盐水8 ml/kg。采用结扎左冠状动脉前降支40 min再灌注120 min制备心肌缺血再灌注损伤模型。SFI组缺血前15 min静脉输注SFI 8 ml/kg,SG组给予格列苯脲0．33 mg/kg和SFI 8 ml/ kg。再灌注120 min后从心尖穿刺抽血,测定血清cTnI与IL-6浓度,抽血后立即取心肌组织,测定心肌组织SOD活性、MDA含量、TNF-α表达,并在电镜下观察心肌超微结构。结果与C组比较,I/R组心肌SOD活性降低,心肌MDA、TNF-α和血清IL-6、cTnI水平升高（P＜0．05）;与I/R组比较,SFI组、SG组心肌SOD活性升高,心肌MDA、TNF-α和血清cTnI、IL-6水平降低（p＜0．05）;SG组与SFI组比较上述指标差异无统计学意义（P＞0．05）。SFI组与SG组心肌超微结构损伤程度明显轻于I/R组。结论参附注射液可以减轻大鼠心肌缺血再灌注损伤,其作用机制与KATP通道的激活无关。     

电针足三里穴对兔肺缺血再灌注损伤的影响

目的探讨电针足三里穴对兔肺缺血再灌注损伤的影响及其机制。方法健康成年雄性新西兰家兔28只,体重1．7～2．3kg,随机分为4组,每组7只,假手术组（A组）：左侧开胸游离支气管和肺动脉、肺静脉后机械通气180min；缺血再灌注组（B组）：左侧开胸游离支气管和肺动脉、肺静脉后阻断左肺门60min后,开放左肺门行机械通气120min；非穴位＋缺血再灌注组（C组）：阻断左肺门60min后,开放左肺门行机械通气即刻电针双侧足三里穴旁5mm处30min,继续机械通气90min；足三里穴＋缺血再灌注组（D组）：阻断左肺门60min后,开放左肺门机械通气即刻电针双侧足三里穴30 min,继续机械通气90min。记录各组缺血30、60min、再灌注30、45、60、90、120min时平均动脉压（MAP）和心率（HR）,颈动脉抽血,行动脉血气分析,抽血后立即处死大鼠,取左肺,测定丙二醛（MDA）和髓过氧化物酶（MPO）水平及肺组织湿/干重比（W/D）。结果各组HR差异无统计学意义（P＞0．05）；与A组比较,C组再灌注90、120min MAP降低,B组和C组肺组织MDA和MPO水平、W/D及PaCO2升高,pH值和PaO2降低（P＜0．05或0．01）；与B组比较,C组再灌注期间MAP降低,D组肺组织MDA和MPO水平、W/D及PaCO2降低,pH值和PaO2升高（P＜0．05或0．01）。结论电针足三里穴可明显减轻家兔肺缺血再灌注损伤,其机制可能与降低脂质过氧化反应、抑制中性粒细胞的浸润有关。     

复方丹参对心内直视手术心肌缺血再灌注后血清过氧化脂质及前列环素变化的影响

目的：观察复方丹参对心肺转流（CPB）心内直视手术心肌缺血再灌注后血清过氧化脂质及前列环素（PGI2）变化的影响。方法：20例先天性室间隔缺损或房间隔缺损患者麻醉后随机分为对照组（I组，n=10）及丹参组（Ⅱ组，n=10）。Ⅱ组患者于手术开始前及复温后心脏复跳前分别静注复方丹参200mg/kg，I组给予等容量复方乳酸钠。于手术开始前（T0）、心肌缺血前（T1）、心肌缺血30分钟（T2）、再灌注后10分钟（T3）和30分钟（T4）、停CPB30分钟（T5）及再灌注后24小时（T6）抽中心静脉血测丙二醛（MDA）及前列环素。结果：I组血清MDA于CPB后逐渐升高，再灌注后迅速增加，于T4、T5、T6显著高于其T2时值（P＜0．05或P＜0．01）。Ⅱ组再灌注后未出现显著的血清MDA升高，且缺血及再灌注后各时期Ⅱ组MDA均显著低于I组（P＜0．05）。CPB后再组前列环素均显著上升，而再灌注后迅速下降，但T2及T6时Ⅱ组前列环素均显著低于I组（P＜0．01，P＜0．05）。术后Ⅱ组心功能的恢复优于I组。结论：复方丹参能显著降低心脏缺血及再灌注期脂质过氧化程度，抑制缺血期前列环素的急剧增加，促进术后心肌功能的恢复。     

腹主动脉局部灌注丙泊酚减轻脊髓缺血-再灌注损伤的研究

目的 建立兔脊髓缺血-再灌注损伤模型，研究经腹主动脉局部灌注丙泊酚对脊髓缺血-再灌注损伤的作用。方法 新西兰大耳白兔30只，随机均分为A、B、C三组，诱导后气管插管，持续监测平均动脉压、心率、脉搏血氧饱和度及肛温。左股动脉切开置管至腹主动脉分出左肾动脉远端1．0cm处，于左肾动脉开口远端0．5cm处阻断腹主动脉，同时阻断双侧髂总动脉，自阻断即刻开始经置入导管分别向阻断的腹主动脉远端灌注5ml／kg丙泊酚溶液（A组）、10％脂肪乳（B组）和生理盐水（C组），30min后开放。于动物完全清醒即刻、再灌注后6、24和48h对双后肢神经功能进行评分，光镜观察脊髓前角正常运动神经元并计数。结果 清醒即刻、再灌注后6、24和48hA组神经行为学评分明显高于B和C组（P〈0．05），B、C两组比较差异无统计学意义。三组脊髓前角正常运动神经元中位数分别为11、1和0，A组明显高于B、C两组（P〈0．05）。结论 腹主动脉阻断期间经阻断的腹主动脉局部灌注丙泊酚可减轻脊髓缺血一再灌注损伤。     

异氟醚对家兔肺缺血-再灌注损伤的影响

目的 研究异氟醚对体家兔肺缺血－再灌注（I－R）损伤的影响。方法 32只新西兰家兔根据Eppinger模型加以改进,建立在体兔肺缺血再灌注模型,随机分四组（n＝8）,A组：假手术组,开胸后维持通气120min。B组：缺血再灌注组,阻断左肺门60min,开放再通气60min。C组：异氟醚＋缺血再灌主组,缺血前吸入1MAC异氟醚30min,开放再通气时也吸入1MAC异氟醚。D组：异氟醚组,持续吸入1MAC异氟醚120min,观察各组实验结束时肺湿－干重比（W／D）,肺内二醛含量（MDA）和肺组织学改变以及术中血流动力学的改变。结果 B组及C组W／D,肺MDA含量均较A、D两组显著增高,（P＜0．05）,且病理切片显示,部分肺泡结构破坏,肺泡间隔增宽,肺泡腔水肿并有白细胞渗出,但B组改变明显严重,且B组W／D,肺MDA含量也明显高于C组（P＜0．05）,血液动力学基本维持正常。结论 异氟醚在体家兔肺I－R损伤有一定的保护作用。     

两种兔可控性急性心肌缺血再灌注模型的比较

目的 完善兔可控性急性心肌缺血再灌注(I/R)动物模型的制备,提高模型成功率和动物成活率.方法 成年健康家兔60只,随机分为假手术组30只(Sham组)、I/R1组15只和I/R2组15只.Sham组仅穿线不接扎,I/R1组选择左冠状动脉前降支,I/R2组选择冠状动脉左缘支.开胸后以5-0 prolene线穿过冠状动脉,硅胶管圈套5-0 prolene线,用血管钳收紧硅胶管阻断冠状动脉血流,制备兔可控性心肌缺血再灌注模型.四肢安装肢体导联,通过心电图sT段的改变作为心肌缺血的评定指标.结果 Sham组30只动物手术前后心电图均无变化;I/R1组结扎后,13只动物ST段无明显变化;2只动物ST段轻度压低,再灌注时无心律失常表现;I/R2组15只动物结扎后ST段均抬高明显,并渐与QRS波融合,QRS波幅随着时间的延长逐渐变小,再灌注时11只出现室性早搏,4只出现室性心动过速.结论 兔可控性心肌缺血再灌注模型应选择冠状动脉左缘支.用血管钳收紧硅胶管圈套5-0 prolene线的方法 可以准确地复制兔心肌缺血再灌注的实验模型,简化实验操作步骤.     

异丙酚预先给药对心肌缺血再灌注损伤大鼠炎性反应的影响

目的探讨异丙酚预先给药对心肌缺血再灌注损伤大鼠炎性反应的影响。方法健康雄性SD大鼠48只，随机分为4组（n=12）：假手术组（S组）、缺血再灌注组（I／R组）、低剂量异丙酚组（L组）、高剂量异丙酚组（H组）。结扎左冠状动脉前降支（LAD）30min、再灌注120min，建立大鼠心肌缺血再灌注损伤模型。分别于再灌注30min（T1）、120min（T2）时采集股动脉血1ml，ELISA法测定血浆肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）的浓度，再灌注120min时TTC法测心肌梗死面积，电镜下观察心肌细胞超微结构。结果与S组比较，I／R组、L组、H组在T1、T2时TNF-α、IL-10浓度升高（P〈0．05）；与I／R组比较，L组、H组在T1、T2时TNF-α浓度降低（P〈0.05），IL-10浓度升高（P〈0．05），心肌梗死面积减小（P〈0．05）；L组比较，H组T1、T2时，TNF-α浓度降低，IL-10浓度升高，心肌梗死面积减小（P〈0.05）。电镜下观察I／R组心肌细胞超微结构改变严重，L组、H组心肌细胞超微结构改变程度较I／R组轻。结论异丙酚预先给药通过抑制再灌注诱发的炎性反应减轻了大鼠心肌缺血再灌注损伤。     

Effective administration method of recombinant superoxide dismutase in acute myocardial ischemia and reperfusion

To determine the efficacy of direct versus systemic administration of human recombinant superoxide dismutase (rt-SOD) in acute myocardial ischemia and reperfusion, the following experimental model was applied. Twenty-one dogs were subjected to 30 minutes normothermic global ischemia caused by the occlusion of the ascending aorta followed by 60 minutes reperfusion. To eliminate collateral blood flows during the ischemia, bipulmonary hilus were cross clamped. The dogs were randomly assigned to three groups: group A (n = 7), 12 ml of normal saline was injected through the aortic root into the coronary artery 1 minute prior to reperfusion, in addition to a 30 minute continuous infusion of 50 ml of saline into the cardiopulmonary bypass circuit beginning just after reperfusion; group B (n = 7), rt-SOD (10,000 U/kg) dissolved in 12 ml saline was administered by bolus injection through the aortic root and an additional 30,000 U/kg of rt-SOD dissolved in 50 ml of saline was injected into the cardiopulmonary bypass circuit as the same manner as the group A; group C (n = 7), the treatment was similar to the group B except the bolus injection of rt-SOD was into the cardiopulmonary bypass circuit. The left ventricular stroke work index (LVSWI) was determined by a right heart bypass technique and expressed as a percent recovery of pre-occlusion state. Morphologic structures were observed by the electron microscope. The coronary sinus blood was assessed for malondialdehyde (MDA) measured by TBA method and creatine phosphokinase (CPK). The percent of recovery of LVSWI after 60 minutes reperfusion was superior in group B (121 +/- 82%) than groups A (24 +/- 38%*, *p less than 0.05) and C (52 +/- 21%*). In group B, the myocardial cell structure had a normal appearance in most areas, but swollen mitochondria and disrupted myofibrils were observed in groups A and C. Serum MDA levels did not change in all groups. Increasing CPK levels after reperfusion were less in group b than group A. These results suggest that an adequate concentration of rt-SOD in the interstitial fluid or cell surface at the time of reperfusion may be required to prevent reperfusion injury.     

Improvement of myocardial function by trifluoperazine, a calmodulin antagonist, after acute coronary artery occlusion and coronary revascularization

Activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Trifluoperazine, a calmodulin antagonist, was used before ischemia to enhance myocardial preservation by preventing intracellular calcium accumulation. The experimental model used an isolated in situ pig heart (19 control animals and 15 trifluoperazine-treated animals) subjected to occlusion of the left anterior descending coronary artery for 60 minutes followed by 60 minutes of hypothermic potassium crystalloid cardioplegic arrest and 60 minutes of reperfusion. Myocardial segmental function measured by ultrasonic crystals showed that active systolic segment shortening was abolished in the distribution of the left anterior descending artery after 60 minutes of occlusion irrespective of the treatment, whereas that not in the distribution of the left anterior descending artery increased by about 15% in both groups of animals. Restoration of systolic segment shortening in the distribution of the left anterior descending artery 60 minutes after reperfusion was 12% and 42% of baseline levels in untreated and trifluoperazine-treated animals, respectively (p less than 0.01). This improvement in segmental function by trifluoperazine was reflected in significantly (p less than 0.05) better global myocardial contractility and compliance and in significantly (p less than 0.01) greater total coronary blood flow and myocardial oxygen consumption. Trifluoperazine also increased myocardial creatine phosphate content in the distribution of the left anterior descending artery (p less than 0.01) during reperfusion, and creatine kinase release was reduced (p less than 0.05). Our results suggest that trifluoperazine improved regional myocardial function after acute occlusion of the left anterior descending artery and reperfusion and that global cardiac performance was thereby improved. The beneficial effects of trifluoperazine may be exerted by prevention of myocardial injury associated with the calcium-calmodulin complex in ischemic and reperfused myocardium.     

The effect of direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX therapy) on pulmonary ischemia-reperfusion injury in a canine model

This study evaluates the effectiveness of direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX therapy) on warm ischemia-reperfusion injury of the lung using a canine mode. MATERIALS AND METHODS: Ten adult mongrel dogs weighing 13-16 kg were used. After a left thoracotomy, the left pulmonary artery and vein were clamped. The left main bronchus was also clamped and then divided, and complete ischemia of the left lung was maintained for 3 h. The left main bronchus was re-anastomosed before reperfusion of the left lung. The right pulmonary artery was ligated immediately after reperfusion of the left lung. The dogs were divided into two groups: the DHP-PMX group (n = 5, DHP-PMX was performed for 120 min, from 30 min before reperfusion to 90 min after reperfusion) and the control group (n = 5). The body temperature of the animals was maintained at 36 degrees C-37 degrees C during the experiment. The PaO2/FiO2 (P/F ratio), AaDO2, and lt-pulmonary vascular resistance (PVR) were measured at 30, 60, 120, 180, and 240 min after reperfusion in both groups, and the two groups were compared. The water content of the lung tissues and histopathology was also analyzed. RESULTS: The P/F ratio decreased remarkably after reperfusion in the control group, and was significantly (p < .05) lower than that in the PMX-DHF group until 240 min after reperfusion. The AaDO2 was significantly (p < .05) lower in the DHP-PMX group than in the control group at 30, 60, and 120 min after reperfusion. The lt-PVR level differed significantly (p < .05) between the two groups until 240 min after reperfusion. The water content in the control group was significantly (p < .05) higher than that in the DHP-PMX group at 240 min after reperfusion. Lung tissues at 120 and 240 min after reperfusion were better preserved pathologically in the DHP-PMX group. CONCLUSION: DHP-PMX therapy reduced warm ischemia-reperfusion injury in the lung using a canine model.     

抑制核转录因子减轻心肌缺血再灌注损伤

目的　观察核转录因子(NF-κB)激活抑制剂吡咯二硫氨基甲酸酯(PDTC)对心肌缺血和再灌注损伤的影响。方法　结扎和开放新西兰白兔心脏左冠状动脉前降支,造成局部心肌缺血45min和再灌注120min。缺血前静脉注射PDTC(15mg/kg),对照组给予生理盐水。将压力传感探头包埋于缺血区心外膜下,测定局部心肌的缩短度;再灌注末用氯化三苯四唑啉法计算心肌缺血区梗死面积,并做心肌病理观察和NF-κB免疫电泳活性测定。结果　与对照组相比,实验组在再灌注30min以后心肌缩短度显著改善(P＜0.05);缺血心肌梗死面积显著减小［(19.3±5.2)%对(54.7±6.5)%,P＜0.05］;心肌血管内皮白细胞粘附和浸润减少,结构损害较轻;NF-κB活性明显减弱。结论　核转录因子激活抑制剂PDTC可减轻白细胞介导的心肌缺血再灌注损伤。     

左心室及双心室辅助装置对缺血心肌的影响

目的 比较左心室辅助装置（LVAD）和双心室辅助装置（BVAD）对缺血心肌再灌注后心脏血流动力学、心肌能量代谢物质和心肌超微结构中线粒体形态的影响。方法 将16只绵羊随机分为LVAD组和BVAD组,每组8只,常温阻断升主动脉25分钟,造成双心室缺血损伤的动物模型。结扎右颈内动脉远端,在心脏复跳后应用转子泵分别行LVAD（左心室－右颈内动脉径路）和BVAD（左心室－右颈内动脉和右心室－肺动脉径路）辅助循环120分钟,测定血流动力学,心肌三磷酸腺苷、磷酸肌酸、观察心肌超微结构变化。结果 施行BVAD或LVAD辅助循环的同时增加容量负荷能够显著改善心脏血流动力学,但LVAD组右心房压显著高于BVAD组（P＜0．05）;BVAD组右心室心肌三磷酸腺苷、磷酸肌酸含量和心肌线粒体比表面值均高于LVAD组（P＜0．05）。结论 BVAD与LVAD更有助于促进双心室缺血损伤心肌的功能恢复。     

Hydroxyethyl starch macromolecules reduce myocardial reperfusion injury.

We assessed the value of a fraction of hydroxyethyl starch (HES Pz) in reducing the myocardial reperfusion injury in a canine open-chest model in which 1 hour of left anterior descending coronary artery occlusion was followed by 24 hours of reperfusion. Three treatment infusions (5% of blood volume) were compared: Ringer's lactate, serum albumin, and HES Pz (70% of the macromolecules between 100,000 and 1,000,000 d). When compared with Ringer's lactate and albumin, HES Pz significantly reduced the ratio of 24-hour infarct size to pretreatment area at risk (3% vs 19% and 16%, respectively) and myocardial water content (0.5% vs 3% and 1%). Potassium content differences between injured and normal myocardium were significantly less in the infarct regions of animals receiving HES Pz. In the canine model, HES Pz reduced 1-hour myocardial ischemia reperfusion injury significantly.     

七氟醚对未成熟兔在体心肌缺血/再灌注血清IL-6、TNF-α的影响

目的 研究七氟醚对未成熟兔在体心肌缺血,再灌注血清IL-6、TNF-α水平的影响.方法 1～2周龄未成熟兔随机分为对照组(C组)、缺血,再灌注组(I/R组)和七氟醚预处理组(S组),每组8只.分别于缺血前(T0)、缺血30 min再灌注前(T1)、再灌注120 min后(T2)采取静脉血,ELISA法检测血清中IL-6和TNF-α的水平;再灌注120 min后取心肌组织,HE染色光镜下观察其病理学改变.结果 T2时S组IL-6水平(66.07±24.12) pg/μl,低于I/R组的(200.37±93.07)pg/μl,P<0.05;,INF-α水平(6.56±3.61) pg/μl,略低于I/R组(8.59±2.68)pg/μl,但差异无统计学意义(P>0.05).光镜下S组心肌组织病理改变较I/R组轻.结论 七氟醚可通过降低血浆IL-6、TNF-α水平,减轻机体的炎症反应来对未成熟兔在体心肌缺血/再灌注损伤起保护作用.     

Experimental off-pump coronary artery revascularization with adenosine-enhanced reperfusion

OBJECTIVE: Although beating heart coronary artery bypass grafting has recently gained popularity, it eliminates the protective strategies (ie, cardioplegia) developed for use in conventional cardiac operations. We recently introduced the technique of perfusion-assisted direct coronary artery bypass to perfuse the grafted vessels during multivessel off-pump coronary artery bypass grafting. In the present study we tested the hypothesis that intracoronary reperfusion with the cardioprotective agent adenosine during simulated perfusion-assisted direct coronary artery bypass attenuates reperfusion injury. METHODS: In anesthetized dogs the heart was exposed, and the left anterior descending coronary artery was ligated for 75 minutes. Reperfusion was achieved through a catheter in the left anterior descending coronary artery by means of a computer-controlled pump. Intracoronary left anterior descending coronary artery perfusion pressure was continuously matched to mean arterial blood pressure. In one group (adenosine group) 10 micromol/L adenosine was added to the blood during the first 30 minutes of reperfusion, whereas another group (vehicle group) received a comparable volume of saline solution. RESULTS: During the first 30 minutes of reperfusion, blood flow through the left anterior descending coronary artery was significantly greater (P <.05) in the adenosine group than in the vehicle group (150.6 +/- 21.9 vs 50.2 +/- 11.3 mL/min at 15 minutes of reperfusion). Although there were no group differences in postischemic wall motion, infarct size was significantly smaller in the adenosine group than in the vehicle group (11.1% +/- 3.0% vs. 28.0% +/- 4.0% of area at risk, P <.05). Myeloperoxidase activity in the necrotic tissue, an index of neutrophil accumulation, tended to be lower in the adenosine group than in the vehicle group (58.6 +/- 14.2 vs. 91.0 +/- 21.6 DeltaAbs Units x min(-1) x g(-1) tissue). In isolated postischemic left anterior descending coronary artery rings, the maximal relaxation response to the endothelium-dependent vasodilator acetylcholine was significantly greater in the adenosine group than in the vehicle group (97.9% +/- 5.6% vs. 64.7% +/- 6.5%, P<.05). CONCLUSION: This novel reperfusion strategy for off-pump coronary artery bypass grafting can be used not only in cases requiring multiple grafting but also to attenuate necrosis and endothelial dysfunction in acute evolving infarction.     

Inhibition of Inducible Nitric Oxide Synthase Ameliorates Myocardial Ischemia/Reperfusion Injury − Induced Acute Renal Injury

Objectives

Acute kidney injury occurs frequently in patients subsequent to coronary artery revascularization or myocardial ischemia and reperfusion (MIR). Hypotension and excessive nitric oxide (NO) production through inducible nitric oxide synthase (iNOS) were implicated in renal injury. On the other hand, NO may have a protective role during early reperfusion. In this study, we aim to compare protective effectiveness of 1400W, a highly selective iNOS inhibitor, and L-NG-nitroarginine methyl ester (L-NAME), a non-specific nitric oxide synthase (NOS) inhibitor, against MIR-induced hemodynamic stabilization and kidney injury.

Methods

Male Sprague-Dawley rats were evenly divided in four groups including sham-operated, MIR, and groups pretreated with 1400W (20 mg/kg, intraperitoneally, [ip]) or L-NAME (30 mg/kg, ip) 15 minutes before MIR. Ischemia was conducted by occluding the left coronary artery for 30 minutes, followed by 120 minutes of reperfusion. We determined the measured aortic pressure (MAP) and assessed kidney injury through serum levels of blood urea nitrogen (BUN), methylguanidine (MG), malondialdehyde (MDA) and NO at different phases during the study.

Results

MAP, decreased during myocardial ischemia, increased during early reperfusion; however, that was abolished with L-NAME pretreatment, and the increase was moderate with 1400W pretreatment. Serum MDA, MG and BUN levels, although relatively unaltered during ischemia, significantly increased after 120 minutes of reperfusion. Treatment with 1400W reduced post-reperfusion MDA and MG levels (P < .05), but the improvement was not significant with L-NAME.

Conclusions

1400W was effective in reducing MIR-induced hemodynamic instability and kidney injury, in contrast to no apparent protection with L-NAME administration.