Improvement of pulmonary graft after storage for twenty-four hours by in vivo administration of lazaroid U74389G: functional and morphologic analysis.
BACKGROUND
We examined the effects of in vivo administration of a potent inhibitor of iron-dependent lipid peroxidation, lazaroid U74389G, on lung preservation.


METHODS
Lungs isolated from Sprague-Dawley rats (n = 23) were either immediately reperfused after removal (control, n = 8) for 2 hours by means of an isolated, pulsatile blood perfusion system or reperfused after cold storage (4 degrees C) for 24 hours in the University of Wisconsin solution with (n = 7) or without (n = 8) lazaroid. The lazaroid group had in vivo infusion of lazaroid U74389G (6 mg/kg) before lung harvest plus addition to the perfusate (50 mu mol/L) at the onset of reperfusion. Routine aerodynamics, hemodynamics, and blood gases were assessed during the perfusion period. Lipid peroxidation in the lung tissue was assayed with the thiobarbituric acid-reactive product, malondialdehyde. Histologic evaluation was performed with light microscopic and transmission electron microscopic analyses.


RESULTS
All lungs in the University of Wisconsin solution group (24-hour storage without lazaroid) failed within 1 hour of reperfusion. Lungs in control and University of Wisconsin solution + lazaroid group survived the 2-hour perfusion period. University of Wisconsin solution + lazaroid group showed significantly better arterial oxygen tension values relative to those in the University of Wisconsin solution group (control, 85.2 +/- 1.9; University of Wisconsin solution, 53.9 +/- 3.2 [p < 0.05 versus control group and University of Wisconsin solution + lazaroid]; University of Wisconsin solution + lazaroid, 74.8 +/- 1.4; arterial oxygen tension (mm Hg) at 30 minutes). Lipid peroxide in University of Wisconsin solution + lazaroid group was significantly lower than that of the University of Wisconsin solution group (65.0 +/- 5.0 versus 495 +/- 105 nmol malondialdehyde/gm wet lung tissue; p < 0.01). Transmission electron microscopic analysis showed that University of Wisconsin solution + lazaroid group significantly attenuated lung damage when compared with University of Wisconsin solution group.


CONCLUSIONS
Administration of lazaroids in vivo before organ harvest and in situ at the onset of the reperfusion enhances lung preservation in this model.
Sasaki
S
S
Section of General Thoracic Surgery, Harvard Medical School, New England Deaconess Hospital, Boston, MA 02215, USA.
Alessandrini
F
F
Lodi
R
R
McCully
J
J
LoCicero
J
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D016040:Lung Transplantation / Q000473:pathology / Q000502:physiology; D008297:Male; D008854:Microscopy, Electron; D009926:Organ Preservation / Q000379:methods*; D010477:Perfusion / Q000379:methods; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion / Q000379:methods; D013997:Time Factors
D000975:Antioxidants; D011281:Pregnatrienes; C074965:U 74389F