Effect of cyclooxygenase inhibition in a canine model of unilateral pulmonary occlusion and reperfusion.
OBJECTIVE
To assess the effects of the cyclooxygenase inhibitor diclofenac in a canine model of pulmonary occlusion and reperfusion of the left lower lobe (LLL).


METHODS
Twelve adult beagle dogs (13-17 kg) were randomly assigned to a control group (n = 6) and a diclofenac-treated group (n = 6). Animals in the treatment group received 20 mg diclofenac sodium/kg as a single dose both before the experiment and at the end of surgical preparation; six animals served as controls.


METHODS
In the anesthetized animals, the left upper and middle lobes were resected. Circulation and ventilation of the LLL were selectively blocked by clamping. Complete occlusion of the LLL (30 min) was followed by periods of selective reperfusion (10 min, RP) and combined reperfusion and reventilation (120 min, RP/RV).


RESULTS
Reperfusion of the LLL resulted in a significant increase in pulmonary arterial pressure (Ppa) in the early RP/RV period as compared to baseline values (25.3 +/- 4.7 vs 15.8 +/- 1.9 mmHg, p < 0.05, paired t-test). This increase was significantly inhibited in the diclofenac-treated animals (17.0 +/- 2.0 mmHg, p < 0.01 vs controls, ANOVA). Gravimetrically determined extravascular lung water (EVLW) showed no significant difference in the continuously ventilated lobes of the right lung between diclofenac-treated animals (3.8 ml/g dry weight) and controls (3.9 +/- 0.9 ml/g dry weight) at the end of the experiment. EVLW, however, increased significantly in the LLL of control animals after 2 h of combined reperfusion and reventilation, whereas this increase was significantly inhibited in the diclofenac-treated animals (4.5 +/- 0.7 ml/g dry weight in the diclofenac group vs 6.5 +/- 1.3 ml/g dry weight in the control group, p < 0.05).


CONCLUSIONS
Diclofenac inhibits the increase in both pulmonary arterial pressure and EVLW during reperfusion and reventilation of LLL. Thus, these changes appear to be mediated by cyclooxygenase metabolites.
Segiet
W
W
Institute of Anesthesiology, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.
Krieter
H
H
Stieber
C
C
Albrecht
D M
DM
van Ackern
K
K
D000704:Analysis of Variance; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004008:Diclofenac / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D015633:Extravascular Lung Water / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D011292:Premedication; D011655:Pulmonary Embolism / Q000188:drug therapy*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy*
D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac