Physiologic Changes in the Heart Following Cessation of Mechanical Ventilation in a Porcine Model of Donation After Circulatory Death: Implications for Cardiac Transplantation

Abstract

Hearts donated following circulatory death (DCD) may represent an additional source of organs for transplantation; however, the impact of donor extubation on the DCD heart has not been well characterized. We sought to describe the physiologic changes that occur following withdrawal of life-sustaining therapy (WLST) in a porcine model of DCD. Physiologic changes were monitored continuously for 20 min following WLST. Ventricular pressure, volume, and function were recorded using a conductance catheter placed into the right (N ¼ 8) and left (N ¼ 8) ventricles, and using magnetic resonance imaging (MRI, N ¼ 3). Hypoxic pulmonary vasoconstriction occurred following WLST, and was associated with distension of the right ventricle (RV) and reduced cardiac output. A 120-fold increase in epinephrine was subsequently observed that produced a transient hyperdynamic phase; however, progressive RV distension developed during this time. Circulatory arrest occurred 7.6AE0.3 min following WLST, at which time MRI demonstrated an 18AE7% increase in RV volume and a 12AE9% decrease in left ventricular volume compared to baseline. We conclude that hypoxic pulmonary vasoconstriction and a profound catecholamine surge occur following WLST that result in distension of the RV. These changes have important implications on the resuscitation, preservation, and evaluation of DCD hearts prior to transplantation.Abbreviations: C a O 2 , arterial oxygen content; CO, cardiac output; DCD, donation after circulatory death; LV, left ventricle; MRI, magnetic resonance imaging; P a CO 2 , arterial partial pressure of carbon dioxide; P a O 2 , arterial partial pressure of oxygen; RV, right ventricle; UHPLC, ultra-high-performance liquid chromatography; WLST, withdrawal of life-sustaining therapy

Mechanical Postconditioning Promotes Glucose Metabolism and AMPK Activity in Parallel with Improved Post-Ischemic Recovery in an Isolated Rat Heart Model of Donation after Circulatory Death

“…This study does possess some limitations. Our experimental (ex-situ) model and the specific conditions were chosen in order to limit variability and strictly control the energy substrate availability and duration and temperature of ischemia to simulate DCD conditions; however, it does not incorporate the physiologic changes in the body following withdrawal of life sustaining therapy (typical DCD heart donor), such as the catecholamine storm or pulmonary vasoconstriction leading to a pressure-volume overload in the right heart [51,52]. Furthermore, although we provide new information about potential mechanisms of MPC-mediated cardioprotection, additional studies are required to fully characterize the precise molecular causes of MPC-induced effects.…”

Heart transplantation from donation after circulatory death donors: Present and future

“…In a porcine DCD model, White et al 7 established that similar to a DBD animal model, the DCD donor process also produces a catecholamine surge (up to 591 times the baseline value) with an increase in heart rate and contractility, followed by a decrease in blood pressure and tissue oxygenation. It is important to note that oxygen delivery to tissue ceases within 4 minutes following the withdrawal of ventilation.…”

Transplantation of Hearts Donated after Circulatory Death

“…The FWIT is meant to provide a more accurate estimate of the actual ischemic injury sustained by donor organs following WLST. However, insufficient end-organ oxygen delivery and the onset of organ ischemia (evidenced by rising systemic lactate concentrations) may occur before a significant decline in blood pressure has occurred ( 24 ). Oxygen desaturation may be a more sensitive indicator of end-organ ischemia and should be included in the FWIT definition ( 24 ).…”

“…Understanding the physiologic impact of donor extubation and warm ischemia on the DCD heart is fundamental to developing a successful resuscitation strategy ( 24 ). After extubation, the DCD heart is forced to function in an increasingly hypoxemic environment while attempting to maintain systemic oxygen delivery ( 24 ). Progressive hypoxemia and hypercarbia cause constriction of the pulmonary vasculature and distention of the right ventricle.…”