超极化停搏与高钾停搏对心肌保护效果的比较

目的 比较观察超极化停搏与高钾停搏的心肌保护效果,并评价低温对心脏超极化停搏的影响。方法 １８条犬分为三组,每组６条。低温高钾组、常渐超极化组和低温超极化组,分别以４℃标准Ｓｔ．Ｔｈｏｍａｓ液（Ｋ＾＋１６ｍｍｏｌ／Ｌ）、含吡那地尔５０μｍｍｏｌ／Ｌ的３７℃Ｓｔ．Ｔｈｏｍａｓ液（Ｋ＾＋５ｍｍｏｌ／Ｌ）和含吡那地尔５０μｍｏｌ／Ｌ的４℃Ｓｔ．Ｔｈｏｍｓａ液（Ｋ＾＋５ｍｍｏｌ／Ｌ）为心停搏液。结果 低温     

钾通道开放剂诱导超极化停跳对离体心脏的保护作用

目的 探讨ＡＴＰ第三性钾通道开放剂（ＫＣＯｓ）Ｐｉｎｃａｉｄｉｌ（５０μｍｏｌ／Ｌ对Ｌａｎｇｅｎｄｏｒｆｆ灌注兔心模型超极化停跳的保护作用。方法 选用离体免心脏２４个，随机分成３组：对照组（Ｃ组）；低温超极化组（ＬＨ组）；常温超极化组（ＷＨ组）。离体兔心Ｌａｎｇｅｎｄｏｒｆｆ模型灌注充氧的Ｋｒｅｂｓ－Ｈｅｎｓｅｌｅｉｔ（Ｋ－Ｈ）液稳定后，ＬＨ组或ＷＨ组分别灌注含Ｐｉｎａｃｉｄｉｌ的４℃或３７℃的Ｓ     

改良的St.Thomas停跳液对未成年兔心肌的保护作用

目的 探讨不同停跳液对未成年兔心肌缺血再灌注损伤的保护作用。方法 应用离体心脏工作模型对１６只未成年兔心脏灌注改良的Ｓｔ．ＴｈｏｍａｓＮｏ１停跳液（Ａ组）及改良的Ｓｔ．ＴｈｏｍａｓＮｏ２停跳液（Ｂ组）,观察经１５℃缺血１２０ｍｉｎ再灌注６０ｍｉｈ后兔心功能恢复情况。结果 离体心脏再灌注后,１５℃血２ｈ条件下,Ｂ组心功能恢复明显好于Ａ组,而心肌含水率,冠脉漏出液的肌酸磷酸激酶及乳酸脱氢酶及心肌细胞超     

吡那地尔预处理和超极化停搏的心肌保护效果研究

ＡＴＰ敏感性钾通道的开放与缺血心肌保护有密切的关系 ,为了解其开放程度及给药方式对心肌保护效果的影响 ,我们拟用不同浓度的吡那地尔 (ｐｉｎａｃｉｄｉｌ) ,分别模拟缺血预处理和心脏超极化停搏 ,观察体外循环中对犬缺血心肌的保护效果。实验方法　 18条犬随机分成 3组 ,每组 6条 :对照组间断灌注 4℃标准Ｓｔ.Ｔｈｏｍａｓ停搏液 (Ｋ 16ｍｍｏｌ/Ｌ) ;预处理组 ,阻断升主动脉后 ,灌注含吡那地尔 10 μｍｏｌ/Ｌ的 4℃充氧Ｓｔ.Ｔｈｏｍａｓ液 (Ｋ 5ｍｍｏｌ/Ｌ) 10ｍｉｎ ,开放循环 5ｍｉｎ ,再阻断升主动脉后实施对照组实验步骤 ;…     

血液超极化停搏对体外循环缺血心肌保护的研究

目的：评价含ATP敏感性钾通道开放剂吡那地尔的血液停搏液诱导的心脏起极化停搏在常温与低温体外循环下对缺血心肌的保护效果。方法：18只犬随机分为对照组（A组）、常温血液超极化组（B组）、低温血液超极化组（C组）,每组6只。对照组以4℃标准St.Thomas液（K^ 16mmol/L)为心脏停搏液,常温血液超极化组和低温血液超极化组分别以含吡那地尔50μmol/L的37℃St.Thomas液（K^ 5mmol/L,含血比例1：1）和含吡那地尔50μmol/L和4℃St.Thomas液（K^ 5mmol/L,含血比例1：1）为心脏停搏液。体外循环期间,A组和C组温度保持在26℃-28℃,B组温度保持在35℃-37℃。三组体外循环（CPB）期间,均全心缺血60min,恢复灌注30min。对比观察阻断升主动脉前、后心肌腺苷酸（ATP、ADP、AMP、TAN、EC）含量、心肌超微结构、脂质过氧化物丙二醛（MDA）含量以及血液动力学多项参数的变化。结果：对照组在阻断50min和开放30min,心肌各项指标均显示有明显的缺血和再灌注损害;而血液超极化组损害较轻,特别是低温血液超极化组,损害最轻。结论：含吡那地尔的血液停搏液诱导的超极化停搏,其心肌保护效果明显优于传统的高钾去极化停搏;低温血液超极化停搏又优于常温血液超极化停搏。     

药物预处理与诱导超极化对离体心脏的保护研究

目的：探讨AT敏感性钾通道开放剂（KCOs)吡那地尔对Langendorff灌注兔心脏模型药物预处理与药物诱导超极化停跳的保护作用。方法：离体兔心40个,随机等分5组。对比研究2种浓度吡那地尔在4℃或37℃全心缺血40min,复灌20min的心肌组织腺苷酸含量,脂质过氧化物的变化,以及再灌注后10、20min心功能恢复的情况。结果（1）心脏诱导停跳以4℃超极化与药物预处理组迅速,37℃超极化组较为缓慢;再灌注后仅对照组心脏复跳较慢。（2）与对照组同期比较,比吡那地尔预处理以及超极化的心脏再灌注后心肌收缩力与左心室内压恢复较快,其中心肌收缩力的恢复更为显著;（3）再灌注后,对照组心肌ATP、总腺苷量、细胞能荷水平低于预处理与超极化组（P＜0．05或0．01）其中以37℃预处理ATP含量较高,而经吡那地尔处理的4组,丙二醛则不同程度的低于对照组,结论：吡那地尔诱导心脏超极化停跳以及药物预处理,有助于降低心肌ATP的消耗,减少脂质过氧化物的形成,明显改善离体兔心脏缺血／再灌注后期心功能。     

外源性磷酸肌酸对离体鼠心能量代谢及线粒体功能的影响

目的 应用改良离休做功鼠心模型,探讨外源性磷酸肌酸（ＣＰ）抗心肌缺血再灌注损伤的作用机制。方法将７２只鼠分为５组,将５组Ｌａｎｇｅｎｄｏｒｆｆ灌注鼠心在３７℃下缺血４０分钟后恢复灌注２０分钟。Ａ组不灌注Ｓｔ．Ｔｈｏｍａｓ液;Ｂ组和Ｃ组于缺血开始灌注Ｓｔ．Ｔｈｏｍａｓ液,Ｃ组的Ｓｔ．Ｔｈｏｍａｓ液中加入ＣＰ（１０ｍｍｏｌ／Ｌ）;Ｄ组和Ｅ组于缺血１５分钟后灌注Ｓｔ．Ｔｈｏｍａｓ液,Ｅ组的Ｓｔ．Ｔｈｏｍ     

自血心停跳液复灌对兔心肌保护的观察

采用两种不同的复灌方法，观察复灌早期自血心停跳液控制性灌注对缺血后心肌的保护作用。２０只离体兔心低温、多剂量冷晶体心停跳液维持停跳１５０ｍｉｎ后，随机分为，Ａ组立即恢复３７℃正常动脉血灌注３５ｍｉｎ，Ｂ组为复灌时先用高钾、高渗、碱化、富含Ｌ－谷氨酸的自体３７℃动脉血心停跳液低压灌注５ｍｉｎ再以３７℃正常动脉血灌注３０ｍｉｎ。结果表明复灌期间Ｂ组释放入血５的ＣＰＫ显著低于Ａ组（Ｐ＜０．０１）；心肌收     

St.ThomasⅡ液对心肌微循环及内皮细胞的作用

目的 观察Ｓｔ．ＴｈｏｍａｓⅡ液对心肌微循环及内皮细胞（ＥＣ）的作用。方法 制作离体心灌注模型，分缺血停跳组（Ａ）；单次灌注停跳液组（Ｂ）；多次灌注停跳液组（Ｃ）。测定生理指标及毛细血管密度和充盈率；观察心肌及内皮细胞超微结构的改变。结果复跳后三组ｄｐ／ｄｔ均有下降，Ａ组尤明显（Ｐ〈０．０１）；五羟色胺只增加Ｂ、Ｃ组冠状血管流量（Ｐ〈０．０１）；硝酸甘油增加冠状血管流量，Ｂ、Ｃ组多于Ａ组（Ｐ〈０     

常温不停跳心内直视手术围术期甲状腺激素代谢变化

探讨常温心脏不停跳（非停跳组）心内直视手术病例围术期低三碘甲状腺原氨酸（Ｔ３）综合征发生程度,并与低温停循环（停跳组）心内直视手术病例比较,分析其临床意义。选择非停跳组２１例,术中鼻咽温维持在（３３～３７）℃,不阻断主动脉,心脏空跳下手术;停跳组２３例,术中降温致鼻咽温（２７～３１）℃,阻断升主动脉,灌注高钾心脏停跳液,心脏停跳下操作。两组病人选择在病种分布、术前心功能、体外循环时间无差异,术前均无甲状腺功能障碍,均在静脉复合麻醉下手术。于术前,体外循环（ＣＰＢ）转流１０分钟,停ＣＰＢ１０分钟,…     

超极化停搏对体外循环中心肌细胞膜微粘度变化的影响

目的比较超极化停搏和去极化停搏对体外循环(CPB)中心肌细胞膜流动性变化的影响,评价超极化停搏液的心肌保护作用. 方法根据随机数字表法将72只家猫均分为3组,每组24只.对照组:不阻断上、下腔静脉和主动脉,仅行并行循环180分钟;去极化停搏组:阻断主动脉60分钟,再灌注90分钟,心脏停搏液使用St.Thomas液(K 16mmol/L);超极化停搏组:心脏停搏液使用含吡那地尔的St.Thomas液(K 5mmol/L),其余处理与去极化停搏组相同.应用荧光偏振法测定心肌细胞膜的微粘度(η),以η的倒数表示心肌细胞膜流动性. 结果去极化停搏组主动脉阻断期间心肌细胞膜η值明显上升,且于再灌注期间进一步升高;超极化停搏组主动脉阻断期间亦呈升高趋势,但各时间点η值均明显低于去极化停搏组(P＜0.01). 结论超极化停搏比去极化停搏能更有效地维持CPB中缺血-再灌注心肌细胞膜的流动性,从而起到更好的心肌保护作用.     

吡那地尔预处理对缺血心肌的保护效果

目的观察心肺转流(cardiopulmonory bypass,CPB)下,ATP敏感性钾通道开放剂(KCOs)吡那地尔(pinacidil)预处理分别对常温和低温高钾停跳心肌的保护作用.方法18只犬均分为三组,CPB心脏高钾停跳,全心缺血60 min,恢复灌注30 min.常温吡那地尔组(NP组)、低温吡那地尔组(HP组)CPB前主动脉根部灌注浓度为10 μmol/L的吡那地尔5 min.对比观察阻断主动脉前、后心肌超微结构、丙二醛(MDA)含量、血清心肌酶含量以及血液动力学的变化.结果(1)电镜:HP组除阻断60min外的其他时点心肌的正常线粒体及糖原含量均接近缺血前水平,明显高于C组和NP组;(2)心肌MDA的含量:HP组阻断30 min和开放20 min以及NP组开放20 min与C组有显著性差异;(3)血清心肌酶:HP组,除阻断30 min,CK-MB均明显低于同期C组;(4)血液动力学变化:HP组开放循环后心输出量(CO)、左室搏出功(LVSW)恢复比C组迅速.结论吡那地尔明显增强低温CPB心肌缺血-再灌注期超微结构的保护效果.     

超极化停搏对家猫体外循环时心肌细胞膜脂区域流动性的影响

目的 探讨超极化停搏对猫体外循环(CPB)时心肌细胞膜脂区域流动性的影响.方法 家猫75只,体重3～4 kg,随机分为3组(n=25),CPB组:CPB建立后不阻断上腔静脉、下腔静脉和主动脉,仅行CPB 150 min;去极化停搏组:主动脉阻断60 min,再灌注60 min,心脏停搏液使用高钾St Thomas液;超极化停搏组:心脏停搏液使用含吡那地尔的低钾St Thomas液,余处理与去极化停搏组相同.应用自旋标记-电子自旋共振技术测定CPB时心肌细胞膜脂区域流动性.结果 与CPB组比较,去极化停搏组主动脉阻断30 min后心肌细胞膜脂S和τc均升高,超极化停搏组主动脉阻断60 min后心肌细胞膜脂S和τc均升高(P＜0.01);与去极化停搏组比较,超极化停搏组主动脉阻断30 min后心肌细胞膜脂S和τc均降低(P＜0.01).结论 与去极化停搏相比,超极化停搏能够更好地维持家猫CPB时心肌细胞膜脂的区域流动性.     

Comparison of myocardial protective effects between GIK solution and St. Thomas solution by use of canine isolated heart-lung preparations

The myocardial protection afforded by GIK solution, widely used as cardioplegic solution in this country, was compared with that provided by St. Thomas solution or oxygenated St. Thomas solution. Eighteen isolated heart-lung preparations of dogs were made and their hearts were subjected to 3 hours cold (4 degrees C) cardioplegic arrest. GIK group hearts (n = 6) received 20 ml/kg of GIK solution at the time of aortic cross-clamp perfused through the aortic root and were subsequently given 10 ml/kg of GIK solution every 30 minutes. St. Thomas group hearts (n = 6) and oxygenated St. Thomas group hearts (n = 6) were treated identically except that cardioplegic solution were St. Thomas solution or fully oxygenated one. Four hearts of GIK group showed ventricular fibrillation immediately after reperfusion that required DC countershock. Temporary A-V block was recognized in two hearts. In the other two groups, however, neither ventricular fibrillation nor A-V block was found. Heart rate, coronary flow, aortic flow and LVSW were measured before arrest and after 60 minutes of reperfusion (mean aortic pressure 70 mmHg, left atrial pressure 4 mmHg). Post reperfusion % recovery rates (post-reperfusion/before arrest) of heart rate, coronary flow, aortic flow and LVSW (mean value +/- standard deviation) were 93.4 +/- 10.32%, 104.6 +/- 24.91%, 18.8 +/- 8.54%, 32.6 +/- 6.12% respectively for GIK group, 81.4 +/- 6.50%, 125.9 +/- 15.23%, 35.4 +/- 9.91%, 56.3 +/- 12.90% for St. Thomas group and 83.1 +/- 8.40%, 121.6 +/- 16.92%, 47.0 +/- 7.89%, 69.1 +/- 9.71% for oxygenated St. Thomas group. St. Thomas and oxygenated St. Thomas groups revealed significantly (p less than 0.05, p less than 0.01 respectively) more excellent functional preservation than GIK group. Intramyocardial pH was also measured by use of glass needle pH electrode punctured into the anterior interventricular septum. Preischemic intramyocardial pH (at 37 degrees C) was 7.49 +/- 0.106 in GIK group, 7.48 +/- 0.113 in St. Thomas group and 7.43 +/- 0.114 in oxygenated St. Thomas group. During 3 hours of cardioplegic arrest, intramyocardial pH (at 4 degrees C) decreased to 6.84 +/- 0.101 in GIK group, 7.03 +/- 0.088 in St. Thomas group and 7.23 +/- 0.239 in oxygenated St. Thomas group, which was significantly higher than GIK group (p less than 0.01). Therefore oxygenated St. Thomas solution was found to maintain more favorable energy supply to ischemic myocardium. These results clearly evidenced that St. Thomas and oxygenated St. Thomas solutions would provide more effective myocardial protection during ischemic arrest than GIK solution.     

Enhancement of beta-adrenoceptor function after reperfusion following cardioplegic arrest in rat hearts.

We investigated alterations in a beta-adrenoceptor (BAR) system after reperfusion following hypothermic ischemia induced by a high-potassium (18 meq/liter) cardioplegic solution in isolated rat hearts. Materials were divided into two groups: the reperfusion group (Gr-R, n = 5) with 40 min reperfusion following 40 min cardioplegic arrest (10 degrees C) and the control group (Gr-C, n = 5) with no ischemia as time-matched perfused control. BAR and adenylate cyclase activities in crude membrane fractions were compared. Results showed that basal, NaF-, and forskolin-stimulated adenylate cyclase activity did not differ between the two groups. The maximal enzyme activity in the presence of 10(-4) M (-)-isoproterenol was higher in Gr-R than in Gr-C, while the net activity stimulated by (-)-isoproterenol was 74% higher in Gr-R than in Gr-C. The [125I]Iodocyanopindolol [( 125I]CYP) binding assay showed that BAR density was 14% higher in Gr-R than in Gr-C, while the affinity was not significantly different. The IC50 values of (-)-isoproterenol for [125I]CYP binding were lower in Gr-R than in Gr-C and the proportion of high-affinity binding sites was higher in Gr-R than in Gr-C. These data showed that 40 min reperfusion following hypothermic cardioplegic arrest (40 min) resulted in significant increases in myocardial BAR density and maximal (-)-isoproterenol-stimulated adenylate cyclase activity, and enhancement of BAR affinity for beta-adrenergic agonists due to the increase in the proportion of high-affinity binding sites.     

Developments in cardioprotection: "polarized" arrest as an alternative to "depolarized" arrest

During cardiac surgery or cardiac transplantation, the heart is subjected to varying periods of global ischemia. The heart must be protected during this ischemic period to avoid additional injury, and techniques have been developed that delay ischemic injury and minimize reperfusion injury. Almost universally, this involves using a hyperkalemic cardioplegic solution and these solutions have become the gold standard for myocardial protection for more than 20 years. Despite the extensive and continued research aimed at improving these basic hyperkalemic cardioplegic solutions, patients undergoing surgery almost invariably experience some degree of postoperative dysfunction. It is likely that this relates to the depolarizing nature of hyperkalemic solutions, which results in ionic imbalance caused by continuing transmembrane fluxes and the consequent maintenance of high energy phosphate metabolism, even during hypothermic ischemia. A potentially beneficial alternative to hyperkalemic cardioplegia is to arrest the heart in a "hyperpolarized" or "polarized" state, which maintains the membrane potential of the arrested myocardium at or near to the resting membrane potential. At these potentials, transmembrane fluxes will be minimized and there should be little metabolic demand, resulting in improved myocardial protection. Recent studies have explored these alternative concepts for myocardial protection. The use of compounds such as adenosine or potassium channel openers, which are thought to induce hyperpolarized arrest, have demonstrated improved protection after normothermic, or short periods of hypothermic, ischemia when compared to hyperkalemic (depolarized) arrest. Similarly, studies from our own laboratory, in which the sodium channel blocker, tetrodotoxin, was used to induce polarized arrest (demonstrated by direct measurement of membrane potential during ischemia) was also shown to provide better recovery of function after 5 hours of long-term hypothermic (7.5 degrees C) storage. These promising initial studies need to be consolidated before experimental promise becomes clinical reality.     

Protective effect of an asanguineous reperfusion solution on myocardial performance following cardioplegic arrest

This study assesses whether an appropriately designed asanguineous initial reperfusate effectively reduces the reperfusion injury following prolonged global ischemia and improves the recovery of cardiac performance after cardioplegic arrest. Forty-eight isolated perfused working rat hearts underwent two hours of hypothermic (15 degrees to 18 degrees C) ischemic arrest followed by 30 minutes of normothermic reperfusion. During ischemic injury, multidose cardioplegia was delivered at 30-minute intervals. The reperfusion solution under study was infused during the last 3 minutes of ischemia, just prior to release of the aortic clamp. The usual hemodynamic variables of this preparation (heart rate, aortic pressure, aortic flow, coronary flow, and stroke volume) were serially recorded and expressed as percent of recovery of control values. The influence of the concentration of Ca2+, pH, and buffer was more specifically investigated. A reperfusate containing 1 mM of Ca2+ was found to result in higher postischemic hemodynamic values than a Ca2+-poor (0.25 mM) reperfusate. The best functional recovery was provided by an alkalotic (pH 7.70 at 28 degrees C), glutamate-enriched initial reperfusate, which, by 30 minutes of reperfusion, yielded a 93.5 +/- 2.3% recovery of aortic flow versus 83.6 +/- 1.8% in the control group receiving unmodified reperfusion (p less than 0.01). We conclude that an appropriate composition of the initial reperfusate can improve the recovery of cardiac function significantly following two hours of cardioplegic arrest and that such an improvement can be achieved by an asanguineous reperfusate provided its composition is properly designed with respect to electrolytes, pH, and substrates.     

Superior 12-hour heart preservation with pinacidil hyperpolarizing solution compared to University of Wisconsin solution.

BACKGROUND: novel donor heart preservation solution was formulated to produce hyperpolarized arrest with the potassium channel opener, pinacidil. The superior cardioprotective efficacy of this solution has been demonstrated previously when compared to University of Wisconsin solution following 4 hours of hypothermic ischemia. This study tested the hypothesis that pinacidil solution may extend preservation time and provide superior cardioprotective efficacy following 12 hours of ischemia. METHODS: Sixteen rabbit hearts were assigned to receive either pinacidil solution or University of Wisconsin solution in a crystalloid-perfused Langendorff model. Thirty minutes of initial perfusion preceded baseline data acquisition. Left ventricle pressure-volume curves were generated by inflating an intra-ventricular latex balloon. Following cardioplegic administration, hearts underwent 12 hours of hypothermic storage. After 60 minutes of reperfusion, post-ischemic data were acquired. RESULTS: Pinacidil solution demonstrated significantly better myocardial preservation compared to University of Wisconsin solution, with better recovery of developed pressure (53.0 +/- 11.1% vs 20.7 +/- 4.3%, p = 0.017, respectively), post-ischemic coronary flow (55.3 +/- 12.6% vs 23.9 +/- 4.3%, p = 0.034), maximum systolic dP/dT (46.4 +/- 8.3% vs 20.2 +/- 5.1%, p = 0.018) and minimum diastolic -dP/dT (65.3 +/- 10.8% vs 20.2 +/- 5.1%, p = 0.002). Diastolic compliance, expressed as baseline/post-ischemic diastolic slope ratios, was also better preserved by pinacidil solution (0.55 +/- 0.09) vs University of Wisconsin solution (0.40 +/- 0.03) (p = 0.135). CONCLUSIONS: A novel pinacidil solution resulted in improved donor heart preservation during 12 hours of hypothermic ischemia compared to the "gold standard," University of Wisconsin solution. Adopting alternative strategies of hyperpolarized arrest may allow extension of preservation time beyond the limits of traditional depolarizing solutions.     

Myocardial blood flow and oxygen consumption after aortic cross-clamping

The effect of four repetitive periods of 10 min global ischemia, followed by 15 min of reperfusion on myocardial blood flow and oxygen consumption at 34 degrees C (group N) and 25 degrees C (group H) were studied in comparison with that of 60 min continuous ischemia combined with multidose St. Thomas Cardioplegia (group C) in dogs on cardiopulmonary bypass (CPB). Two groups, in which a protocol comparable to the groups N and H, respectively, but without repetitive periods of ischemia was followed, served as control. In all groups a hyperemic response was observed after release of aortic cross-clamping (AC). Myocardial blood flow was not diminished at the end of CPB as compared to the values at the start of CPB. We conclude that the no-reflow phenomenon did not occur after these procedures of intermittent or continuous AC. Immediately following release of AC the arterial-coronary sinus difference of oxygen content reached a peak value in groups N and H indicating rapid replenishment of the low tissue oxygen content. These peak values appeared to be much smaller after cardioplegia. After 10 min of reperfusion a significant lower oxygen consumption was observed at 25 degrees C (0.2 mumole.g-1.min-1 O2) as compared to 34 degrees C (1.5 mumole.g-1.min-1 O2). This difference cannot be explained by temperature alone because oxygen consumption did not decrease below 0.5 mumole.g-1.min-1 in the control group of dogs put on CPB at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)