Effect of pentoxifylline on cytokine- and eicosanoid-induced acute pulmonary hypertension in piglets.
The methylxanthine derivative pentoxifylline (PTF) demonstrates vasodilatory properties in vivo. We tested the hypothesis that PTF infusion would blunt or inhibit tumor necrosis factor-alpha (TNF alpha)-induced and U46,619-induced increases in mean pulmonary artery pressure and pulmonary vascular resistance (PVR) in the neonatal piglet and would do so by altering production of eicosanoid vasoactive mediators. Anesthetized, paralyzed piglets (age 10-29 d) were randomized and treated with a 30-min infusion of TNF alpha alone (n = 13 animals), with a combination of TNF alpha plus pretreatment and continuous infusion with PTF (n = 6), or with a combination of U46,619 for 30 min plus pretreatment and continuous infusion of PTF (n = 5). There was no difference in pulmonary or systemic hemodynamic indices between the three groups at baseline. PVR was significantly elevated at 15 min and at 2 h in the TNF alpha-only group. The TNF alpha-induced rise in mean pulmonary artery pressure and PVR was inhibited by the PTF until 2 h, by which time PVR was elevated above baseline and was comparable to the value found in animals treated with only TNF alpha. PTF produced no inhibition in the U46,619-induced elevation of PVR during the 30-min simultaneous treatment. In the PTF + TNF alpha group, mean systemic blood pressure declined to 50% of baseline value (p less than 0.02) by 2 h of age. No significant decline was noted in mean systemic arterial pressure of the TNF alpha-only or the U46,619-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
Truog
W E
WE
Department of Pediatrics, University of Washington School of Medicine, Seattle 98195.
Gibson
R L
RL
Henderson
W R
WR
Redding
G J
GJ
Standaert
T A
TA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010431:Pentoxifylline / Q000627:therapeutic use*; D011450:Prostaglandin Endoperoxides, Synthetic; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D013552:Swine; D014409:Tumor Necrosis Factor-alpha; D014655:Vascular Resistance / Q000187:drug effects
D001095:Arachidonic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D014409:Tumor Necrosis Factor-alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D010431:Pentoxifylline