三甲氧苄嗪对幼兔心肌缺血再灌注保护作用的研究

目的:探讨四种晶体停搏液(MST、Tyers、HTK和Roe)中加入细胞保护剂三甲氧苄嗪(TMZ)对未成熟心肌的作用。方法:以离体灌注幼兔心为研究对象,观察四种晶体停搏液在幼兔心14℃缺血2h后血流动力学、冠脉流出液心肌酶和心肌生化的变化。结果:与对照组相比,TMZ可显著提高晶体停搏液离体灌注幼兔心功能的恢复,明显减少心肌酶的漏出和氧自由基的生成,增加高能磷酸盐的储存(P<0.05)。结论:TMZ可明显提高晶体停搏液对未成熟心肌的保护效果。     

三甲氧苄嗪对幼兔心肌作用的研究

目的探讨于4种常用晶体停搏液中加入细胞保护剂三甲氧苄嗪(trimetazidine,TMZ)对幼兔心肌的保护效应.方法以离体灌注的幼兔心为研究对象,观察4种晶体停搏液在幼兔心14℃缺血2 h后血流动力学、冠状动脉流出液心肌酶和心肌生化的变化.结果与对照组EO[AF恢复率(78.23±3.45)%,CO恢复率(80.43±3.62)%]相比,TMZ显著提高离体灌注幼兔心功能的恢复E1组AF恢复率(89.54±3.04)%(P＜0.01),CO恢复率(91.54±2.55)%(P＜0.01),其余各组的变化趋势同E1组;减少心肌酶的漏出E1组CK漏出量(14.33±1.63)IU/L,而对照组EO为(23.00±3.10)IU/L(P＜0.01),其余各组的变化趋势同E1组;降低氧自由基的生成E1组MDA为(1.02±0.09)μmol/g,对照组EO为(1.77±0.09)μmol/g(P＜0.05),其余各组的变化趋势同E1组;增加高能磷酸盐的储存El组(2.11±0.31)μmmol/g.干重对照组EO为(1.68±0.11)μmmol/g.干重(P＜0.05),其余各组的变化趋势同E1组.结论于心停搏液中加入TMZ将明显改善对未成熟心肌的保护效果.     

三甲氧苄嗪对心肌缺血/再灌注损伤的保护作用

目的 :探讨三甲氧苄嗪增补于停搏液中对缺血 /再灌注离体鼠心的保护作用。方法 :将 2 4只 Wistar大鼠随机分为三甲氧苄嗪组 （A）和对照组 （B）。离体鼠心在改良的 L angendorff- Neely灌注模型上预灌注 30 min,停搏 12 0min、再灌注 30 min。缺血前及再灌注期间测定血流动力学指标、心肌酶 （CPK,L DH ）、心肌超氧化物歧化酶 （SOD）、过氧化脂质 （L PO）含量、心肌 ATP水平。电镜观察心肌超微结构。结果 :再灌注后 ,A组心功能、心肌超微结构的改善 ,明显优于 B组 ;心肌酶 （CPK ,L DH）、L PO含量显著低于 B组 （P<0 .0 1） ;SOD含量和 ATP水平显著高于 B组（P<0 .0 1）。结论 :三甲氧苄嗪增补于停搏液中可显著减轻心肌缺血 /再灌注损伤 ,具有良好的心肌保护作用     

超极化停搏液对幼兔心肌缺血再灌注损伤的保护作用

目的     

三甲年头苄嗪对心肌缺血的保护作有研究进展

三甲氧苄嗪[又称心康宁、曲美它嗪,Ｔｒｉｍｅｔａｚｉｄｉｎｅ(ＴＭＺ)]最早由Ｓｃｈｍｉｔｔ报道[1]其药理学特性,属于抗心绞痛类药物。Ｍｏｄｙ等[2]研究表明,与其它抗心绞痛药物相比,其显著特点是不引起或引起极小的血流动力学改变,但对缺血心肌有明显的保护作用,是一种严格意义上的细胞保护剂[3]。本文综述近年来三甲氧苄嗪心肌保护的研究进展。1　对血流动力学的作用ＴＭＺ与其它同类抗心绞痛药物相比,其最大特点是不引起或引起最小的血流动力学的改变[2,4]。在离体工作的鼠心[2],兔心[5],豚鼠[6],ＴＭＺ不引起冠脉血流的改变,对缺血…     

三甲氧苄嗪和缺血性心脏病

心肌缺血主要是一种代谢性事件。通过药物干预可以直接刺激葡萄糖代谢或抑制脂肪酸beta氧化间接促进葡萄糖代谢,减少组织损害。三甲氧苄嗪（TMZ）可以有效的改善心肌在缺氧状态下的葡萄糖代谢水平,可以增加心肌对缺血再灌注损伤的耐受性,维持细胞膜电活动的稳定性,缩小心肌梗死面积,改善心功能,而对血流动力学没有明显影响。近年来逐渐受到关注。本文回顾了近年来国外进行的临床观察和基础研究的结果。     

六甲氧苄嗪对大鼠的降压作用及其机理研究

本文用动脉插管直接测压的方法，研究了六甲氧苄嗪（ＨＭＺ）对麻醉大鼠正常血压的影响。结果表明，ＨＭＺ能降低血压，以降低舒张压和平均压为主，且能部份对抗去甲肾上腺素的升压作用，同时与异丙肾上腺素合用时似有协同作用。初步认为ＨＭＺ的降压效应与α受体和β受体无明显关系，可能与抑制Ｃａ２＋通道有关。     

改良式氧合血停搏液对未成熟心肌的保护作用

目的:证实氧合血停搏液对未成熟心肌的保护作用。方法:以18例婴幼儿复杂先心病患者为对象.分为晶体组和氧合血停搏液组,观察转流中及术后各项指标,并进行比较。结果:两组患者术前情况都比较接近,转流时间,阻断时间、复跳情况,术后并发症均未见明显差异,但晶体组预充总量大,停跳液晶体回收量大,转中多应用超滤.利尿剂等,血球压积变化较大和库血用量多(P均<0.05)。结论:氧合血停搏液可为婴幼儿提供良好的心肌保护条件。     

三甲氧苄嗪对梗死后心功能不全患者的抗心肌缺血作用

目前认为三甲氧苄嗪是一种有效且安全的抗心肌缺血药物。已被欧洲心血管协会推荐为治疗和二级预防心肌缺血。特别是心绞痛的药物。本文报告作者用三甲氧苄嗪对梗死后心功能不全患者的抗心肌缺血作用进行研究的结果。     

三种心脏停搏液对未成熟猪体外循环中的心肌保护效果

目的比较St．Thomas停搏液（STH液）、氧合血停搏液和组氨酸一色氨酸一酮戊二酸停搏液fhistidine—tryptophan—ketoglutarate,HTK液）对未成熟猪围体外循环（cardiopulmonarybypass,CPB）期的心肌保护效果。方法21只年龄为（15～20）天、体重为（4．5～8．0）kg的中华小型猪随机分为STH液组、氧合血停搏液组和HTK液组,每组7只。分别于CPB前（T1）、升主动脉阻断（aorticcross—clamping,ACC）后10min（T2）、升主动脉开放（cross—clampingremission,CCR）后5min（T3）、CPB后5min（T4）、CPB后60min（T5）、CPB后120min（T6）抽取颈动脉血,实验结束后取少量右房心肌组织。ELISA法测肌酸激酶同工酶（CK—MB）、肌钙蛋白T（cTnT）和肌钙蛋白Ⅰ（cTnI）的含量,电镜下观察心肌超微结构的变化;同时记录每只动物的用血量。结果停跳前各组血浆CK—MB、cTnI、cTnT组间差异均无统计学意义（P〉0．05）;随着体外循环进行,各组血浆心肌生化标志物含量逐渐增加,HTK液组和氧合血停搏液组心肌生化标志物漏出率小于STH液组,差异有统计学意义（P〈0．05）。氧合血停搏液组和HTK液组相比,血浆心肌生化标志物含量无明显差异（P〉0．05）。氧合血停搏液组、HTK液组动物心肌细胞线粒体超微结构Flameng评分低于sTH液组（P〈0．05）。结论氧合血停搏液和HTK液组心肌细胞线粒体的损伤程度小,对未成熟心肌的保护效果均优于STH液组。     

Sex differences in the tolerance of immature rat myocardium to global ischemia

Summary Currently there is considerable interest in the metabolism of the immature myocardium and in particular the mechanisms underlying its greater tolerance to ischemia than that of the adult heart. In order to investigate whether this tolerance is sex-related, we compared the recovery of function in isolated hearts from male and female neonatal rats (three to five days old) following 60 min of normothermic global ischemia and 30 min of reperfusion (n=8 per group). The female hearts exhibited significantly better (p<0.05) recovery of rate (81±5% vs. 65±5%) and the rate-pressure product (73±9% vs. 37±8%), and a tendency towards better recovery of contractile function (left ventricular developed pressure, 89±9% vs. 59±12%; dP/dt, 84±12% vs. 54±13%). This evidence for greater resistance of female hearts to ischemic injury was supported by a delayed onset of contracture (mean time to onset, 29.4±2.7 min vs. 24.9±2.6 min). The loss in left ventricular compliance during ischemia and reperfusion was also smaller in the female hearts (increase in left ventricular end diastolic pressure, 6.5±1.2 mm Hg vs. 13.6±3.8 mm Hg). These results suggest that there may be sex-related differences in the tolerance of immature hearts to ischemia, a factor which should be taken into account in the design and interpretation of experimental studies.     

Ventricular fibrillation during no-flow global ischemia in isolated rabbit hearts

Introduction: The dominant frequency (DF) during ventricular fibrillation (VF) in Langendorff-perfused guinea pig hearts is higher in left ventricle (LV) than in right ventricle (RV). However, the onset of VF invariably leads to global ischemia. Whether or not a high DF source exists in LV during global ischemia is unknown.
Methods and Results: By using a two-camera optical mapping system, epicardial activation patterns of VF were studied in 12 isolated rabbit hearts during baseline, no-flow global ischemia, and reperfusion. Simultaneous endocardial electrode recording was performed in 4 of the 12 hearts. Optical mapping showed type 1 VF at baseline, with multiple wandering and short-lived wavelets. After the onset of global ischemia, VF showed progressively increased spatiotemporal periodicity. The majority (65%) of VF recorded after 7 minutes of global ischemia showed type 2 VF, containing a single epicardial site with stable (≥3.85 seconds in duration) repetitive activities. Among the 33 sites with these activities, 24 were located near the interventricular septum, and 27 showed an epicardial breakthrough pattern with centrifugal propagation and wavebreaks distant from the focal site. After 10 minutes of global ischemia, the DF was lower on LV epicardium (5.0 ± 1.4 Hz) than on RV epicardium (8.6 ± 2.5 Hz, P < 0.001). However, there was no DF gradient between RV and LV endocardium (9.7 ± 1.0 vs 9.6 ± 0.9 Hz).
Conclusions: VF during prolonged global ischemia is consistent with type 2 VF with a single subepicardial source of rapid activation, mostly near the interventricular septum. The DF in LV is not higher than in RV.     

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。     

Heterogeneity of ventricular fibrillation dominant frequency during global ischemia in isolated rabbit hearts

Introduction : Ventricular fibrillation (VF) studies show that ECG‐dominant frequency (DF) decreases as ischemia develops. This study investigates the contribution of the principle ischemic metabolic components to this decline. Methods and Results: Rabbit hearts were Langendorff‐perfused at 40 mL/min with Tyrode's solution and loaded with RH237. Epicardial optical action potentials were recorded with a photodiode array (256 sites, 15 × 15 mm). After 60 seconds of VF (induced by burst pacing), global ischemia was produced by low flow (6 mL/min), or the solution changed to impose hypoxia (95% N₂/5% CO₂), low pH_o (6.7, 80% O₂/20% CO₂), or raised [K⁺]_o (8 mM). DF of the optical signals was determined at each site. Conduction velocity (CV), action potential duration (APD90), effective refractory period (ERP), activation threshold, dV/dt_max, and membrane potential were measured in separate experiments during ventricular pacing. During VF, ischemia decreased DF in the left ventricle (LV) (to [58 ± 6]%, P < 0.001), but not the right (RV) ([93 ± 5]%). Raised [K⁺]_o reproduced this DF pattern (LV: [67 ± 12]%, P < 0.001; RV: [95 ± 9]%). LV DF remained elevated in hypoxia or low pH_o. During ventricular pacing, ischemia decreased CV in LV but not RV. Raised [K⁺]_o did not change CV in either ventricle. Ischemia and raised [K⁺]_o shortened APD90 without altering ERP. LV activation threshold increased in both ischemia and raised [K⁺]_o and was associated with diastolic depolarization and decreased dV/dt_max. Conclusions: These results suggest that during VF, decreased ECG DF in global ischemia is largely due to elevated [K⁺]_o affecting the activation thresholds in the LV rather than RV.     

Changes in work rate to oxygen consumption ratio during hypoxia and ischemia in immature and mature rabbit hearts

This study was designed to evaluate the relative response of myocardial efficiency to reduced oxygen supply (hypoxia and ischemia) in immature and mature isolated rabbit hearts. Hearts were subjected to either 15 min of hypoxia (60% or 30% O2) or reductions in coronary flow to 75%, 50%, 25%, and 15% of basal flow followed by 12 min of total global ischemia and 15 min of reperfusion. In order to examine changes in cardiac efficiency, we utilized the ratio of isovolumic contractile function (rate-pressure product) to myocardial oxygen consumption (RPP/MVO2). Under basal conditions, immature hearts displayed lower aortic pressure. RPP, coronary resistance and RPP/MVO2. Moderate hypoxia (60% O2) resulted in similar reductions in RPP and MVO2 in both age groups, with RPP/MVO2 remaining unchanged. During severe hypoxia, RPP/MVO2 increased significantly in mature hearts but not in immature hearts (P < 0.05). Underperfusion produced greater reductions in RPP and heart rate, whereas reperfusion after ischemia resulted in greater recovery of RPP, dP/dt and MVO2 in immature compared to mature hearts. When oxygen supply was limited by reductions in coronary perfusion. RPP/MVO2 tended to increase in mature hearts, whereas the ratio declined significantly in immature hearts. These data demonstrate that, in this model, a reduction in oxygen supply by hypoxia or hypoperfusion decreases efficiency in immature hearts, but increases efficiency in mature hearts under the same conditions.     

曲美他嗪对心肌缺血时细胞骨架损伤的作用

目的　探讨心肌缺血时细胞骨架改变并观察曲美他嗪对心肌缺血时细胞骨架损伤的影响 ,为临床应用提供理论依据。方法　将大白鼠随机分为对照组和用药组并制成缺血模型 ,分别于缺血 30 m in、6 0 min、12 0 min时取心肌组织用免疫组化的方法观察肌动蛋白、波形蛋白、肌球蛋白、结蛋白等心肌细胞骨架蛋白的改变 ,并用计算机图象模拟分析系统计算骨架蛋白量的变化。结果　心肌缺血 30 min即有肌动蛋白、肌球蛋白损伤 ,12 0 min时有结蛋白损伤 (P<0 .0 5 )。曲美他嗪干预后 ,心肌缺血 6 0 min、12 0 min时肌动蛋白、肌球蛋白损伤明显减少 (P<0 .0 5 )。结论　心肌缺血时可以导致细胞骨架损伤 ,曲美他嗪对心肌缺血时细胞骨架损伤有保护作用     

转染人白介素-10基因对未成熟心肌缺血再灌注损伤的影响

目的:观察转染人白细胞介素10(hIL-10)基因对未成熟心肌缺血再灌注(IR)的影响并探讨其可能作用机制。方法:24只3~4周龄的幼兔被随机分为空白对照组、空载对照组和基因转染组,每组8只。以阻断左冠左室支30 min再开放120 min,建立IR动物模型;阻断前经左室内注射重组腺病毒转染hIL-10。结果:IR后,空载对照组的血流动力学各项指标恢复率明显差于空白对照组(P均0.05),基因转染组的各项指标明显优于空载对照组(P0.05);与空白对照组比较,空载对照组和基因转染组的丙二醛(MDA)含量[(6.33±1.03)μmol/gwet∶(14.35±1.28)μmol/g wet∶(8.78±1.22)μmol/g wet]和髓过氧化物酶(MPO)活性[(5.42±0.72)U/g wet∶(19.35±2.32)U/g wet∶(9.26±1.26)U/g wet]明显升高(P均0.05),超氧化物歧化酶(SOD)活性明显下降[(215.25±26.65)U/g wet∶(93.82±12.61)U/g wet∶(176.33±19.84)U/g wet,P均0.05];与空载对照组比较,基因转染组的MDA含量和MPO活性明显下降,SOD活性明显升高(P均0.05)。结论:经左室内注射重组腺病毒载体介导hIL-10转基因有效可行,可减轻未成熟心肌缺血再灌注损伤。     

Ultrastructural evaluation of the effects of global ischemia and reperfusion on human myocardium

During open-heart surgery, myocardial biopsies were taken from 31 patients undergoing aortic valve replacement on total cardiopulmonary bypass. The first needle biopsy was taken before the induction of cardiac arrest (Kirsch cardioplegia), the second at the end of global ischemia, and the third during the reperfusion period. The tissue was investigated by electron microscopy using a semiquantitative scoring system for changes in both myocytes and blood vessels. Mitochondrial volume and surface density were determined by morphometry. Reversible ischemic injury of moderate to severe degree occurred in cardiac cells and in small blood vessels. On reperfusion, signs of damage regressed earlier in myocardial than in vascular tissue. Morphometry revealed significant mitochondrial swelling during the reperfusion phase, but this was not present after ischemia alone. It is concluded that Kirsch cardioplegia as applied here, is unable to protect the heart from ischemic cellular damage.