Novel Portable Hypothermic Cardiac Preservation Device Extends Cardiac Viability and Function Beyond the Standard of Care Using Isolated Porcine Hearts

Abstract

<h3>Purpose</h3> The standard of care: cold static storage (CSS), limits the time a heart can be preserved to 4-6 hours. Machine perfusion preservation has been shown to improve organ viability. However, current machine perfusion technology is complex and requires the use of blood or blood products. The purpose of this study was to test the efficacy of a portable hypothermic oxygenated and acellular perfusion machine device, in preserving cardiac viability and function in comparison to CSS for 4 hours at different perfusion times using an isolated heart porcine model. <h3>Methods</h3> Isolated porcine hearts (N=17) were recovered under anesthesia and by inducing cardiac arrest through cardioplegia administration. Experimental hearts were perfused using a novel cardiac preservation device with an acellular perfusate at 4-8°C for 4 hours(n=3), 8 hours(n=4), and 24 hours(n=3). In addition, 3 hearts were perfused for 2 hours and then kept inside the perfusor at 4-8°C for an additional 4 hours without perfusion (extended mode), to determine efficacy during inoperable conditions. Controls (n=4) were hearts kept in CSS for 4 hours. Hourly flow, pressure, temperature, and blood gas measurements were taken from perfused hearts. After preservation, the hearts were placed in a Langendorff for functional recovery determined by +/- dP/dT and maximum pressure. Biopsy samples were taken before and at the end of either preservation method for histological and gene expression analyses. <h3>Results</h3> Control hearts weight gain (%) was -3.4 ± 4.9 and perfused hearts was 1.52 ± 7.6. Venous and arterial lactate concentrations were less than 2.5 mmol/L across all experiments. Perfused hearts at 4 hours, 8 hours, and extended mode had significantly increased contractility (p<0.05) than CSS demonstrated by +dP/dT and peak pressure. Gene expression showed a significant reduction (p<0.005) of inflammation (IL-6, IL-8, TNFα) and cell death markers (p53,cTnI) in perfused hearts compared to control hearts. Furthermore, histological assessment confirmed greater myocardium damage in CSS hearts. <h3>Conclusion</h3> This novel cardiac preservation device enhances cardiac viability and function compared to CSS. Furthermore, it allows for 4 hours of CSS after 2 hours of perfusion in case of cessation of perfusion. Animal transplant studies will be conducted to verify these results.