Tadalafil improves oxygenation in a model of newborn pulmonary hypertension.

Abstract

OBJECTIVES:

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.

DESIGN:

Laboratory experiment.

SETTING:

University laboratory.

SUBJECTS:

Seven anesthetized and mechanically ventilated newborn piglets.

INTERVENTIONS:

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.

MEASUREMENTS AND MAIN 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.

• Authors: Rogerio B Tessler, Mariutska Zadinello, Humberto Fiori, Mauricio Colvero, Jaques Belik, Renato Machado Fiori
• Journal: Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies (Pediatr Crit Care Med) Vol. 9 Issue 3 Pg. 330-2 (May 2008) ISSN: 1529-7535 [Print] United States
• PMID: 18446109 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Carbolines
• Phosphodiesterase Inhibitors
• Tadalafil
• Oxygen

Topics

• Animals
• Animals, Newborn
• Carbolines (pharmacology, therapeutic use)
• Disease Models, Animal
• Echocardiography
• Hemodynamics (drug effects)
• Hypertension, Pulmonary (drug therapy, physiopathology)
• Oxygen (metabolism)
• Phosphodiesterase Inhibitors (pharmacology, therapeutic use)
• Swine
• Tadalafil