It has been reported that ischemic preconditioning of the heart or brain has a possible relevance to heat shock protein (HSP). It is still unknown, however, whether HSP induced by means of ischemic preconditioning of the liver is a direct factor in the acquisition of tolerance to succeeding ischemia-reperfusion injury. In the present study we used ischemic preconditioning of the liver to verify the effects of induced HSP72 in the liver on the subsequent longer warm ischemia and reperfusion. Rats preconditioned with short-term (15-minute) ischemia were compared with rats preconditioned by heat exposure or with control rats. After a 48-hour recovery from the sublethal stress for preconditioning, all rats were exposed to longer (30-minute) warm ischemia and reperfusion. Forty-eight hours after ischemic preconditioning, HSP72 was clearly induced in the liver, as well as in the liver preconditioned with heat shock, but not in the kidney or heart. This ischemic preconditioning also attenuated the liver damage in the subsequent ischemia-reperfusion injury, improving the restoration of hepatic function during reperfusion and resulting in higher postischemic rat survival. According to the proposed model of tolerance acquisition for ischemia-reperfusion injury by stress preconditioning, these observations support the speculation that the induced HSP72 plays some beneficial role in this protection mechanism.

The present study establishes a new perspective for the use of ischemically altered livers from nonheartbeating donors for organ transplantation under clinical circumstances.

Retrograde oxygen persufflation as a supplement of cold storage during the preservation period has the potential to better utilize ischemically damaged marginal livers in the experimental setting. Retrograde oxygen persufflation was applied in selected livers to demonstrate feasibility in the clinical setting and to investigate potential beneficial effects. Between 4/04 and 3/05 5 marginal otherwise discarded livers with warm ischemic damages from deceased donors (age 52 ) were accepted for transplantation. All organs were distantly procured and shipped to our center. Immediately after arrival, filtered humidified gaseous oxygen was given via the hepatic veins for at least 60 minutes with a pressure up to 18 mm mercury. Liver biopsies were analyzed for ATP content before and after persufflation. All patients (age 55 [46 -66]) survived without retransplantation, had good initial function and are alive and well after minimum follow-up of two years. Bleeding from pinpricks stopped spontaneously after 5-10 minutes after reperfusion but was prolonged in one patient with severe coagulopathy until correction. One patient developed arterial thrombosis at postop day 0. He fully recovered after thrombectomy. Another patient developed subcapsular hematoma, which was removed at postop day 10. On routine postoperative biopsies vascular structures appeared undamaged. ATP levels in pre-reperfusion biopsies revealed a more than twofold increase of ATP content compared to biopsies before persufflation. Retrograde oxygen persufflation preservation is feasible and save in the clinical setting, improves early aerobic metabolism and therefore potentially improves primary organ function after liver transplantation. Organ shortage is the main problem in liver transplantation leading to a high mortality rate on the waiting list. Possible mechanisms to alleviate this difficulty include extension of living donations, split liver transplantation, and, increasingly, the use of marginal organs. 1 The outcome of the use of potentially critical marginal organs could be enhanced by the improvement of preservation and revitalization techniques applied during the cold ischemia time period.Experimental studies investigating the effect of hypothermic liver perfusion pump systems with oxygenation reveal promising results. 2,3 However, these perfusion system machines are expensive, technically complex, and not yet fully developed for clinical application. 4 Machine perfusion, although analyzed in experimental studies up to now, does not have a clinical impact on the preservation of livers.In several ex vivo studies and recently in an in vivo study, we demonstrated successful extension of ischemic tolerance of porcine livers by cold preservation including postconditioning with gaseous oxygen [retrograde oxygen persufflation (ROP)]. 5,6 Also, the detrimental effects of 60 minutes of warm ischemia for kidneys were completely reversible with ROP. 7 On the basis of our experimental results, we applied ROP in Abbreviations: ALAT, alanine aminotransferase;...

The use of carbon dioxide gas warmed to body temperature to produce a pneumoperitoneum during short-term laparoscopic surgery has no clinically important effect.