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Since the last review on lung preservation in 1985, enormous progress has been made in experimental and clinical lung transplantation. This comprehensive review examines recent advances in the experimental laboratory in optimizing conditions during organ procurement, lung storage, and reperfusion to minimize ischemia-reperfusion injury in lung allografts.

The role of prostaglandin E1 (PgE1) and prostacyclin in enhancing the ischemic tolerance of single-lung grafts was investigated. Fifteen donor dogs underwent pulmonary artery flushing with 60 mL/kg of 4 degrees C modified Euro-Collins solution; 5 dogs each received a 15-minute infusion of PgE1, prostacyclin, or saline solution before flushing. After 12 hours of storage at 4 degrees C, left lung transplantation was performed in 15 recipient dogs. Measurements were performed after 10 minutes of right pulmonary artery snaring before transplantation, after transplantation, and after 2, 4, and 6 hours of reperfusion. At 6 hours, the oxygen tensions (on 100% O2) were 478 +/- 64, 296 +/- 75, 79 +/- 12, and 71 +/- 23 mm Hg in control (nontransplanted), prostacyclin-, PgE1-, and saline-treated dogs, respectively (p less than 0.05, prostacyclin or control versus saline and PgE1 dogs). Mean pulmonary artery pressures increased within each group during reperfusion, but were not significantly different among groups. Similarly, peak inspiratory pressures and wet weight to dry weight ratios were not significantly different among groups after 6 hours of reperfusion. We conclude that donor pretreatment with prostacyclin is associated with superior oxygen transfer in canine lung allografts after 12 hours of cold storage, transplantation, and 6 hours of reperfusion. In this model, donor pretreatment with PgE1 conferred no benefit to prolonged lung allograft preservation.

Biolaser induced endothelial injury combined with rabbit ear chamber techniques offers a simple and precise method of measuring platelet reactivity in vivo in conscious animals. By using this method a consistent and significant depression in the number of platelet microemboli from sites of fresh endothelial injury was found during sodium pentobarbital anaesthesia (30 mg/kg). There was no consistent barbiturate induced alteration in microcirculatory blood flow, nor could the in vivo effect be related to changes in platelet count or acid base status. However, adenosine diphosphate (ADP) induced platelet aggregation in citrated rabbit platelet rich plasma (PRP) was significantly depressed during pentobarbital anaesthesia. Observations on platelet function, in vitro or in vivo , on animals subjected to barbiturate anaesthesia must therefore be interpreted with caution.

The possibility of modifying the in vivo behaviour of platelets by drugs which inhibit the platelet ‘release reaction’ is currently a subject of considerable interest. The suppressive effect of amitriptyline and acetylsalicylic acid (ASA) on collagen induced platelet aggregation in vitro is ascribed to inhibition of the release mechanism. The effects of these materials on the platelet response to biolaser induced endothelial injury in conscious rabbits and the formation and stability of haemostatic plugs formed in transected mesenteric vessels of anaesthetised rabbits were studied. Neither ASA (200 mg/kg body weight i.v. given in THAM buffered saline) nor amitriptyline chloride (5 mg/kg b.w., i.v.) had any effect on platelet reactivity at sites of biolaser induced endothelial injury in rabbit ear chamber preparations. The same dose of amitriptyline given i.v. to urethane anaesthetised rabbits did not alter arteriolar or venular bleeding time from transected mesenteric vessels. In contrast, while ASA (200 mg/kg i.v.) did not alter the arteriolar bleeding time, the venular bleeding time was significantly decreased when compared with saline treated animals. The same result was obtained when ASA was given i.v. to pentobarbital anaesthetised animals or 2 h after oral administration of the drug. ASA had no effect on portal or central venous pressures and measurements of plasma salicylate levels after THAM-ASA gave results similar to those reported in man. The results show that, in the experimental models used, aggregation and adhesion of platelets at sites of vessel damage are not suppressed by drugs which inhibit the platelet release reaction.

Highly specific nerve staining using thiocholine techniques has been applied to a study of nerve regeneration in titanium rabbit ear chambers. Early and extensive ingrowth of nerves rich in true cholinesterase activity was demonstrated.