Duignan Thomas, Guariento Alvise, Doulamis Ilias P, Kido Takashi, Regan William L, Saeed Mossab, Hoganson David M, Emani Sitaram M, Del Nido Pedro J, McCully James D, Matte Gregory S
Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
J Extra Corpor Technol. 2020 Dec;52(4):303-313. doi: 10.1182/ject-2000034.
Ex situ heart perfusion (ESHP) has proven to be an important and valuable step toward better preservation of donor hearts for heart transplantation. Currently, few ESHP systems allow for a convenient functional and physiological evaluation of the heart. We sought to establish a simple system that provides functional and physiological assessment of the heart during ESHP. The ESHP circuit consists of an oxygenator, a heart-lung machine, a heater-cooler unit, an anesthesia gas blender, and a collection funnel. Female Yorkshire pig hearts (n = 10) had del Nido cardioplegia (4°C) administered, excised, and attached to the perfusion system. Hearts were perfused retrogradely into the aortic root for 2 hours before converting the system to an isovolumic mode or a working mode for further 2 hours. Blood samples were analyzed to measure metabolic parameters. During the isovolumic mode (n = 5), a balloon inserted in the left ventricular (LV) cavity was inflated so that an end-diastolic pressure of 6-8 mmHg was reached. During the working mode (n = 5), perfusion in the aortic root was redirected into left atrium (LA) using a compliance chamber which maintained an LA pressure of 6-8 mmHg. Another compliance chamber was used to provide an afterload of 40-50 mmHg. Hemodynamic and metabolic conditions remained stable and consistent for a period of 4 hours of ESHP in both isovolumic mode (LV developed pressure: 101.0 ± 3.5 vs. 99.7 ± 6.8 mmHg, = .979, at 2 and 4 hours, respectively) and working mode (LV developed pressure: 91.0 ± 2.6 vs. 90.7 ± 2.5 mmHg, = .942, at 2 and 4 hours, respectively). The present study proposed a novel ESHP system that enables comprehensive functional and metabolic assessment of large mammalian hearts. This system allowed for stable myocardial function for up to 4 hours of perfusion, which would offer great potential for the development of translational therapeutic protocols to improve dysfunctional donated hearts.
体外心脏灌注(ESHP)已被证明是朝着更好地保存用于心脏移植的供体心脏迈出的重要且有价值的一步。目前,很少有ESHP系统能够方便地对心脏进行功能和生理评估。我们试图建立一个简单的系统,在ESHP过程中对心脏进行功能和生理评估。ESHP回路由一个氧合器、一台心肺机、一个加热 - 冷却单元、一个麻醉气体混合器和一个收集漏斗组成。对10只雌性约克夏猪心脏给予del Nido心脏停搏液(4°C),切除后连接到灌注系统。心脏在主动脉根部逆行灌注2小时,然后将系统转换为等容模式或工作模式再持续2小时。分析血样以测量代谢参数。在等容模式(n = 5)下,插入左心室(LV)腔的球囊充气,使舒张末期压力达到6 - 8 mmHg。在工作模式(n = 5)下,使用一个顺应性腔室将主动脉根部的灌注重新导向左心房(LA),该腔室维持LA压力为6 - 8 mmHg。另一个顺应性腔室用于提供40 - 50 mmHg的后负荷。在等容模式(LV发育压力:分别在2小时和4小时时为101.0±3.5 vs. 99.7±6.8 mmHg,P = 0.979)和工作模式(LV发育压力:分别在2小时和4小时时为91.0±2.6 vs. 90.7±2.5 mmHg,P = 0.942)下,在4小时的ESHP期间,血流动力学和代谢状况保持稳定且一致。本研究提出了一种新型ESHP系统,该系统能够对大型哺乳动物心脏进行全面的功能和代谢评估。该系统在长达4小时的灌注过程中可使心肌功能保持稳定,这将为开发改善功能失调的捐赠心脏的转化治疗方案提供巨大潜力。