Tadalafil improves oxygenation in a model of newborn pulmonary hypertension.
OBJECTIVE
Sildenafil, a phosphodiesterase-5 inhibitor, significantly improves oxygenation when used in animal models and patients with pulmonary hypertension. Tadalafil is a new and clinically available phosphodiesterase-5 inhibitor that, aside from causing pulmonary vasodilation, has been shown to increase cardiac output in pulmonary hypertensive adults. Its hemodynamic effects on the newborn, however, have not been tested. The objective was to evaluate the effect of tadalafil on central hemodynamics and arterial oxygenation in a piglet model of acute pulmonary hypertension.


METHODS
Laboratory experiment.


METHODS
University laboratory.


METHODS
Seven anesthetized and mechanically ventilated newborn piglets.


METHODS
Pulmonary hypertension was induced and maintained in seven anesthetized and mechanically ventilated newborn piglets following acute exposure to 11% oxygen. The experimental animals received orla tadalafil (1 mg/kg), whereas the control animals were given an equal volume of normal saline. Systemic and pulmonary hemodynamic variables were measured, and the cardiac output and ejection fraction were obtained from two-dimensional echocardiogram and Doppler measurements in all animals. Serial arterial blood gases were also obtained, and the alveolar-arterial oxygen gradient was calculated.


RESULTS
In contrast with the control animals, in which no significant changes were noted, in the experimental animals pulmonary arterial pressure decreased on average by 54% and cardiac output increased by 88% following tadalafil administration (p < .05). Tadalafil increased the PaO2 by 48% +/- 21% (p < .01), likely as a result of a 74% +/- 13% reduction in the alveolar-arterial oxygen gradient (p < .01).


CONCLUSIONS
In a newborn animal model of acute pulmonary hypertension, oral tadalafil administration reduces pulmonary vascular resistance and increases arterial oxygenation by increasing cardiac output and reducing the lung shunt fraction. This previously untested compound deserves additional investigation in laboratory models of persistent pulmonary hypertension of the newborn.
Tessler
Rogerio B
RB
Department of Pediatrics, Hospital Sao Lucas, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil. tessler@hu.ufsc.br
Zadinello
Mariutska
M
Fiori
Humberto
H
Colvero
Mauricio
M
Belik
Jaques
J
Fiori
Renato Machado
RM
D000818:Animals; D000831:Animals, Newborn; D002243:Carbolines / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004452:Echocardiography; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013552:Swine; D000068581:Tadalafil
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil; D010100:Oxygen