Hearts From DCD Donors Display Acceptable Biventricular Function After Heart Transplantation in Pigs

Abstract

Cardiac transplantation is in decline, in contrast to other solid organs where the number of solid organ transplants from donors after circulatory death (DCD) is increasing. Hearts from DCD donors are not currently utilized due to concerns that they may suffer irreversible cardiac injury with resultant poor graft function. Using a large animal model, we tested the hypothesis that hearts from DCD donors would be suitable for transplantation. Donor pigs were subjected to hypoxic cardiac arrest (DCD) followed by 15 min of warm ischemia and resuscitation on cardiopulmonary bypass, or brainstem death (BSD) via intracerebral balloon inflation. Cardiac function was assessed through loadindependent measures and magnetic resonance imaging and spectroscopy. After resuscitation, DCD hearts had near normal contractility, although stroke volume was reduced, comparable to BSD hearts. DCD hearts had a significant decline in phosphocreatine and increase in inorganic phosphate during the hypoxic period, with a return to baseline levels after reperfusion. After transplantation, cardiac function was comparable between BSD and DCD groups. Therefore, in a large animal model, the DCD heart maintains viability and recovers function similar to that of the BSD heart and may be suitable for clinical transplantation. Further study is warranted on optimal reperfusion strategies.

Increasing the Tolerance of DCD Hearts to Warm Ischemia by Pharmacological Postconditioning

“…Previous studies of myocardial recovery in large animal DCD models have exposed the heart to WITs ranging from 15 to 30 min, with varying results (2,3,26). Ali et al (3) in a porcine model demonstrated good biventricular functional recovery postorthotopic transplantation following 20.9 AE 2.8-min WIT, while Osaki et al (26) reported partial recovery of hearts subjected to 30-min WIT in a porcine transplant model using controlled initial reperfusion.…”

“…Ali et al (3) in a porcine model demonstrated good biventricular functional recovery postorthotopic transplantation following 20.9 AE 2.8-min WIT, while Osaki et al (26) reported partial recovery of hearts subjected to 30-min WIT in a porcine transplant model using controlled initial reperfusion. Similarly, Repse et al (2) also showed inferior cardiac power recovery of canine hearts subjected to 30-min WIT compared with normal control hearts.…”

“…Despite these insults, several preclinical studies in porcine, canine and primate models have suggested the potential use of DCD hearts for cardiac transplantation. These studies employed varying WITs and differing models of cardiocirculatory death (2)(3)(4). However, to our knowledge, no study has compared the recovery of DCD hearts following various WITs, to ascertain the limit of warm ischemia prior to irreversible myocardial damage.…”

“…The paucity of available NDD donor hearts has limited the number of transplants that can be performed, resulting in substantial recipient waiting list mortality (1). Several groups have proposed the use of donation after circulatory death (DCD) hearts as an additional source of cardiac allografts for transplantation (2)(3)(4); however, the possibility of irreversible myocardial damage during the unavoidable warm ischemic period has limited clinical translation.…”

Heart transplantation from donation after circulatory determined death

“…The use of normothermic regional perfusion, originating from Barnard's clinical work, was explored by Ali et al using a porcine model of hypoxic induced DCD (12). Following death, cardio-pulmonary bypass was established and after allowing for a period of less than hour with the heart offloaded and allowed to recover, bypass was weaned and the heart functionally assessed using load independent contractility.…”