We demonstrated sustained improvement in our incidence of CLD between 2005 and 2013. We speculate that a multifaceted strategy of avoiding intubation and excessive oxygen in the delivery room, the early use of CPAP, as well as the use of volume targeted ventilation, when needed, may help significantly reduce the incidence of CLD.
We have previously found an age-dependent relaxing effect of furosemide in normal fetal, newborn, and adult guinea pig airways with fetal trachea exhibiting the greatest relaxation and adult tissue the least. This study was designed to expand upon this finding by determining if in vivo hyperoxic exposure would influence in vitro airway relaxation mediated by the loop diuretics, furosemide and ethacrynic acid, and the P2-adrenoceptor agonist, salbutamol. Newborn guinea pigs were raised in >95% FiO, until ill; controls in room air. Isometric relaxation to 3 X lop5 M furosemide, 3 X 10-% ethacrynic acid, or 1 0~' -1 0~" M salbutamol was recorded in 3 X lop" M histamine-constricted airway rings. Ethacrynic acid, like furosemide, relaxed newborn Recent evidence suggests that furosemide modulates airway reactivity in vivo. Inhaled furosemide attenuates exercise-(I), allergen-(2), and cold air-(3, 4) induced bronchoconstriction in asthmatic adults, and cold air-induced bronchospasm in asthmatic children (5). Furthermore, systemic furosemide decreases airway resistance in infants with bronchopulmonary dysplasia (6-10). Although the mechanisms of furosemide's pulmonary effects have yet to be fully established, most researchers conclude that these effects are unrelated to diuresis. Various mechanisms have been espoused, including inhibition of pulmonary nerves ( l l ) , increased pulmonary venous capacitance (12), increased efferent pulmonary lymph flow (13) Medical Center; University of Hawaii Leahi Trust; and National Institutes of Health Grant guinea pig airways. Hyperoxia did not alter the contractile effect of 3 X 1 0 -M histamine but did significantly decrease the relaxing effect of furosemide, ethacrynic acid, and salbutamol. Loop diuretic mediated airway relaxation was accentuated in HEPES buffer when compared with Krebs, whereas salbutamolmediated relaxation was unaffected. These results suggest that hyperoxia nonspecifically decreases airway responsiveness to the relaxing agents studied. (Pediatr Res 38: 280-285, 1995) Abbreviations ORT, optimal resting tension FiO,, fraction of inspired oxygen increased oncotic pressure leading to decreased efferent pulmonary transcapillary flow (12,14). Stevens et al. (15) found that furosemide directly relaxes normal isolated guinea pig airways, suggesting another possible mechanism.Furosemide, bumetanide, and ethacrynic acid bind to a Na+-K+-Cl-cotransporter in the thick ascending loop of Henle (16,17). This transporter is also functional in other tissues (18). The possible role of this cotransporter in vascular smooth muscle function was first hypothesized by Deth and coworkers (19) who found evidence for a functional Na+-K+-C1-cotransporter in vascular smooth muscle by demonstrating that: 1) '%b uptake (a marker for Kt transport) is inhibited by furosemide in the presence of ouabain (to inhibit Na-KATPase) and is ~a + -, K+-, and C1--(substrate) dependent; and 2) uptake of 4 5~a in rat aorta is reduced by furosemide. They further suggest that HEPES buffer increases...
Airway hyperresponsiveness in neonatal chronic lung disease is treated with both furosemide, a diurectic that inhibits the Na-K-2Cl cotrasporter, and salbutamol, a β2-adrenoceptor agonist. Tachyphylaxis to both drugs in vitro has been described. This study was conducted to determine if the relaxation response in newborn guinea pig airways to furosemide and salbutamol can be cross-desensitized in vitro. Tracheal ring segments from 4- to 7-day-old guinea pigs were suspended in HEPES buffer for measurement of isometric tension. Segments were pre-treated with either furosemide (300 μM, 1 h) or salbutamol (10 μM, 30 min). After constriction with 3 μM acetylcholine, relaxation response to salbutamol or furosemide, respectively, was measured. Pretreatment with furosemide diminished relaxation response to salbutamol [87 ± 3% (n = 11) vs. 117 ± 8% (n = 10), p < 0.05], as compared to saline-treated controls. In addition, pretreatment with salbutamol diminished relaxation response to furosemide [53 ± 2% (n = 11) vs. saline-treated (83 ± 7%, n = 7, p < 0.05) and DMSO-treated controls (69 ± 5%, n = 5, p < 0.05)]. Measurements of 86Rb uptake, cyclic AMP levels and responses in the presence of charybdotoxin make it unlikely that Na-K-2Cl cotransporter activity, stimulation of cAMP, or opening of maxi-K+ channels are mechanisms involved in the cross-desensitization to furosemide and salbutamol in vitro.
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