Andrijauskaite Kristina, Veraza Rafael J, Lopez Riley P, Maxwell Zach, Cano Isabella, Cisneros Exal E, Jessop Israel J, Basurto Maria, Lamberson George, Watt Michelle D, Nespral Joseph, Ono Masahiro, Bunegin Leonid
Vascular Perfusion Solutions, Inc., San Antonio, TX, United States.
Texas Organ Sharing Alliance (TOSA), San Antonio, TX, United States.
Front Cardiovasc Med. 2024 Apr 2;11:1376101. doi: 10.3389/fcvm.2024.1376101. eCollection 2024.
Heart transplant remains the gold standard treatment for patients with advanced heart failure. However, the list of patients waiting for a heart transplant continues to increase. We have developed a portable hypothermic oxygenated machine perfusion device, the VP.S ENCORE®, to extend the allowable preservation time. The purpose of this study was to test the efficacy of the VP.S. ENCORE® using deceased donors derived hearts.
Hearts from brain-dead donors not utilized for transplant ( = 11) were offered for research from the Texas Organ Sharing Alliance (TOSA), South and Central Texas' Organ Procurement Organization (OPO) and were preserved in the VP.S ENCORE® for 4 ( = 2), 6 ( = 3), and 8 ( = 3) hours or were kept in static cold storage (SCS) ( = 3). After preservation, the hearts were placed in an isolated heart Langendorff model for reperfusion and evaluated for cardiac function.
The mean donor age was 37.82 ± 12.67 with the youngest donor being 19 and the oldest donor being 58 years old. SCS hearts mean weight gain (%) was -1.4 ± 2.77, while perfused at 4 h was 5.6 ± 6.04, perfused at 6 h 2.1 ± 6.04, and 8 h was 7.2 ± 10.76. Venous and arterial lactate concentrations were less than 2.0 mmol/L across all perfused hearts. Left ventricular contractility (+dPdT, mmHg/s) for 4 h (1,214 ± 1,064), 6 (1,565 ± 141.3), and 8 h (1,331 ± 403.6) were within the range of healthy human heart function. Thus, not significant as compared to the SCS group (1,597 ± 342.2). However, the left ventricular relaxation (mmHg/s) was significant in 6-hour perfused heart ( < 0.05) as compared to SCS. Gene expression analysis of inflammation markers (IL-6, IL-1β) showed no significant differences between SCS and perfused hearts, but a 6-hour perfusion led to a downregulated expression of these markers.
The results demonstrate that the VP.S ENCORE® device enhances cardiac viability and exhibits comparable cardiac function to a healthy heart. The implications of these findings suggest that the VP.S ENCORE® could introduce a new paradigm in the field of organ preservation, especially for marginal hearts.
心脏移植仍然是晚期心力衰竭患者的金标准治疗方法。然而，等待心脏移植的患者名单持续增加。我们开发了一种便携式低温氧合机器灌注装置，即VP.S ENCORE®，以延长允许的保存时间。本研究的目的是使用脑死亡供体心脏测试VP.S ENCORE®的功效。
来自德克萨斯州器官共享联盟（TOSA）、德克萨斯州南部和中部器官采购组织（OPO）未用于移植的脑死亡供体心脏（n = 11）被提供用于研究，并在VP.S ENCORE®中保存4小时（n = 2）、6小时（n = 3）和8小时（n = 3），或置于静态冷藏（SCS）中（n = 3）。保存后，将心脏置于离体心脏Langendorff模型中进行再灌注，并评估心脏功能。
供体平均年龄为37.82±12.67岁，最年轻的供体为19岁，最年长的供体为58岁。SCS组心脏平均重量增加百分比（%）为-1.4±2.77，4小时灌注组为5.6±6.04，6小时灌注组为2.1±6.04，8小时灌注组为7.2±10.76。所有灌注心脏的静脉和动脉乳酸浓度均低于2.0 mmol/L。4小时（1,214±1,064）、6小时（1,565±141.3）和8小时（-1,331±403.6）的左心室收缩力（+dPdT，mmHg/s）在健康人心脏功能范围内。因此，与SCS组（1,597±342.2）相比无显著差异。然而，与SCS组相比，6小时灌注心脏的左心室舒张（mmHg/s）有显著差异（P<0.05）。炎症标志物（IL-6、IL-1β）的基因表达分析显示，SCS组和灌注心脏之间无显著差异，但6小时灌注导致这些标志物的表达下调。
结果表明，VP.S ENCORE®装置可增强心脏活力，并表现出与健康心脏相当的心脏功能。这些发现的意义表明，VP.S ENCORE®可能会在器官保存领域引入一种新的模式，特别是对于边缘心脏。
