Cariporide improves long term cardiac preservation in a porcine model of heart transplantation

Donor brain death and hypothermic ischaemic storage subject the transplanted heart to a series of injuries that may result in primary graft failure. The aim of this study was to assess whether pre-treatment of the donor and recipient with cariporide after donor hormone resuscitation (HR) allowed viable recovery of the transplanted heart after long-term hypothermic storage. A porcine model incorporating donor brain death, static preservation and orthotopic heart transplantation was used. Brain dead donors were managed for 6h using noradrenaline and included HR (methylprednisolone, triiodothyronine, vasopressin and insulin) in the final 3h. Hearts in the control group (CON, n=5) and treatment group (CAR, n=5) were arrested and stored for 14h using Celsior. In the CAR group, both the donor and recipient animals were given cariporide (2 mg/kg) prior to harvesting and reperfusion. Animals were monitored for 3h after weaning from cardiopulmonary bypass. All 5 CAR animals were weaned successfully from bypass compared with only 1 CON animal (p=0.0476). Mean cardiac output prior to brain death was 3.2±1.0 L/min, prior to harvest 3.9±0.2 L/min, 1h post weaning 4.1±0.1 L/min and 3h post weaning 4.5±0.7 L/min. Left ventricular contractility (preload recruitable stroke work relationship) was decreased post transplant compared with prior to harvest with the stroke work index falling from 1.1 to 0.9 at 1h and 3h post weaning (p<0.001). We have found that pre-treatment of donors and recipients with cariporide after donor HR allows viable recovery of the transplanted heart after long-term hypothermic storage in a clinically relevant model. Whilst contractility was decreased post transplant, this did not decline further for up to 3h post weaning from bypass.