In this prospective, randomized, controlled study, we tested the hypothesis that the topical use of a NF-kappaB inhibitor (IkappaB kinase-NF-kappaB essential modulator binding domain [IKK-NBD] peptide), together with surfactant as a carrier substance, improves surfactant function by attenuation of pulmonary inflammation during 24 hrs of mechanical ventilation in a neonatal piglet model of acute respiratory distress syndrome by repeated airway lavage.
SUBJECTS:: A total of 24 anesthetized, mechanically ventilated newborn piglets.
INTERVENTIONS:: After 20 +/- 6 (mean +/- sd) lavages to induce lung failure and inflammation, a porcine surfactant (100 mg/kg) with (S+IKK) or without (S) 1.25 mg of IKK-NBD peptide, or an air bolus (control) was administered into the airways. Lung function was monitored throughout 24 hrs of mechanical ventilation and completed by ex vivo analyses.
MEASUREMENTS AND MAIN RESULTS:: Pao2 (S+IKK, 125 +/- 16 mm Hg; S, 105 +/- 33; control, 61 +/- 20), ventilation efficiency index, functional residual capacity, compliance of the respiratory system, and extravascular lung water (S+IKK, 24 +/- 2 mL/kg; S, 30 +/- 7; control, 34 +/- 8) were all significantly improved in S+IKK piglets after 24 hrs.
Decreased leukocyte concentrations in bronchoalveolar lavage (S+IKK, 152 +/- 94 cells/muL; S, 202 +/- 100; control, 276 +/- 57) were observed together with reduced acid sphingomyelinase activity, lowered ceramide concentrations, improved surfactant function (minimum surface tension: S+IKK, 10.8 +/- 6.1 mN/m; S, 13.2 +/- 3.9; control, 20.9 +/- 8.5), and decreased NF-kappaB activation in lung tissue.
CONCLUSION:: Supplementation of exogenous surfactant with a NF-kappaB inhibitor to create a `fortified` surfactant improves gas exchange, lung function, and pulmonary edema during 24 hrs of mechanical ventilation, without a secondary functional relapse.
Inhibition of NF-kappaB suppressed acid sphingomyelinase activity and ceramide generation, indicating a novel proinflammatory link of NF-kappaB.
Source: von Bismarck P, Klemm K, Wistädt CF, Winoto-Morbach S, Uhlig U, Schütze S, Uhlig S, Lachmann B, Krause MF (2007): Surfactant `fortification` by topical inhibition of nuclear factor-kappaB activity in a newborn piglet lavage model. In: Crit Care Med. 2007 Jul 24;Publish Ahead of Print [Epub ahead of print]
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