Novel portable hypothermic machine perfusion preservation device enhances cardiac viability of donated human hearts

Kristina Andrijauskaite,Rafael J. Veraza, Riley P. Lopez, Zach Maxwell, Isabella Cano,Exal E. Cisneros,Israel J. Jessop, Maria Basurto, George Lamberson, Michelle D. Watt, Joseph Nespral, Masahiro Ono,Leonid Bunegin

FRONTIERS IN CARDIOVASCULAR MEDICINE(2024)

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摘要
Introduction: 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 (R), to extend the allowable preservation time. The purpose of this study was to test the efficacy of the VP.S. ENCORE (R) using deceased donors derived hearts. Methods: Hearts from brain-dead donors not utilized for transplant (n = 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 (R) for 4 (n = 2), 6 (n = 3), and 8 (n = 3) hours or were kept in static cold storage (SCS) (n = 3). After preservation, the hearts were placed in an isolated heart Langendorff model for reperfusion and evaluated for cardiac function. Results: 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 (p < 0.05) as compared to SCS. Gene expression analysis of inflammation markers (IL-6, IL-1 beta) showed no significant differences between SCS and perfused hearts, but a 6-hour perfusion led to a downregulated expression of these markers. Discussion: The results demonstrate that the VP.S ENCORE (R) device enhances cardiac viability and exhibits comparable cardiac function to a healthy heart. The implications of these findings suggest that the VP.S ENCORE (R) could introduce a new paradigm in the field of organ preservation, especially for marginal hearts.
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organ preservation,hypothermic machine perfusion,cardiac grafts,heart transplant,VP.S ENCORE (R) preservation device,deceased DBD donors,prolonged preservation
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