Hemodynamic resuscitation with arginine vasopressin reduces lung injury after brain death in the transplant donor.
BACKGROUND
The autonomic storm accompanying brain death leads to neurogenic pulmonary edema and triggers development of systemic and pulmonary inflammatory responses. Neurogenic vasoplegia exacerbates the pulmonary injury caused by brain death and primes the lung for ischemia reperfusion injury and primary graft dysfunction in the recipient. Donor resuscitation with norepinephrine ameliorates the inflammatory response to brain death, however norepinephrine has deleterious effects, particularly on the heart. We tested the hypothesis that arginine vasopressin is a suitable alternative to norepinephrine in managing the hypotensive brain dead donor.


METHODS
Brain death was induced in Wistar rats by intracranial balloon inflation. Pulmonary capillary leak was estimated using radioiodinated albumin. Development of pulmonary edema was assessed by measurement of wet and dry lung weights. Cell surface expression of CD11b/CD18 by neutrophils was determined using flow cytometry. Enzyme-linked immunosorbent assays were used to measure the levels of TNFalpha, IL-1beta, CINC-1, and CINC-3 in serum and bronchoalveolar lavage. Quantitative reverse-transcription polymerase chain reaction was used to determine the expression of cytokine mRNA (IL-1beta, CINC-1 and CINC-3) in lung tissue.


RESULTS
There was a significant increase in pulmonary capillary permeability, wet/dry lung weight ratios, neutrophil integrin expression and pro-inflammatory cytokines in serum (TNFalpha, IL-1beta, CINC-1 and CINC-3), bronchoalveolar lavage (TNFalpha and IL-1beta) and lung tissue (IL-1beta and CINC-1) in braindead animals compared to controls. Correction of neurogenic hypotension with either arginine vasopressin or norepinephrine limits edema, reduces pulmonary capillary leak, and modulates systemic and pulmonary inflammatory responses to brain death.


CONCLUSIONS
Arginine vasopressin and norepinephrine are equally effective in treating the hypotensive pulmonary donor in this rodent model.
Rostron
Anthony J
AJ
Applied Immunology and Transplant Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. a.j.rostron@ncl.ac.uk
Avlonitis
Vassilios S
VS
Cork
David M W
DM
Grenade
Danielle S
DS
Kirby
John A
JA
Dark
John H
JH
D000818:Animals; D001127:Arginine Vasopressin / Q000627:therapeutic use*; D001926:Brain Death; D002463:Cell Membrane Permeability / Q000187:drug effects; D005434:Flow Cytometry; D006439:Hemodynamics; D008168:Lung / Q000187:drug effects / Q000473:pathology; D055370:Lung Injury; D008297:Male; D023421:Models, Animal; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation / Q000379:methods*; D014019:Tissue Donors
D001127:Arginine Vasopressin; D009638:Norepinephrine