Nitroprusside Ameliorates Lung Allograft Reperfusion Injury

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Background

Nitric oxide is believed to play a critical role in the maintenance of vascular integrity through its interaction with neutrophils, platelets, and cellular components of the vessel wall. It has been reported that endogenous nitric oxide level was depressed after ischemia, reperfusion, or both. Furthermore, exogenous as well as endogenous nitric oxide decreases reperfusion-induced vascular dysfunction. We hypothesized that nitroprusside, a potent nitric oxide donor, might enhance lung preservation and reduce posttransplantation lung allograft dysfunction.

Methods

Ten dogs underwent left lung allotransplantation. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1°C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gas analysis (inspired oxygen fraction, 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase activity and wet-to-dry weight ratio were assessed. Group 1 (n = 5) animals received no nitroprusside. In group 2 (n = 5), the donor lung received nitroprusside in the flush solution (10 mg/L) and recipient animals received 0.2 mg/kg just before reperfusion as well as a continuous infusion (0.11 ± 0.01 mg · kg−1 · h_1) during the assessment period.

Results

Superior gas exchange and hemodynamics were noted in lungs receiving nitroprusside. Although allograft myeloperoxidase activity and the total amount of fluid suctioned from the allograft were significantly reduced in group 2, protein levels in bronchoalveolar lavage fluid were not statistically different.

Conclusions

Nitroprusside administration in the flush solution and during reperfusion improves lung allograft function and blood flow, and reduces pulmonary vascular resistance and myeloperoxidase activity in the transplanted lung. Nitroprusside reduces lung allograft reperfusion injury.

Section snippets

Material and Methods

Weight-matched pairs of 10 adult mongrel dogs were used. All animals received humane care in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the National Academy of Science and published by the National Institutes of Health (NIH publication 85–23, revised 1985).

Results

There were no significant differences among groups with respect to donor weight, recipient weight, flushing times, preservation time, and warm ischemic time (see Table 1). However flushing pressures in group 2 were significantly lower than those in group 1 (group 1, 18.8 ± 1.1 mm Hg; group 2, 15.1 ± 1.1 mm Hg; p < 0.05). Flushing times in group 1 and 2 were 87 ± 7 and 93 ± 8 seconds, respectively. Preservation time of groups 1 and 2 were 21 hours 7 minutes ± 4 minutes and 20 hours 58 minutes ± 7 minutes,

Comment

Despite a large number of studies, the specific pathophysiologic mechanism of ischemia-reperfusion injury remains unclear. However, it has been demonstrated that endothelial dysfunction [4, 7], neutrophil activation [5, 12], oxygen free radicals [13, 14], platelet activation [15], and various cytokines [16] are involved in ischemia-reperfusion injury. The endothelium appears to play a critical role in maintaining vascular homeostasis in ischemic heart [7], lung [8], and intestine [4, 17].

Nitric

Discussion

DR WALTER KLEPETKO (Vienna, Austria): Doctor Yamashita, I congratulate you on this well-designed, timely, and interesting study.

Nitric oxide has played an important role within the last years. Although its mechanism of acting is by far not completely understood, it has a tremendous potential and striking effects on pulmonary circulation and gas exchange as well. This has led to a widespread application of its inhaled form for treatment of patients with different forms of pulmonary

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