Direct comparison of the effects of nebulized nitroprusside versus inhaled nitric oxide on pulmonary and systemic hemodynamics during hypoxia-induced pulmonary hypertension in piglets.
OBJECTIVE
To test the hypothesis that nebulized nitroprusside and inhaled nitric oxide would not differ in producing selective pulmonary vasodilation during hypoxia-induced pulmonary hypertension in piglets.


METHODS
University laboratory.


METHODS
Five piglets.


METHODS
Piglets (n = 5) were anesthetized and instrumented to monitor systemic arterial pressure, pulmonary artery pressure, and cardiac output continuously. Hypoxia was induced (DeltaFio2 from 0.5 to 0.08), and either nebulized nitroprusside (5 mg/mL at 4 L/min flow; total dose 25 mg) or inhaled nitric oxide (20 ppm) was introduced into the ventilator circuit for 15 mins. Normoxia was then restored, and a repeat cycle of hypoxia followed by the alternate vasodilator treatment was initiated.


RESULTS
Hypoxia significantly reduced Pao2 (from 206 to 30 torr) and elevated pulmonary artery pressure (from 18 to 33 torr) while not significantly affecting systemic arterial pressure or cardiac output. During hypoxia, inhaled nitric oxide reduced pulmonary artery pressure from 33 to 21 torr (p <.01), whereas systemic arterial pressure and cardiac output were unchanged. During hypoxia, nebulized nitroprusside also reduced pulmonary artery pressure from 33 to 23 mm Hg (p <.01; p = nonsignificant vs. inhaled nitric oxide), whereas systemic arterial pressure and cardiac output again remained constant. The time course of the reduction in pulmonary artery pressure during inhaled nitric oxide was roughly ten-fold more rapid (<5 secs) than during nebulized nitroprusside ( approximately 1 min). Neither inhaled nitric oxide nor nebulized nitroprusside altered pH, Pao2, or Paco2.


CONCLUSIONS
Both inhaled nitric oxide and nebulized nitroprusside produced prompt, significant, selective reduction of pulmonary artery pressure and pulmonary vascular resistance in piglets with hypoxia-induced pulmonary hypertension, without apparent effects on systemic hemodynamics or pulmonary gas exchange. The equivalence of the two effects in this animal model suggests that cautious extrapolation of the use of nebulized nitroprusside as a convenient bridge to inhaled nitric oxide in selected clinical contexts for human infants may be warranted.
Schreiber
Michael D
MD
Department of Pediatrics, University of Chicago, IL 60637, USA.
Dixit
Rajeev
R
Rudinsky
Brian
B
Hipps
Robert
R
Morgan
Sherwin E
SE
Keith RRT
Alfred
A
Meadow
William
W
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D000860:Hypoxia / Q000150:complications; D007231:Infant, Newborn; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D009599:Nitroprusside / Q000494:pharmacology / Q000627:therapeutic use*; D010547:Persistent Fetal Circulation Syndrome / Q000188:drug therapy; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011897:Random Allocation; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide