The feasibility of organ salvage from non-heart-beating trauma donors

BACKGROUND: Blunt trauma patients without vital signs on admission are potential non-heart-beating donors. OBJECTIVE: To review the feasibility of postmortem visceral perfusion and organ donation in blunt trauma patients without vital signs. DESIGN: A retrospective case series of blunt trauma victims who were declared dead in the emergency department. SETTING: A level I trauma center. MAIN OUTCOME MEASURES: Factors potentially precluding donation and potential donor yield. RESULTS: The mean trauma-to-death interval was 71 minutes (< 60 minutes in 57% of the cases). Injuries likely to interfere with in situ perfusion were present in 41% of the cases. The tissue donation consent rate was 45%. Assuming a similar organ donation consent rate, the potential donor yield was 9% after excluding victims who were younger than 60 years of age, warm ischemia times that were less than 60 minutes, and patients who had injuries precluding perfusion. CONCLUSIONS: The potential organ yield from non-heart-beating, blunt trauma victims is low, which highlights the ethical and legal problems of this approach.     

The potential pool of non-heart-beating kidney donors

Entry of Shigella flexneri into epithelial cells and lysis of the phagosome involve the secreted IpaA-D proteins. A complex containing IpaC and IpaB is able to promote uptake of inert particles by epithelial cells. This suggested that Ipa proteins, either individually or as a complex, might interact with the cell membrane. We have purified IpaC and demonstrated its interaction with lipid vesicles. This interaction is modulated by the pH, which might be relevant to the dual role of Ipa proteins, in induction of membrane ruffles upon entry and lysis of the endosome membrane thereafter.     

A rapid organ recovery program for non-heart-beating donors

We report a successful method for rapid organ recovery from the non-heart-beating donor, which can open a new resource of organs for transplantation. The RORP is not controversial, is simple in design and execution, and results in kidneys that are viable for transplantation. Special personnel and equipment are needed but are easily incorporated in the overall budget of an OPO or donor hospital. Clearly more research is needed to rebuild ischemically damaged cells ex vivo and to develop new agents/methods to minimize the reperfusion response. When these processes are better understood and managed, the full potential of the NHBD as a donor resource will be fully achieved. We agree with others that the donor shortage could be entirely relieved by routine organ recovery from NHBD trauma victims.     

Liver transplantation using grafts from donors over 65

OBJECTIVE: Donors age 50 years was an exclusion criteria in past decades. The increase of patients in the waiting list has determined the acceptance of older donors (over 65 years old). We analyze our results in liver transplantation using donors over 65 years. PATIENTS: From 1986 to may 1994, we performed 381 OLT. In five cases (1.3%) the OLT was performed using donors over 65 years of age (66, 67, 68, 70 and 71). The selection criteria for donors and recipients were similar to the other transplanted patients. Immunosuppression included cyclosporine or FK-506, prednisone and azathioprine. RESULTS: There were no primary graft failures and preservation damage, biochemical and clinical evolution were not different to the procedures using younger donors. Three grafts presented non-corticoresistant acute rejection. After a follow-up of 11.6 mo (range 4-37 mo) only one graft was lost (Kaposi's sarcoma in the liver). Four grafts and four patients are in excellent biochemical and clinical condition. CONCLUSIONS: Donor age should not be an exclusion criteria. Grafts from older donors (over 65 years old) may be considered safe and will permit to increase the number of OLT.     

Hemodynamic follow-up of cardiac allografts from poisoned donors

BACKGROUND: The current shortage of donor organs, combined with an increasing demand for cardiac allografts, means that extended donor criteria are becoming more and more accepted. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion; few data are currently available in the medical literature. We describe our experience with 19 orthotopic heart transplant recipients of organs from donors after acute intoxication with different agents. METHODS: Between March 1989 and December 1997, 883 orthotopic heart transplantations were performed at our transplant unit. Within this group, we accepted donor hearts after ethanol intoxication (n=1), benzodiazepine (n=1), alkylphosphate (E 605) in combination with beta-blocker intoxication (n=1), carbon monoxide poisoning (n=5), digitalis (n=1), digitalis/glibenclamide (n=1), chlormethiazole (n=1), propoxyphene (n=1), alkylphosphate (E 605) (n=1), insulin (n=2), neprobamate/ thiocyacide/flurazepam (n=1), paracetamol (n=1), carbamazepine (n=1), and cyanide (n=1) intoxication. At the time of organ explantation, hemodynamic data were available from all patients. RESULTS: Early mortality in this group was 11%; cumulative survival after 5 years was 74%. CONCLUSIONS: Based on our limited experience, cardiac allografts from donors exposed to different kinds of poisons can be transplanted in selected cases. If the donor organ is not hemodynamically compromised, showing regular filling pressures on low or mild inotropic support just before explantation, and if there are no electrocardiographic changes in combination with elevation of the transaminases, cardiac allograft transplantation seems to be a safe and life-saving procedure.     

Controlled reperfusion and pentoxifylline modulate reperfusion injury after single lung transplantation

OBJECTIVE: Rodent models have suggested that initial low-pressure reperfusion of transplanted lungs reduces injury after ischemia. We investigated this phenomenon and the use of pentoxifylline in a porcine model of left single lung transplantation. METHODS: Donor lungs were preserved with Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft, pulmonary artery pressure, and gas exchange were assessed over a 12-hour period. Partial occlusion of the contralateral pulmonary artery allowed manipulation of the pulmonary artery pressure in the transplanted lung. Group A (n = 5) was perfused at a mean pulmonary artery pressure of 20 mm Hg, group B was reperfused at a mean pulmonary artery pressure of 45 mm Hg for 10 minutes before reducing the pressure to the same as group A, and group C was reperfused at a mean pressure of 20 mm Hg for 10 minutes, then increased to a mean of 45 mm Hg for the remainder of the experiment. Group D was reperfused as in group A with the addition of intravenous pentoxifylline. RESULTS: Leukocyte sequestration was observed in the first 10 minutes after reperfusion in groups A, B, and C, with maximal sequestration at 2 minutes. Significantly more sequestration was observed in the first 6 minutes in group B than in groups A and C, which were similar. Pentoxifylline significantly reduced leukocyte sequestration. Pulmonary venous oxygen tension in the allograft lung was worst in group B. Groups A and C were similar, but group D was superior to all other groups (p < 0.001). CONCLUSIONS: Low-pressure reperfusion, even when limited to the first 10 minutes, modulates reperfusion injury possibly through a leukocyte-dependent mechanism. The addition of pentoxifylline in the recipient confers significant additional benefit.     

Enhancement of endogenous cyclic AMP signal: a new approach to allow for cold preservation of rat livers from non-heart-beating donors?

BACKGROUND: The organ donor shortage has led to a reconsideration of the use of non-heart-beating donors (NHBDs). However, graft injury due to warm ischemia in NHBD livers strongly affects posttransplant outcome. The present study was aimed at investigating the role of the cellular cyclic (c)AMP second messenger signal with regard to hepatic viability after cold preservation of NHBD livers. METHODS: Cardiac arrest was induced in Wistar rats by frenotomy of the anesthetized nonheparinized animal. After 30 min, the livers were excised and flushed with 20 ml of heparinized saline solution, rinsed with 10 ml of University of Wisconsin (UW) solution, and stored submerged in UW solution at 4 degrees C for 24 hr. In half of the experiments, UW solution was supplemented with glucagon (0.5 microg/ml) to increase the cAMP signal in the liver. Reperfusion was carried out in vitro after all livers were incubated at 25 degrees C in saline solution to replicate the period of slow rewarming during surgical implantation in vivo. RESULTS: Hepatic levels of cAMP (nmol/g dry weight) declined from 1.21+/-0.05 to 0.53+/-0.03 (P<0.01) at 30 min after cardiac arrest. Subsequent storage in UW solution resulted in a further decline to 0.35+/-0.04 after 24 hr in group A, whereas glucagon treatment enhanced cellular cAMP signal to 0.64+/-0.06 (P<0.01). Upon reperfusion, liver integrity was significantly improved after glucagon administration, with 66% reduction in alanine aminotransferase release and a threefold increase in hepatic bile production as compared with untreated livers. Moreover, liver ATP tissue levels were restored to only 2.19+/-0.51 micromol/g in the untreated group but reached 4.97+/-0.41 micromol/g (P<0.05) after treatment with glucagon. CONCLUSIONS: Posthoc conditioning of predamaged livers by glucagon enhances cAMP tissue levels during ischemic preservation and improves hepatic integrity upon reperfusion. This may represent a promising approach for the use of livers from non-heart-beating donors in clinical transplantation.     

Assessment of viability of pancreas transplants from non-heart-beating cadaver

In adult rats, oxytocin (OT) has been shown to reduce the intake of both food and fluids, and oxytocinergic cells are activated by gastric distension and administration of the intestinal peptide cholecystokinin (CCK-8). These and other findings indicate that OT can play a role in inhibiting ingestion under some conditions. A previous study has shown, however, that oxytocinergic cells are unresponsive to CCK-8 in 2-day-old rats. We report here that OT is elevated in the plasma of 10-day-old rats after induction of gastric distension with both mother's milk and saline. These results indicate that the vagal-hypothalamic axis becomes mature between 2- and 10-days of age in infant rats.