improved the excretion of indocyanine green which is a known marker of parenchymal and nonparenchymal cell integrity, from bile, improved nutritive perfusion after small-bowel transplantation, attenuated the leukocyte-endothelial cell interaction, and almost completely prevented mucosal ischemia reperfusion injury. Additional studies showed that Ringer's solution containing adenosine (0.1 mM) increased the survival time when it was used to rinse cold-stored liver grafts. Despite the improved survival following liver transplantation, however, Ringer's solution with adenosine did not prevent parenchymal cell injury, suggesting that the adenosine in the Carolina Rinse solution may work via non-hepatic mechanisms (Gao et al., 1991).
In a human clinical trial, the use of the Carolina Rinse solution improved the transaminase release by transplanted human livers. Recently, a modified Carolina Rinse solution has been examined in a cardiac preparation; coronary artery occlusion in open-chest pigs produced myocardial infarction, as expected. Modified Carolina Rinse solution plus cyclosporine, used as the initial solution for reperfusion of the cardiac tissue, decreased creatine kinase release, confirming the significant rescue of ischemic and hypoxic tissue (J. Lemasters, 1998, School of Medicine, University of North Carolina at Chapel Hill, personal communication). The inclusion of an immunosuppressant such as cyclosporine likely modulated the reperfusion injury via several mechanisms, including blockade of the mitochondrial transition pore and altered translation of protein synthesis. Despite the advantages of the Carolina Rinse solution in attenuating postischemic microvascular injury after small-bowel or liver transplantation, the value of this solution for volume replacement after trauma or hemorrhage has not been evaluated. However, the value of adding antioxidants, cytoprotective amino acids, or adenosine to resuscitation fluids warrants further study.
Numerous recent studies have raised questions about the type, volume, and rate of fluid resuscitation from shock. The incidence of ARDS and MODS in patients who have received large-volume crystalloid resuscitation is a significant concern. The finding that lactated Ringer's solution and artificial colloids increase the levels of expression of adhesion molecules, promote the release of proinflammatory cytokines, and promote cellular apoptosis suggests that fluid resuscitation has significant immunologic consequences. It was of interest that hypertonic saline solutions, shown to stabilize arterial blood pressure and cardiac output with small-volume infusion, have been shown to have no deleterious effects on immune function or to promote programmed cell death. Valid concerns have been raised regarding the composition of lactated Ringer's solution, and the omission of D-lactate with a concomitant reduction in the total L-lactate load appears feasible. The increasing availability of solutions with improved oxygen transport capabilities coupled with therapeutic strategies that limit reperfusion injury (antioxidants, iNOS inhibitors) have great potential. However,