PHARMACOLOGICAL STRATEGIES FOR IMPROVING DIASTOLIC DYSFUNCTION IN THESETTING OF CHRONIC PULMONARY-HYPERTENSION

Background-Right ventricular (RV) hypertrophy is an adaptive process t hat 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 dias tolic 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 underwe nt percutaneous pulmonary artery (PA) catheterization to measure pulmo nary hemodynamics before and 8 weeks after injection of 3 mg/kg MCTP ( n=8) or placebo (control, n=8), Eight weeks after injection, all heart s were instrumented with a PA flow probe, sonomicrometric dimension tr ansducers, and micromanometers, Data were collected at baseline and af ter both NO and milrinone administration. Diastolic properties were qu antified by use of the end-diastolic pressure-volume relationship and the time constant of ventricular isovolumic relaxation. Eight weeks af ter 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 incr eases in the ratio of RV dry weight to LV+septal dry weight. NO and mi lrinone administration both led to significant improvements in RV dias tolic properties. Conclusions-In the setting of MCTP-induced CPH, sign ificant 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 hyp ertrophy. The significant improvement in RV diastolic properties after both NO and milrinone administration suggests that these agents may b e effective forms of pharmacological therapy for improving RV diastoli c dysfunction in the setting of CPH.