EXPERIMENTAL EVALUATION OF CELSIOR((R)), A NEW HEART PRESERVATION SOLUTION

An original heart preservation solution (Celsior) has been developed, the formulation of which has been designed to fulfil two major objectives: (1) to combine the general principles of hypothermic organ preservation with those specific for the myocardium, and (2) to offer the possibility of being used not only as a storage medium but also as a perfusion fluid during initial donor heart arrest, poststorage graft reimplantation and early reperfusion. The major principles addressed by the Celsior formulation include (1) prevention of cell swelling (by mannitol and lactobionate), (2) prevention of oxygen-derived free radical injury (by reduced glutathione, histidine and mannitol), and (3) prevention of contracture by enhancement of energy production (glutamate) and limitation of calcium overload (high magnesium content, slight degree of acidosis). Two experimental preparations were used: The isolated isovolumic buffer-perfused rat heart model and the heterotopic rabbit heart transplantation model. In isolated heart experiments, hearts were arrested with and stored in Celsior for 5 h at 4-degrees-C and subsequently reperfused for 1 h. A similar protocol was used in the transplantation experiments except that the total ischemic time was approximately 1 1/2 h longer (corresponding to 6 h of storage followed by the 25 additional minutes of cold ischemia required for graft implantation). In both models, the results were primarily assessed on isovolumic measurements of left ventricular diastolic pressure, developed pressure and peak positive rate of the rise of the left ventricular pressure (dP/dt), and compared with those obtained in control hearts arrested with and stored in St Thomas' Hospital cardioplegic solution No 2 under similar experimental conditions. The isolated rat heart experiments show that Celsior-preserved hearts incurred significantly smaller losses of compliance after ischemia than hearts exposed to St Thomas' Hospital solution whereas they demonstrated significantly higher values of contractile indices throughout the period of reperfusion. Qualitatively similar patterns of recovery were seen in the rabbit transplantation experiments. We conclude that the functional preservation of cardioplegically arrested cold-stored cardiac allografts can be improved by their exposure to a single solution, the formulation of which combines the major protective features of cardioplegic perfusates with those of organ storage media.