Effects of heparin and lisofylline on pulmonary function after smoke inhalation injury in an ovine model

Abstract

Objective: This study evaluates the effects of heparin alone and in combination with lisofylline, 1-(5-R-hydroxyhexyl)3,7-dimethylxanthine, on severe smoke injury.

Design: Prospective animal study with concurrent controls.

Setting: An animal laboratory.

Subjects: Eighteen 1-yr-old female sheep, weighing 24-32 kg.

Interventions: After smoke exposure and tracheostomy, animals were divided into three groups. Group S (n = 6) received nebulized saline through an endotracheal tube every 4 hrs for 48 hrs. Group H (n = 6) received 10,000 units of nebulized heparin every 4 hrs. Group LH (n = 6) was treated with nebulized heparin and intravenous infusion of lisofylline (10 mg x kg(-1) x hr(-1)) for 48 hrs after a bolus injection (20 mg/kg). Animals initially breathed room air spontaneously. If PaO2 was <50 torr and PaCO2 >60 torr, animals were mechanically ventilated. Sheep were killed 48 hrs postinjury.

Measurements and main results: Blood gases were measured serially. At 48 hrs, ventilation perfusion distribution mismatching was analyzed by using the multiple inert gas elimination technique. Lung malondialdehyde was determined. The postinjury increase in alveolar-arterial oxygen tension gradient (LH, 36.7 +/- 3.5 vs. S, 89.0 +/- 24.6 torr at 48 hrs) was significantly attenuated in those animals receiving LH. The percentage of pulmonary shunt, Qs/Qt (LH, 20.8 +/- 4.9 vs. S, 36.6 +/- 4.6%), and the percentage of animals that required ventilation (LH, 0 vs. S, 67%) were significantly reduced in LH. Multiple inert gas elimination technique study showed that the true shunt fraction was decreased in LH. Lung malondialdehyde was significantly less in LH (LH, 0.33 +/- 0.06 vs. S, 0.56 +/- 0.09 nmol/mg protein). There was no significant difference in any of these variables between H and S.

Conclusion: Treatment with heparin alone did not attenuate pulmonary dysfunction after severe smoke injury. Combined treatment with nebulized heparin and systemic lisofylline had beneficial effects on pulmonary function in association with a decrease in blood flow to poorly ventilated areas and less lipid peroxidation.