GIK对缺血/再灌注犬心肌超微结构的影响

目的:观察葡萄糖-胰岛素-钾液（GIK）、葡萄糖-钾液（GK）对急性心肌缺血/再灌注（MI/R）犬心肌缺血区内心肌细胞改变的影响,分析GIK中的胰岛素对MI/R心肌细胞的保护作用。 方法: 将犬心肌定量缺血(左前降支血流量降低80%) 50 min,再灌注4 h,建立犬MI/R模型。24只杂种犬随机分为GIK组、GK组和盐水对照组(n=8),于再灌注前5 min,分别输注GIK、GK和生理盐水。再灌注4 h后,计算梗死区占缺血区重量的百分比,并制作电镜切片于透射电镜下观察。 结果: GIK可显著减少心肌梗死(MI)的范围［GIK组（5.2±0.8）% vs. 盐水对照组（9.4±0.8）%,P<0.05］;而GK组MI的范围（8.5±0.9）%则与盐水对照组无明显差异。与盐水对照组相比,GIK组对非缺血心肌的超微结构无影响,对缺血心肌有一定的保护作用。GK对缺血心肌无保护作用。结论: 再灌注时,静脉输注GIK可减轻心肌超微结构的损伤,其中的胰岛素是GIK上述作用的关键成分。     

胰岛素抑制缺血-再灌大鼠心肌细胞凋亡及其信号转导机制

目的　观察胰岛素对在体缺血 /再灌 (MI/R)大鼠心肌细胞凋亡的影响并探讨其主要细胞内信号转导机制。方法　常规制备大鼠MI/R模型 ,于再灌前 5min给大鼠随机静脉输注生理盐水、胰岛素或胰岛素 +磷脂酰肌醇 3激酶 (PI3K)抑制剂渥曼青霉素。分别以DNA梯带形成和TUNEL方法定性和定量检测心肌细胞凋亡 ;以激酶反应法测定蛋白激酶B(Akt)及p38丝裂素活化蛋白激酶(MAPK)活性 ,以化学发光法测定心肌一氧化氮 (NO)。结果　MI 30min/R 4h可在缺血区心肌检测到大量凋亡细胞 (1 9 3± 4 6) % ,再灌时输注胰岛素显著降低心肌细胞凋亡指数 [AI:(8 0± 2 9) % ,q =1 0 2 ,P <0 0 1 ] ,并明显减弱DNA梯形成 ;此时 ,胰岛素使心肌Akt活性增加了 2 7倍 (q =1 0 5 ,P <0 0 1 ) ,心肌NO增加 2 8% (q=3 4,P <0 0 5) ,而p38MAPK活性无明显变化。上述Akt的激活及NO增加均可被渥曼青霉素阻断 ,且此时胰岛素抗凋亡效应几乎消失。结论　胰岛素可通过PI3K Akt信号转导途径明显抑制MI/R心肌细胞凋亡 ,其中Akt激活是胰岛素上述抗凋亡效应的关键环节     

葡萄糖-胰岛素-钾极化液对犬重度心肌缺血/再灌注后心律失常和心电图的影响

目的探讨葡萄糖-胰岛素-钾合剂（GIK）对犬重度心肌缺血/再灌注（MI/R）后心律失常和心电图的影响。方法制备犬重度MI/R模型。再灌注前5min静脉分别输注生理盐水、GIK或GK（葡萄糖-钾液）。观察动物心电、血糖等的变化。结果犬重度MI/R引起心律失常,包括室性早搏、室速和室颤。再灌注期间静脉输注生理盐水、GIK或GK,未观察到室性心律失常发生率和严重程度有显著差异。但GIK可缩短再灌注期间心电图QRS波群时间。其中,再灌注4hQRS波群时间显著缩短,由对照组0.077±0.006s缩短至GIK组0.058±0.003s（n=6,P<0.01）。GK组与对照组比较无显著差异（n=6,P>0.05）。结论GIK对犬重度MI/R引起的室性心律失常无显著改善作用,但可缩短缺血/再灌注心脏的QRS波群时间,提示胰岛素可能影响MI/R心室除极。     

胰岛素对心肌缺血/再灌注损伤兔心肌组织中髓过氧化物酶活性的影响及意义

目的观察胰岛素是否能够通过减轻中性粒细胞(PMN)在心肌组织中的浸润、聚集而抑制炎症反应,从而减轻心肌缺血/再灌注(MI/R)损伤。方法建立兔MI/R模型,分为假手术组、GIK组、GK组和对照组,后三组缺血45 min/再灌注6 h,检测各组血浆肌酸激酶同工酶(CK-MB)活性、高敏C反应蛋白(hs-CRP)水平,以及心肌组织中髓过氧化物酶(MPO)活性,利用Evans blue-TTC染色法测定心脏梗死面积。结果与对照组相比,GIK组CK-MB活性下降(P<0.01)、心肌梗死面积减小(P<0.01)、MPO活性降低(P<0.01)、hs-CRP水平下降(P<0.01),GK组上述各指标则无明显变化(P均>0.05)。结论胰岛素能够减轻兔MI/R过程中PMN在心脏组织中的聚集,这可能是胰岛素保护MI/R心脏的重要机制之一。     

高、低剂量极化液对缺血/再灌注心肌细胞凋亡及相关基因的影响

目的 :探讨高、低两种剂量葡萄糖 -胰岛素 -钾极化液 （GIK）对缺血 /再灌注 （MI/R）心肌超微结构 ,细胞凋亡及其相关基因的影响。方法 :制备兔MI/R模型 ,分别用生理盐水 ,低剂量极化液 （LGIK） ,高剂量极化液 （HGIK）干预分组。检验心肌组织SOD活性 ,原位末端标记 （TUNEL）法测定凋亡心肌细胞 ,免疫组化SP法测定Bcl 2 ,Fas的含量 ,在电镜下观察心肌细胞的超微结构。结果 :与对照组比较 ,HGIK组SOD活性增加 （P <0 .0 1） ,凋亡指数 （AI）和Fas含量减少 （P <0 .0 1） ,Bcl 2含量增加 （P <0 .0 1）。心肌细胞超微结构表现为损伤减轻。LGIK亦可增加SOD活性和Bcl 2含量 （P <0 .0 5 ） ,减少AI和Fas（P <0 .0 5 ）含量。结论 :GIK具有抗缺血 /再灌注损伤的作用 ,其机制可能是通过调节Bcl 2和Fas介导的心肌缺血 /再灌注细胞凋亡而实现。高剂量GIK对缺血 /再灌注心肌细胞的保护作用显著大于低剂量GIK（P <0 .0 5 ）。     

作者单位：030001山西省太原市 山西医科大学基础医学院生理学系,细胞生理学山西省重点实验室通讯作者：贺忠梅,E-mail：hezmei@126.com

目的 探讨低氧诱导因子-1α(HIF-1α)稳定表达对大鼠心肌缺血再灌注细胞凋亡的影响及可能机制。方法 采用结扎冠脉左前降支45min,再灌注3h的方法,构建大鼠心肌缺血再灌注损伤模型;实验分为假手术组(Sham)、心肌缺血/再灌注组(MI/R)、HIF-1α活化剂DMOG 心肌缺血/再灌注组(D MI/R)、HIF-1α抑制剂YC-1 心肌缺血/再灌注组(YC-1 MI/R);采用全自动生化分析仪测定血清心肌酶(CK-MB,LDH)活性;Western blot检测心脏组织HIF-1α蛋白表达;Evens blue/TTC染色测定心肌梗死面积;TUNEL染色及Caspase-3,8,9活性测定心肌细胞凋亡。结果 (1)与MI/R 组相比,D MI/R 组的HIF-1α蛋白表达量明显增加,心肌酶CK-MB、LDH的活性降低,心肌梗死面积明显减小,并且心肌组织的病理损伤减轻;(2)稳定HIF-1α表达可明显降低心肌细胞凋亡率,且部分逆转了缺血再灌注后心肌组织Caspase-9与Caspase-3的活性升高。结论 HIF-1α稳定表达可抑制线粒体途径介导的心肌细胞凋亡,从而发挥对缺血再灌注损伤的心脏保护效应。     

葡萄糖-胰岛素-钾液对缺血/再灌注心肌的保护作用

目的:观察极化液（葡萄糖-胰岛素-钾液,G IK）对急性心肌缺血/再灌注（M I/R）犬心脏功能、冠脉血流量及心肌损伤的影响,分析胰岛素在G IK上述效应中的作用。方法:制备犬M I/R模型,心肌定量缺血（左前降支血流量降低80%）50 m in,再灌注4 h。24只杂种犬随机分为G IK、葡萄糖-钾液（GK）和盐水对照组（n=8/组）,再灌注前5m in输注G IK、GK、生理盐水。观察冠脉血流量及血流动力学指标;检测不同时间血清乳酸脱氢酶（LDH）、肌酸激酶（CK）活性;再灌注4 h后测量并计算心肌梗死范围。结果:与盐水对照组相比,G IK明显增加左前降支冠脉血流量（CBFLAD）,改善再灌注后左室收缩及舒张功能,降低血清CK、LDH,减少心肌梗死范围,而GK无上述作用。结论:再灌注时输注G IK可促进再灌注心脏功能恢复及减轻心肌损伤,该作用可能与G IK增加冠脉血流量有关;胰岛素是G IK上述作用的关键成分。     

胰岛素对缺血/再灌注心肌的保护作用

目的 :探讨胰岛素在心肌缺血 /再灌注 （I/ R）期间对心肌细胞的保护作用。方法 :制备兔 I/ R模型并将其随机分为 3组 ,分别于缺血前 30 min予以葡萄糖 -胰岛素 -钾 （GIK） （葡萄糖 15 0 g/ L ,胰岛素 10 0 U/ L ,钾 80 m mol/ L ）、胰岛素 （10 0 U / L ）、生理盐水静脉注射 （1.2 m l/ h） ,然后实施 40 min的心肌局部缺血和 3h的再灌注。采集并处理心肌血流动力学指标 ,检验乳酸脱氢酶 （L DH ）、肌酸激酶 （CK）活性。 3h后 ,采用 E- vans蓝 - TTC法测量心肌梗死范围。结果 :与对照组比较 ,GIK及胰岛素组在血流动力学 （L VEDP,± dp/ dtmax） ,CK,L DH、梗死范围测量等均表现为损伤减轻 ,且这两组间未见明显差异。结论 :在 I/ R的过程中 ,GIK合剂除了提供能量外 ,其中的胰岛素也发挥了重要的心肌保护作用     

衰老大鼠心肌对缺血再灌注损伤的敏感性研究

目的观察衰老大鼠心肌对缺血再灌注损伤的敏感性,并探讨其可能的机制。方法成年和老年雄性Wistar大鼠各12只,分为4组：成年假手术组、成年缺血再灌注组、老年假手术组和老年缺血再灌注组,每组6只,进行缺血30 min再灌注3 h。脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法检测心肌细胞凋亡,比色法检测心肌组织半胱胺酸蛋白酶蛋白-3 (caspase-3)活性,化学发光法测定心肌组织总一氧化氮(NOx)含量,ELISA法检测心肌过氧亚硝基(ONOO~-)含量。结果老年组缺血再灌注引起心肌细胞凋亡的程度明显高于成年组,凋亡指数分别为(14．6±1.7)%、(19．0±2．1)%,差异有统计学意义(P＜0．05)；caspase-3活性：成年组为(340±32)μmol/mg,老年组为(436±35)μmol/mg,差异有统计学意义(P＜0．05)；心肌组织中NOx含量：成年缺血再灌注组、老年缺血再灌注组分别为成年假手术组的(2．1±0．2)、(4．4±0．5)倍,差异有统计学意义(P＜0．05)；ONOO~-含量：成年缺血再灌注组和老年缺血再灌注组分别为(4．68±0．15)nmol/g、(7．25±0．18)nmol/g,差异有统计学意义(P＜0．05)。结论老年大鼠对心肌缺血再灌注损伤的敏感性增加,可能的原因是老年鼠心脏中NO的毒性衍生物ONOO~-含量增加,从而导致功能蛋白的硝基化。     

葡萄糖-胰岛素钾液对心肌缺血/再灌注犬血液流变学和血糖的影响

目的:观察近年推荐使用的大剂量葡萄糖胰岛素钾液（GIK）对急性心肌缺血/再灌注（MI/R）犬血液流变学特性的影响。方法:定量狭窄冠状动脉左前降支（血流量降低80%）制作犬心肌缺血/再灌注模型。将24只杂种犬随机分为GIK组、葡萄糖钾液（GK）组及生理盐水对照组（n=8）。再灌注同时分别静脉输注GIK、GK、生理盐水（2ml·h-1·kg-1）。在狭窄冠脉前和再灌注即刻及再灌注后1h、2h、4h抽取冠状静脉窦血,测定血液流变学和血糖变化。结果:缺血50min时各组犬血细胞比容、全血高切粘度、全血低切粘度较缺血前均有不同程度增高（P<0.05）。GIK组再灌注后各时间点血糖和血液流变学指标与缺血前及生理盐水对照组相比均无显著差异。GK组再灌注后2h和4h时血细胞比容（HCT）较生理盐水对照组增高（P<0.05）。再灌注后GIK组与生理盐水组血糖无明显升高,GK组再灌注后2h和4h血糖较对照组分别增加76%和92%（P<0.01）。结论:急性心肌缺血可致血液流变学特性显著改变,主要表现为HCT、ηbh、ηbl增高。本研究所用GIK的剂量不会导致血糖明显变化,且对MI/R过程中犬血液流变学无明显影响;本研究结果还提示,单独输注高糖可能对急性心肌缺血患者不利。     

梓醇减轻心肌缺血/再灌注损伤及机制

目的:观察梓醇是否可减轻急性心肌缺血/再灌注（MI/R）损伤。方法:建立大鼠MI/R模型,随机给予生理盐水和梓醇预处理,全程检测大鼠的心脏功能。再灌注末检测大鼠心肌梗死(MI)面积、心肌细胞凋亡指数、血清肌酸激酶和乳酸脱氢酶的活性、心肌组织过氧亚硝基阴离子（ONOO-）、一氧化氮（NO）、超氧化物及超氧化物歧化酶（SOD）的含量。结果:梓醇预处理可明显改善心脏功能,减少心肌梗死面积和心肌细胞的凋亡与坏死（均P<0.05）。同时,ONOO-和超氧化物的产生也显著减少（P<0.05）;NO和SOD的含量显著增加（均P<0.05）。缺血前给予ONOO-清除剂尿酸（UA）显著减少ONOO-生成及MI范围（P<0.05）,但不能额外增强梓醇降低ONOO-及减小MI范围的效应（MI/R+梓醇+UA组 vs. MI/R+梓醇组）。结论:梓醇可抑制ONOO-形成,从而减轻MI/R损伤,其机制可能与增加NO水平及减少超氧化物生成有关。     

Estrogen improves cardiac recovery after ischemia/reperfusion by decreasing tumor necrosis factor-alpha

BACKGROUND: Estrogen has cardioprotective effects on ischemia/reperfusion (I/R). Tumor necrosis factor alpha (TNFalpha) is an inflammatory cytokine with depressor effects on myocardial function and has been suggested to mediate I/R injury. Whether cardiac TNFalpha levels are influenced by estrogen status is unknown. We investigated the effect of estrogen on TNFalpha levels and TNFalpha receptors in the ischemic heart and its role in estrogen modulation of I/R injury. METHODS: Hearts were isolated from ovariectomized Sprague-Dawley female rats that were treated with either estrogen or placebo for 4 weeks. Working heart preparations were subjected to global, no-flow ischemia (25 min) followed by reperfusion (40 min). RESULTS: I/R increased TNFalpha levels in coronary effluent and in the left ventricle (LV) of estrogen-deficient rats, which were decreased by estrogen replacement. Moreover, estrogen improved functional recovery (55.0+/-5.0% vs. 22.0+/-7.0%, P<0.05), decreased LV apoptosis, and reduced myocardial necrosis. To further evaluate the role of TNFalpha in I/R injury, a selective TNFalpha inhibitor (etanercept) was used in vitro before the ischemic insult. TNFalpha inhibition improved functional recovery (39+/-4.4% vs. 22.0+/-7.0%, P<0.05) and reduced apoptosis and myocardial necrosis in estrogen-deficient animals but did not have a summative protective effect in the hearts of estrogen-replaced animals. CONCLUSIONS: These data indicate that estrogen modulates cardiac expression of TNFalpha and TNFalpha receptors. Moreover, the cardioprotective effects of estrogen are in part mediated by regulation of TNFalpha levels in the ischemic heart.     

人脐血单个核细胞移植治疗大鼠急性心肌梗死的实验研究

目的探讨人脐血单个核细胞(HUCBC)移植治疗急性心肌梗死(AMI)的可行性及疗效。方法雄性Wistar大鼠45只随机分为:心肌梗死(MI)对照组、MI+细胞移植组和正常组(每组各15只)。结扎冠状动脉左前降支制作大鼠AMI模型,以HES沉淀加Ficoll密度梯度离心的方法制备HUCBC,并以BrdU标记细胞。移植组大鼠模型制作成功后即刻在梗死区周边注射经分离并标记的HUCBC混悬液,在MI对照组相同位置注入等量DMEM培养液,正常组不做任何处理。移植4周后用超声评价心功能和左心导管检测血流动力学改变,并取心脏组织行HE染色、抗血管性血友病因子(vWF)和BrdU组化染色,观察心肌病理改变、毛细血管增生及移植细胞成活情况。结果在移植组显示移植的单个核细胞可在梗死心肌内存活并参与梗死心肌修复。超声心动图见移植组各项心功能指标改善。血流动力学检查显示移植组与MI对照组相比,左心室舒张末压明显降低[LNEDP (21．08±8．10)mm Hg(1 mm Hg=0．133 kPa)比(30．82±9．59)mm Hg,P<0．05],左心室内压力最大上升速率明显增快[+dp／dtmax(4．29±1．27)mm Hg／ms比(3．24±0．75)mm Hg／ms,P< 0．05],最大下降速率亦显著提高[-dp／dtmax(3．71±0．79)mm Hg／ms比(3．00±0．49)mm Hg／ms, P<0．05]。免疫组化染色发现移植组梗死区周边毛细血管数显著增加(P<0．01)。结论HUCBC在未使用免疫抑制剂的条件下可成功移植到大鼠MI区,并提示能改善MI大鼠心功能,促进新生血管形成。     

Cardiomyocyte-restricted over-expression of C-type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

OBJECTIVE: Infused C-type natriuretic peptide (CNP) was recently found to play a cardioprotective role in preventing myocardial ischaemia/reperfusion (I/R) injury and improving cardiac remodelling after myocardial infarction (MI) in rats. Our study aimed to investigate the effect of cardiomyocyte-specific CNP over-expression on I/R injury and MI in transgenic mice. METHODS AND RESULTS: We generated transgenic (TG) mice over-expressing CNP in cardiomyocytes. Elevated CNP expression on RNA and protein levels was demonstrated by RNase-protection assay and radioimmunoassay. Male TG mice and age-matched wild-type (WT) littermates were subjected to 1-hour global myocardial ischaemia and 23 h of reperfusion or permanent ligation of the coronary artery for 3 weeks. Infarct size did not differ between the WT and TG groups in mice subjected to I/R. In mice that underwent permanent ligation of coronary arteries, both left and right ventricular hypertrophy were prevented by CNP over-expression 3 weeks post-MI. Histological analysis revealed less necrosis, muscular degeneration and inflammation in infarcted TG mice. Impairment of cardiac function was less pronounced in transgenic animals than in the wild-type controls. CONCLUSIONS: Over-expression of CNP in cardiomyocytes does not affect I/R-induced infarct size but prevents cardiac hypertrophy induced by MI. Therefore, CNP may represent a potent therapeutic target for the treatment of patients with cardiac hypertrophy induced by myocardial infarction or other aetiology.     

Endogenous cannabinoids mediate hypotension after experimental myocardial infarction

OBJECTIVES: We sought to determine whether endocannabinoids influence hemodynamic variables in experimental models of acute myocardial infarction (MI). BACKGROUND: Hypotension and cardiogenic shock are common complications in acute MI. Cannabinoids are strong vasodilators, and endocannabinoids are involved in hypotension in hemorrhagic and septic shock. METHODS: The early effect of left coronary artery ligation on hemodynamic variables was measured in rats pretreated with the selective cannabinoid(1) receptor (CB(1)) antagonist SR141716A (herein referred to as SR, 6.45 micromol/kg body weight intravenously) or vehicle. Endocannabinoids produced in monocytes and platelets were quantified by liquid chromatography/mass spectrometry (LC/MS), and their effects on blood pressure and vascular reactivity were determined. RESULTS: After MI, mean arterial pressure (MAP) dropped from 126 +/- 2 mm Hg to 76 +/- 3 mm Hg in control rats, whereas the decline in blood pressure was smaller (from 121 +/- 3 mm Hg to 108 +/- 7 mm Hg, p < 0.01) in rats pretreated with SR. SR increased the tachycardia that follows MI (change [Delta] in heart rate [HR] = 107 +/- 21 beats/min vs. 49 +/- 9 beats/min in control rats, p < 0.05). The MI sizes were the same in control rats and SR-treated rats. Circulating monocytes and platelets isolated 30 min after MI only decreased MAP when injected into untreated rats (DeltaMAP = -20 +/- 5 mm Hg), but not in SR-pretreated rats. The endocannabinoids anandamide and 2-arachidonyl glycerol were detected in monocytes and platelets isolated after MI, but not in cells from sham rats. Survival rates at 2 h after MI were 70% for control rats and 36% for SR-treated rats (p < 0.05). Endothelium-dependent arterial relaxation was attenuated in SR-treated rats (maximal relaxation: 44 +/- 3% [p < 0.01] vs. 70 +/- 3% in control rats) and further depressed by SR treatment (24 +/- 5%, p < 0.01 vs. MI placebo). CONCLUSIONS: Cannabinoids generated in monocytes and platelets contribute to hypotension in acute MI. Cannabinoid(1) receptor blockade restores MAP but increases 2-h mortality, possibly by impairing endothelial function.     

C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction

OBJECTIVES: We assessed the hypothesis that in vivo administration of C-type natriuretic peptide (CNP) might attenuate cardiac remodeling after myocardial infarction (MI) through its antifibrotic and antihypertrophic action. BACKGROUND: Recently, we have shown that CNP has more potent antifibrotic and antihypertrophic effects than atrial natriuretic peptide (ANP) in cultured cardiac fibroblasts and cardiomyocytes. METHODS: Experimental MI was induced by coronary ligation in male Sprague-Dawley rats; CNP at 0.1 mug/kg/min (n = 34) or vehicle (n = 35) was intravenously infused by osmotic mini-pump starting four days after MI. Sham-operated rats (n = 34) served as controls. After two weeks of infusion, the effects of CNP on cardiac remodeling were evaluated by echocardiograpic, hemodynamic, histopathologic, and gene analysis. RESULTS: C-type natriuretic peptide markedly attenuated the left ventricular (LV) enlargement caused by MI (LV end-diastolic dimension, sham: 6.7 +/- 0.1 mm; MI+vehicle; 8.3 +/- 0.1 mm; MI+CNP: 7.7 +/- 0.1 mm, p < 0.01) without affecting arterial pressure. Moreover, there was a substantial decrease in LV end-diastolic pressure, and increases in dP/dt(max), dP/dt(min), and cardiac output in CNP-treated MI rats compared with vehicle-treated MI rats. Importantly, CNP infusion markedly attenuated an increase in morphometrical collagen volume fraction in the noninfarct region (sham: 3.1 +/- 0.2%; MI+vehicle: 5.7 +/- 0.5%; MI+CNP: 3.9 +/- 0.3%, p < 0.01). In addition, CNP significantly reduced an increase in cross-sectional area of the cardiomyocytes. These effects of CNP were accompanied by suppression of MI-induced increases in collagen I, collagen III, ANP, and beta-myosin heavy chain messenger ribonucleic acid levels in the noninfarct region. CONCLUSIONS: These data suggest that CNP may be useful as a novel antiremodeling agent.     

Initial experience with hyperoxemic reperfusion after primary angioplasty for acute myocardial infarction: results of a pilot study utilizing intracoronary aqueous oxygen therapy

OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety of intracoronary hyperoxemic reperfusion after primary angioplasty for acute myocardial infarction (MI). BACKGROUND: Hyperoxemic therapy with aqueous oxygen (AO) attenuates reperfusion injury and preserves left ventricular (LV) function in experimental models of MI. METHODS: In a multi-center study of patients with acute MI undergoing primary angioplasty (PTCA), hyperoxemic blood (pO(2): 600 to 800 mm Hg) was infused into the infarct-related artery for 60 to 90 min after intervention. The primary end points were clinical, electrical and hemodynamic stability during hyperoxemic reperfusion and in-hospital major adverse cardiac events. Global and regional LV function was evaluated by serial echocardiography after PTCA, after AO infusion, at 24 h and at one and three months. RESULTS: Twenty-nine patients were enrolled (mean age: 58.9+/-12.6 years). Hyperoxemic reperfusion was performed successfully in all cases (mean infusion time: 80.8+/-18.2 min; mean coronary perfusate pO(2): 631+/-235 mm Hg). There were no adverse events during hyperoxemic reperfusion or the in-hospital period. Compared with baseline, a significant improvement in global wall motion score index was observed at 24 h (1.68+/-0.24 vs. 1.48+/-0.24, p < 0.001) with a trend toward an increase in ejection fraction (48.6+/-7.3% vs. 51.8+/-6.8%, p = 0.08). Progressive improvement in LV function was observed at one and three months, primarily due to recovery of infarct zone function. CONCLUSIONS: Intracoronary hyperoxemic reperfusion is safe and well tolerated after primary PTCA. These preliminary data support the need for a randomized controlled trial to determine if hyperoxemic reperfusion enhances myocardial salvage or improves long-term outcome.