Aass Terje, Stangeland Lodve, Moen Christian Arvei, Salminen Pirjo-Riitta, Dahle Geir Olav, Chambers David J, Markou Thomais, Eliassen Finn, Urban Malte, Haaverstad Rune, Matre Knut, Grong Ketil
Department of Heart Disease, Haukeland University Hospital, Bergen, Norway Faculty of Medicine and Dentistry, Department of Clinical Science, University of Bergen, Bergen, Norway
Faculty of Medicine and Dentistry, Department of Clinical Science, University of Bergen, Bergen, Norway.
Eur J Cardiothorac Surg. 2016 Jul;50(1):130-9. doi: 10.1093/ejcts/ezv488. Epub 2016 Feb 2.
Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable myocardial protection in a clinically relevant animal model.
Twenty anaesthetized young pigs, 42 ± 2 (standard deviation) kg on standardized tepid cardiopulmonary bypass (CPB) were randomized (10 per group) to depolarizing or polarizing cardiac arrest for 60 min with cardioplegia administered in the aortic root every 20 min as freshly mixed cold, intermittent, oxygenated blood. Global and local baseline and postoperative cardiac function 60, 120 and 180 min after myocardial reperfusion was evaluated with pressure-conductance catheter and strain by Tissue Doppler Imaging. Regional tissue blood flow, cleaved caspase-3 activity, GRK2 phosphorylation and mitochondrial function and ultrastructure were evaluated in myocardial tissue samples.
Left ventricular function and general haemodynamics did not differ between groups before CPB. Cardiac asystole was obtained and maintained during aortic cross-clamping. Compared with baseline, heart rate was increased and left ventricular end-systolic and end-diastolic pressures decreased in both groups after weaning. Cardiac index, systolic pressure and radial peak systolic strain did not differ between groups. Contractility, evaluated as dP/dtmax, gradually increased from 120 to 180 min after declamping in animals with polarizing cardioplegia and was significantly higher, 1871 ± 160 (standard error) mmHg/s, compared with standard potassium-based cardioplegic arrest, 1351 ± 70 mmHg/s, after 180 min of reperfusion (P = 0.008). Radial peak ejection strain rate increased and the load-independent variable preload recruitable stroke work was increased with polarizing cardioplegia after 180 min, 64 ± 3 vs 54 ± 2 mmHg (P = 0.018), indicating better preserved left ventricular contractility with polarizing cardioplegia. Phosphorylation of GRK2 in myocardial tissue did not differ between groups. Fractional cytoplasmic volume in myocytes was reduced in hearts arrested with polarizing cardioplegia, indicating reduction of cytoplasmic oedema.
Polarizing oxygenated blood cardioplegia with esmolol/adenosine/magnesium offers comparable myocardial protection and improves contractility compared with the standard potassium-based depolarizing blood cardioplegia.
以间歇性含氧量充足的血液给予基于钾的去极化圣托马斯医院心脏停搏液2号,被认为是心脏手术中心肌保护的金标准。然而,极化停搏的替代概念可能具有有益的保护作用。我们假设在冷的、间歇性含氧量充足的血液中使用艾司洛尔/腺苷/镁(圣托马斯医院极化心脏停搏液)进行极化停搏,在临床相关动物模型中能提供相当的心肌保护。
20只麻醉的幼猪,体重42±2(标准差)千克,在标准化的温热体外循环(CPB)下,随机(每组10只)分为去极化或极化心脏停搏组60分钟,每20分钟经主动脉根部给予心脏停搏液,作为新鲜混合的冷的、间歇性含氧量充足的血液。在心肌再灌注后60、120和180分钟,使用压力-电导导管和组织多普勒成像应变评估整体和局部基线及术后心脏功能。评估心肌组织样本中的局部组织血流、裂解的半胱天冬酶-3活性、GRK2磷酸化以及线粒体功能和超微结构。
CPB前两组的左心室功能和一般血流动力学无差异。在主动脉交叉阻断期间实现并维持心脏停搏。与基线相比,两组在脱离CPB后心率增加,左心室收缩末期和舒张末期压力降低。两组之间的心指数、收缩压和径向峰值收缩应变无差异。以dP/dtmax评估的收缩性,在极化心脏停搏的动物中,在松开夹闭后120至180分钟逐渐增加,与标准的基于钾的心脏停搏相比,再灌注180分钟后显著更高,为1871±160(标准误)mmHg/s对1351±70 mmHg/s(P = 0.008)。180分钟后,极化心脏停搏使径向峰值射血应变率增加,且与负荷无关的变量可招募前负荷搏功增加,为64±3对54±2 mmHg(P = 0.018),表明极化心脏停搏能更好地保留左心室收缩性。两组心肌组织中GRK2的磷酸化无差异。极化心脏停搏的心脏中,心肌细胞的细胞质分数体积减少,表明细胞质水肿减轻。
与标准的基于钾的去极化血液心脏停搏相比,使用艾司洛尔/腺苷/镁的极化含氧量充足的血液心脏停搏提供了相当的心肌保护并改善了收缩性。