Abstract
The methylxanthine derivative pentoxifylline (PTF) demonstrates vasodilatory properties in vivo. We tested the hypothesis that PTF infusion would blunt or inhibit tumor necrosis factor-α (TNFα)-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 TNFα alone (n = 13 animals), with a combination of TNFα 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 TNFα-only group. The TNFα-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 TNFα. PTF produced no inhibition in the U46, 619-induced elevation of PVR during the 30-min simultaneous treatment. In the PTF + TNFα group, mean systemic blood pressure declined to 50% of baseline value (p < 0.02) by 2 h of age. No significant decline was noted in mean systemic arterial pressure of the TNFα-only or the U46, 619-treated group. Plasma 6-keto-prostaglandin F1α increased above baseline values by 2 h only in the PTF + TNFα-treated group (p < 0.02); no significant change from baseline in thromboxane B2 levels was found in any experimental group. We conclude that treatment with PTF transiently inhibited the TNFα-induced elevation in mean pulmonary artery pressure and PVR but was associated also with significant systemic hypotension. PTF failed to counteract elevated PVR produced by the thromboxane mimetic, U46, 619.
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Truog, W., Gibson, R., Henderson, W. et al. Effect of Pentoxifylline on Cytokine- and Eicosanoid-Induced Acute Pulmonary Hypertension in Piglets. Pediatr Res 31, 163–169 (1992). https://doi.org/10.1203/00006450-199202000-00015
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DOI: https://doi.org/10.1203/00006450-199202000-00015