Alemany Victor S, Nomoto Rio, Saeed Mossab Y, Celik Aybuke, Regan William L, Matte Gregory S, Recco Dominic P, Emani Sitaram M, Del Nido Pedro J, McCully James D
Department of Cardiac Surgery, Boston Children's Hospital, Boston, Mass.
Department of Cardiac Surgery, Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
J Thorac Cardiovasc Surg. 2024 Jan;167(1):e6-e21. doi: 10.1016/j.jtcvs.2023.05.010. Epub 2023 May 20.
Mitochondrial transplantation has been shown to preserve myocardial function and viability in adult porcine hearts donated after circulatory death (DCD) . Herein, we investigate the efficacy of mitochondrial transplantation for the preservation of myocardial function and viability in neonatal and pediatric porcine DCD heart donation.
Circulatory death was induced in neonatal and pediatric Yorkshire pigs by cessation of mechanical ventilation. Hearts underwent 20 or 36 minutes of warm ischemia time (WIT), 10 minutes of cold cardioplegic arrest, and then were harvested for ex situ heart perfusion (ESHP). Following 15 minutes of ESHP, hearts received either vehicle (VEH) or vehicle containing isolated autologous mitochondria (MITO). A sham nonischemic group (SHAM) did not undergo WIT, mimicking donation after brain death heart procurement. Hearts underwent 2 hours each of unloaded and loaded ESHP perfusion.
Following 4 hours of ESHP perfusion, left ventricle developed pressure, dP/dt max, and fractional shortening were significantly decreased (P < .001) in DCD hearts receiving VEH compared with SHAM hearts. In contrast, DCD hearts receiving MITO exhibited significantly preserved left ventricle developed pressure, dP/dt max, and fractional shortening (P < .001 each vs VEH, not significant vs SHAM). Infarct size was significantly decreased in DCD hearts receiving MITO as compared with VEH (P < .001). Pediatric DCD hearts subjected to extended WIT demonstrated significantly preserved fractional shortening and significantly decreased infarct size with MITO (P < .01 each vs VEH).
Mitochondrial transplantation in neonatal and pediatric pig DCD heart donation significantly enhances the preservation of myocardial function and viability and mitigates against damage secondary to extended WIT.
线粒体移植已被证明可在成年猪心脏循环死亡(DCD)后捐献时维持心肌功能和活力。在此,我们研究线粒体移植在新生儿和小儿猪DCD心脏捐献中维持心肌功能和活力的效果。
通过停止机械通气诱导新生和小儿约克夏猪循环死亡。心脏经历20或36分钟的热缺血时间(WIT)、10分钟的冷停搏,然后取出进行离体心脏灌注(ESHP)。ESHP 15分钟后,心脏接受载体(VEH)或含分离自体线粒体的载体(MITO)。假手术非缺血组(SHAM)未经历WIT,模拟脑死亡后心脏获取的捐献情况。心脏分别进行2小时的无负荷和有负荷ESHP灌注。
ESHP灌注4小时后,与SHAM心脏相比,接受VEH的DCD心脏左心室舒张末压、dP/dt max和缩短分数显著降低(P <.001)。相比之下,接受MITO的DCD心脏左心室舒张末压、dP/dt max和缩短分数显著维持(与VEH相比,每项P <.001,与SHAM相比无显著差异)。与VEH相比,接受MITO的DCD心脏梗死面积显著减小(P <.001)。经历延长WIT的小儿DCD心脏,使用MITO后缩短分数显著维持,梗死面积显著减小(与VEH相比,每项P <.01)。
新生儿和小儿猪DCD心脏捐献中的线粒体移植显著增强了心肌功能和活力的维持,并减轻了延长WIT继发的损伤。