A Device and Methodology for Continuous Hypothermic Perfusion of Explanted Large Mammalian Hearts, Followed by In Vitro Langendorff Reanimation: Pilot Studies

Abstract

The current methodologies of clinical heart transplantation limit the ischemic window to 4–6 h. Periods longer than this can induce dysfunction in the organ and can lead to increased patient morbidity and mortality. An alternative to the current methods of static cold storage (CS) is continuous hypothermic perfusion (CHP), where a hypothermic oxygenated crystalloid solution is mechanically perfused through the coronary arteries. This has been shown to preserve the function for up to 72 h, but the techniques have yet to be optimized. We have developed an apparatus and methodology for performing CHP on large mammalian hearts, followed by reanimation in our in vitro Langendorff apparatus (The Visible HeartTM ). We are also investigating the utility of the cardioprotective agents docosahexaenoic acid and [D-Ala2, D-Leu5] enkephalin, both of which have shown cardioprotective effects in our laboratory, and we believe that their addition to the preservation solution can further extend the transplant window. A series of pilot studies has been performed to date, with modestly successful results. Hearts preserved with CHP seem to show better functionality than CS hearts but far worse functionality than hearts reanimated immediately after explant. We hope to use this system to optimize CHP methodology and eventually develop a system for prolonging the window for heart transplantation.