IMPACT OF INITIAL ACIDIC REPERFUSION ON THE FUNCTIONAL RECOVERY OF DCD HEARTS DURING EX VIVO HEART PERFUSION

Abstract

Donor hearts following circulatory death (DCD) have been proposed as an alternative source of organs for transplant. DCD hearts experience significant ischemia during the hypoxemic cardiac arrest and warm-ischemic standoff period that ethically define death. Subsequent initial reperfusion (IR) causes intracellular sodium and calcium overload, which play an important role in the pathogenesis of ischemia-reperfusion injury. However, initial acidic reperfusion may minimize sodium and calcium overload, limit ischemia-reperfusion injury, and optimize functional recovery. We investigated the impact of IR pH on the recovery of myocardial function during ex vivo heart perfusion (EVHP). Twenty-two pigs were anesthetized, mechanical ventilation was discontinued, and cardiac arrest ensued. A 15-minute warm-ischemic standoff period was observed and then hearts were procured and reperfused with an oxygenated, normokalemic, adenosine-lidocaine, cardioplegia with a pH of 6.4 (N=6), 6.9 (N=8), or 7.4 (N=8) for 3 minutes at 35°C. Hearts were then perfused ex vivo in a normothermic beating state and transitioned into working mode for assessment of myocardial function by measuring the cardiac index (mL/minute/gram heart tissue) achieved at a left atrial pressure of 8 mmHg and an aortic diastolic pressure of 40 mmHg. Hearts sustained an equivalent period of warm ischemia (6.4=27.0±0.7, 6.9=27.5±0.3, 7.4=27.9±0.4 minutes, p=0.39) prior to IR. Coronary blood flow (6.4=910±21, 6.9=871±31, 7.4=868±34 mL/min, p=0.60) and coronary sinus lactate concentration (6.4=1.6±0.5, 6.9=1.3±0.1, 7.4=1.9±0.1 umol/L, p=0.25) were comparable among treatment groups during IR. The pH of the cardioplegic solution delivered during the 3-minute IR period significantly impacted the development of myocardial edema (6.4=15.2±2.9, 6.9=8.5±1.2, 7.4=10.1±0.9 grams/hour weight gain, p=0.03) and the recovery of indexed cardiac output (6.4=3.1±0.8, 6.9=8.4±1.8, 7.4=6.1±0.9 mL/minute/gram, p=0.04) during subsequent EVHP. IR of DCD hearts with a profoundly acidic (pH=6.4) cardioplegic solution is associated with the development of myocardial edema and impaired functional recovery during EVHP, while IR under moderately acidic (pH=6.9) conditions appears to be protective.