Heart Research Laboratory, Department of Physiology and Pharmacology, James Cook University, Townsville, Queensland, Australia.
J Thorac Cardiovasc Surg. 2011 Dec;142(6):1552-61. doi: 10.1016/j.jtcvs.2011.05.023. Epub 2011 Jul 13.
Most cardiac preservation solutions provide safe cold ischemic storage times for 4 to 5 hours. Our aim was to investigate the effects of 8 hours of cold static storage (4°C) using 2 normokalemic, polarizing adenosine-lidocaine (Adenocaine; Hibernation Therapeutics Global Ltd, Kilquade, Ireland) solutions and to compare their functional recovery with hearts preserved in gold standard histidine-tryptophan-ketoglutarate (Custodiol-HTK; Essential Pharma, Newtown, Pa) and Celsior (Genzyme, Cambridge, Mass) solutions.
Male Sprague-Dawley rats (350-450 g) were randomly assigned to 1 of 4 groups (n = 8): (1) adenosine-lidocaine cardioplegia with low Ca(2+)/high Mg(2+); (2) 2× adenosine-lidocaine cardioplegia, low Ca(2+)/high Mg(2+), melatonin, and insulin (2× adenosine, lidocaine, melatonin, and insulin); (3) histidine-tryptophan-ketoglutarate solution; or (4) Celsior. Hearts were perfused in working mode, arrested (37°C), removed, stored for 8 hours at 4°C, reattached in Langendorff mode and rewarmed for 5 minutes (37°C), and switched to working mode for 60 minutes. Myocardial oxygen consumption, effluent lactates, and troponin T levels were measured.
Hearts preserved for 8 hours in adenosine-lidocaine and 2× adenosine, lidocaine, melatonin, and insulin returned 50% and 76% of aortic flow and 70% and 86% of coronary flow, respectively, at 60 minutes of reperfusion. In contrast, Custodiol-HTK and Celsior hearts returned 2% and 17% of aortic flow and 11% and 48% of coronary flow, respectively, at 60 minutes of reperfusion. Hearts preserved in adenosine-lidocaine and 2× adenosine, lidocaine, melatonin, and insulin returned 90% and 100% of developed pressures and 101% and 104% of heart rate, respectively. Hearts preserved in histidine-tryptophan-ketoglutarate failed to increase systolic pressure greater than 14 mm Hg (11% baseline) and diastolic pressure greater than 10 mm Hg (17% baseline), and recovered only 16% of heart rate. Hearts preserved in Celsior developed 70% of baseline systolic pressures and 86% recovery of heart rate. At 5 minutes of rewarming after cold storage, the myocardial oxygen consumption for hearts preserved in adenosine-lidocaine, 2× adenosine, lidocaine, melatonin, and insulin, Custodiol-HTK, and Celsior was 23.0 ± 5, 20 ± 4, 15 ± 1, and 10 ± 2 μmol O(2)/min/g dry wt, respectively, with corresponding lactate outputs of 1.8 ± 0.8, 1.5 ± 0.7, 2.6 ± 0.7, and 3.2 ± 1.4 μmol lactate/min/g dry weight. Troponin T was not detected in the coronary effluent of adenosine-lidocaine or 2× adenosine, lidocaine, melatonin, and insulin hearts, whereas Custodiol-HTK and Celsior hearts had troponin T levels of 0.08 and 0.24 μg/mL, respectively.
We report a 78% return of cardiac output, 90% to 100% return of developed pressures, and 101% to 104% return of heart rate after 8 hours of cold static storage using normokalemic, adenosine, lidocaine, melatonin, and insulin preservation solution in the isolated rat heart compared with 55% cardiac output with polarizing adenosine-lidocaine cardioplegia alone, 4% cardiac output with Custodiol-HTK, and 25% cardiac output in Celsior preservation solutions.
大多数心脏保存液在 4 至 5 小时的冷缺血保存时间内提供安全保障。我们的目的是研究使用 2 种低钾、极化的腺苷-利多卡因（Adenocaine；Hibernation Therapeutics Global Ltd，Kilquade，爱尔兰）溶液进行 8 小时冷静态保存（4°C）的效果，并将其与使用金标准组氨酸-色氨酸-酮戊二酸（Custodiol-HTK；Essential Pharma，Newtown，Pa）和 Celsior（Genzyme，Cambridge，Mass）溶液保存的心脏进行比较，观察其功能恢复情况。
雄性 Sprague-Dawley 大鼠（350-450g）随机分为 4 组（n=8）：（1）低钾/高镁（2）2×腺苷-利多卡因心脏停搏液，低钾/高镁，褪黑素，胰岛素（2×腺苷、利多卡因、褪黑素、胰岛素）；（3）组氨酸-色氨酸-酮戊二酸溶液；或（4）Celsior。心脏在工作模式下灌注，停搏（37°C），取出，在 4°C 下保存 8 小时，重新连接在 Langendorff 模式下复温 5 分钟（37°C），然后切换到工作模式 60 分钟。测量心肌耗氧量、流出液中乳酸盐水平和肌钙蛋白 T 水平。
在 8 小时的腺苷-利多卡因和 2×腺苷、利多卡因、褪黑素和胰岛素保存液中保存的心脏，在再灌注 60 分钟时，主动脉流量分别恢复了 50%和 76%，冠状动脉流量分别恢复了 70%和 86%。相比之下，Custodiol-HTK 和 Celsior 心脏在再灌注 60 分钟时，主动脉流量分别恢复了 2%和 17%，冠状动脉流量分别恢复了 11%和 48%。在 8 小时的腺苷-利多卡因和 2×腺苷、利多卡因、褪黑素和胰岛素保存液中保存的心脏，收缩压和心率分别恢复到 90%和 100%。在组氨酸-色氨酸-酮戊二酸保存液中保存的心脏，收缩压大于 14mmHg（11%基础值）和舒张压大于 10mmHg（17%基础值）的情况未超过 14mmHg，且心率仅恢复 16%。在 Celsior 保存液中保存的心脏，收缩压恢复到基础值的 70%，心率恢复到 86%。在冷保存后 5 分钟复温时，腺苷-利多卡因、2×腺苷、利多卡因、褪黑素和胰岛素、Custodiol-HTK 和 Celsior 保存液保存的心脏的心肌耗氧量分别为 23.0±5、20±4、15±1 和 10±2μmol O(2)/min/g 干重，相应的乳酸盐输出量分别为 1.8±0.8、1.5±0.7、2.6±0.7 和 3.2±1.4μmol 乳酸盐/min/g 干重。在冠状流出液中未检测到腺苷-利多卡因或 2×腺苷、利多卡因、褪黑素和胰岛素心脏的肌钙蛋白 T，而 Custodiol-HTK 和 Celsior 心脏的肌钙蛋白 T 水平分别为 0.08 和 0.24μg/mL。
与单独使用极化的腺苷-利多卡因心脏停搏液（55%心输出量）、Custodiol-HTK（4%心输出量）和 Celsior 保存液（25%心输出量）相比，我们在分离的大鼠心脏中使用低钾、腺苷、利多卡因、褪黑素和胰岛素保存液进行 8 小时冷静态保存后，观察到心输出量恢复 78%，收缩压和心率恢复 90%至 100%。
