WHEN DOES THE LUNG DIE - TIME-COURSE OF HIGH-ENERGY PHOSPHATE-DEPLETION AND RELATIONSHIP TO LUNG VIABILITY AFTER DEATH

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, O-2) or 100% nitrogen (n = 40, N-2) 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 O-2-ventilated cadaver rat lungs, significantly higher than in the N-2-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 O-2-ventilated cadaveric rat lung. In the control group, the level of TAN was 10.2 +/- 0.9 mu moles/g dry weight, while TAN levels fell to 5.8 +/- 0.9 in O-2-ventilated lungs, 4.4 +/- 0.6 in N-2-ventilated lungs, and 3.3 +/- 0.2 in nonventilated lungs 4 hr after death. As TAN levels declined, lung tissue levels of hypoxanthine and xanthine increased after death, more so in nonventilated cadaver lungs, and less so in O-2-ventilated cadaveric rat lung. TAN levels correlated well with the viability of pulmonary parenchymal cells in the postmortem lung across all of the groups and times postmortem (r = 0.88). O-2 ventilation of the nonperfused lung preserved adenine nucleotides, compared with N-2 ventilation or nonventilation, and this correlated with increased pulmonary parenchymal cell viability. Viability of the postmortem lung may allow retrieval from cadavers and successful transplantation in the clinical setting. (C) 1995 Academic Press, Inc.