Amelioration of post-ischemic lung reperfusion injury by prostaglandin E1.
To reduce ischemia-reperfusion injury, a number of clinical lung transplant programs employ prostaglandin E1 (PGE1) or prostacyclin (PGI2) before donor lung flush and harvest. The effect of prostaglandins on the reperfusion component of this ischemia-reperfusion complex is unknown. We investigated the effect of PGE1 given only during the period of reperfusion, on ischemic lung injury in an in situ rabbit model. To examine the mechanisms involved, we measured pulmonary hemodynamics as well as myeloperoxidase, circulating platelet, and tumor necrosis factor (TNF) values. Two hours of warm ischemia of the left lung was produced in anesthetized New Zealand white rabbits. The animals were randomly allocated into four groups based on treatment received only during reperfusion: PGE1, PGI2, nitroprusside (NP), or no treatment (controls). After 2 h of reperfusion, PaO2 in the PGE1 group was significantly higher (423 +/- 52.7 mm Hg) than in all other groups (PGI2, 239 +/- 43.4, p < 0.05; NP, 146 +/- 14.2 p < 0.01; controls, 74 +/- 19.1 mm Hg, p < 0.01), despite similar pulmonary vascular resistance in the PGE1 and NP groups. Although lower than in the PGE1 group, PaO2 in the PGI2 group was still significantly higher than that in controls. Wet/dry lung weight ratios were significantly lower in the PGE1 and PGI2 groups (6.5 +/- 0.2 [p < 0.01] and 6.9 +/- 0.6 [p < 0.05], respectively, versus 8.2 +/- 0.1 in controls). There were no significant differences in plasma TNF levels, platelet sequestration across the lungs, or lung myeloperoxidase activity in the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Matsuzaki
Y
Y
Department of Surgery, University of Toronto, Toronto General Hospital, Ontario, Canada.
Waddell
T K
TK
Puskas
J D
JD
Hirai
T
T
Nakajima
S
S
Slutsky
A S
AS
Patterson
G A
GA
D000527:Alprostadil / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D011464:Epoprostenol / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000098:blood supply* / Q000503:physiopathology; D008171:Lung Diseases / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D011817:Rabbits; D011897:Random Allocation; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D013997:Time Factors
D011464:Epoprostenol; D000527:Alprostadil