New Methods to Extend Perfusion Duration of Rat Cardiac Grafts

Abstract

<h3>Purpose</h3> Cardiac transplant is an established treatment for end-stage heart disease; however, there is a shortage of viable organs. Extending preservation time or reviving marginal grafts would greatly reduce the current shortage. Machine perfusion holds promise to overcome these challenges. Murine models are used due to their low cost, and availability of transgenic lines; however, perfusion are limited to ∼2 hours. Most rat retrograde perfusions apply aortic root pressures of 75-90 mmHg, and flows between 5-25 ml/min. As perfusion time extends, valvular injury, hypertrophy, edema, and graft disfunction can be observed. Methods to avoid these issues include a left ventricular apical drain and increasing oncotic pressure/oxygen delivery using packed red blood cells (pRBCs). Our research tests the effect of lower pressures/flow rates, 30-35 mmHg, 3.5-5 mL/min during a 4-hour normothermic perfusion. <h3>Methods</h3> Hearts from Sprague Dawley rats were retrogradely perfused for 4 hours, under varying flow, pressure, and perfusate parameters (Table 1). <h3>Results</h3> Group 3 (G3) had stable perfusion parameters over 4 hours with high oxygen uptake (average 22.53 mmHg•min•mL⁻¹/gram tissue) and low resistance (average 3.34 mmHg•min•mL⁻¹/gram tissue). Weight was significantly different at 4 hours comparing G3 with no weight gain, to the Controls that had 23% weight gain. Lactate rose in both G3 and Control but was not significant. Finally, G3 sustained full ventricular contraction (>150 bpm), with no arrhythmia, or tachycardia; whereas Control heart rate decreased throughout perfusion, and arrhythmia and tachycardia was noted within 2 hours. <h3>Conclusion</h3> We demonstrate the ability to prolong murine heart perfusion for up to 4 hours. With prolonged function and viability in a murine heart model, this opens a greater potential of low-cost mammalian heart perfusions for research.