Comparison of different porcine models simulating myocardial cold ischemia of pediatric donor hearts

Background Our team previously identified a stem cell-derived cardioprotective additive that can be added to standard cardioplegia to extend myocardial viability during prolonged myocardial cold ischemic time (CIT) in rodent models. The purpose of this study was to utilize a porcine model to compare in-vivo versus ex-vivo porcine simulation of CIT that accompanies cardiac transplantation in humans, in order to determine an optimal method for translation of our studies to larger animals.Methods Eight 39-55 kg Yorkshire X pigs were randomly assigned to either in-vivo or ex-vivo simulation. After administration of general anesthesia and endotracheal intubation, baseline measurement of left ventricular performance was obtained via transesophageal echocardiography (TEE). After midline sternotomy and heparin administration, the aorta was cross-clamped and two liters of HTK-Custodiol were introduced via the aortic root. The in-vivo method utilized cold ischemic heart storage in the chest cavity while supporting the experimental animal with cardiopulmonary bypass (CPB). The ex-vivo method involved standard cardiac procurement, cold ischemic storage outside of the body, and subsequent cardiac reperfusion utilizing cardiac reanimation in a Langendorff heart perfusion mode. After CIT, measurements of post-ischemic left ventricular performance were obtained via echocardiography. Results are presented as: Mean +/- Standard Deviation (Median, Minimum-Maximum).Results Weight (kilograms) was similar in the in-vivo group and the ex-vivo group: 44 +/- 1.8 (44, 42-46) versus 44 +/- 5.1 (43.5, 39-51), respectively. Cold ischemic time (minutes) was longer in the ex-vivo group: 360 +/- 0 (360, 360-360) versus 141 +/- 26.7 (149, 102-163). Temperature (degrees Celsius) was colder in the ex-vivo group: 8 +/- 0 (8, 8-8) versus 16.5 +/- 4.2 (16, 12-16). In the in-vivo group, baseline ejection fraction and ejection fraction after CIT were: 48.25% +/- 14.95% (48.5%, 33%-63%) and 41.25% +/- 22.32% (41.5%, 20%-62%), respectively. In the ex-vivo group, baseline ejection fraction and ejection fraction after CIT were: 56.4% +/- 5.9% (57%, 50%-67%) and 60.4% +/- 7.7% (61.5%, 51.9%-67%), respectively.Results Weight (kilograms) was similar in the in-vivo group and the ex-vivo group: 44 +/- 1.8 (44, 42-46) versus 44 +/- 5.1 (43.5, 39-51), respectively. Cold ischemic time (minutes) was longer in the ex-vivo group: 360 +/- 0 (360, 360-360) versus 141 +/- 26.7 (149, 102-163). Temperature (degrees Celsius) was colder in the ex-vivo group: 8 +/- 0 (8, 8-8) versus 16.5 +/- 4.2 (16, 12-16). In the in-vivo group, baseline ejection fraction and ejection fraction after CIT were: 48.25% +/- 14.95% (48.5%, 33%-63%) and 41.25% +/- 22.32% (41.5%, 20%-62%), respectively. In the ex-vivo group, baseline ejection fraction and ejection fraction after CIT were: 56.4% +/- 5.9% (57%, 50%-67%) and 60.4% +/- 7.7% (61.5%, 51.9%-67%), respectively.Conclusion The ex-vivo technique is suitable to evaluate cardioplegia additives that may substantially extend myocardial tolerance to cold ischemia.