normothermic-ex-situ-heart-perfusion-working-mode-assessment-cardiac

Normothermic Ex Situ Heart Perfusion in Working Mode: Assessment of Cardiac Function and Metabolism

The current standard method for organ preservation (cold storage, CS), exposes the heart to a period of cold ischemia that limits the safe preservation ...

University of Alberta

Normothermic ex vivo heart perfusion (EVHP) has been shown to improve the preservation of hearts donated after circulatory arrest and to facilitate clinical successful transplantation. Steroids are added to the perfusate solution in current clinical EVHP protocols; however, the impact of this approach on donor heart preservation has not been previously investigated. We sought to determine the impact of steroids on the inflammatory response and development of myocardial edema during EVHP.

Steroids Limit Myocardial Edema During Ex Vivo Perfusion of Hearts Donated After Circulatory Death.

Cardiac transplantation has become limited by a critical shortage of suitable organs from brain-dead donors. Reports describing the successful clinical transplantation of hearts donated after circulatory death (DCD) have recently emerged. Hearts from DCD donors suffer significant ischemic injury prior to organ procurement; therefore, the traditional approach to the transplantation of hearts from brain-dead donors is not applicable to the DCD context. Advances in our understanding of ischemic post-conditioning have facilitated the development of DCD heart resuscitation strategies that can be used to minimize ischemia-reperfusion injury at the time of organ procurement. The availability of a clinically approved  heart perfusion device now allows DCD heart preservation in a normothermic beating state and minimizes exposure to incremental cold ischemia. This technology also facilitates assessments of organ viability to be undertaken prior to transplantation, thereby minimizing the risk of primary graft dysfunction. The application of a tailored approach to DCD heart transplantation that focuses on organ resuscitation at the time of procurement,  preservation, and pre-transplant assessments of organ viability has facilitated the successful clinical application of DCD heart transplantation. The transplantation of hearts from DCD donors is now a clinical reality. Investigating ways to optimize the resuscitation, preservation, evaluation, and long-term outcomes is vital to ensure a broader application of DCD heart transplantation in the future.

Transplantation of Hearts Donated after Circulatory Death.

Ex vivo lung perfusion (EVLP) shows promise in ameliorating pretransplant acute lung injury (ALI) and expanding the donor organ pool, but the mechanisms of ex vivo repair remain poorly understood. We aimed to assess the utility of gene expression for characterizing ALI during EVLP. One hundred sixty-nine porcine lung samples were collected in vivo (n = 25), after 0 (n = 11) and 12 (n = 11) hours of cold static preservation (CSP), and after 0 (n = 57), 6 (n = 8), and 12 (n = 57) hours of EVLP, utilizing various ventilation and perfusate strategies. The expression of 53 previously described ALI-related genes was measured and correlated with function and histology. Twenty-eight genes were significantly upregulated and 6 genes downregulated after 12 hours of EVLP. Aggregate gene sets demonstrated differential expression with EVLP (P < .001) but not CSP. Upregulated 28-gene set expression peaked after 6 hours of EVLP, whereas downregulated 6-gene set expression continued to decline after 12 hours. Cellular perfusates demonstrated a greater reduction in downregulated 6-gene set expression vs acellular perfusate (P < .038). Gene set expression correlated with relevant functional and histologic parameters, including P/F ratio (P < .001) and interstitial inflammation (P < .005). Further studies with posttransplant results are warranted to evaluate the clinical significance of this novel molecular approach for assessing organ quality during EVLP.

Article	Year
Steroids Limit Myocardial Edema During Ex Vivo Perfusion of Hearts Donated After Circulatory Death. The Annals of thoracic surgery\| PubMed ID: 29382512	2018
Transplantation of Hearts Donated after Circulatory Death. Frontiers in cardiovascular medicine\| PubMed ID: 29487855	2018
Ex vivo perfusion induces a time- and perfusate-dependent molecular repair response in explanted porcine lungs. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons\| PubMed ID: 30230229	2018

Christopher W. White

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