Inhalation of Nitric Oxide: Effect on Cerebral Hemodynamics and Activity, and Antioxidant Status in the Newborn Lamb

Abstract

Ventilation with nitric oxide (NO) is increasingly being used to treat pulmonary hypertension in the newborn. In the brain, NO has vasoactive properties and is involved in neurotransmission. However, the effect of inhaled NO on the cerebral blood flow (CBF) and on the cerebral activity is not known. Furthermore, there is little information on the influence of this free radical gas on the redox status in pulmonary vessels. We therefore investigated the effect of inhaled NO (2–60 ppm) on CBF, cerebral activity and redox status in blood effluent from the pulmonary circulation in 6 ventilated newborn lambs before and during group B streptococci (GBS)-induced pulmonary hypertension. Blood pressure in the pulmonary artery (P_ap) and aorta (P_ao), carotid artery blood flow (Q_car) to assess changes in CBF, and electrocortical activity were measured. Blood gases, indices of free radical status and methemoglobin were determined in blood samples obtained from the left ventricle. Inhalation of NO, before and during GBS-induced pulmonary hypertension, decreased P_ap and P_CO2 and increased P_O2. Multiple linear regression revealed that Q_car was positively related to P_CO2, but not to inhaled NO or P_O2 before or during GBS conditions. Electrocortical activity and indices of antioxidative capacity and lipid peroxidation did not change significantly. Methemoglobin was not detected. In conclusion, inhalation of NO (up to 60 ppm) lowered Pap without directly affecting CBF, electrocortical activity, and redox status in the pulmonary vessels. CBF, however, can indirectly be influenced by NO-mediated changes in P_CO2·

Effect of Exchange Transfusion on Brain Perfusion and Electrocortical Brain Activity in Newborn Lambs

“…Baseline values of all variables before the exchange transfusion were within the normal range [8]. The blood pressure-related changes in Q car we observed during exchanging blood in this animal study were in accordance with the findings in an earlier study we performed in newborn infants [3].…”

Inhaled Nitric Oxide neither Alters Oxidative Stress Parameters nor Induces Lung Inflammation in Premature Lambs with Moderate Hyaline Membrane Disease

“…Especially, MDA levels were not increased, suggesting that increased lipid peroxidation did not occur. Cardozo et al [21] found similar results in full-term newborn lambs after shortterm exposure (20-30 min) to various concentrations of inhaled NO -2, 4, 10, 20 and 60 ppm. NO reacts readily with sulfhydryl to form nitrosothiols.…”

Nitric Oxide: Considerations for the Treatment of Ischemic Stroke

“…Recently, there is growing evidence that iNO might be protective in reducing ischemiareperfusion injury within mesentery (Fox-Robichaud et al, 1998), and myocardium (Nagasaka et al, 2008), thus reducing tissue damage. While experimental (Rosenberg et al, 1995;Lopes Cardozo et al, 1996;Kusuda et al, 1999) and clinical (Vavilala et al, 2001) studies could not detect changes in CBF during iNO therapy, one experimental study revealed that while it did not alter cerebral perfusion, iNO was shown to possess a cerebrovascular effect (Kuebler et al, 2003). Nitric oxide inhalation is a clinically approved treatment that has few side effects that might positively influence the outcome following ischemic stroke.…”