Cerebral hemodynamics and distribution of left ventricular output during inhalation of nitric oxide.
OBJECTIVE
Inhaled nitric oxide is being utilized as a selective pulmonary vasodilator in the treatment of persistent pulmonary hypertension of the newborn. However, the effects of inhaled nitric oxide on cerebral hemodynamics and distribution of left ventricular output in newborn subjects have not been studied. This study was designed to measure quantitatively the effect of inhaled nitric oxide on the distribution of left ventricular output and on cerebral hemodynamics in a perinatal animal model.


METHODS
Prospective, controlled, experimental study.


METHODS
Research laboratory.


METHODS
Eight fetal sheep.


METHODS
Each animal was exposed to three separate study periods: a) mechanical ventilation with low FIO2 (maintaining fetal levels of PaO2); b) inhalation of nitric oxide (20 parts per million) during mechanical ventilation and low FIO2; and c) mechanical ventilation with an FIO2 of 1.0.


RESULTS
Left ventricular output and cerebral blood flow were measured with radiolabeled microspheres. Cerebral oxygen delivery and consumption variables were calculated using measurements of arterial and cerebral venous (sagittal sinus) oxygen content. Total left ventricular output did not differ among the three treatment groups: 235 +/- 16 mL/min/kg with hypoxic ventilation; 283 +/- 13 mL/min/kg with nitric oxide inhalation; and 242 +/- 17 mL/min/kg with an FIO2 of 1.0. Lung blood flow increased 2.7-fold with inhaled nitric oxide and 1.6-fold during mechanical ventilation with an FIO2 of 1.0. With a left ventricle microsphere injection, increased lung blood flow is indicative of increased systemic-to-pulmonary shunt across the ductus arteriosus. Whole brain blood flow did not differ between the three groups: 49.6 +/- 6.7 mL/min/100 g with hypoxic ventilation; 46.4 +/- 7.4 mL/min/100 g with nitric oxide inhalation; and 36.4 +/- 3.8 mL/min/100 g with an FIO2 of 1.0. Cerebral oxygen delivery increased during inhalation of an FIO2 of 1.0 when compared with nitric oxide inhalation (p < .007); fractional extraction of oxygen decreased (p < .004 compared with hypoxic ventilation, p < .0005 compared with nitric oxide inhalation). Cerebral oxygen consumption did not differ between the three groups (1.11 +/- 0.12 microns/min/100 g with hypoxic ventilation, 0.95 +/- 0.12 microns/min/100 g with nitric oxide inhalation, and 0.96 +/- 0.08 microns/min/100 g with an FIO2 of 1.0).


CONCLUSIONS
Acute pulmonary vasodilation caused by inhalation of nitric oxide does not change left ventricular output, cerebral blood flow, or cerebral oxygen consumption, despite an increased systemic-to-pulmonary shunt across the ductus arteriosus.
Rosenberg
A A
AA
Department of Pediatrics, University of Colorado School of Medicine, Denver, USA.
Kinsella
J P
JP
Abman
S H
SH
D000280:Administration, Inhalation; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005333:Fetus; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D007231:Infant, Newborn; D009569:Nitric Oxide / Q000494:pharmacology* / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects; D010547:Persistent Fetal Circulation Syndrome / Q000188:drug therapy; D011652:Pulmonary Circulation / Q000187:drug effects; D012121:Respiration, Artificial; D012756:Sheep; D016277:Ventricular Function, Left / Q000187:drug effects*
D009569:Nitric Oxide