Mitochondrial Injuries in Rat Lungs Preserved for 17 h: An Ultrastructural Study

Abstract

Mitochondria of the small vasculature endothelial cells were examined in preserved rat lungs before and after reperfusion, and the ultrastructural changes were correlated with pulmonary function after reperfusion. Rat lungs were flushed with perfusate and prostaglandin E1 and divided into five groups (n = 5 in each group): group A, normal control group; group B, University of Wisconsin solution; group C, Euro-Collins solution; group D, ET-Kyoto solution, and group E, new ET-Kyoto solution. After preservation at 4°C for 17 h, the left lungs were reperfused at 37°C for 60 min. Tissue was sampled and mitochondria of the small vasculature endothelial cells were ultrastructurally analyzed by transmission electron microscopy before and after reperfusion. The ultrastructure of the mitochondria was well maintained in groups A, B and E before and after reperfusion. In group C, the number of severely degenerated mitochondria in the sectional area of 100 μm² before reperfusion was 18.0 ± 3.9, which was significantly larger than in the other groups (p < 0.01), and the total number of mitochondria significantly decreased with reperfusion (from 24.8 ± 3.5 to 8.2 ± 2.4, p < 0.05). In group C, the shunt fraction, mean pulmonary arterial pressure and the wet-dry ratio of the lung tissue after reperfusion C were significantly higher than in the other groups (p < 0.05; 76.3 ± 1.5%, 54.8 ± 4.2 mm Hg, and 20.6 ± 2.5, respectively). A positive correlation was found between the percentage of the mitochondrial degeneration before reperfusion and the physiological parameters after reperfusion. Mitochondrial damage associated with cold ischemia is probably involved in lung injury caused by cold preservation and reperfusion.

The Mitochondrial K-ATP Channel Opener, Diazoxide, Prevents Ischemia-Reperfusion Injury in the Rabbit Spinal Cord

“…Similar changes in structure have been correlated to physiological function in rat lung cells subject to ischemia and reperfusion in vitro. 41 To our knowledge, this is the first report that correlates mitochondrial structure and function in an in vivo model of neurological injury.…”

Prevention of Cold-Preservation Injury of CulturedEndothelial Cells by Catecholamines and Related Compounds

“…Attempts to prevent neutrophil infiltration, by using soluble P‐selectin glycoprotein ligand (sPSGL) or neutralizing chemokine antibodies, have shown benefit in animal models for IR injury (10,17) but may not be effective in situations where the endothelium is severely damaged such as during prolonged cold preservation. Changes in pH homeostasis or cytosolic calcium (18) and impairment of the mitochondrial respiratory function (19) are only a few examples of cell‐damaging events occurring as a consequence of prolonged hypothermic preservation.…”

Effect of Adenosine Triphosphate–Sensitive Potassium Channel Openers on Lung Preservation

“…We also found that pinacidil maintained the mitochondrial respiratory function during preservation and that this effect was lost by a KATP blocker, glibenclamide. We reported previously that during lung preservation, the degree of morphologic injury in the mitochondria correlated with the levels of pulmonary dysfunction such as impairment of the lung oxygenation capacity and lung compliance as well as with the level of pulmonary edema (19). We also reported that the degree of mitochondrial morphologic injury became more severe with prolongation of the preservation time and that the concentrations of ATP and TAN decreased after reperfusion (18).…”

“…We also reported that the postreperfusion recovery of ATP levels was correlated with the lung reperfusion injury (18) and that mitochondrial dysfunction was likely to be involved in the lung reperfusion injury (19). To clarify the effectiveness of KATP openers in lung preservation, we examined the effect of pinacidil on pulmonary function after reperfusion.…”