A novel cardioprotective perfusion protocol prevents functional decline during extended normothermic ex situ heart perfusion of marginal porcine hearts

Background: A common limitation to normothermic ex situ heart perfusion (ESHP) is functional decline. We previously designed a cardioprotective normothermic perfusion protocol, incorporating adenosine-lidocaine cardioplegia, subnormothermic reperfusion, pyruvate and methylprednisolone supplementation, and hemofiltration to prevent myocardial functional decline over 4 hours. In this study, we added continuous catecholamine infusion and protective loading conditions to assess the effectiveness of this enhanced cardioprotective perfusion protocol in preventing functional decline during extended normothermic perfusion in marginal porcine hearts. Methods: Six slaughterhouse pig hearts underwent 9 hours of normothermic ESHP using the enhanced cardioprotective protocol. Cardiac function was assessed at 90, 120, 240, 360, 480 and 540 minutes of ESHP. Subsequently, a preload-challenge was conducted after 9 hours to assess preload-responsiveness (mimicking the Frank-Starling principle) and suitability for transplantation. Results: During perfusion, myocardial function remained stable, indicated by consistent mean cardiac index (9.2 liter/min/kg at 90; 9.3 liter/min/kg at 540 minutes of ESHP), left ventricular stroke work index (6,258 mm Hg*ml/kg at 90; 6,707 mm Hg*ml/kg at 540 minutes) and rate of ventricular pressure change over time. In response to a preload-challenge, there was a notable increase of 34% in mean cardiac index and 58% in mean stroke work. Conclusions: Our study demonstrates that the implementation of a cardioprotective protocol enables (very) marginal porcine slaughterhouse hearts, subjected to both a warm and cold ischemic insult prior to ESHP, to sustain satisfactory cardiac function without notable decline during 9 hours of normothermic ESHP, while also preserving their preload-responsiveness. The latter finding might indicate suitability for transplantation. This study provides a groundwork for further extending normothermic ESHP, unlocking the full potential of this promising technology.