Protective Effects of Hyperpolarizing Cardioplegia with Pinacidil on Myocardium in Rats

Whether the ATP-sensitive potassium channel opener pinacidil can provide myocardial protective effects in prolonged isolated global ischemic rat heart was investigated. On modified isolated rat working heart model, 40 hearts were divided into four groups randomly: Hyperpolarized arrest H-K solution containing pinacidil (50 tmol/L) (P1 and P2) and depolarized arrest St. Thomas‘ solution (S1 and S2) subjected to 15 C hypothermia, 60 min (P1 and S1) or 120 min (P1 and S2) of ischemia and 30 min reperfusion. The experimental indices included cardioplegic efficiency, cardiac function, coronary blood flow, myocardial enzyme release, myocardial water and ATP content. Hyperpolarized arrest provided significantly better recovery of cardiac function than depolarized arrest.Postischemic coronary flow and myocardial ATP content were higher. The arrest time of electro-mechanical activities were longer than depolarized arrest. There were no differences among the groups in myocardial water contents. The hyperpolarized arrest solution containing pinacidil can provide a marked myocardial protective effect during prolonged hypothermic myocardial ischemia.     

Closed-Chest Cardiopulmonary Bypass and Cardioplegia: Basis for Less Invasive Cardiac Surgery

Background. We developed a method of closed-chest cardiopulmonary bypass to arrest and protect the heart with cardioplegic solution. This method was used in 54 dogs and the results were retrospectively analyzed.

Methods. Bypass cannulas were placed in the right femoral vessels. A balloon occlusion catheter was passed via the left femoral artery and positioned in the ascending aorta. A pulmonary artery vent was placed via the jugular vein. In 17 of the dogs retrograde cardioplegia was provided with a percutaneous coronary sinus catheter.

Results. Cardiopulmonary bypass time was 111 ± 27 minutes (mean ± standard deviation) and cardiac arrest time was 66 ± 21 minutes. Preoperative cardiac outputs were 2.9 ± 0.70 L/min and postoperative outputs were 2.9 ± 0.65 L/min (p = not significant). Twenty-one-French and 23F femoral arterial cannulas that allowed coaxial placement of the ascending aortic balloon catheter were tested in 3 male calves. Line pressures were higher, but not clinically limiting, with the balloon catheter placed coaxially.

Conclusions. Adequate cardiopulmonary bypass and cardioplegia can be achieved in the dog without opening the chest, facilitating less invasive cardiac operations. A human clinical trial is in progress.     

温血诱导及终未再灌注对未成熟心肌保护的实验研究

为研究温血停搏液（谷氨酸加天门冬氨酸强化）诱导停跳和主动脉开放前再灌注的未成熟心肌保护的效果。用12只新西兰幼免（3～4周），体重450～550g，随机分成2组：冷血停搏液（谷氨酸加天门冬氨酸强化）组（Ⅰ组，n＝6）；温血停搏浪诱导及再灌注血组（Ⅱ组，n＝6）。结果：1．心功能；CO±dp0／dt恢复百分率Ⅱ组明显优于Ⅰ组（P＜0．01）；LVSP恢复百分率Ⅱ组优于Ⅰ组（P＜0．05）。2．LDH和CK漏出量（U／l）Ⅱ组明显优于Ⅰ组（P＜0．01）；3。心肌含水量（％）Ⅱ组优于Ⅰ组（P＜0．01）；4．心肌结构保护Ⅱ组明显优于Ⅰ组。本实验提示：温血诱导停跳与主动脉开放前温血再灌注对于未成熟心肌有良好的心肌保护效果。     

Cardioprotective Effect of Succinate Against Ischemia/Reperfusion Injury

(Received for publication on Sept. 12, 1996; accepted on May 12, 1997)     

Effects of calcium in continuous cardioplegia on myocardial protection

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca(0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37°C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1±2.9%, 80.6±2.0%, and 71.5±3.7% (mean±SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.     

缺血预处理结合心麻痹液保护未成熟兔心肌的效果

目的 探讨缺血预处理（IPC）结合心麻痹液对未成熟兔心肌的保护作用。方法 采用体外左心作功模型,比较缺血5min再灌注5min的缺血预处处理加ST.ThomasⅡ液（IPC组）和仅ST,ThomasⅡ液（对照组）对幼兔（3-4周）心脏缺血再灌注后心脏功能,冠脉微循环、能量代谢及超微结构的影响。结果 IPC组心脏收缩功能、冠脉流量及阻力恢复更佳,冠脉流出液中的一氧化氮含量较高而内皮素较低,能量物质含量高,心肌细胞超微结构的影响。结果 IPC组心脏收缩功能、冠脉流量及阻力恢复更佳,冠脉流出液中后 氧化氮含量较高而内皮素较低,能量物质含量高。心肌细胞超微结构损害轻,结论 缺血预处理结合心麻痹液对未成熟兔心肌提供更佳的保护。     

Prevention of postischemic reperfusion injury: The improvement of myocardial tissue blood flow after ischemia by terminal Nicorandil-Mg cardioplegia

We evaluated the preventive effect of postischemic reperfusion injury by Nicorandil-Mg cardioplegia given just prior to reperfusion as terminal cardioplegia. Twenty seven dogs were placed on cardiopulmonary bypass and the aorta was cross-clamped for 90 min under hypothermic (17–19°C) cardioplegic arrest. The canine hearts were divided into three groups: in group A (n=10) the hearts were reperfused without any treatment; in group B (n=9) the hearts received coronary perfusion with Nicorandil-Mg solution (Nic, 8 mg/l; Mg, 20 mEq/l; glucose, 50 g/l) for 2 min just prior to reperfusion; and in group C (n=8) the hearts received coronary perfusion with Nicorandil-Mg free solution (glucose, 50g/l). During and after ischemia, the myocardial tissue PCO₂ (t-PCO₂) was continuously monitored by an ion-sensitive field effective transistor (ISFET) sensor. In addition, the myocardial tissue blood flow (TBF), oxygen consumption, and lactate flux were then calculated at 5, 10, 20, and 40 min of reperfusion. In the initial reperfusion period, Group B showed an improved TBF compared to group A and C (at 5 min, group B was 42.7±11.9; group A was 29.4±11.2, P<0.025; and group C was 33.9±9.2% of the preischemic control level, P<0.05). T-PCO₂ in group B was significantly decreased at 5 min of reperfusion (group B, 127.5±22.5 42.5±9.7; group A, 117.5±23.0 85.2±17.4, P<0.001; group C, 122.3 mmHg 68.2±18.7 mmHg, P<0.01), and group B had a better metabolic recovery. These results suggest that terminal Nicorandil-Mg cardioplegia might reduce the rate of postischemic reperfusion injury.     

常温氧合血性心停搏液持续灌注心肌保护效应的实验研究

目的　采用随机对比的实验研究方法从测定心肌酶学、氧自由基代谢产物及心肌特异性蛋白几个方面来探讨冷晶体心停搏液间断灌注及常温氧合血性心停搏液连续灌注两种灌注方法的心肌保护效应。方法１４只犬随机分为①对照组：冷晶体心停搏液间断灌注;②实验组：常温氧合血性心停搏液连续灌注。采集不同时点的犬冠状静脉窦血为测定标本,测定心肌特异性酶ＣＫ－ＭＢ、心肌特异性钙蛋白Ｔ（ｃＴｎ－Ｔ）,氧自由基代谢产物丙二醛（ＭＤＡ）。结果对照组在主动脉开放后,ＣＫ－ＭＢ、ＭＤＡ、ｃＴｎ－Ｔ明显升高,实验组升高幅度较小。两组间比较有显著差异（Ｐ＜０．０１）。结论常温氧合血性心停搏液连续灌注,可以充分保证心肌在常温停跳期间的血供和氧供,避免了心肌缺血缺氧,明显地减轻了心肌缺血再灌注损伤,是一种非缺血性、比较理想的心肌保护方法。     

心脏停搏液pH值对大鼠未成熟心肌的影响

目的　探讨心脏停搏液 p H值对离体未成熟大鼠心肌的影响 .方法　采用 SD幼鼠 (18～ 2 1d)离体工作心模型 ,14℃低温缺血 12 0 min,缺血前分别以 p H为 6 .40 ,7.0 0 ,7.2 5 ,7.40 ,7.80和 8.2 0的 St.Thomas' 液单次灌注 ,观察记录缺血前后心功能的变化及心肌 CPK漏出量 .结果　1缺血再灌注 30 m in后主动脉流量恢复百分比依次为 (6 2±5 ) % ,(72± 4) % ,(83± 4) % ,(78± 3) % ,(70± 3) %和 (5 8±4) % ,以 p H 7.2 5组保护效果最好 .2心肌 CPK漏出量各组间无显著差异 .结论　 p H值为 7.2 5的弱酸性心脏停搏液对大鼠未成熟心肌可提供良好的保护作用 ,同时大鼠未成熟心肌可耐受较大范围的 p H变化 .