SERIAL ECHOCARDIOGRAPHIC-DOPPLER ASSESSMENT OF LEFT-VENTRICULAR GEOMETRY AND FUNCTION IN RATS WITH PRESSURE-OVERLOAD HYPERTROPHY - CHRONIC ANGIOTENSIN-CONVERTING ENZYME-INHIBITION ATTENUATES THE TRANSITION TO HEART-FAILURE

Background Although chronic pressure overload may progress to left ven tricular (LV) failure, the pathophysiology of this transition is not w ell understood. In addition, the effects of chronic angiotensin-conver ting enzyme (ACE) inhibition on this transition are largely undefined. Methods and Results To examine changes in LV structure and function d uring the transition to heart failure, rats with LV hypertrophy due to banding of the ascending aorta (LVH, n=22) and age-matched sham-opera ted rats (n=6) were studied 6, 12, and 18 weeks after aortic banding. Two-dimensionally guided transthoracic M-mode echocardiograms and tran smitral Doppler spectra were recorded for assessment of LV geometry an d systolic and diastolic functions. LVH rats were randomized to no tre atment (n=10) or treatment with the ACE inhibitor fosinopril (50 mg/kg per day, n=12) after the baseline echocardiogram. Six weeks after ban ding, LVH rats had increased LV wall thickness with normal cavity dime nsions and supranormal endocardial systolic shortening. However, midwa ll shortening was mildly depressed, and a restrictive diastolic fillin g pattern was present. After 18 weeks of untreated pressure overload, LV wall thickness was unchanged, but cavity dilation, a fall in endoca rdial shortening, and further deterioration of diastolic filling were evident. In contrast to untreated LVH rats, the fosinopril-treated rat s showed no change in LV diastolic cavity dimension, and systolic and diastolic functions did not deteriorate or improved. Closed chest LV s ystolic pressures at 18 weeks were not different in LVH or LVH-fosinop ril rats (197 versus 198 mm Hg), although end-diastolic pressure was h igher in the untreated rats (18 versus 11 mm Hg). Calculated LV systol ic wall stress was lower in fosinopril-treated than untreated LVH rats . The severity of LV diastolic filling abnormalities correlated strong ly with operating LV chamber stiffness (r=.88, P<.0001). Conclusions T his model of pressure overload is characterized initially by concentri c LV hypertrophy with compensated LV chamber performance; however, mar kedly abnormal diastolic filling is present. The transition from compe nsated hypertrophy to early failure is heralded by LV dilation, impair ment of systolic function, and progression of the abnormalities in LV filling. Chronic ACE inhibition in rats with supravalvular aortic band ing (1) does not change in vivo LV systolic pressure but prevents incr eased LV cavity size and increased LV wall stress and (2) attenuates i mpairment of (or improves) both systolic and diastolic functions. The effects of fosinopril could be explained in part by inhibition of an i ntracardiac renin-angiotensin system.