Perfusate Composition

A diverse number of perfusates have been utilized both clinically and experimentally to extend the ischemic procurement time and decrease the incidence of ischemia-reperfusion injury and acute lung rejection. Lung preservation solutions are variably referred to as pulmonoplegia or pneumoplegia. The Euro-Collins (EC) solution contains a high concentration of K+ and is typical of the "intracellular"-type solution, which became the benchmark for human kidney preservation and has had widespread use in lung transplantation. The high potassium content ex erts its effect by suppression of K+ efflux across the cell membrane during hypothermic ischemic storage; thus near normal intracellular K+ concentrations, and consequently Na+ concentrations, would be available to the cell during reperfusion.

The high potassium concentration has been perceived by some to contribute to endovascular injury during the flush and storage phases of preservation, deemed an important step in the ischemia-reperfusion phenomenon. High K+ causes vasoconstriction, inhomogeneous flushing of the graft, and elevated pulmonary vascular resistance during reperfusion. Some centers have reported that prostaglandin administration and/or hyperinflation ameliorates this effect and offers results indistinguishable from low K+, extracellular type solutions.6

Another prototypical intracellular-type solution is the University of Wisconsin (UW, Viaspan, Belzer) solution. It differs from EC solution due to many additives, and has been demonstrated to enhance and extend the preservation of hepatic, pancreatic and renal allografts relative to the EC solution. High molecular weight impermeants (lactobionate), colloid (hydroxyethylstarch, HES) and trisac-charide (raffinose) are osmotically active agents which help prevent edema formation. Glutathione is added for the antioxidant effect of its sulfhydryl group, adenosine is added as an ATP precursor and pulmonary vasodilator, and hydroxyethyl starch as a stable nontoxic colloid. Allopurinol is added as a xan-thine oxidase inhibitor and free radical scavenger. Two canine lung allotransplantation studies comparing EC to UW demonstrated improved gas exchange, lung compliance, lower pulmonary vascular resistance, and improved histologic indices of pulmonary edema in the UW treated group.7,8 One clinical trial comparing EC to UW solution in a nonrandomized fashion showed that UW solution conferred equivalent gas exchange and chest radiograph exams despite a longer preservation period than in the EC solution group.9

Which of the numerous components of the UW solution confer the additive benefit over the EC solution is a matter of debate. A rat model using paracorporeal perfusion of preserved lungs and sequentially depleted UW components indicates that it is the impermeant trisaccharide raffinose which appears to be the major factor responsible for its efficacy.10

"Extracellular-type" solutions, such as LPD (low potassium dextran) have been found both clinically and experimentally to avoid this observed high K+-induced pulmonary vascular injury.11,12 In a primate bilateral allotransplantation model, antegrade LPD pulmonary artery perfusion conferred excellent acute graft function after 12 hours of ischemic time.13 Attempts to modify the standard UW solution to avoid high K+-induced pulmonary vascular injury have found no significant change in organ storage efficacy, raising questions about the mechanism of intracellular solution preservative effect. Rabbit lung preservation studies looking at low-potassium UW solution demonstrated that a lower concentration of K+ (from 120 mmol/L to 3 mmol/L) was associated with improved gas exchange and organ wet/dry weight ratios than standard UW solution.14,6

A more complete discussion of the components of organ preservation solutions and their effect can be found in Chapter 5.

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