The Journal of Thoracic and Cardiovascular Surgery, Vol 103, 589-594, Copyright © 1992 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
Evaluation of direct effects of enoximone on systemic and pulmonary vascular bed in animals with a Jarvik total artificial heart
PH Deleuze, JL Rande, J Okude, F Wan, S Brunet, FR Thoraval, JP Cachera and DY Loisance
Centre de Recherches Chirurgicales, CNRS UA 1431, C.H.U. Henri Mondor, Universite Paris XII, Creteil, France.
Enoximone, a phosphodiesterase inhibitor, has positive inotropic and
vasodilating actions. To evaluate specific effects of this drug on the
systemic and pulmonary vascular bed, we administered enoximone as a 10-
minute intravenous bolus at two different doses of 2 and 3 mg/kg of body
weight, at different days, to five Holstein calves with a Jarvik 7- 70 ml
total artificial heart (Symbion, Inc., Salt Lake City, Utah). The calves
were monitored for aortic pressure, right atrial pressure, pulmonary
arterial pressure, and left atrial pressure. For each experiment cardiac
output was maintained constant, and systemic and pulmonary vascular
resistances were calculated at 0, 15, 30, and 60 minutes and every hour for
8 hours after infusion. Statistical analysis used analysis of variance and
the paired t test with Bonferroni's correction. Data showed the following:
(1) a marked systemic vasodilating action of enoximone at peak effect at 30
minutes with a 20% decrease in systemic vascular resistance from baseline
value under constant cardiac output, returning progressively to normal
values throughout the 8 hours; (2) a comparable effect for the two separate
doses tested; (3) no specific action on the pulmonary vascular bed with
"nonunidirectional" changes in pulmonary vascular resistance. This model
was validated by the infusion of prostaglandin I2 in the same animals, at
different days, which significantly decreased pulmonary vascular resistance
of 50% at peak effect, under constant cardiac output. In summary, enoximone
showed a proper systemic vasodilating effect with no specific action on the
pulmonary vascular bed in an animal model of the total artificial heart.
Decrease in pulmonary vascular resistances obtained with enoximone in
clinical practice seems more related to the inotropic properties of the
drug. Enoximone should not be administered in pulmonary hypertension, as
suggested before.
