Nitric Oxide Contributes to Surfactant-Induced Vasodilatation in Surfactant-Depleted Newborn Piglets

Abstract

To investigate whether nitric oxide (NO) is involved in surfactant-induced systemic and pulmonary vasodilatation in newborn piglets with surfactant deficiency, 2-6-d-old piglets were subjected to repeated saline lung lavages. They were then randomly assigned to one of two groups (seven in each group): the N(omega)-nitro-L-arginine methyl ester (L-NAME) group received 3 mg/kg L-NAME i.v. 45 min before endotracheal instillation of 200 mg/kg porcine surfactant; the saline group received saline i.v. at the same time point, and instillation of 200 mg/kg surfactant. Mean arterial blood pressure, systemic vascular resistance, pulmonary arterial pressure, and pulmonary vascular resistance increased significantly after injection of L-NAME (all p < 0.01), whereas the cardiac index decreased significantly (p < 0.05). Saline injection did not change any variable. Significant decreases in mean arterial blood pressure (from a mean +/- SD of 66 +/- 10 to 53 +/- 9 mm Hg, p < 0.01), pulmonary arterial pressure (from 29 +/- 6 to 23 +/- 6 mm Hg, p < 0.01), and systemic vascular resistance (from 0.40 +/- 0.13 to 0.33 +/- 0.12 mm Hg/mL/min/kg, p < 0.05) were observed only in the saline group after surfactant instillation, whereas the decrease in pulmonary vascular resistance was not significant after surfactant instillation (p = 0.06). In contrast to the saline group, these variables were not modified in the L-NAME group after surfactant instillation. We conclude that the vasodilatory effect of porcine surfactant instillation in newborn piglets with surfactant deficiency is associated with activation of NO synthase.

Nitric Oxide Synthesis Inhibition during Cerebral Hypoxemia and Reoxygenation with 100% Oxygen in Newborn Pigs

“…It has become clear that the inhibitor response requires time [38] and differs considerably depending on the concentration used, and to some extent on the species. In rats considerably higher doses are needed [40], whereas in newborn pigs, obviously, the activity of NO synthase can be inhibited by 3 mg/ kg of L-NAME [41], probably with effects on all three NO synthase isoforms. Gibson et al [42] showed that larger doses of L-NAME caused a severe decline in cardiac output.…”

Cerebral Blood Flow Velocity Changes After Bovine Natural Surfactant Instillation

“…In animals, the vasodilator effect after porcine surfactant administration can be inhibited by nitric oxide synthase inhibitor. 19 Thus, the mechanism of CBFV and other physiological changes associated with surfactant need further investigation. Our study supports the reported pressure-passive cerebral circulation with a direct relationship between CBFV and blood pressure in sick preterm infants.…”

Circulatory Effects of Surfactant Therapy

“…We have also studied the effect of 100 mg/kg ofSurvanta®, and a significant vasodilatation similar to that seen after 100 mg/kg of Curo surf was found. Further, we have shown a complete inhibition of the vasodilatation by inhibiting nitric oxide synthetase with Nwnitro-L-arginine methyl ester (L-NAME) [14].…”