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Background: Pressure to expand the donor pool has required the use of lungs from older donors or from more-distant procurement areas. The long-term consequences of this policy have not yet been fully addressed. The effect of donor age and donor ischemic time on intermediate survival and important secondary end points after lung transplantation was therefore examined., Methods: A cohort of 1,800 lung transplant recipients with complete 2-year follow-up, operated on in the United States between April 1, 1993, and March 31, 1996, was studied to assess survival. For analysis of secondary end points, the cohort was limited to 1,450 patients., Results: Donor age when analyzed independently did not significantly affect intermediate survival (p = 0.4). Secondary end points were also not affected by age, with the exception of the incidence of hospitalization for rejection in the univariate analysis (p = 0.02) and in the multivariate analysis (p = 0.04). Moreover, there was not a significant impact of donor age or ischemic time independently on survival in the multivariate analysis. Similarly, when the interaction between ischemic time and donor age was examined in all of the multivariate models, none of the secondary end points were found to be significantly influenced. However, the combined interaction between donor age and ischemia time demonstrated a significantly worse survival at 2 years (p = 0.02) with donor age of > 50 years and donor ischemic time > 7 h., Conclusions: Donor age and donor ischemic time did not independently influence survival or important secondary end points after lung transplantation. However, intermediate-term survival was affected by the use of older donors when combined with a prolonged ischemic time. The impact of this combination should be considered when attempting to expand the donor pool.

Background: The advances in immunotherapy, along with a liberalization of eligibility criteria have contributed significantly to the ever increasing demand for donor organs. In an attempt to expand the donor pool, transplant programs are now accepting older donors as well as donors from more remote areas. The purpose of this study is to determine the effect of donor age and organ ischemic time on survival following orthotopic heart transplantation (OHT)., Methods: From April 1981 to December 1996 372 adult patients underwent OHT at the University of Western Ontario. Cox proportional hazards models were used to identify predictors of outcome. Variables affecting survival were then entered into a stepwise logistic regression model to develop probability models for 30-day- and 1-year-mortality., Results: The mean age of the recipient population was 45.6 +/- 12.3 years (range 18-64 years: 54 < or = 30; 237 were 31-55; 91 > 56 years). The majority (329 patients, 86.1%) were male and the most common indications for OHT were ischemic (n = 180) and idiopathic (n = 171) cardiomyopathy. Total ischemic time (TIT) was 202.4 +/- 84.5 minutes (range 47-457 minutes). In 86 donors TIT was under 2 hours while it was between 2 and 4 hours in 168, and more than 4 hours in 128 donors. Actuarial survival was 80%, 73%, and 55% at 1, 5, and 10 years respectively. By Cox proportional hazards models, recipient status (Status I-II vs III-IV; risk ratio 1.75; p = 0.003) and donor age, examined as either a continuous or categorical variable ([age < 35 vs > or = 35; risk ratio 1.98; p < 0.001], [age < 50 vs > or = 50; risk ratio 2.20; p < 0.001], [age < 35 vs 35-49 versus > or = 50; risk ratio 1.83; p < 0.001]), were the only predictors of operative mortality. In this analysis, total graft ischemic time had no effect on survival. However, using the Kaplan-Meier method followed by Mantel-Cox logrank analysis, ischemic time did have a significant effect on survival if donor age was > 50 years (p = 0.009). By stepwise logistic regression analysis, a probability model for survival was then developed based on donor age, the interaction between donor age and ischemic time, and patient status., Conclusions: Improvements in myocardial preservation and peri-operative management may allow for the safe utilization of donor organs with prolonged ischemic times. Older donors are associated with decreased peri-operative and long-term survival following. OHT, particularly if graft ischemic time exceeds 240 minutes and if these donor hearts are transplanted into urgent (Status III-IV) recipients.

The practice of lung transplantation is constrained by a shortage of suitable donor organs. Furthermore, even "optimal" donor lung grafts are at risk of significant dysfunction perioperatively. Significant insights into the cellular and molecular mechanisms of pulmonary ischemia-reperfusion injury have occurred since the publication of previous reviews on lung preservation 3 to 4 years ago. Recent evidence indicates that the endothelium plays an essential role in regulating the dynamic interaction between pulmonary vasodilatation and vasoconstriction and is a major target during lung injury. In addition, the composition, function, and metabolism of pulmonary surfactant produced by alveolar type II cells are increasingly being recognized as important factors in pulmonary ischemia-reperfusion injury. We hypothesize that reperfusion after a period of pulmonary ischemia results in significant endothelial and alveolar type II cell dysfunction and that an important strategy in lung preservation is to preserve the integrity of these cells in the face of this injury. Given the persistent shortage of lungs available for transplantation, laboratory studies need to focus also on the "rescue" of compromised donor lungs that would have been previously regarded as unsuitable. Importantly, innovative work from the laboratory needs to be translated into clinical practice via prospective, randomized trials to ensure that the prevalence of postoperative lung graft dysfunction is reduced and the shortage of lung grafts for transplantation is alleviated.

We have previously documented alterations in endogenous surfactant after lung transplantation and improved graft function in some dogs after instillation of bovine lipid extract surfactant (bLES) into the recipient. To determine the effect of bLES delivery method and timing of treatment on physiologic response and surfactant recovery, 21 canine left lung grafts were divided into four groups: (1) Treatment of the donor for 3 h with aerosolized bLES prior to graft storage (Donor Aerosol); (2) Treatment of the recipient with instilled bLES immediately after transplantation (Recipient Instilled); (3) No bLES treatment (Control); and (4) Aerosolized bLES in donors and instilled bLES in recipients (Combined Therapy). Aerosolized bLES was labeled with [3H]-dipalmitoylphosphatidylcholine (DPPC) and instilled bLES with [14C]-DPPC. Grafts were stored for 36 h, transplanted and reperfused for 6 h. The native right and transplanted left lungs were then lavaged and protein yield, surfactant aggregates, and bLES recovery were measured. After 6 h of reperfusion, PO2/FlO2 ratio was significantly better after Combined Therapy (372 +/- 52 mm Hg) than in the Recipient Instilled (117 +/- 47 mm Hg) and Control groups (87 +/- 26 mm Hg), with intermediate values in Donor Aerosol dogs (232 +/- 64 mm Hg). The recovery of donor aerosolized bLES from transplanted lungs was increased in dogs given Combined Therapy versus Donor Aerosol treatment alone (p = 0.03). Furthermore, with Combined Therapy there was an increased percentage of instilled bLES recovered from transplanted lungs compared with the Recipient Instilled group. We conclude that surfactant treatment strategies influence physiologic response and bLES recovery after prolonged lung preservation. Treatment of lung donors with exogenous surfactant prior to graft storage was associated with less severe lung injury. Combined donor and recipient bLES therapy resulted in a superior physiologic response during reperfusion in this model.

Previous work in our laboratory has documented alterations in surfactant composition and function after prolonged lung graft storage and transplantation in dogs (Am Rev Respir Dis 1993;148:208-15). To determine whether exogenous surfactant therapy was beneficial, we pretreated 13 canine double lung blocks with prostacyclin, flushed them with 4 degrees C modified Euro-Collins solution, and stored them at 4 degrees C for 37 to 38 hours. After left lung transplantation and immediately before reperfusion, eight dogs were administered 50 mg of bovine lung lipid extract surfactant per kilogram (50 mg/ml) directly into the left main bronchus and five served as nontreated control animals. Blood gases, peak inspired pressures, and individual pulmonary artery blood flows were measured every 30 minutes during 6 hours of reperfusion. The native right and transplanted left lungs were then lavaged and surfactant large and small aggregates and protein yields were analyzed. All nontreated animals had physiologic evidence of severe ischemia-reperfusion lung injury during reperfusion. Three of eight dogs treated with bovine lung lipid extract surfactant had near normal lung function at 6 hours of reperfusion, as reflected by maintenance of an oxygen tension/inspired oxygen fraction ratio of more than 400 mm Hg and a normal carbon dioxide tension. Five of eight dogs did not respond to surfactant therapy and had decreases in gas exchange identical to those of the control animals. Blood flow through the left pulmonary artery was maintained in the three animals that responded to exogenous surfactant, whereas flow significantly decreased to the left lung in all other animals, reflecting the patterns of gas exchange. In addition, the ratio of poorly functioning small surfactant aggregates to the well-functioning large aggregates isolated from lung lavage after 6 hours of reperfusion was decreased in surfactant-treated animals, especially in those exhibiting a beneficial physiologic response to surfactant therapy. We conclude that therapy with bovine lung lipid extract surfactant can result in excellent preservation of lung grafts after prolonged storage and transplantation, but that the results are not consistent. Further investigations are required to determine the factors responsible for the differential response to surfactant therapy.

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.

Of 219 heart transplant patients with follow up for at least 3 months after transplantation, cardiac allograft ischemic time was more than 4 hours in 28% and more than 5 hours in 10%. In 1988 and 1989 grafts with ischemic times longer than 4 hours were used in 44% and 45% of cases, respectively. Overall, donor age has been 35 or more years in 22% and 45 or more in 9%. In 1989 donor age was 35 or more years in 39% of cases and 45 or more in 18%. Fifteen of 20 grafts from donors 45 years or older were used for patients aged 50 or older. There was no relationship between donor age or ischemic time and 90-day graft loss. At 3 and 12 months, cardiac function, assessed by treadmill exercise duration, radionuclide angiography, and rest and peak supine exercise hemodynamics, was also unrelated to donor age or ischemic time. Therefore by careful selection of appropriate donors, extending both graft ischemic time and donor age has increased the potential donor pool and has not to date been associated with increased graft loss or adverse effects on cardiac function 3 months and 1 year after heart transplantation.