银杏叶提取物对糖尿病大鼠一氧化氮水平的影响

目的研究银杏叶提取物(EGb)对糖尿病大鼠心肌、睾丸、脑组织一氧化氮水平的影响。方法用链脲佐菌素制备SD大鼠糖尿病模型。测定EGb对糖尿病大鼠心肌、睾丸、脑组织一氧化氮(NO)的含量及一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)、结构型一氧化氮合酶(cNOS)的活性的影响。结果与正常组相比,糖尿病大鼠心肌、睾丸组织NO含量及NOS、iNOS活性升高,脑组织NO含量及NOS活性升高。与糖尿病组相比,EGb治疗组大鼠心肌、睾丸组织NO含量及NOS、iNOS活性下降。结论EGb能够对抗糖尿病大鼠过量NO对心肌、睾丸组织的损伤。     

银杏叶提取物对糖尿病大鼠一氧化氮水平的影响

目的 研究银杏叶提取物(EGb)对糖尿病大鼠心肌、睾丸、脑组织一氧化氯水平的影响。方法用链脲佐菌素制备SD大鼠糖尿病模型。测定EGb对糖尿病大鼠心肌、睾丸、脑组织一氧化氯(NO)的含量及一氧化氯合酶(NOS)、诱导型一氧化氯合酶(iNOS)、结构型一氧化氯合酶(cNOS)的活性的影响。结果与正常组相比，糖尿病大鼠心肌、睾丸组织NO含量及NOS，iNOS活性升高，脑组织NO含量及NOS活性升高。与糖尿病组相比，EGb治疗组大鼠心肌、睾丸组织NO含量及NOS、iNOS活性下降。结论 EGb能够对抗糖尿病大鼠过量NO对心肌、睾丸组织的损伤。     

二氮嗪对大鼠心肌线粒体膜电位及呼吸功能的影响

目的 :研究二氮嗪对大鼠心肌线粒体功能的影响 ,以探讨其心肌保护作用的可能机理。方法 :以罗丹明 12 3为荧光探针测定线粒体膜电位 ,氧电极法测线粒体呼吸 ,观察二氮嗪对正常大鼠心肌线粒体跨膜电位及呼吸的影响。结果 :5 0 μmol·L-1的二氮嗪可引起线粒体膜电位去极化 ,此影响可被钾通道阻滞剂消除 ;二氮嗪 10 0 μmol·L-1可降低大鼠心肌线粒体琥珀酸链的R3、R4速率 ,但不影响呼吸控制率。结论 :二氮嗪可调节大鼠心肌线粒体功能 ,这与其抗心肌缺血保护作用有关。     

红景天苷对力竭大鼠心肌线粒体呼吸功能的影响

目的研究红景天苷（Salidroside,SAL）对力竭运动导致大鼠心肌结构损伤和线粒体呼吸功能障碍的影响。方法将40只雄性SD大鼠随机分为对照（C）组、力竭（EE）组、低剂量SAL（LS）组、高剂量SAL（HS）组（n=10）。C组与EE组分别给予生理盐水[10 ml/（kg·d）]、其他两组给予低剂量SAL[100 mg/（kg·d）]及高剂量SAL[300mg/（kg·d）]灌胃2周。除C组外,其余各组建立一次性力竭游泳运动后心肌损伤模型,于力竭游泳运动后即刻取材,C组同时在安静状态下取材。应用光镜及电镜观察大鼠心肌显微结构及超微结构。采用原位法应用高分辨呼吸仪分别测定大鼠心肌线粒体呼吸链复合物Ⅰ、Ⅱ、Ⅳ的态3呼吸速率。结果①与C组比较,EE组大鼠心肌线粒体呼吸链复合物Ⅰ、Ⅱ、Ⅳ的态3呼吸速率明显降低（P〈0.05）;形态学观察可见心肌细胞损伤严重,心肌纤维出现断裂,间质水肿,可见畸形线粒体以及线粒体嵴有断裂。②与EE组比较,LS组大鼠心肌线粒体呼吸链复合物Ⅰ的态3呼吸速率明显增高（P〈0.05）,HS组线粒体呼吸链复合物Ⅰ、Ⅱ、Ⅳ的态3呼吸速率明显增高（P〈0.05）;形态学观察偶见肌纤维断裂、心肌细胞基质水肿,线粒体部分嵴和少部分膜融合、模糊不清或缺失。③与LS组比较,HS组线粒体呼吸链复合物Ⅰ、Ⅱ、Ⅳ的态3呼吸速率明显增高（P〈0.05）,心肌纤维的完整性好于LS组,线粒体变异程度轻,膜结构相对完整。结论 SAL对力竭运动导致大鼠心肌结构损伤和线粒体呼吸功能障碍有保护作用,且这种作用呈剂量依赖性。     

胰岛素对糖尿病大鼠肝线粒体氧自由基和氧化磷酸化的影响(英文)

目的:研究胰岛素对糖尿病大鼠肝线粒体功能,质子ATP酶活力及超氧阴离子的影响。方法:大鼠尾静脉注射四氧嘧啶,造成糖尿病动物模型。离心制备线粒体,测氧仪测定态3呼吸率、态4呼吸率、呼吸控制率和磷氧比。用化学发光法测定超氧阴离子生成量,质子ATP酶合成与水解活力分别采用荧光素-荧光素酶法和无机磷法测定。结果:(1)糖尿病大鼠超氧阴离子生成增多,皮下注射胰岛素治疗9周后,Q_2~(·-)生成量减少。(2)在糖尿病状态下,胰岛素治疗能提高质子ATP合成酶活力,降低质子ATP水解酶活力。(3)胰岛素通过改善态3呼吸率调节呼吸控制率和磷氧比。结论:胰岛素能抑制O_2~(·-)生成,提高ATP的合成,改善肝线粒体氧化磷酸化功能。     

早期糖尿病肾病大鼠肾脏线粒体功能及超微结构变化

目的观察早期糖尿病肾病大鼠肾脏线粒体功能和结构变化。方法将20只健康雄性大鼠随机分为正常对照组和糖尿病组,每组10只。糖尿病组大鼠采用链脲佐菌素诱导糖尿病模型。第10周末测定2组血糖、肾重/体质量、24h尿蛋白定量;检测各组肾脏线粒体丙二醛（MDA）、一氧化氮（NO）含量及锰超氧化物歧化酶（Mn-S0D）、总一氧化氮合酶（T-NOS）、组分ATP酶活性和线粒体呼吸控制率（RCR）,分析线粒体比表面。结果与正常对照组比较,糖尿病组血糖、肾重/体质量、24 h尿蛋白定量明显增加（P〈0.01）,肾脏线粒体MDA、NO含量、T-NOS明显增加（P〈0.01）,Mn-S0D、组分ATP酶活性、线粒体RCR及比表面明显减少（P〈0.01）。结论早期糖尿病肾病大鼠肾脏线粒体存在明显的氧化损伤和功能、结构障碍。     

靶向心肌线粒体ATP敏感性钾通道苯并噻二嗪类新衍生物的药理学特征

目的：设计合成苯并噻二嗪类新衍生物,研究其激活心肌线粒体ATP敏感性钾通道的药理学活性并与二氮嗪进行对比分析。方法：采用氧电极法评价新衍生物对心肌线粒体态3呼吸（R3）、态4呼吸（R4）以及呼吸控制率（RCR）等呼吸功能参数的影响。戊巴比妥钠麻醉Wistar大鼠,颈总动脉插管,连接八导生理记录仪记录二氮嗪及新衍生物对大鼠血压的影响。结果：100μmol／L衍生物16和17可同时降低心肌线粒体琥珀酸氧化呼吸链中的R3和R4,但不影响RCR,作用与二氮嗪类似;衍生物15在降低心肌线粒体R3和R4的同时可显著提高线粒体RCR。静脉注射10mg／kg二氮嗪具有迅速的降压作用,与对照组对比,在3min时血压下降约为28％,而20种衍生物均无降压作用。结论：衍生物15可激活心肌线粒体ATP敏感性钾通道,提高线粒体RCR,且无降压作用,其心血管选择性优于二氮嗪。     

银杏叶提取物对糖尿病模型大鼠肾脏ET-1、TGF-β_1的影响

目的:研究银杏叶提取物(EGb)对糖尿病模型大鼠肾组织中内皮素-1(ET-1)、转化生长因子β1(TGF-β1)水平变化的影响。方法:SD大鼠24只随机分为3组,即正常对照、糖尿病模型和EGb组,经相应处理后8周,观察大鼠血糖、胰岛素、总胆固醇(TC)、三酰甘油(TG)、肌酐清除率(Ccr)、尿白蛋白排泄率(UAE)、尿β2微球蛋白排泄率(β2-MG)等水平变化;以放射免疫法检测血浆、尿液及肾组织中ET-1水平;以ELISA法检测血清、尿液中TGF-β1水平。结果:糖尿病大鼠的血糖、胰岛素、TC和TG升高;经EGb治疗后,血糖、血胰岛素、TC和TG显著降低。糖尿病模型组血、尿中ET-1、TGF-β1及肾组织中ET-1水平均显著高于正常对照组;EGb可显著降低血、尿中ET-1、TGF-β1和肾组织中ET-1水平及Ccr、UAE、β2-MG。结论:EGb对糖尿病大鼠的肾脏具有保护作用,而抑制糖尿病大鼠ET-1、TGF-β1水平可能是其重要作用机制。     

银杏叶提取物对老龄大鼠心肌老化的影响

目的 研究银杏叶提取物对老龄大鼠心肌老化的影响.方法 老龄雄性大鼠10只(老龄治疗组)用银杏叶提取物灌胃治疗16周;另设老龄对照组和成年对照组各10只.比较各组大鼠心肌电镜下超微结构改变、血清氧化指标超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-Px)、丙二醛(MDA)、心肌糖基化终末产物(AGEs)含量以及心肌线粒体DNA缺失率的差别.结果 老龄对照组大鼠心肌组织电镜下结构发生明显老化病理变化,间质增生,线粒体肿大,闰盘模糊.而在老龄治疗组,病理情况明显改善,与成年对照组有比较相似的超微结构.老龄治疗组大鼠血清SOD、GSH-Px与老龄对照组相比显著增多(P＜0.05),而血清MDA、心肌AGEs含量及心肌线粒体DNA缺失率显著下降(P＜0.05),且都与成年对照组无显著性差异(P＞0.05).结论 银杏叶提取物可以抑制氧化、抑制非酶糖基化,从而减缓心肌老化.     

银杏叶提取物对实验性糖尿病大鼠脑组织的保护作用

目的:研究银杏叶提取物(extractofGinkgobi-loba,EGB)对糖尿病大鼠脑的保护作用及其机制。方法:选用雄性SD大鼠,随机分为糖尿病组、银杏叶组和正常对照组。应用链脲佐菌素(STZ)诱导制备大鼠糖尿病模型。银杏叶组腹腔注射银杏叶提取物注射液,其余两组给予同容积的生理盐水,用药5周后,测定脑组织内皮素(ET)、丙二醛(MDA)、NO产物NO2-/NO3-的含量及超氧化物歧化酶(SOD)、一氧化氮合酶(NOS)的活性,以及血清中的血糖、胰岛素、ET水平,并作光镜及透射电镜观察。结果:糖尿病脑组织光镜下可见脑水肿、脑软化、神经细胞变性、白质脱髓鞘,透射电镜下可见神经元及神经胶质细胞内线粒体肿胀、嵴变短、神经纤维脱髓鞘、血脑屏障受损。EGB治疗后光镜、电镜下的病变明显减轻。与糖尿病组相比,银杏叶组大鼠血糖、血浆ET水平下降、胰岛素水平升高,脑组织内SOD活性明显升高,NOS活性、ET、MDA、NO2-/NO3-的含量明显下降。结论:EGB可能通过抗脂质过氧化及降低NO、ET水平,对糖尿病大鼠脑组织产生保护作用。     

Protection of mitochondrial respiration activity by bilobalide.

Mitochondria alteration is an early event in ischemia-induced damage, and its prevention improves tissue survival upon reperfusion. Adenine translocase and complex I activities are rapidly affected by ischemia. Ginkgo biloba extract demonstrates anti-ischemic properties attributable to the terpenoid fraction, mainly due to the presence of bilobalide. The mechanism of the protection afforded by bilobalide is not yet known. In this work, the effects of bilobalide on mitochondrial respiration were investigated. Mitochondria isolated from rats treated with bilobalide (2 to 8 mg/kg) showed a dose-dependent increase in the respiratory control ratio, due to a lower oxygen consumption during state 4. Bilobalide also decreased the sensitivity of oxygen consumption to inhibition of complex I by Amytal or to inhibition of complex III by antimycin A or myxothiazol. There was no protection of complexes IV and V. It also increased the activity of complex I but not of adenine translocase. Similar effects were also obtained in vitro when control mitochondria were preincubated for 1 hr with 0.8 microg/mL bilobalide. Treatment of the rats with 8 mg/kg bilobalide also prevented the ischemia-induced decrease in state 3 of the mitochondrial respiration and thus the decrease in RCR. The protective effect of bilobalide on cellular ATP content observed under ischemic conditions can be correlated with the above observations. By protecting complex I and III activities, bilobalide allows mitochondria to maintain their respiratory activity under ischemic conditions as long as some oxygen is present, thus delaying the onset of ischemia-induced damage. This mechanism provides a possible explanation for the anti-ischemic properties of bilobalide and of Ginkgo biloba extract in therapeutic interventions.     

银杏叶提取物在治疗慢性肺心病中的抗血小板作用

目的：观察银杏叶提取物（Ｅｇｂ７６１）在肺心病治疗中的作用,特别是抗血小板作用。方法：用流式细胞方法测定了２组慢性肺心病患者治疗前后的血小板表面ＣＤ４１和ＣＤ６２ｐ表达变化。结果：２组病人治疗后ＣＤ４１和ＣＤ６２ｐ表达均显著降低,Ｅｇｂ７６１治疗组较一般治疗更明显。结论：Ｅｇｂ７６１具有良好的改善血小板功能的作用,是一种有效的肺心病治疗辅助药。     

Egb761对哮喘模型大鼠MMP-9及TIMP-1表达的影响和对气道重构的干预研究

目的:研究银杏叶提取物(Egb761)对哮喘大鼠气道上皮细胞基质金属蛋白酶-9(MMP-9)及其抑制剂-1(TIMP-1)表达的影响和对气道重构的干预作用。方法:40只大鼠随机均分为4组,即正常对照、哮喘模型、地塞米松及Egb761组,以吸入卵蛋白复制大鼠哮喘模型,用免疫组化技术结合计算机病理图像分析技术,测定各组大鼠气道形态学参数和气道上皮细胞MMP-9及TIMP-1表达的相对含量。结果:哮喘模型组大鼠气道壁的总厚度及内壁厚度和平滑肌层的厚度均显著高于正常对照、地塞米松和Egb761组(P<0.05);哮喘模型组MMP-9及TIMP-1表达量也显著高于上述3组(P<0.01);哮喘模型组MMP-9与TIMP-1的比例显著失衡。结论:少量多次的卵蛋白吸入可以导致大鼠气道重构的发生,MMP-9及TIMP-1在气道重构中发挥着重要作用,Egb761对哮喘模型大鼠的气道重构有干预作用。     

银杏叶提取物预防离体大鼠心肌缺血再灌注损伤

探讨银杏叶提取物在心肌缺血再灌注损伤中的预防作用。方法取３０只ＳＤ大鼠平均为３组,采用改良Ｌａｎｇｅｎｄｏｒｆｆ法建立离体大鼠心脏缺血再灌注模型,以Ｋｒｅｂｓ－Ｈｅｎｓｅｌｅｉｔ碳酸氢盐酸冲液（ＫＨＢＢ）灌注１０ｍｉｎ后,实验组和对照组分别予以Ｅｇｂ７６１加晶体停搏液或晶体停搏液停搏,停搏６０ｍｉｎ后再以ＫＨＢＢ缓冲灌注６０ｍｉｎ,在复灌１５、３０、６０ｍｉｎ时点测定冠脉量,心率、左心室压力,心收     

Functional and toxicological characteristics of isolated renal mitochondria: impact of compensatory renal growth.

Mitochondria were isolated from renal cortical homogenates from control rats and rats that had undergone uninephrectomy and compensatory renal growth (NPX rats). Activities of selected mitochondrial processes, including key enzymes of intermediary metabolism, glutathione-dependent enzymes, and glutathione transport, were measured, and the effects of three mitochondrial toxicants were assessed to test the hypothesis that compensatory renal growth is accompanied by increases in mitochondrial metabolism and that this is associated with increased susceptibility to injury from oxidants or other mitochondrial toxicants. Activities of malic and succinic dehydrogenases were significantly higher in mitochondria from NPX rats than in mitochondria from control rats. Although the rates of state 3 respiration were significantly higher in mitochondria from NPX rats, the rates of state 4 respiration and respiratory control ratios were not different between mitochondria from control and NPX rats. Activities of glutathione redox cycle enzymes did not differ significantly between mitochondria from control and NPX rats. However, the rates of uptake of glutathione into mitochondria were approximately 2.5-fold higher in tissue from NPX rats than in tissue from control rats. Incubation of mitochondria from NPX rats with three mitochondrial toxicants [tert-butyl hydroperoxide, methyl vinyl ketone, and S-(1,2-dichlorovinyl)-L-cysteine] caused greater inhibition of state 3 respiration and larger increases in malondialdehyde formation than similar incubations of mitochondria from control rats. These results indicate that mitochondria from hypertrophied renal cells are more sensitive to oxidants or mitochondrial toxicants. Baseline levels of malondialdehyde were also significantly higher in mitochondria from NPX rats, suggesting that a basal oxidant stress exists in mitochondria from hypertrophied cells.     

The regulation of mitochondrial respiration by opening of mKCa channels is age-dependent

The protective potency of ischemic preconditioning decreases with increasing age. A key step in ischemic preconditioning is the opening of mitochondrial Ca(2+) sensitive K(+) (mK(Ca)) channels, which causes mild uncoupling of mitochondrial respiration. We hypothesized that aging reduces the effects of mK(Ca) channel opening on mitochondrial respiration. We measured the effects of mK(Ca) channel opener NS1619 (30 microM) on mitochondrial respiration in isolated heart mitochondria from young (2-3 months) and old (22-26 months) Wistar rats. Oxygen consumption was monitored online after addition of 250 microM ADP (state 3 respiration), and after complete phosphorylation of ADP to ATP (state 4 respiration) in the presence or absence of the mK(Ca) channel blocker paxilline (5 microM). The respiratory control index (RCI) was calculated as state 3/state 4. In mitochondria from young rats, NS1619 increased state 4 respiration by 11.9+/-4.1% (mean+/-S.E.M.), decreased state 3 respiration by 7.6+/-2.5%, and reduced the RCI from 2.6+/-0.03 (control) to 2.1+/-0.06 (all P<0.05, n=12 for all groups). Paxilline blocked the effect of NS1619 on state 4 respiration (0.7+/-2.8%), but did not affect the decrease in state 3 respiration; paxilline blunted the decrease of RCI. In mitochondria from old rats, NS1619 had neither effect on state 4 (0.4+/-1.6%), and state 3 respiration (-7.4+/-1.5%), nor on RCI (3.0+/-0.13 vs. 3.2+/-0.11, n=12). Increasing age reduced the effects of mK(Ca) opening on mitochondrial respiration. This might be one underlying reason of the decreased protective potency of ischemic preconditioning in the aged myocardium.     

Effects of chronic ethanol feeding on rat liver mitochondrial energy metabolism.

Chronic alcohol consumption is known to decrease hepatic mitochondrial respiration rate. It was shown here that the proton leak through the mitochondrial inner membrane was unaffected by chronic ethanol treatment. This indicates that changes in proton leak are not responsible for the alterations in respiration found in mitochondria isolated from ethanol-treated rats. Therefore, the lowered coupled respiration rate is solely due to a decrease in the activity of the electron transport chain. However, this alteration was only evident in coupled respiration (i.e. state 4) and was not apparent in uncoupled respiration. Thus, chronic ethanol treatment decreases the activity of the mitochondrial electron transport chain components which have control over coupled, but not uncoupled, respiration. Mitochondrial energy metabolism is regulated by thyroid hormone status. It was shown that the chronic alcohol treatment did not affect the circulating levels of thyroxine. Furthermore, the activity of mitochondrial alpha-glycerophosphate dehydrogenase, which is strongly affected by thyroid hormones, was unaltered by alcohol treatment. Thus, the effects of ethanol treatment on mitochondria occur independently of changes in circulating thyroid hormone levels.     

BCNU-induced gR2 DEFECT mediates S-glutathionylation of Complex I and respiratory uncoupling in myocardium

A deficiency of mitochondrial glutathione reductase (or GR2) is capable of adversely affecting the reduction of GSSG and increasing mitochondrial oxidative stress. BCNU [1,3-bis (2-chloroethyl)-1-nitrosourea] is an anticancer agent and known inhibitor of cytosolic GR ex vivo and in vivo. Here we tested the hypothesis that a BCNU-induced GR2 defect contributes to mitochondrial dysfunction and subsequent impairment of heart function. Intraperitoneal administration of BCNU (40 mg/kg) specifically inhibited GR2 activity by 79.8 ± 2.7% in the mitochondria of rat heart. However, BCNU treatment modestly enhanced the activities of mitochondrial Complex I and other ETC components. The cardiac function of BCNU-treated rats was analyzed by echocardiography, revealing a systolic dysfunction associated with decreased ejection fraction, decreased cardiac output, and an increase in left ventricular internal dimension and left ventricular volume in systole. The respiratory control index of isolated mitochondria from the myocardium was moderately decreased after BCNU treatment, whereas NADH-linked uncoupling of oxygen consumption was significantly enhanced. Extracellular flux analysis to measure the fatty acid oxidation of myocytes indicated a 20% enhancement after BCNU treatment. When the mitochondria were immunoblotted with antibodies against GSH and UCP3, both protein S-glutathionylation of Complex I and expression of UCP3 were significantly up-regulated. Overexpression of SOD2 in the myocardium significantly reversed BCNU-induced GR2 inhibition and mitochondrial impairment. In conclusion, BCNU-mediated cardiotoxicity is characterized by the GR2 deficiency that negatively regulates heart function by impairing mitochondrial integrity, increasing oxidative stress with Complex I S-glutathionylation, and enhancing uncoupling of mitochondrial respiration.     

银杏叶提取物对大鼠局灶性脑缺血后血管新生的影响

目的探讨银杏叶提取物是否可以促进大鼠局灶性脑缺血后梗死周围区的血管新生,寻求促使脑缺血后血管新生、开发脑储备能力的有潜力的中医药疗法。方法采用线栓法建立大鼠大脑中动脉闭塞（MCAO）模型,术后24h采用银杏叶注射液以10mg／（kg体重·d）的剂量连续腹腔注射治疗6d,于缺血后第7d、14天分别观察银杏叶组和对照组大鼠脑梗死体积、脑梗死灶周围血管密度（层粘连蛋白,Laminin的表达）和神经功能缺失评分的变化。结果与对照组比较,大鼠局灶性脑缺血后第7天和14天银杏叶组的梗死体积明显减小,梗死周围血管密度较对照组明显增加,并显示出更好的神经功能评分（P〈0．05）。结论银杏叶提取物可促进局灶性脑缺血后大鼠脑梗死周围区的血管新生,从而开发脑储备能力,这可能是银杏叶提取物改善脑缺血后神经功能恢复的机制之一。     

Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischaemic dog hearts.

1. Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on the myocardial level of coenzyme Q10, and on mitochondrial respiration were examined in dogs. 2. Either vehicle (control), pravastatin (4 mg kg-1 day-1), or simvastatin (2 mg kg-1 day-1) was administered orally for 3 weeks. First, the myocardial tissue level of coenzyme Q10 was determined in the 3 groups. Second, ischaemia was induced by ligating the left anterior descending coronary artery (LAD) in anaesthetized open chest dogs, pretreated with the inhibitors. After 30 min of ischaemia, nonischaemic and ischaemic myocardium were removed from the left circumflex and LAD regions, respectively, and immediately used for isolation of mitochondria. The mitochondrial respiration was determined by polarography, with glutamate and succinate used as substrates. 3. Simvastatin significantly decreased the myocardial level of coenzyme Q10, but pravastatin did not. 4. Ischaemia decreased the mitochondrial respiratory control index (RCI) in both groups. Significant differences in RCI between nonischaemic and ischaemic myocardium were observed in the control and simvastatin-treated groups. 5. Only in the simvastatin-treated group did ischaemia significantly decrease the ADP/O ratio, determined with succinate. 6. The present results indicate that simvastatin but not pravastatin may cause worsening of the myocardial mitochondrial respiration during ischaemia, probably because of reduction of the myocardial coenzyme Q10 level.