Deceased donor as a source of organs for heart transplantation
The number of heart transplants performed worldwide has declined dramatically over the past decade. This has been due to a progressive decrease in the number of suitable organ donors. Conventional cardiac organ donors are brainstem dead, but the heart and other organs continue to function. In an attempt to address the serious problem of donor organ shortage we have identified a potential alternative source of donor hearts, the deceased donor. Organs are recovered from deceased donors after they suffer cardiac arrest. deceased donors have been successfully used for liver, kidney and more recently lung transplantation. It is our hypothesis that hearts from deceased donor can be resuscitated after cardiac arrest. Following resuscitation we believe they can recover adequate function to be used for transplantation. We hope to prove this hypothesis through concurrent animal and clinical studies aimed at evaluating function of the resuscitated deceased donor heart. This will help us to establish whether non-heart beating heart transplantation is feasible. The identification of a new source of donor hearts would lead to an immediate increase in the number of hearts available for transplantation worldwide.
Recently the Papworth hospital group described the first case of functional recovery in a human deceased donor heart following in-vivo perfusion of the coronary circulation with normothermic blood using an extracorporeal circuit. After 23 minutes of warm ischemia the asystolic heart was perfused and reverted into sinus rhythm. Extracorporeal support was weaned after 2 hours following which the heart was able to support the circulation independently. Further study to understand and optimize such cardiac recovery is essential. We believe that continued study using an animal model is imperative. This will allow us to gain further insight into recovery of cardiac function following profound global myocardial ischemia. Accordingly we have developed a small animal model of non-heart beating heart resuscitation aimed at evaluating the contractile function of the post-ischemic heart in this setting.
To enable us to assess cardiac function in the post-ischemic heart we have developed a rat extracorporeal perfusion model. An anesthetized mechanically ventilated adult rat is cannulated onto the perfusion apparatus after systemic heparinization. Venous blood from the animal is obtained via free drainage through a cannula placed in the right internal jugular vein. The drained venous blood is then propelled via tygon tubing through a micro-peristatlic pump and a mini-oxygenator and returned into the animal via a cannula in the right femoral artery. To simulate the clinical situation observed in the deceased donor the trachea is clamped to induce hypoxic cardiac arrest. The majority of deceased donors succumb from asphyxiation after withdrawal of supportive therapy which includes extubation from mechanical ventilation. In our preliminary experiments we have subjected the animal to a further 15 minutes of warm ischemia after hypoxic cardiac arrest. Following this period extracorporeal perfusion is commenced by turning on the peristaltic pump. On reperfusion we have noted prompt recovery of cardiac function with resumption of normal cardiac rate and rhythm. Invasive assessment of load independent left ventricular function has been obtained via the pressure-volume conductance method. Our preliminary data suggests that the there is only a modest decrease in contractile function following hypoxic cardiac arrest and 15 minutes of warm ischemia. This suggests that hearts from non-heart beating donors may be potentially suitable for cardiac transplantation.
