缺血心肌细胞骨架损伤研究

目的建立动物心肌缺血模型，探讨心肌缺血时细胞骨架的改变。方法15只清洁级健康成年雄性Wistar大白鼠，采用左冠状动脉结扎术造成部分心肌缺血，分别于缺血30min、60min、120min时取缺血心肌组织用免疫组织化学方法观察心肌细胞骨架蛋白肌动蛋白（α-actin）、波形蛋白（vimentin）、肌球蛋白（myosin）、结蛋白（desmin）的变化，与未缺血部分心肌对比，并用计算机图像模拟分析系统计算细胞骨架蛋白量的变化。结果心肌缺血时30min时即有骨架蛋白actin、myosin的损伤，随后见desmin、vimentin受损。结论心肌缺血时可以早期导致心肌细胞的细胞骨架损伤。     

曲美他嗪对人再灌注损伤心肌蛋白酶活化受体-2表达的影响

目的:观察曲美他嗪口服预处理对再灌注损伤心肌蛋白酶活化受体-2(PAR-2)的表达影响,探讨其对心肌缺血再灌注损伤的保护作用。方法:将40例行体外循环二尖瓣瓣膜置换术患者随机分为曲美他嗪组和对照组,每组20例,曲美他嗪组术前予以曲美他嗪预处理2周(曲美他嗪片20mg/次,3次/d)。术中取开放升主动脉恢复心肌血供30min时的右房心肌,采用实时定量PCR检测心肌组织PAR-2的mRNA水平;免疫组织化学法检测心肌组织PAR-2的蛋白水平;在主动脉开放后30min、6h、24h经颈内中心静脉置管处取血,测定肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)和肌红蛋白(MYO)的水平。结果:①与对照组比较,曲美他嗪组心肌组织PAR-2的mRNA及蛋白表达水平明显升高(P<0.05),CK-MB、cTnI、MYO的水平(主动脉开放后30min、6h)显著降低(P<0.05)。结论:曲美他嗪对心肌缺血再灌注损伤具有显著的保护作用,其机制可能与上调PAR-2的表达有关。     

曲美他嗪对大鼠缺血再灌注心肌线粒体的保护作用

目的探讨曲美他嗪对缺血再灌注损伤心肌线粒体的保护作用及其机制.方法将50只SD雄性大鼠随机分为假手术组、生理盐水组和曲美他嗪组(5mg/kg组及10mg/kg组)4组,假手术组只开胸,不结扎冠状动脉.余3组复制缺血再灌注损伤模型,缺血前分别静脉注射曲美他嗪(5或10mg/kg)及等量生理盐水,在缺血30min及再灌注40min时测定缺血再灌注损伤区心肌线粒体丙二醛、超氧化物歧化酶、谷胱甘肽、谷胱甘肽过氧化物酶及总钙浓度,并通过电镜观察心肌超微结构的改变.结果与假手术组比较,生理盐水组及曲美他嗪组线粒体中的丙二醛及总钙显著增高,超氧化物歧化酶、谷胱甘肽及谷胱甘肽过氧化物酶显著降低.与生理盐水组比较,曲美他嗪组的丙二醛及总钙水平显著降低,超氧化物歧化酶、谷胱甘肽及谷胱甘肽过氧化物酶显著增高.电镜观察显示曲美他嗪组线粒体损伤较生理盐水组明显减轻.结论以上提示曲美他嗪能减轻缺血再灌注心肌线粒体的脂质过氧化损伤,其机制可能是通过提高线粒体内谷胱甘肽含量及超氧化物歧化酶和谷胱甘肽过氧化物醇活性,以增强其抗氧化能力,并通过减轻线粒体内钙聚积在细胞水平提供心肌保护作用.     

曲美他嗪对冠状动脉介入治疗患者的心脏保护作用

目的 评价曲美他嗪对经皮冠状动脉介入治疗(PCI)患者的心肌保护作用.方法 在国内5家医院入选拟进行介入治疗的稳定性或不稳定性心绞痛患者共101例,随机分为曲美他嗪组(54例)和对照组(47例).曲美他嗪组在术前(5±2)d开始服用曲美他嗪20 mg,3次/d,手术当天至少提前30 min给予60 mg负荷最,术后继续服用4周.对照组给予常规药物治疗.观察术中心绞痛发作及心电图变化情况;检测术前、术后12 h及24 h磷酸肌酸激酶同工酶浓度;观察术前、术后4周的心脏功能变化.结果 曲美他嗪组介入治疗术中心绞痛发生率显著低于对照组,差异有统计学意义(0%比25.5%,P<0.001).术中球囊扩张时曲美他嗪组出现缺血性心电图改变的比例小于对照组(60.8%比78.3%,P<0.05).PCI术后4周曲美他嗪组左室射血分数值高于对照组[(66.6±7.1)%比(63.0±7.7)%,P=0.03].结论 PCI围手术期应用曲美他嗪可以减少术中心绞痛发作,减轻心肌损伤,进一步改善PCI术后的左心功能.     

养心氏片对慢性心力衰竭病人焦虑、抑郁及生活质量的影响

目的观察养心氏对慢性心力衰竭病人焦虑、抑郁状态及生活质量的影响。方法选取2017年10月—2018年4月因慢性心力衰竭急性加重于大连大学附属中山医院心内科住院,病情平稳2~4周的病人80例,随机分为对照组(30例)、养心氏组(30例)、曲美他嗪组(10例)、养心氏+曲美他嗪组(10例)。分别采用焦虑自评量表(SAS)、抑郁自评量表(SDS)评估焦虑与抑郁状态,采用明尼苏达心力衰竭生活质量量表(MLHFQ)评价生活质量,采用6 min步行试验(6-MWT)评价病人运动耐量。结果6个月随访时,养心氏组、曲美他嗪组、养心氏+曲美他嗪组SAS、SDS评分均较治疗前明显降低(P<0.05),养心氏组、养心氏+曲美他嗪组治疗后SAS、SDS评分均较对照组明显降低(P<0.05)。养心氏组、曲美他嗪组、养心氏+曲美他嗪组治疗后6 min步行距离均较治疗前明显增加(P<0.05),且均较对照组治疗后明显增加(P<0.05)。4组治疗后MLHFQ评分均较治疗前明显降低(P<0.05),养心氏组、曲美他嗪组、养心氏+曲美他嗪组治疗后MLHFQ评分均较对照组明显降低(P<0.05)。结论在优化药物治疗基础上,口服养心氏片可以改善慢性心力衰竭病人的焦虑、抑郁状态,增加运动耐量,改善生活质量。     

曲美他嗪对冠心病心绞痛的疗效观察

目的:探讨曲美他嗪对冠心病心绞痛的疗效。方法:45例确诊的冠心病患者随机分为两组,治疗组(曲美他嗪治疗)30例,对照组(消心痛治疗)15例。观察曲美他嗪抗心绞痛疗效,改善心电图缺血型sT-T改变的状况。结果:(1)抗心绞痛:治疗组显效率为76.7％,对照组为53.3％,两组有显著差异(P<0.05);(2)心电图改善有效率:治疗组为61.7％,对照组为36.7％(P<0.01);(3)未发现曲美他嗪有明显毒、副作用。结论:曲美他嗪在预防冠心病心绞痛发作,改善心电图方面均较消心痛为好。     

曲美他嗪后处理对心肌缺血再灌注损伤大鼠细胞凋亡的保护性作用

目的研究曲美他嗪后处理对大鼠急性心肌缺血再灌注损伤后细胞凋亡的影响。方法实验大鼠40只,随机分为5组：假手术组（n＝8）、再灌注损伤模型组（n＝8）、曲美他嗪低剂量组（10mg/kg,n＝8）、曲美他嗪高剂量组（20mg/kg, n＝8）,后处理组（n＝8）。制作再灌注损伤模型后,观察各组大鼠心肌梗死面积、Bcl2/bax蛋白表达以及电子显微镜下心肌组织切片观察。结果（1）各组大鼠心肌梗死面积测定：假手术组未见梗死,其余各组大鼠心肌组织不同程度梗死,以后处理组及曲美他嗪高剂量组最轻,差异具有统计学意义（P＜0.01）。（2）各组大鼠Bcl2/Bax蛋白表达比较：在模型组中Bax蛋白强阳性表达,表现为软件分析结果灰度值最低。而曲美他嗪高剂量组及后处理组灰度值较模型组比较灰度值明显增大（P＜0.01）。Bcl2蛋白在模型组中表达较少,在曲美他嗪高剂量组中及后处理组中明显表达,且差异具有统计学意义（P＜0.01）。（3）电子显微镜下观察：除假手术组大鼠外,各组大鼠均有不同程度损伤及细胞凋亡,后处理组及曲美他嗪高剂量组损伤较轻。结论高剂量曲美他嗪（20mg/kg）对大鼠心肌缺血再灌注损伤后细胞凋亡有抑制作用。     

卡尼汀与曲美他嗪对稳定型劳力性心绞痛患者运动耐量的影响

目的　比较卡尼汀与曲美他嗪对稳定型劳力性心绞痛患者临床疗效及运动耐量的影响。方法　选择 6 0例经冠状动脉造影确诊冠心病稳定型心绞痛伴高脂血症患者 ,经随机分为两组 ,分别予卡尼汀及曲美他嗪治疗 12W ,比较平均每周心绞痛发作次数 ,每周硝酸甘油消耗量 ,平板运动试验检测运动耐量及血脂水平。结果　卡尼汀及曲美他嗪均使心绞痛发作次数、硝酸甘油消耗量明显减少(P <0 0 1) ,运动至出现ST段压低 1mm所需时间、运动至出现心绞痛所需时间、运动诱发ST段缺血型下移之和∑ST明显减少 ,运动持续时间显著延长 (P <0 0 5 ) ,卡尼汀还降低总胆固醇、甘油三酯分别为 17%和 15 % ,高密度脂蛋白升高14 % (P <0 0 5 )。结论　卡尼汀及曲美他嗪均有效缓减稳定型心绞痛患者临床症状 ,改善运动诱发的心肌缺血 ,提高运动耐量 ,疗效相同 ,卡尼汀还改善血脂。     

复方丹参滴丸联合曲美他嗪治疗不稳定型心绞痛的疗效及对QTd的影响

目的观察复方丹参滴丸联合曲美他嗪治疗不稳定型心绞痛(UAP)疗效以及对QT间期离散度(QTd)的影响。方法将102例患者随机分为两组,对照组予以常规的抗心绞痛治疗,包括抗凝、抗血小板、调脂、扩张冠脉等;治疗组则在常规治疗的基础上加用复方丹参滴丸和曲美他嗪口服,4周为1个疗程。观察两组治疗前后心绞痛发作的次数,心肌缺血总负荷的变化,以及心肌QT离散度的改变。结果治疗组治疗心绞痛的总有效率为96.2%,与对照组相比有统计学意义(P<0.05)。治疗组心肌缺血总负荷改善也明显优于对照组(P<0.05)。治疗组治疗后可明显降低QTd和QTcd(P<0.01)。结论复方丹参滴丸联合曲美他嗪治疗不稳定型心绞痛效果显著,可改善心肌缺血以及QT离散度。     

曲美他嗪对缺血性心肌病伴心力衰竭患者心功能的影响

目的观察曲美他嗪对缺血性心肌病伴心力衰竭患者心功能的影响。方法选取84例β-受体阻滞剂和血管紧张素转换酶抑制剂(ACEI)/血管紧张素受体拮抗(ARB)使用禁忌的缺血性心肌病伴心力衰竭患者,随机分为曲美他嗪组和对照组各42例。曲美他嗪组在常规治疗基础上加用曲美他嗪20 mg,3次/d;对照组给予常规药物治疗,不加用曲美他嗪。随访12个月,分析治疗前、治疗后6个月和治疗后12个月时两组心率、脑利钠肽前体(proBNP)、6 min步行距离、左室射血分数(LVEF)和左室舒张末期内径(LVEDD)变化情况。结果曲美他嗪组治疗后12个月与治疗前及对照组相比,心率、proBNP明显降低,6 min步行距离明显增加,LVEF明显升高,LVEDD明显减小(均P0.05)。结论不能使用β-受体阻滞剂和ACEI/ARB的缺血性心肌病伴心力衰竭患者加用曲美他嗪治疗,可显著改善心功能。     

Disruption of microtubules as an early sign of irreversible ischemic injury. Immunohistochemical study of in situ canine hearts.

Structural disruption of the cytoskeleton may be involved in irreversible ischemic injury. In the present study, ischemic changes in microtubules during various periods of myocardial ischemia were studied with an immunohistochemical technique in open-chest dogs. In intact myocardium, microtubules were stained as a filamentous network throughout cytoplasm and a circular network around the nucleus, which disappeared with colchicine treatment. In brief ischemia of less than 15 minutes, microtubule patterns were unaltered. After 20 minutes, however, characteristic microtubule stains were partly lost in patchy lesions. As an increase in ischemic period, lesions of loss of microtubule stains were increased in number and size. After 120 minutes of reperfusion following 60 minutes of ischemia, the lesions with intact actin filaments but with disrupted microtubules were replaced by the severely injured cells in which the regular myofibrillar registrations were distinctly disrupted. After 24 hours of reperfusion following 40 minutes of occlusion of the left circumflex artery, the percent area of disrupted microtubules at 40 minutes of ischemia was replaced by that of irreversibly injured lesions in the posterior papillary muscle. These results indicate that disruption of microtubules during ischemia heralds irreversible ischemic injury. However, in in vitro study, the myocardium incubated in hypoxic solution for 60-120 minutes demonstrated earlier disruption of the microtubules than the vinculin. Electron microscopic study also showed minimal irreversible changes in the lesions with disrupted microtubules. Thus, taken together, we conclude that microtubules that support the structural integration of myofibrils and other organelles are disrupted in severe myocardial ischemia before the irreversible injury, promoting the irreversible change after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temporal and spatial development of myocardial infarcts in porcine hearts without significant collateral blood flow

To evaluate the time-dependent beneficial effect of reperfusion on infarct size, we investigated the temporal and spatial development of infarcts in porcine hearts. The left anterior descending coronary artery was occluded in 17 pigs for different periods of time. Ischemia was always followed by 4 hours of reperfusion. After 60 minutes of ischemia, transmural needle biopsies subdivided into subendocardial and subepicardial halves were removed from the ischemic apex to determine the tissue concentrations of adenosine triphosphate and nicotinamide adenine dinucleotide. The myocardium at risk was determined with a fluorescent dye, and the infarcted tissue with nitroblue tetrazolium stain. Infarct size was expressed as the ratio of the infarcted myocardium over the risk region. Ischemic cell death began in the jeopardized left ventricular subendocardial septum after about 30 minutes of ischemia. Further progress involved the right subendocardial septum and the subendocardium of the left anterior free wall. After 75 minutes of ischemia, most of the myocytes were already irreversibly injured. Tissue damage from the infarctions was complete after 90 to 120 minutes of ischemia. These results indicate that in hearts without a significant collateral blood flow, reperfusion can only reduce infarct size if initiated within 60 to 75 minutes of ischemia. As in canine hearts, infarctions in porcine hearts progress from the ischemic subendocardium toward the outer layers.     

The experimental study of the coronary reperfusion in the acute myocardial ischemia: the feasibility of the myocardial salvage

In order to know the feasibility of coronary reperfusion by thrombolysis or aorto-coronary bypass graft in the early stages of the acute myocardial infarction, we studied the effect of the coronary artery reperfusion to acutely ischemic myocardium induced by the coronary artery occlusion in ninety-five anesthetized open-chest dogs. The major factors determining the extent of the myocardial salvage by the reperfusion were the duration of the occlusion time and the degree of the reperfusion injury. These two determinants were analysed by coronary circulation, the regional myocardial function, the mitochondrial metabolism, mitochondrial Ca and Mg contents, and morphological findings of the myocardium by electron-microscopy. The regional myocardial contractility (% systolic shortening) and the mitochondrial metabolism (oxidative phosphorylation) were significantly damaged by the reperfusion more in 60 minute occlusion than in 30 minute occlusion, although the coronary circulation (coronary blood flow, regional myocardial blood flow and coronary vascular resistance) and myocardial gas contents (PO2, PCO2 and pH) in the ischemic myocardium induced by less than 60 minute occlusion were almost recovered to the pre-occluded level by 60 minutes after reperfusion. By 120 minute reperfusion, the ischemic damage calculated from mitochondrial Ca and Mg contents (MC index: 1-[Mg/Ca] ischemia/[Mg/Ca] non-ischemia) was not changed in 30 minute occlusion but was significantly deteriorated in 60 minute occlusion. Therefore, coronary reperfusion must be started within 60 minutes or less after occlusion. A supplementary way to protect the myocardium from ischemia is needed as soon as possible before reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

缺血心肌细胞钙分布变化的细胞化学研究

本文报道用细胞化学的磷酸盐—焦锑酸盐(PPA)法观察大鼠心肌缺血时心肌细胞钙分布变化。用PPA法显示正常心肌细胞钙定位在肌膜包括T管及闰盘的肌膜。钙沉淀物分布在肌膜的胞质面,沉淀物大小不超过20nm。在冠状动脉结扎30min后,肌膜的结合钙沉淀物减少甚至消失。当缺血超过60min,心肌细胞损伤严重,肌膜结合钙消失,细胞内肿胀线粒体的基质内积聚了丝团状的钙沉淀物。说明肌膜和钙结合能力是心肌细胞生存的重要特性。     

The pathophysiology of myocardial stunning: reversibility, accumulation and continuity of the ischemic myocardial damage after reperfusion.

In order to understand the pathophysiology of myocardial stunning, reversibility, accumulation and continuity of ischemic myocardial damage after reperfusion should be studied. Then, to analyze these three factors, myocardial function, metabolism and morphology under ischemia and reperfusion were studied in anesthetized, open-chest dogs. When myocardial ischemia was induced by occlusion of the left anterior descending coronary artery, percentage regional systolic shortening (%SS) of ischemic myocardium sharply decreased and became stable 10 min after occlusion. After reperfusion, ischemic myocardium showed active shortening after within 30-min occlusion, but did not after more than 60-min occlusion. During 90-min of ischemia, extracellular K+ concentration (Ke) steeply increased for first 10 min and was almost stable for next 10 min. Then, Ke straightly increased till 90 min. Metabolic rates, calculated from myocardial tissue CO2 and pH, steeply increased for first 20 min and sharply decreased for next 10 min. After 30 min, these two variables were almost stable, near zero. By electron-microscopy with cytochemistry, distribution of Na/K ATPase to myocardial cell membrane was observed to be almost after 15-min occlusion but distinctly sparse with destruction of cell membrane after 30-min occlusion. Therefore, irreversible myocardial damage appears after about 20-min ischemia and is almost complete after 60 min. Reversibility of damage to ischemic myocardium after reperfusion may mainly occur within 60-min ischemia. Although stunned myocardium in a narrow sense is may appear after reperfusion within less than 20-min of ischemia, stunned myocardium in a broad sense may appear within less than 60-min ischemia. When reversible myocardial ischemia (4- or 15-min occlusion) was repeated after short time intervals (20-min reperfusion), %SS of ischemic myocardium was gradually decreased with each ischemic episode. Active shortening of ischemic myocardium disappeared after more than two episodes of 15-min occlusion. Fluctuation of PCO2, pH and Ke of ischemic myocardium was gradually depressed with each occlusion. Metabolic viability of ischemic myocardium was cumulatively depressed by repeated brief occlusion. Naturally, myocardial damage was more severe after repeated 15-min occlusion than after 4-min occlusion. Accumulation of ischemic myocardial damage may arise as brief ischemia, which only induces reversible damage, is repeated. At last, continuity of ischemic myocardial damage was studied. The effect of 5-min occlusion to %SS of ischemic myocardium was apparently reversed after 90-min reperfusion. Early contractile failure was advanced even after very short duration of ischemia. Thus, myocardial function will be latently damaged.(ABSTRACT TRUNCATED AT 400 WORDS)     

Protective Effect of FK506 on Myocardial Ischemia/Reperfusion Injury by Suppression of CaN and ASK1 Signaling Circuitry

We investigated protective effect of FK506 on rat hearts subjected to ischemia/reperfusion (I/R) injury by regulating CaN and ASK1. Wistar rats were divided into four groups: Ischemia/reperfusion group (I/R), FK506 + Ischemia/reperfusion group (FK506-I/R), sham group, and FK506 + sham group (FK506-sham). Ischemia/reperfusion was achieved by occluding left coronary artery for 30 min and subsequently reperfusing for 120 min. FK506 was administered 15 min before ischemia. Rats in sham group and FK506-sham group were operated only by placing a ligature around the coronary artery, and the blood supply was not blocked. I/R group showed a rapid increase in TUNEL-positive cells and high risks of histopathological changes in damaged cardiac tissues. FK506 reduced the infarct size and inhibited the activation of CaN enzyme in FK506-I/R group. Increase in Bcl-2/Bax ratio in FK506-IR group indicated that FK506 protected myocardium from apoptosis induced by IR. The activity of CaN and ASK1 protein level decreased significantly after I/R injury in FK506-treated I/R heart. FK506 suppresses the activation of CaN and ASK1 through CaN-mediated apoptosis pathway, and ASK1 negatively regulates CaN activity. Suppression of CaN and ASK1 signaling circuitry are involved in protective effect of FK506 on rat myocardium I/R injury.     

Disruption of sarcolemmal integrity during ischemia and reperfusion of canine hearts as monitored by use of lathanum ions and a specific probe

Myocellular injury induced by acute ischemia and subsequent reperfusion was studied in 38 dogs, with special reference to sarcolemmal permeability as determined by the vital ionic lanthanum (La³⁺) probe technique and electron microscopy. The left anterior descending coronary artery (LAD) was occluded in 14 dogs for 10 to 60 min, and the ischemic zone was perfused slowly for 7 min with a La³⁺-containing solution. In 21 dogs, the LAD was released for 10 min after occlusion and was then reperfused for 7 min with arterial blood plus the La³⁺-containing solution. Subsequently, in both groups of animals, the ischemic myocardium was subjected to perfusion fixation in preparation for electron microscopy. In normal cardiac myocytes, La³⁺ was localized exclusively in the extracellular space. After 10 to 20 min of ischemia, more than 80% of myocytes appeared normal or were damaged only slightly, and the majority continued to exclude La³⁺. After 10 min of ischemia, deposits of lanthanum were detected in 1 and 6 % of myocytes in the absence or presence of reperfusion, respectively. The number of cells with such deposits was markedly increased after 30 min of ischemia (19%), as well as after 20 min of ischemia followed by reperfusion (17%), prior to the development of irreversible myocardial damage. After 60 min of ischemia with or without reperfusion, about 30% of myocytes showed severe injury with particulate deposits of lanthanum throughout the entire cell.These results indicate that sarcolemmal permeability increases during the early stage of myocardial injury due to ischemia or ischemiareperfusion and contributes to the development of myocardial damage.     

对心肌缺血与体外反搏时血管紧张素转换酶的研究

目的 :探讨体外反搏对心肌缺血犬循环和局部血管紧张素转换酶的影响及机制。方法 :采用冠状动脉结扎法复制犬急性心肌缺血模型 ,外加体外反搏治疗 ,观测循环血液中以及缺血心肌、肺组织局部ANGⅡ水平、ACE活性的改变 ,用RT PCR方法检测局部ACEmRNA的表达。结果 :循环ANGⅡ水平、ACE活性随缺血时间的延长逐步上升 ,反搏能抑制其活性 ;体外反搏还能抑制缺血激活的缺血心肌ACE活性、ANGⅡ水平 ;抑制缺血心肌、肺组织ACEmRNA的表达 ,其中肺脏ACE达正常水平。结论 :体外反搏能抑制缺血心肌局部ACE的表达抑制局部RAS ,还对循环RAS有抑制作用 ,这可能是体外反搏保护缺血心肌的作用机制之一     

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.