Yu Frank, Ribeiro Roberto, Rosales Roizar, Hauck Ludger, Grothe Daniela, Alvarez Juglans, Adamson Mitchell, Rao Vivek, Badiwala Mitesh, Billia Filio
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
Division of Cardiovascular Surgery, Peter Munk Cardiac Center, Toronto Ontario, Canada.
JHLT Open. 2024 Feb 24;4:100074. doi: 10.1016/j.jhlto.2024.100074. eCollection 2024 May.
Ex situ heart perfusion (ESHP) has been used to optimize donor organs before heart transplantation. However, cardiac function often deteriorates with the development of myocardial edema. The use of dialysis during ESHP could assist in cardiac preservation.
Male Yorkshire pig hearts were subjected to ESHP for 8 hours with or without dialysis. Hearts were supported during nonworking mode and working mode, and pressure-volume loops and coronary vasomotor function were evaluated. Finally, tissue biopsies were assessed for mitochondrial function, oxidative stress, and inflammation.
Adding dialysis to ESHP significantly enhanced cardiac function, with improved preload recruitable stroke work at 4 hours (64.09 ± 20.13 vs 35.08 ± 13.52, = 0.010) and 8 hours (64.31 ± 9.08 vs 23.30 ± 19.25, = 0.0002), maximal elastance at 8 hours (24.67 ± 10.75 vs 10.62 ± 8.471, = 0.0477), and end diastolic pressure volume relationship at 8 hours (644.7 ± 566.68 vs 86.63 ± 72.05, = 0.0187). Coronary vasomotor function improved in the dialysis group in endothelium dependent (LogIC50 -7.39 ± 0.25 vs -2.22 ± 0.76, < 0.0001) and independent (LogIC50 -6.11 ± 0.19 vs -4.79 ± 0.11, < 0.0001) vasorelaxation. Dialyzed hearts also had reduced sensitivity to endothelin-1 (LogEC50 -7.94 ± 0.5 vs -8.54 ± 0.06, = 0.0449) and significant changes in endothelin receptor-related protein expression related and oxidative stress.
The combination of dialysis with ESHP improves myocardial and coronary vasomotor preservation and may allow for longer perfusion times.
心脏移植前,体外心脏灌注(ESHP)已被用于优化供体器官。然而,随着心肌水肿的发展,心脏功能常常恶化。ESHP期间使用透析有助于心脏保存。
对雄性约克夏猪心脏进行8小时的ESHP,分为有透析和无透析两组。在非工作模式和工作模式下对心脏进行支持,并评估压力-容积环和冠状血管舒缩功能。最后,对组织活检进行线粒体功能、氧化应激和炎症评估。
ESHP中加入透析显著增强了心脏功能,4小时时可招募的前负荷搏功改善(64.09±20.13对35.08±13.52,P = 0.010),8小时时改善(64.31±9.08对23.30±19.25,P = 0.0002),8小时时最大弹性(24.67±10.75对10.62±8.471,P = 0.0477),8小时时舒张末期压力-容积关系(644.7±566.68对86.63±72.05,P = 0.0187)。透析组冠状血管舒缩功能在内皮依赖性(LogIC50 -7.39±0.25对-2.22±0.76,P<0.0001)和非依赖性(LogIC50 -6.11±0.19对-4.79±0.11,P<0.0001)血管舒张方面均有改善。透析后的心脏对内皮素-1的敏感性也降低(LogEC50 -7.94±0.5对-8.54±0.06,P = 0.0449),且内皮素受体相关蛋白表达和氧化应激有显著变化。
透析与ESHP相结合可改善心肌和冠状血管舒缩功能的保存,并可能允许更长的灌注时间。