Abstract 16801: Effect of Cyclosporine A on Infarct Size in Rat Hearts Donated After Circulatory Death

Abstract

Introduction: Ischemia-reperfusion injury (IRI) is inherent in heart donation after circulatory death (DCD), hence only hearts with <30 minutes of ischemia are used for transplantation. Mitochondrial permeability-transition pore (MPTP) opening has been implicated in IRI. Cyclosporine A (CyA) is known to inhibit MPTP opening. No data on infarct size reduction with CyA exists in a DCD heart. Hypothesis: CyA given during reperfusion will reduce infarct size in DCD hearts. Methods: Male Sprague-Dawley rats were assigned to either DCD + CyA, DCD + vehicle, or control-beating heart donors (CBD) (n=10 per group). Rats were anesthetized with pentobarbital, intubated and ventilated. Vecuronium and heparin were given for muscle paralysis and anticoagulation respectively. For DCD group, ventilation was terminated (start of anoxia/ischemia time), and hearts procured after 5, 10, 15, 20, 25 minutes. CBD hearts were procured without ischemia. Hearts were then perfused on a Langendorff setup for 90 minutes. Vehicle and CyA groups received DMSO and CyA (2μM) in KH buffer, respectively, for first 15 minutes followed by 75 minutes of KH buffer. Developed pressure (DP) was measured via a balloon tip catheter placed in the left ventricle. Infarct size was measured using triphenyltetrazolium chloride staining. CBD hearts perfused with KH buffer only served as controls. Results: Percent infarct size following 5, 10, 15, 20, and 25 minutes of ischemia was 17.7 ± 4, 19.3 ± 6, 25 ± 4, 27.3 ± 3, and 25.4 ± 11 respectively. CyA given to 25 minutes ischemia group reduced infarct size to 14.7%, corresponding to 6 minutes of ischemia. At 60 minutes CyA treated hearts had higher DP (mmHg) compared to vehicle group (34 ± 13 vs. 51 ± 17, p=0.017 ). Conclusions: CyA given during reperfusion to DCD hearts significantly reduced infarct size and preserved function. CyA use may allow for longer ischemia times during DCD heart procurement.