From the Departments of Medicine and Physiology and Biophysics, The
University of Calgary, Alberta, Canada.
Correspondence to John V. Tyberg, MD, PhD, Professor of Medicine and Physiology and Biophysics, The University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada. E-mail jtyberg{at}cvr.ucalgary.ca
Background—Toborinone (OPC-18790), a
phosphodiesterase III inhibitor, enhances cardiac
contractility and is an arterial dilator.
However, its effects on the venous system have not yet been clearly
defined. Because toborinone administration reduces left
ventricular (LV) end-diastolic pressure, it is
probably also a venodilator. Because of the known arterial
effects and the hypothesized venous effects, we compared changes in
systemic vascular conductance (the inverse of resistance) with changes
in venous capacitance.
Methods and Results—In 15 anesthetized, splenectomized
dogs (10 treatment, 5 control), pressures were measured in the right
atrium, aorta, portal vein, and LV. A cuff constrictor was placed
around the portal vein. Cardiac output was measured by thermodilution,
and splanchnic vascular capacitance was measured by blood-pool
scintigraphic methods. Data were collected at baseline, after induction
of heart failure (microsphere embolization into the left
coronary artery), and then after toborinone boluses of 0.1,
0.2, 0.4, and 0.8 mg/kg. Heart failure was associated with decreased
capacitance and conductance (to 87±3% and 64±4% of baseline values,
respectively, P<0.05). After administration of the
lower doses of toborinone, capacitance increased more than conductance;
however, the effects were more balanced at the higher doses. Compared
with nitroglycerin, hydralazine, and
enalaprilat (results of an earlier study) in the same model, toborinone
increased capacitance to a degree similar to that with
nitroglycerin, at higher doses increased conductance
similarly to hydralazine, and increased both capacitance and
conductance considerably more than did enalaprilat.
Conclusions—Toborinone is a potent balanced venous and
arterial dilator in experimental acute heart failure. These
marked effects suggest that it may prove to be a clinically important
alternative to other vasodilators.
© 1998 American Heart Association, Inc.
Basic Science Reports
Acute Effects of Toborinone on Vascular Capacitance and Conductance in Experimental Heart Failure
Key Words: circulation • vasodilation • heart failure • veins • hemodynamics