We have investigated the effect of indomethacin on histamine- and acetylcholine (ACh)-induced responses in the intact and denuded epithelium of guinea pig isolated tracheal smooth muscle. Epithelium removal resulted in increased responsiveness to ACh and histamine. Indomethacin (2.8 microM) enhanced the sensitivity of both intact and denuded preparations to histamine and ACh. These findings suggest that the tracheal epithelium of guinea pig plays a protective role against bronchoconstrictors, such as ACh and histamine. Furthermore, indomethacin-mediated hyperresponsiveness caused by these agonists in epithelium denuded preparations might be a reflection of removal of prostaglandin (PG) biosynthesis. A similar process of interaction in indomethacin-treated asthmatic patients (with damaged airway epithelium) might take place. The significance of these findings is discussed.
Introduction: The aim of this study was to determine predictors of failed closure of patent ductus arteriosus (PDA) following a single course of indomethacin in symptomatic preterm infants.
Methods: This prospective observational study was carried out on 60 preterm infants weighing less than 1,750 g with symptomatic PDA confirmed by echocardiography. At a median age of 7.0 days (interquartile range 4.0), they were given indomethacin of 0.1 mg/kg/day intravenously daily for six days. Closure of PDA was reassessed by echocardiography upon completion of therapy.
Results: The PDA of 40 percent (n=24) of these infants remained patent. Forward logistic regression analysis showed that the only significant predictors of failed PDA closure in these infants were: PDA size (adjusted odds-ratio [OR] is 7.0; 95 percent confidence interval [CI] of OR is 2.0, 24.8; p-value is 0.002), birth weight (adjusted OR is 0.996; 95 percent CI of OR is 0.993, 1.000; p-value is 0.03) and platelet count (adjusted OR is 0.987; 95 percent CI is 0.975, 1.000; p-value is 0.045). Gestational age, maternal age and left atrium/aorta ratios were not significant predictors.
Conclusion: Larger PDA, lower birth weight and lower platelet count were significant predictors of high failure in indomethacin therapy given late at one week of life.