Nitroglycerin alters alveolar type II cell ultrastructure after ischemia and reperfusion

Background: Although administration of nitric oxide (NO) has been suggested to reduce pulmonary reimplantation response, concerns remain about cytotox ic side effects. Methods: Using light and electron microscopy, we examined the effects of th e NO donor nitroglycerin (NTG) (0.1 mg/ml) as a supplement to the preservat ion solution Celsior on the structural integrity of rat lungs after extraco rporeal ischemia (4 hours at 10 degreesC) and reperfusion (50 minutes) (IR) . We performed evaluation in comparison with Celsior alone after IR using e ither standard antegrade perfusion through the pulmonary artery or retrogra de perfusion through the left atrium as an alternative way to improve the p reservation quality. Untreated, non-ischemic lungs served as controls (n = 5 per group). We recorded respiratory and hemodynamic parameters during rep erfusion. Tissue collection using systematic uniform random sampling was re presentative for the whole organ and allowed stereologic quantification of structures. Results: After IR, histochemistry revealed no breaks in the alveolo-capilla ry barrier and we detected no alveolar flooding. Edema formed in the peribr onchovascular cuffs, of which the volume fraction was increased (p =.008). Vasoconstriction of the smaller arteries accompanied antegrade flush, which occurred neither after administration of NTG nor after retrograde flush, a s shown by immunostaining for alpha -smooth muscle actin. Treatment with NT G was associated with focal disintegration of Type If cells, which displaye d edematous swelling of distinct cell compartments and lysis of mitochondri a and cells. Nitroglycerin prevented alveolar collapse, which was increased in the other IR groups (p =0.013). We observed alterations in intra-alveol ar surfactant components. Conclusion: These findings indicate pathologic effects of NTG treatment on alveolar epithelial integrity. Therefore, we suggest further critical evalu ation of NTG/NO for therapeutic use in lung transplantation.