When does the lung die? II. Ultrastructural evidence of pulmonary viability after "death"

Abstract

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.