Kirsch M, Baufreton C, Fernandez C, Brunet S, Pasteau F, Astier A, Loisance D Y
Centre de Recherches Chirurgicales Henri Mondor, and Pharmacie Centrale, Hôpital Henri Mondor, Créteil, France.
Ann Thorac Surg. 1998 Aug;66(2):417-24. doi: 10.1016/s0003-4975(98)00357-9.
Myocardial preservation for heart transplantation relies on hyperkalemic cardiac arrest and hypothermic storage. Our study investigated whether pretreatment with a potassium-channel opener (cromakalim) before prolonged storage in an extracellular fluid improves left ventricular recovery.
Rabbit hearts were submitted to 6-hours' cold storage and assessed on a blood-perfused isolated heart preparation. Hemodynamic recovery, enzyme release (creatine kinase and lactate dehydrogenase), and adenine nucleotide content were determined. Five groups were tested: control (n=6), no ischemia; UW group (n=7), hearts arrested with and stored in University of Wisconsin solution; STH group (n=5), hearts arrested with and stored in St. Thomas' Hospital solution; cromakalim group (n=6), hearts pretreated with cromakalim (30 microg/kg) before arrest with and storage in St. Thomas' Hospital solution; and glibenclamide group (n=5), hearts pretreated with cromakalim followed by glibenclamide (a potassium-channel blocker) before arrest with and storage in St. Thomas' Hospital solution.
Hemodynamic recovery was improved and enzyme release was lower in the UW group than in the STH group. Compared with the STH group, the group pretreated with cromakalim had significantly decreased left ventricular end-diastolic pressures, increased left ventricular developed pressures, increased maximal values of positive and negative rates of rise of left ventricular pressure, and increased time constant of isovolumetric relaxation. Hemodynamic recovery was similar in the UW group and cromakalim groups. Glibenclamide did not abolish the effects of cromakalim. None of the protocols affected myocardial energy stores.
Pretreatment with cromakalim affords additional protection to that provided by cardioplegic arrest and prolonged cold storage using an extracellular solution. The intracellular mechanisms involved remain to be determined.
心脏移植中的心肌保护依赖于高钾性心脏停搏和低温保存。我们的研究调查了在细胞外液中长时间保存前用钾通道开放剂（克罗卡林）预处理是否能改善左心室恢复情况。
将兔心脏进行6小时冷保存，并在血液灌注的离体心脏标本上进行评估。测定血流动力学恢复情况、酶释放（肌酸激酶和乳酸脱氢酶）以及腺嘌呤核苷酸含量。测试了五组：对照组（n = 6），无缺血；UW组（n = 7），心脏用威斯康星大学溶液停搏并保存；STH组（n = 5），心脏用圣托马斯医院溶液停搏并保存；克罗卡林组（n = 6）�心脏在停搏并用圣托马斯医院溶液保存前用克罗卡林（30微克/千克）预处理；格列本脲组（n = 5），心脏在停搏并用圣托马斯医院溶液保存前先用克罗卡林预处理，然后用格列本脲（一种钾通道阻滞剂）处理。
UW组的血流动力学恢复情况改善，酶释放低于STH组。与STH组相比，用克罗卡林预处理的组左心室舒张末期压力显著降低，左心室发育压力增加，左心室压力上升和下降的最大速率值增加，等容舒张时间常数增加。UW组和克罗卡林组的血流动力学恢复情况相似。格列本脲并未消除克罗卡林的作用。所有方案均未影响心肌能量储备。
用克罗卡林预处理为心脏停搏和使用细胞外溶液进行长时间冷保存提供了额外的保护。其中涉及的细胞内机制仍有待确定。
