Department of Surgery, The University of Maryland School of Medicine, Baltimore, MD, United States.
Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Front Immunol. 2021 Jun 9;12:667093. doi: 10.3389/fimmu.2021.667093. eCollection 2021.
Perioperative cardiac xenograft dysfunction (PCXD) describes a rapidly developing loss of cardiac function after xenotransplantation. PCXD occurs despite genetic modifications to increase compatibility of the heart. We report on the incidence of PCXD using static preservation in ice slush following crystalloid or blood-based cardioplegia versus continuous cold perfusion with XVIVO heart solution (XHS) based cardioplegia.
Baboons were weight matched to genetically engineered swine heart donors. Cardioplegia volume was 30 cc/kg by donor weight, with del Nido cardioplegia and the addition of 25% by volume of donor whole blood. Continuous perfusion was performed using an XVIVO Perfusion system with XHS to which baboon RBCs were added.
PCXD was observed in 5/8 that were preserved with crystalloid cardioplegia followed by traditional cold, static storage on ice. By comparison, when blood cardioplegia was used followed by cold, static storage, PCXD occurred in 1/3 hearts and only in 1/5 hearts that were induced with XHS blood cardioplegia followed by continuous perfusion. Survival averaged 17 hours in those with traditional preservation and storage, followed by 11.47 days and 15.03 days using blood cardioplegia and XHS+continuous preservation, respectively. Traditional preservation resulted in more inotropic support and higher average peak serum lactate 14.3±1.7 mmol/L compared to blood cardioplegia 3.6±3.0 mmol/L and continuous perfusion 3.5±1.5 mmol/L.
Blood cardioplegia induction, alone or followed by XHS perfusion storage, reduced the incidence of PCXD and improved graft function and survival, relative to traditional crystalloid cardioplegia-slush storage alone.
围手术期心脏异种移植物功能障碍（PCXD）描述了异种移植后心脏功能迅速丧失。尽管进行了基因修饰以提高心脏的相容性，但仍会发生 PCXD。我们报告了使用晶体或基于血液的心脏停搏液进行冰渣静态保存与基于 XVIVO 心脏溶液（XHS）的连续冷灌注的心脏停搏液在 PCXD 发生率方面的差异。
狒狒与基因工程猪心脏供体进行体重匹配。心脏停搏液体积为供体体重的 30 cc/kg，使用 Del Nido 心脏停搏液并添加供体全血的 25%体积。使用 XVIVO 灌注系统进行连续灌注，向其中添加狒狒 RBC。
在使用晶体心脏停搏液进行预处理后，5/8 例使用传统冷静态储存于冰上的心脏发生了 PCXD。相比之下，当使用血液心脏停搏液进行预处理后，冷静态储存时，仅在 1/3 的心脏中观察到 PCXD，并且仅在 1/5 的心脏中观察到 XHS 血液心脏停搏液诱导后进行连续灌注。在传统保存和储存的情况下，平均存活时间为 17 小时，随后使用血液心脏停搏液和 XHS+连续保存的情况下，分别为 11.47 天和 15.03 天。传统保存导致更多的正性肌力支持，并且平均血清乳酸峰值为 14.3±1.7 mmol/L，明显高于血液心脏停搏液的 3.6±3.0 mmol/L 和连续灌注的 3.5±1.5 mmol/L。
与传统的晶体心脏停搏液-冰渣储存相比，单独使用血液心脏停搏液诱导或随后使用 XHS 灌注储存可降低 PCXD 的发生率，改善移植物功能和存活率。
