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The shortage of lung donors for clinical transplantation could be significantly alleviated if lungs could be retrieved from cadavers hours after death. However, the time course of loss of lung viability after circulatory arrest and organism death remains unclear. To determine postmortem adenine nucleotide tissue levels in the lung and their relationship to lung viability, Sprague-Dawley rats were sacrificed and then ventilated with 100% oxygen (n = 50, O2) or 100% nitrogen (n = 40, N2) or left nonventilated (n = 50). Lungs from control rats (n = 20) were retrieved immediately after sacrifice. Lungs in the three study groups were retrieved at successive intervals postmortem. Adenine nucleotides (ATP, ADP, and AMP) and hypoxanthine and xanthine metabolites of adenosine were extracted from lung tissue and measured using high-performance liquid chromatography. Pulmonary parenchymal cell viability was quantified by pulmonary artery infusion of trypan blue vital dye in the contralateral lung of each animal. By 4 hr postmortem, viability was 85 +/- 1% in the O2-ventilated cadaver rat lungs, significantly higher than in the N2-ventilated (43 +/- 8%) and in the nonventilated (48 +/- 4%) lungs, where the percentage of viable cells was similar. All of the groups showed a time-dependent decrement in ATP levels and total adenine nucleotide (TAN) levels after death, but this was markedly attenuated in O2-ventilated cadaveric rat lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung transplantation as a therapy for end-stage lung disease is limited by the paucity of suitable donors. If lungs could be retrieved from circulation-arrested cadavers (that is, after death), then more donors for lung transplantation might be available. This study was undertaken to determine the time course of ultrastructural deterioration of cellular organelles in pulmonary tissue after circulatory arrest and death and to determine the effect, if any, of postmortem ventilation on the development of these ultrastructural changes. Sprague-Dawley rats were sacrificed and then separated into three groups: (1) controls, from which the right lung was immediately harvested (n = 4); (2) ventilated group, in which mechanical ventilation with 100% oxygen was started after death (n = 15); and (3) nonventilated group (n = 15). In the ventilated and nonventilated groups, the right lung was harvested at 2, 4, or 8 hours after death. Portions of the lung from each rat were examined by electron microscopy, and each specimen was assigned a semiquantitative injury score that was based on nuclear chromatin clumping, mitochondrial degeneration, intracellular edema, and cellular membrane integrity. The lung in all four controls was normal. At 4 and 8 hours postmortem, ultrastructural damage was significantly attenuated in rats with oxygen ventilation compared with those in the nonventilated group. The degree of ultrastructural damage observed in the oxygen ventilation group at 2 and 4 hours postmortem was not significantly different from that of normal controls. Thus, mechanical ventilation with oxygen after death appears to preserve lung ultrastructure and may delay cell death. This study supports the hypothesis that lung transplantation from cadaver donors may be feasible.

An inadequate number of lung donors for transplantation results in the death of many potential lung recipients awaiting a transplant. Canine experiments in our laboratory have shown effective gas exchange in lungs transplanted from cadaver donors (lungs retrieved after circulatory arrest). The time course of pulmonary cell death after circulatory arrest is unknown. To address this question, we used trypan blue dye exclusion to quantitate lung cell death at postmortem intervals in rats. One hundred ninety Sprague-Dawley rats were killed and separated into four groups: (1) control (n = 10); (2) nonventilated group (n = 60); (3) oxygen-ventilated group (n = 80); and (4) nitrogen-ventilated group (n = 40). At intervals after the animals' deaths, trypan blue was infused into the pulmonary artery followed by fixative, and the left lung was excised. Histologic sections were prepared for each rat lung, and the percentage of nonviable cells was quantified with light microscopy. Control lungs retrieved immediately after death showed little or no uptake of trypan blue dye. In nonventilated rats, 36%, 52%, and 77% of cells were nonviable in lungs retrieved 2, 4, and 12 hours after death, respectively. These results were similar to 34%, 58%, and 71% nonviability at the same intervals in nitrogen-ventilated cadaver rat lungs. Oxygen-ventilated cadaver rats, however, had significantly fewer nonviable lung cells at each time interval: 13%, 10%, and 26%, respectively (p < 0.01). Thus, postmortem mechanical ventilation with oxygen appears to delay lung death in the rat after circulatory arrest. Nonventilated and nitrogen-ventilated cadaver lungs had a similar severity and progression of ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)