Protective effect of pentoxifylline on phorbol myristate acetate-induced acute lung injury in rats.
The pathogenesis of adult respiratory distress syndrome (ARDS) is not clear, and its therapy is still a problem. Pentoxifylline, a methylxanthine derivative, can inhibit phosphodiesterase activity and thus increase the intracellular cAMP. There are also some hypotheses that pentoxifylline can attenuate pulmonary edema. In order to evaluate the protective effect of pentoxifylline in acute lung injury, we set up an isolated lung perfusion model in rats and induced experimental acute lung injury similar to ARDS by intravenously infused phorbol myristate acetate (PMA) 7.5 micrograms/300 g body weight. Four groups of experimental rats were studied: group 1, normal control group, neither PMA nor pentoxifylline was used in 6 rats; group 2 (acute lung injury group), only PMA was infused in 8 rats; group 3 (protective group), pentoxifylline 100 mg/300 g body weight was given intravenously before PMA infusion in 6 rats; group 4, only pentoxifylline was given in 6 rats. Pulmonary arterial pressure (PAP) as well as lung weight changes were recorded before and 5, 10, 15, 20 and 25 minutes after drug injection. Bronchial lavage fluids were then measured for albumin concentration. We found that PAP was strikingly increased in group 2 (54.0 +/- 8.8 mmHg), but the increase was significantly reduced in group 3 (29.8 +/- 5.8 mmHg, p less than 0.001). Similarly, the lung weight gain was markedly increased in group 2 (4.69 +/- 1.28 g), but was significantly attenuated in group 3 (1.25 +/- 1.60 g, p less than 0.001). There was no apparent change in PAP and lung weight gain throughout the entire procedure in groups 1 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)
Lin
H I
HI
Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan R.O.C.
Hsu
K
K
Yan
H C
HC
Shen
C Y
CY
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D010431:Pentoxifylline