Impact of Myocardial Load on the Preservation of Donor Heart Function during Ex Vivo Perfusion

Abstract

Purpose: Ex vivo heart perfusion (EVHP) has been proposed as a means improving heart preservation and expanding the donor pool. Current clinical EVHP protocols involve preservation in an unloaded and non-working state; however, the impact of this approach on the preservation of donor heart function is unknown. We sought to determine if myocardial load during EVHP impacts the preservation of donor heart function. Methods: Donor porcine hearts were perfused ex vivo in a beating state for 12 hours. Loaded hearts (N= 4) were perfused in a working mode (left atrial pressure= 6 mmHg, heart rate= 100 beats/minute) for the entire EVHP interval. Unloaded hearts (N= 4) were briefly transitioned into a working mode at hours 1 (T1), 5 (T5), and 11 (T11) for metabolic and functional assessments, but were otherwise perfused in a resting mode (left atrial pressure= 0 mmHg). Results: Myocardial function (T11 cardiac index (mL/minute/gram): loaded= 6.9±1.0 vs. unloaded= 2.0±1.2, p= 0.02) and mechanical efficiency (T11: loaded= 11±1 vs. unloaded= 2±1 %, p< 0.01) were better preserved in loaded hearts. Myocardial injury (T11 troponin I (ng/mL): loaded= 11.6±0.4 vs. unloaded= 12.1±0.3, p= 0.39) and edema formation (% weight gain: loaded= 14±8 vs. unloaded= 24±3 %, p= 0.15) did not account for these differences. Free fatty acids were rapidly depleted in both groups; however, triglycerides were continually consumed by loaded hearts and secreted by unloaded heats (Figure 1). Conclusion: EVHP in a loaded state improves the preservation of myocardial function. Uncoupling of fatty acid oxidation may contribute to the decline in myocardial function observed in unloaded hearts; however, further research is required to elucidate the mechanism underlying these observations. These results highlight the need for an EVHP device capable of preserving the donor heart in a physiologic working mode. ( 492)Purpose: Testing genetically modified (gm) porcine hearts in ex vivo perfusions with human blood remain as the final test before introducing

Transplantation of Hearts Donated after Circulatory Death

“…While amino acids are not generally used as primary substrates for energy production, they play important roles in the intermediary metabolism of the cardiomyocytes and may regulate substrate utilization ( 118 ). Free fatty acids are rapidly depleted during ESHP ( 153 ); however, the impact of exogenous supplementation on myocardial function has not been investigated. It appears that the perfusate substrate composition may impact myocardial energy metabolism during ESHP and the preservation of donor heart function.…”

Experimental Investigation Of The Effect Of Compliance Properties On The Flow In An Analogous Ex-Vivo Heart Perfusion System

“…By keeping the heart beating while being transported from the donor to the recipient patient, EVHP technology allows the organ's health to be assessed and the transplant time window can be extended [7]- [9]. The latest improvements in EVHP systems enable the heart to work in a quasi-physiological regime [1], [10]- [17].…”

“…In fact, a recently published study shows that online monitoring of the heart's functional parameters is the most effective way to assess the organ's health [1]. It can be said that such control of the heart's metabolism to keep it healthy is well understood and continues to be optimized [1], [10]- [17]. However, the fluid mechanics intrinsic to the EVHP system, and the corresponding impact on cardiac performance, still need to be better investigated.…”

Experimental investigation into the effect of compliance of a mock aorta on cardiac performance

“…Advancements are currently being made in EVHP technology that enables a near-physiologic working mode [1,[12][13][14][15][16][17][18][19], wherein flow is supplied to the ventricles so they can fill and eject perfusate, a mixture of blood and support nutrients [17], at normothermic temperature (37˚C) as would occur in the body. Since the ventricles are doing mechanical work in the same fashion as they would in-vivo, both metabolic and mechanical conditions can be controlled in response to monitored changes in cardiac performance [1,[12][13][14][15][16][17][18][19]. This provides transplant teams with more functional information that should empower them to make better decisions about transplantation viability [2][3][4][5].…”

“…Recent literature published on this EVHP system concluded that the assessment of functional parameters, such as left ventricular stroke work, was indeed the most reliable means for evaluating organ health [1]. Control of the metabolic environment required to keep the heart healthy in the proposed EVHP system is wellunderstood and continues to be optimized [1,[12][13][14][15][16][17][18][19] but the fluid mechanics of the system and its corresponding impact on cardiac performance have yet to be studied prior to this investigation.…”