(Circulation. 1995;91:2642-2654.)
© 1995 American Heart Association, Inc.
Articles |
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
Presented in part at the American Heart Association 66th Scientific Sessions, Atlanta, Ga, November 1993.
From the Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Department of Medicine (Cardiovascular Division), Beth Israel Hospital and Harvard Medical School, Boston, Mass, and University of Massachusetts Medical School (G.P.A.), Worcester, Mass.
Correspondence to Sheldon E. Litwin, MD, Division of Cardiology, University of Utah Medical Center, 50 N Medical Dr, Salt Lake City, UT 84132.
Background Although chronic pressure overload may progress to left ventricular (LV) failure, the pathophysiology of this transition is not well understood. In addition, the effects of chronic angiotensin-converting enzyme (ACE) inhibition on this transition are largely undefined.
Methods and Results To examine changes in LV structure and function during the transition to heart failure, rats with LV hypertrophy due to banding of the ascending aorta (LVH, n=22) and age-matched sham-operated rats (n=6) were studied 6, 12, and 18 weeks after aortic banding. Two-dimensionally guided transthoracic M-mode echocardiograms and transmitral Doppler spectra were recorded for assessment of LV geometry and systolic and diastolic functions. LVH rats were randomized to no treatment (n=10) or treatment with the ACE inhibitor fosinopril (50 mg/kg per day, n=12) after the baseline echocardiogram. Six weeks after banding, LVH rats had increased LV wall thickness with normal cavity dimensions and supranormal endocardial systolic shortening. However, midwall shortening was mildly depressed, and a restrictive diastolic filling pattern was present. After 18 weeks of untreated pressure overload, LV wall thickness was unchanged, but cavity dilation, a fall in endocardial shortening, and further deterioration of diastolic filling were evident. In contrast to untreated LVH rats, the fosinopril-treated rats showed no change in LV diastolic cavity dimension, and systolic and diastolic functions did not deteriorate or improved. Closed chest LV systolic pressures at 18 weeks were not different in LVH or LVH-fosinopril rats (197 versus 198 mm Hg), although end-diastolic pressure was higher in the untreated rats (18 versus 11 mm Hg). Calculated LV systolic wall stress was lower in fosinopril-treated than untreated LVH rats. The severity of LV diastolic filling abnormalities correlated strongly with operating LV chamber stiffness (r=.88, P<.0001).
Conclusions This model of pressure overload is characterized initially by concentric LV hypertrophy with compensated LV chamber performance; however, markedly abnormal diastolic filling is present. The transition from compensated hypertrophy to early failure is heralded by LV dilation, impairment of systolic function, and progression of the abnormalities in LV filling. Chronic ACE inhibition in rats with supravalvular aortic banding (1) does not change in vivo LV systolic pressure but prevents increased LV cavity size and increased LV wall stress and (2) attenuates impairment of (or improves) both systolic and diastolic functions. The effects of fosinopril could be explained in part by inhibition of an intracardiac renin-angiotensin system.
Key Words: echocardiography • hypertrophy • diastole • angiotensin • heart failure, congestive
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