A LABORATORY MODEL OF ORGAN DONOR CIRCULATORY DEATH WITH DIRECT MEASUREMENT OF CARDIAC GRAFT FUNCTION

Abstract

At present, the only clinical pathway for cardiac transplantation involves the use of an organ donor who meets criteria for neurologic death. Unfortunately, there is a consistent shortage of donor hearts despite a growing number of potential transplant recipients. This supply-demand mismatch is associated with significant waitlist mortality. An alternative to neurologic death, referred to as organ donation after circulatory death (DCD), is currently in use for lung, liver and kidney transplantation. The DCD clinical pathway, however, is associated with a variable and unpredictable duration of donor hypoxia and hypotension, culminating in 5 minutes of total circulatory standstill. As a result of the heart’s unique susceptibility to injury under these conditions, cardiac grafts from DCD donors are currently wasted. Sprague-Dawley rats are deeply anesthetized, tracheotomized and mechanically ventilated. Rats are systemically anticoagulated with unfractionated heparin. Control subjects receive a median sternotomy. The heart is harvested and flushed with ice-cold cardioplegic solution prior to functional assessment. DCD subjects receive invasive blood pressure monitoring via the left femoral artery. Subsequently, a median sternotomy is performed and both pleural spaces are opened. The DCD pathway is initiated by discontinuing mechanical ventilation. Vital sign parameters are monitored regularly until the graft is harvested. When asystole is achieved, 5 minutes of circulatory standstill is observed (to mimic the clinical requirement) prior to harvesting and flushing the cardiac graft. Cardiac grafts are reperfused on a Langendorff rig. After 10 minutes of reperfusion, the rig is switched into a working-heart mode. The left ventricle is catheterized with a calibrated pressure-volume conductance catheter to generate baseline and preload occlusion data. We have established a clinically relevant rodent model of donor circulatory death. Furthermore, we have coupled our DCD protocol with direct phyiosologic assessment of cardiac function, demonstrating a significant difference between control and DCD subjects. Vital sign parameters recorded during the DCD protocol have enabled us to crudely correlate the extent and duration of donor instability with cardiac graft function. Our model of DCD with direct measurement of cardiac graft function is important and clinically relevant. It will be valuable in determining the limits of cardiac viability in the DCD setting, and also in assessing the ability of pre- and post-DCD treatment strategies to salvage cardiac function.