血管内皮细胞生长因子在糖尿病大鼠局灶性脑缺血再灌注模型中的表达

糖尿病大鼠局灶性脑缺血再灌注后各时间点血管内皮细胞生长因子在缺血中心区、半暗带区神经元和微血管的表达均明显低于非糖尿病大鼠。     

药物干预对大鼠急性脑缺血再灌注损伤神经元的保护作用

目的 探讨脑蛋白及银杏叶提取物对大鼠急性脑缺血再灌注损伤后缺血半暗带神经元的保护作用及机制.方法 600只雄性Wistar大鼠随机分为4组(对照组、蛋白组、银杏叶组、联合组),每组大鼠根据缺血后再灌注不同时间又分为缺血2h再灌注6、12、24、72 h、7d五个亚组(30只/亚组).采用线栓法制备大鼠缺血2h再灌注模型,除对照组外,其余三组均采用药物进行干预.分别于再灌注6、24、48、72 h及7d断头取脑,观察缺血半暗带脑组织Na+-K+-ATP酶活性、脑组织水肿程度、脑梗死范围及神经症状评分的变化.结果 对照组大鼠脑缺血半暗带神经元Na+-K+-ATP酶活性于6h开始降低,48 h达最低值,72 h稍有回升,7d趋于稳定.与单一用药组(蛋白组或银杏叶组)比较,联合组能显著提高大鼠缺血半暗带神经元Na+-K+-ATP酶活性(48、72 h亚组,P值均为0.000),降低脑组织含水量(24、48、72 h亚组,P值均为0.000),减小脑梗死面积(24、48、72 h、7d亚组,P值均为0.000),减少神经症状评分(48、72 h、7d亚组,P值均为0.000).结论 联合用药较单一用药能更有效地抑制缺血级联反应,从而最大限度地挽救缺血半暗带神经元的功能.     

肢体缺血后处理对局灶性脑缺血再灌注大鼠Caspase-3和细胞凋亡的影响

目的探讨肢体缺血后处理(Lpost)对大鼠局灶性脑缺血再灌注区半胱氨酸蛋白酶(Caspase)-3和细胞凋亡的影响。方法健康雄性SD大鼠36只,随机分为假手术组(Sham组)、缺血再灌注组(I/R组)、肢体缺血后处理组(Lpost组),I/R组、Lpost组均行缺血2 h再灌注24 h局灶性脑缺血再灌注模型。Lpost组再灌注前实施肢体缺血后处理(缺血15 min,灌注15 min)3个循环。各组大鼠神经功能评分,采用四氮唑红(TTC)染色确定脑缺血半暗带位置,TUNEL测定细胞凋亡,免疫组化测定Caspase-3的表达变化。结果 Sham组神经缺损评分为0分;与Lpost组(1.20±0.41)比较,I/R组神经功能缺损较重(2.40±0.51,P<0.05);TTC染色证实缺血半暗带位于大脑矢状裂至外侧裂上1/3的皮质组织。与Sham组相比,I/R组、Lpost组缺血半暗带内凋亡细胞数、Caspase-3表达均明显增加(P<0.05),且I/R组表达明显增强,高于Lpost组(P<0.05)。结论肢体Lpost可减轻脑缺血再灌注损伤诱导的细胞凋亡,缓解神经细胞的坏死,其作用机制可能与减少Caspase-3表达有关。     

大鼠局灶性脑缺血再灌注后TNF-a、SOCS-3动态表达的实验研究

目的探讨肿瘤坏死因子-a（TNF—a）、细胞因子信号转导抑制因子-3（SOCS-3）在大鼠脑缺血再灌注后的动态表达及特点,阐明TNF-a、SOCS-3在脑缺血再灌注中的作用。方法将雄性sD大鼠48只随机分为假手术组和缺血3h再灌注3h、6h、12h、24h、48h、72h、7d组,6只／组。运用改良线栓法制作大鼠局灶性脑缺血再灌注模型。用放射免疫法测定TNF-a含量及用RT—PCR法测定SOCS-3的含量。结果TNF-a含量变化：与假手术组比较,缺血再灌注纽脑组织TNF—a含量在6h明显增加,12h达到高峰,随后各时间点表达开始下降。在缺血半暗带区,TNF—a含量变化与中心区相同,但含量较低。SOCS-3mRNA含量变化：缺血再灌注组缺血中心区SOCS-3表达在6h开始有明显升高与假手术组相比有显著性差异,再灌注24h时达到高峰,随后备时间点表达相对稳定,至再灌注7d时仍过分表达。在缺血半暗带区,SOCS～3mRNA变化与中心区相同,但含量较低。结论TNF—α在大鼠局灶性脑缺血再灌注损伤中具有重要作用,可诱导SOCS-3基因的产生和表达。而SOCS-3基因是一个脑缺血后上调基因,它参与了脑缺血再灌注损伤的全过程,可能起到了内源性神经保护剂的作用。     

亚低温对大鼠局灶性脑缺血再灌注后凋亡相关蛋白表达的影响及保护作用

目的通过检测丝氨酸-苏氨酸蛋白激酶(AKT)及Caspase-9蛋白的表达,探讨亚低温对局灶性脑缺血再灌注(IR)后神经元存活的影响。方法用Longa线拴法制作局灶性脑IR模型,将40只SD大鼠随机分成正常组、假手术组、常温组和亚低温组,常温组和亚低温组均缺血8 h,再灌注4 h、24 h、72 h、1 w(n=4)与相应时间点处死,亚低温组于脑缺血后12~15 min实施病灶侧亚低温持续4 h。免疫组化法检测AKT及Caspase-9蛋白的表达。结果不同缺血再灌注时间点,亚低温组比常温组缺血侧半暗带AKT表达水平显著增高(P0.05),Caspase-9显著降低(P0.05)。结论亚低温通过促进缺血半暗带脑组织AKT表达,抑制Caspase-9表达,从而抑制神经元凋亡,减少神经元损害。     

大鼠脑缺血再灌注损伤Bcl-2、Bax、FADD表达及对细胞凋亡的影响

目的 观察大鼠脑缺血再灌注损伤后神经细胞凋亡及凋亡相关蛋白Bcl-2、Bax、FADD表达对细胞凋亡的影响.方法 20只SD大鼠随机分为假手术组(n=4)、模型组(n=16).线栓法制备大脑中动脉闭塞模型(MCAO),TUNEL法检测神经细胞凋亡,免疫组织化学法染色检测Bcl-2、Bax、FADD蛋白.结果与假手术组比较,模型组凋亡神经细胞计数随再灌注时间的延长显著增加,再灌注后24 h表达达高峰,差异有统计学意义(P<0.01).模型组Bcl-2、Bax、FADD蛋白表达随再灌注时间的延长,表达逐渐增强.缺血再灌注6 h后Bcl-2蛋白表达达高峰;缺血再灌注24 h后Bax蛋白表达达高峰;缺血再灌注72 h后FADD蛋白表达达高峰,均有统计学意义(P<0.01).结论 Bcl-2、Bax 、FADD表达在脑缺血半暗带区,随再灌注时间延长,表达逐渐增强,与细胞凋亡表达规律一致.     

三七总皂苷对脑缺血再灌注损伤大鼠缺氧诱导因子1α和基质金属蛋白酶表达的影响

目的观察三七总皂苷(PNS)对脑缺血再灌注损伤大鼠血脑屏障损伤相关蛋白缺氧诱导因子1α(HIF-1α)、基质金属蛋白酶(MMP)-2和MMP-9表达的影响。方法选择SD大鼠130只,分为PNS组(60只)、模型组(60只)和假手术组(10只),PNS组于再灌注后给予尾静脉注射PNS 18mg/(kg·d),模型组和假手术组以等体积生理盐水替代。观察PNS组和模型组大鼠7d存活率。再灌注24h取材(每组10只),以脑组织HE和尼氏染色观察缺血半暗带神经元形态以及核心区神经元存活数,以ELISA法检测半暗带皮质HIF-1α、MMP-2及MMP-9蛋白表达水平。结果模型组神经元数量较假手术组明显减少[(190.0±59.4)个/mm2 vs(582.5±31.2)个/mm2,P0.01];PNS组神经元数量较模型组显著增加[(372.5±41.1)个/mm2 vs(190.0±59.4)个/mm2,P0.01]。模型组缺血再灌注24h MMP-2、MMP-9和HIF-1α水平显著高于假手术组(P0.05,P0.01);PNS组缺血再灌注24h MMP-2、MMP-9和HIF-1α水平显著低于模型组,差异有统计学意义(P0.01)。结论 PNS对短暂性大脑中动脉闭塞模型大鼠缺血再灌注损伤早期起到神经元保护作用。     

大鼠局灶性脑缺血再灌流半暗带神经细胞坏死与凋亡的动态 …

目的 探讨脑缺血半暗带转归过程中神经细胞的死亡机制。方法 采用大量大脑中动脉闭塞及再通模型,ＭＣＡ闭塞时间分别为３０,６０,９０,１２０和１８０分钟,再灌注４８小时,用ＨＥ染色和ＴＵＮＥＬ原位标记法分别对缺血半暗带和缺血中心区细胞坏死和凋亡的动态变化进行定量观察,并计算两种死亡细胞在缺血中心区和半暗带所占的百分比。     

缺血后处理对缺血再灌注后海马CA1区神经元蛋白酶体活性的影响

目的 探讨缺血后处理对短暂脑缺血后海马CA1区神经元内蛋白酶体活性及氧化性蛋白质损伤的影响.方法 采用大鼠全脑缺血模型.Wistar大鼠分为缺血组及缺血后处理组,每组按照再灌注时同进一步分为12 h恢复组,24 h恢复组,48 h恢复组及72h恢复组.缺血后处理为在脑缺血结束后给予三个循环的30 s缺血和30 s再灌注处理.采用HE染色光镜观察脑缺血后神经元死亡;用Succinyl-LLVY-AMC作为底物检测蛋白酶体的活性变化;差速离心结合蛋白印迹分析蛋白酶体相关蛋白的表达.结果 HE染色显示缺血后处理显著降低了脑缺血再灌注后海马CA1区神经元死亡;酶活性检测,缺血后处理使得蛋白酶体的活性显著提高;蛋白印迹分析显示,缺血后处理显著提高了蛋白酶表达.结论 缺血后处理能够显著改善脑缺血后海马CA1区神经元内蛋白酶体的活性,降低了缺血再灌注后海马CA1区神经元死亡.     

脑蛋白水解物对鼠缺血半暗带神经元Na+-K+-ATP酶活性影响

目的探讨脑蛋白水解物对大鼠急性脑缺血再灌注损伤后缺血半暗带神经元Na~+-K~+-ATP酶活性的影响。方法选取270只雄性Wistar大鼠随机分为假手术组、模型组、干预组,三组大鼠根据缺血再灌注不同时间又随机分为缺血2 h再灌注6 h、24 h、48 h、72 h、7 d五个亚组,每个亚组18只大鼠。采用线栓法制备大鼠缺血2 h再灌注模型,仅干预组采用药物进行干预。分别于再灌注6 h、24 h、48 h、72 h、7 d后观察大鼠神经症状评分,相应时间断头取脑,测定缺血半暗带脑组织Na~+-K~+-ATP酶活性、脑组织含水量、脑梗死范围的变化。结果模型组大鼠缺血半暗带神经元Na~+-K~+-ATP酶活性于6 h开始下降,48 h达最小值,72 h稍有回升,7 d趋于稳定;干预组大鼠缺血2 h后再灌注24 h、48 h、72 h各时间点Na~+-K~+-ATP酶活性与模型组大鼠相应时间点比较差异有统计学意义(P0.05)。结论脑蛋白水解物可保护大鼠急性脑缺血再灌注损伤后缺血半暗带神经元,该作用可能与提高缺血半暗带神经元Na~+-K~+-ATP酶活性有关。     

Heat shock protein induction in rat hearts. A role for improved myocardial salvage after ischemia and reperfusion?

BACKGROUND. To test the hypothesis that the heat shock response is associated with improved myocardial salvage after myocardial ischemia and reperfusion, rats treated with prior whole-body hyperthermia and 24 hours of recovery (n = 26) or 20 minutes of ischemic pretreatment and 8 hours of recovery (n = 24) and control rats (n = 27, n = 24, for hyperthermic and ischemic pretreatment, respectively) were subjected to 35 minutes of left coronary artery (LCA) occlusion and 120 minutes of reperfusion. METHODS AND RESULTS. Although ventricular samples from rats subjected to either hyperthermia (n = 7) or ischemic pretreatment (n = 6) all showed induction of HSP72 (heat shock protein), Western blot analysis revealed significantly greater amounts of HSP72 in samples obtained from rats subjected to hyperthermia compared with those from rats subjected to ischemic pretreatment. Control rats (n = 7) showed no significant presence of myocardial HSP72. After 35 minutes of LCA occlusion and 2 hours of reperfusion, infarct size was significantly reduced in heat-shocked rats compared with controls (8.4 +/- 1.7%, n = 26 versus 15.5 +/- 1.9%, n = 27; p = 0.007; mean +/- SEM; infarct mass/left ventricular mass x 100). There were no significant differences in left ventricular (LV) systolic pressure, heart rate, LV dP/dt, or rate-pressure product between heat-shocked (n = 11) and control (n = 14) rats during the ischemic period. There were no differences in infarct size between ischemically pretreated and control rats subjected to 35 minutes of ischemia and reperfusion (9.7 +/- 2.1%, n = 23 versus 10.0 +/- 2.1, n = 24; p = NS). CONCLUSIONS. In this model of ischemia and reperfusion, prior heat shock was associated with significantly improved myocardial salvage after 35 minutes of LCA occlusion and reperfusion. This improved salvage was correlated with marked HSP72 induction and was independent of the hemodynamic determinants of myocardial oxygen supply and myocardial oxygen demand during the ischemic period. In contrast, mild HSP72 induction by ischemic pretreatment was not associated with improved myocardial salvage after myocardial ischemia and reperfusion. Thus, the absolute levels of HSP72 may be important in conferring protection from ischemic injury in this animal model.     

降纤酶对大鼠局灶性脑缺血/再灌注血管内皮细胞超微结构及MMP-2和-9表达的影响

目的 观察降纤酶对大鼠局灶性脑缺血/再灌注(I/R)血管内皮细胞(VEC)的保护作用.方法 通过光镜、电镜来观察降纤酶对大鼠局灶性脑I/R VEC超微结构的改变以及采用免疫组织化学技术观察基质金属蛋白酶(MMP)-2和-9的表达.结果 在缺血3 h/6 h、6 h再灌组在缺血中心区及周边区VEC和神经细胞的损伤程度明显较降纤酶组重;I/R 3 h/6 h、I/R 6 h以及I/R 6 h/3 h组在缺血半影区模型组比降纤酶组MMP-9表达增强(P<0.05), 而MMP-2变化不明显.I/R 24 h、I/R 3 h/24 h和I/R 6 h/24 h在缺血半影区降纤酶组较盐水对照组MMP-9表达弱,而MMP-2表达增强(P<0.05).结论 降纤酶对局灶性脑缺血VEC具有保护作用.     

Flavopiridol对大鼠局灶性脑缺血后神经元细胞周期蛋白依赖蛋白激酶-4蛋白表达的影响

目的　观察大鼠局灶性脑缺血后神经元内细胞周期蛋白依赖蛋白激酶 4 (cdk4 )的蛋白表达与神经细胞凋亡的关系以及cdk4阻滞剂———Flavopiridol对其的影响。方法　采用线栓法大鼠大脑中动脉持续栓塞模型 ,应用免疫组织化学和原位末端标记 (TUNEL)染色方法观察缺血组、Flavopiridol治疗组 [根据剂量多少又分为FH(多剂量 )组和FL(少剂量 )组 ]和假手术组神经元阳性细胞染色数量和分布情况。结果　cdk4蛋白和凋亡细胞自缺血后 12h开始表达 ,前者缺血后 4 8h达高峰 ,后者缺血后 72h达高峰 ;FH组和FL组各相应时间点cdk4蛋白表达均明显减少 (P<0 .0 1) ;FL组各相应时间点凋亡细胞明显减少 (P <0 .0 1) ,FH组仅在缺血 4 8h凋亡细胞明显减少。相邻切片可见cdk4蛋白表达和凋亡细胞染色区域基本相同。结论　cdk4的蛋白表达可能诱发缺血神经细胞的凋亡 ,Flavopiri dol通过抑制cdk4的表达而减少缺血后神经细胞的损害 ,但同时Flavopiridol本身也可能引起神经细胞凋亡。     

大鼠脑缺血再灌注后脑源性神经营养因子的表达及意义

目的　研究脑局灶缺血再灌注后脑源性神经营养因子 (BDNF)的表达规律及其意义。方法　健康雄性Wistar大鼠 30只 ,随机分为正常对照组、假手术组和缺血再灌注组 ,按照改良的栓线法建立大脑中动脉缺血再灌注大鼠模型。用免疫组织化学方法检测BDNF在脑组织中的表达情况。结果　BDNF免疫阳性表达在缺血再灌注组的梗死中心区梗死灶边缘带有显著增强的阳性表达。再灌注 15min开始增多 ,再灌注 1h明显增多 ,2h达到高峰 ,4h开始下降 ,2 4h恢复至正常对照组水平。结论　缺血再灌注损伤可诱导BDNF极早表达 ,并迅速升高 ,有利于缺血再灌注损伤后神经细胞的存活及后期神经功能恢复     

Assessment of myocardial salvage after ischemia and reperfusion using magnetic resonance imaging and spectroscopy

To test the hypothesis that contrast-enhanced magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) can differentiate reversible from irreversible myocardial injury, these modalities were used to study ischemia and reperfusion in a rat model. The presence of ischemia and reperfusion were confirmed with radiolabeled microspheres (n = 6). Groups of animals were subjected to either 16 (n = 17), 30 (n = 14), 60 (n = 11), or 90 (n = 14) minutes of left coronary artery (LCA) occlusion and 60 minutes reperfusion. After albumin-gadolinium (Gd)-DTPA injection, contrast-enhanced, T1-weighted, spin-echo proton images were acquired at baseline and every 16 minutes during LCA occlusion and reperfusion. In separate experiments, 31phosphorus (31P) spectra were acquired at similar time points during ischemia and reperfusion. After 16 minutes occlusion, normally perfused myocardium enhanced significantly compared with ischemic myocardium on MRI (104 +/- 7.9% vs. 61 +/- 11.0%, p less than 0.05, n = 5, mean +/- SEM, % of baseline value). MRS showed reduced phosphocreatine (PCr) and adenosine triphosphate (ATP) (58.8 +/- 2.4%, p less than or equal to 0.01; 81.4 +/- 2.4, p less than or equal to 0.01, n = 12). After 16 or 30 minutes ischemia, reflow resulted in uniform MRI signal intensity of the ischemic zone compared with normal myocardium (93.5 +/- 11.3 vs. 80.9 +/- 7.0, p = NS, n = 11, % of baseline value at 30 minutes reperfusion) and PCr recovery on MRS (94.3 +/- 4.0%, p = NS, n = 20, % baseline value at 30 minutes reflow). After 60 and 90 minutes ischemia, reflow resulted in marked enhancement of reperfused compared with normal myocardium on MRI (254.0 +/- 30.0 vs. 78.3 +/- 9.2, p less than or equal to 0.01, n = 10) and no recovery of PCr on MRS (64.1 +/- 3.0, p = NS, n = 14). Triphenyltetrazolium chloride (TTC) staining revealed transmural myocardial infarction (MI) in all hearts subjected to 60 or 90 minutes ischemia and reflow, and small nontransmural MIs in only 2/11 hearts subjected to 16 or 30 minutes ischemia and reperfusion. Thus, 1) MRI with albumin-Gd-DTPA is useful for identifying myocardial ischemia by enhancing the contrast between normally perfused and ischemic myocardia; 2) MRI with albumin-Gd-DTPA is useful for identifying reperfusion after myocardial ischemia; and 3) after reperfusion, reversible can be distinguished from irreversible myocardial injury by characteristic findings on MRI and MRS.     

单相动作电位与兔心室肌缺血-再灌注的实验研究

目的:观察兔缺血再灌注心室肌心外膜单相动作电位(MAP)形态变化及触发活动与缺血再灌注心律失常的关系。方法:应用心外膜接触电极记录单相动作电位,观察在体兔心室肌缺血／再灌注期不同时段MAP各参数的变化。结果:(1)在缺血区,MAP振幅(MAPA)随着缺血时间的延长而缩短,在再灌注期仍未恢复正常,MAP的90％复极化间期(MAPD90)、MAPD50随着时间延长而缩短,而MAPD90改变尤其显著;(2)急性心肌缺血后5minMAP的心室复极离散度(MAPDd)显著增大(P<0.01),缺血30min时达到最大值。再灌注早期MAPDd也明显增大(P<0.01);(3)30％的缺血性心律失常及70％的再灌注心律失常与早期后去极化(EAD)有关,EAD振幅与室性早搏(VPB)的启动电位呈正相关。结论:急性心肌缺血时MAP的特征性形态变化是判断心肌缺血的一种简易、快速、可靠的方法;MAPDd增大是形成缺血性心律失常的重要电生理指标之一;EAD可能是缺血再灌注心律失常的发生机制之一。     

Pathophysiology of superoxide radical as potential mediator of reperfusion injury in pig heart

Summary The role of oxygen0derived free radicals in myocardial reperfusion injury was studied using the isolated in situ pig heart model. The free radical scavengers, superoxide dismutase (SOD) and catalase, protected the ischemic pig heart subjected to one hour of normothermic regional ischemia followed by one hour of global hypothermic arrest and one hour normothermic reperfusion. A significant increase in thiobarbituric acid reactive material and oxidized glutathione appeared in the perfusate demonstrating free radical-mediated lipid peroxidation during reperfusion, and this was prevented by the addition of SOD plus catalase. The values of three important antioxidative enzymes, SOD, catalase, and glutathione peroxidase, showed reduced activities after 2 hours of ischemia. These values did not change significantly after 60 minutes of reperfusion following the 2 hours ischemic insult. The concentrations of high-energy phosphate compounds including creatine phosphate (CP), adenosine triphosphate (ATP), and total adenine nucleotide were reduced significantly during ischemia and reperfusion in hearts which were not protected by SOD and catalase. The plasma creatine phosphokinase levels were lowered appreciably as a result of SOD and catalase treatment. It may be concluded from these experiments that oxygen-derived free radicals are present during reperfusion and SOD and catalase play a significant role in the protection of ischemic myocardium from reperfusion injury.     

Protective effects of ginsenosides in myocardial ischemia and reperfusion injury

To verify whether ginsenosides will attenuate the myocardial ischemia and reperfusion injury, the left anterior descending coronary artery (LAD) was snared for 2 hours in 23 dogs and then the ischemic myocardium was reperfused. 45 minutes after ischemia, the animals were randomly divided into a ginsenosides group (n = 11, receiving a slow IV bolus of ginsenosides 10 mg/kg and then a continuous infusion of 80 micrograms/kg/min) and a saline solution group (n = 12 receiving equal amount of glucose in saline). The treatment was started 45 minutes after coronary occlusion and stopped one hour after reperfusion. 24 hours later, the dogs were killed and the extent of myocardial necrosis was determined histologically. The LVEDP, arterial pressure and heart rate were markedly lower in the ginsenosides group. Electrocardiographic findings of myocardial ischemia were significantly improved in the ginsenosides group. 8 controls developed malignant arrhythmia after reperfusion, but none in ginsenosides group. The myocardial ultrastructure can be protected by ginsenosides during the period of ischemia and reperfusion. The infarct size in saline group was 22.7 +/- 3.2% while in the ginsenosides group it was 5.2 +/- 1.3% (P less than 0.05). These results show that ginsenosides can protect the ischemic myocardium and reperfusion injury of myocardium.     

Effect of increasing degrees of ischemic injury on myocardial oxidative metabolism early after reperfusion in isolated rat hearts

The present investigation studied the effect of increasing severities of ischemic injury on recovery of oxidative metabolism after reperfusion in isolated rat hearts perfused retrogradely with erythrocyte-containing medium. Hearts subjected to 60 minutes of low-flow ischemia (5% of control perfusion) exhibited delayed but sustained recovery of left ventricular pressure development during reperfusion and preservation of ultrastructure delineated with electron microscopy. Immediately after reperfusion, myocardial oxygen consumption returned to control values, well before left ventricular pressure development recovered. Early after reperfusion release of 14CO2 from [1-14C]palmitate was reduced (-53%, p less than 0.01). Conversely, release of 14CO2 from [U-14C]glucose was increased (+131%, p less than 0.05). After 60 minutes of reperfusion 14CO2 release had completely returned to normal for both labeled substrates. Pulse-labeling experiments indicated that during transient depression of [1-14C]palmitate oxidation more tracer was incorporated into myocardial lipid esters, primarily triglycerides. In contrast to hearts subjected to low-flow ischemia, hearts subjected to 60 minutes of no-flow ischemia exhibited poor recovery of contractile function during the reperfusion period. Electron microscopic examination of reperfused hearts showed advanced myocyte damage consistent with irreversible injury. Interestingly, myocardial oxygen consumption in this group also recovered to control values. The substrate pattern during the early reperfusion period was similar to that of hearts subjected to low-flow ischemia. After 120 minutes of no-flow ischemia, recovery of oxidative metabolism was virtually absent. The results indicate a pronounced dissociation between recovery of oxidative metabolism and of contractile function in reperfused myocardium. The oxidative metabolic rate was disproportionately high compared with contractile function, not only in reversibly "stunned" hearts, but also in severely damaged hearts exhibiting signs of irreversible injury.