Alteration of neuropeptides in the lung tissue correlates brain death-induced neurogenic edema.
BACKGROUND
Increased intracranial pressure induces neurogenic pulmonary edema (NPE), potentially explaining why only lungs from less than 20% of brain dead organ donors can be used for transplantation. This study investigated the underlying mechanisms of NPE, focusing on neuropeptides, which potently induce vasoconstriction, vasodilatation, and neurogenic inflammation.


METHODS
Brain death was induced in 10 pigs by increasing the intracranial pressure. Eight additional pigs served as controls. Neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and substance P were analyzed in plasma, bronchoalveolar lavage (BAL) fluid, and homogenized lung tissue 6 hours after brain death. Pulmonary oxygen exchange was estimated using partial pressure of arterial oxygen (Pao2)/fraction of inspired oxygen (Fio2), and pulmonary edema by wet/dry weight ratio.


RESULTS
Brain death induced a decrease in Pao(2)/Fio2 (p < 0.001) and increased the wet/dry weight of both apical (p = 0.01) and basal lobes (p = 0.03). NPY and CGRP concentrations were higher in the BAL fluid of brain-dead animals compared with controls (p = 0.02 and p = 0.02) and were positively correlated with the wet/dry weight ratio. NPY content in lung tissue was lower in brain-dead animals compared with controls (p = 0.04) and was negatively correlated with the wet/dry weight ratio. There were no differences in substance P concentrations between the groups.


CONCLUSIONS
NPY was released from the lung tissue of brain-dead pigs, and its concentration was related to the extent of pulmonary edema. NPY may be one of several crucial mediators of neurogenic pulmonary edema, raising the possibility of treatment with NPY-antagonists to increase the number of available lung donors.
Barklin
Anne
A
Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark. Barklin@ki.au.dk
Theodorsson
Elvar
E
Tyvold
Stig S
SS
Larsson
Anders
A
Granfeldt
Asger
A
Sloth
Erik
E
Tonnesen
Else
E
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001926:Brain Death / Q000175:diagnosis* / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000378:metabolism*; D020078:Neurogenic Inflammation / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D011237:Predictive Value of Tests; D011654:Pulmonary Edema / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D015415:Biomarkers; D009478:Neuropeptide Y; D009479:Neuropeptides; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide