From the Department of Surgery, Division of Cardiovascular and Thoracic
Surgery, Duke University Medical Center, Durham, NC.
Background—Right
ventricular (RV) hypertrophy is an adaptive
process that occurs in the setting of chronic pulmonary
hypertension (CPH) and can lead to alterations in normal RV
diastolic properties. This study was designed to
investigate the effects of NO and milrinone on RV diastolic
dysfunction in the setting of CPH and RV hypertrophy by use
of a canine model of monocrotaline pyrrole (MCTP)–induced
CPH.
Methods and Results—Sixteen mongrel dogs (22 to 24 kg) were used.
Animals underwent percutaneous pulmonary artery
(PA) catheterization to measure pulmonary
hemodynamics before and 8 weeks after injection of 3
mg/kg MCTP (n=8) or placebo (control, n=8). Eight weeks after
injection, all hearts were instrumented with a PA flow probe,
sonomicrometric dimension transducers, and
micromanometers. Data were collected at baseline
and after both NO and milrinone administration. Diastolic
properties were quantified by use of the end-diastolic
pressure-volume relationship and the time constant of
ventricular isovolumic relaxation. Eight weeks after
injection, significant increases in the PA pressure and
pulmonary vascular resistance were observed in MCTP dogs.
Significant worsening of RV diastolic function occurred in
association with significant increases in the ratio of RV dry weight to
LV+septal dry weight. NO and milrinone administration both led to
significant improvements in RV diastolic properties.
Conclusions—In the setting of MCTP-induced CPH, significant
worsening of RV diastolic function was observed in
association with significant increases in the ratio of RV dry weight to
LV+septal dry weight, suggesting that these changes are partially due
to RV hypertrophy. The significant improvement in RV
diastolic properties after both NO and milrinone administration
suggests that these agents may be effective forms of pharmacological
therapy for improving RV diastolic dysfunction in the
setting of CPH.
© 1998 American Heart Association, Inc.
Basic Science Reports
Pharmacological Strategies for Improving Diastolic Dysfunction in the Setting of Chronic Pulmonary Hypertension
Key Words: hypertension, pulmonary • diastole • ventricles • hypertrophy
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