Beta-blocker improves survival, left ventricular function, and myocardial remodeling in hypertensive rats with diastolic heart failure.
BACKGROUND
Chronic beta-blocker therapy improves survival and left ventricular (LV) systolic function in patients with congestive heart failure. However, its efficacy in diastolic heart failure (DHF) with preserved normal LV systolic function remains uncertain.


METHODS
Dahl salt-sensitive hypertensive rats fed a high-salt diet from 7 weeks of age were randomized to groups that were either not treated (DHF; n = 20) or treated with metoprolol (MP) from 7 weeks of age (DHF+7wkMP; n = 22) or from 17 weeks of age (DHF+17wkMP; n = 8). Both LV function and remodeling were evaluated by serial echocardiography, followed by hemodynamic and pathologic studies.


RESULTS
Hypertension and pressure-overload LV hypertrophy were established by 17 weeks of age in DHF rats. At about 20 weeks of age DHF rats experienced overt heart failure, which was accompanied not by a decrease in LV fractional shortening but by diastolic filling abnormalities. The LV concentric hypertrophy was strikingly attenuated in DHF+7wkMP rats but not in DHF+17wkMP rats. However, LV myocardial fibrosis and the further progression of diastolic dysfunction were prevented in both MP-treated groups. Survival at 21 weeks of age was significantly improved in DHF+7wkMP (86%) and DHF+17wkMP (75%) rats compared with DHF rats (25%).


CONCLUSIONS
In this study, MP prevented not only the development of LV hypertrophy but also the progression of diastolic dysfunction, and improved survival in rats with DHF. The preventive effect of MP on myocardial fibrosis is suggested as one of the mechanisms contributing to halt the progression of diastolic dysfunction, a finding that may lead to clinical benefits in regard to DHF caused by hypertension.
Kobayashi
Masayuki
M
Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan. masa-k@cc.tuat.ac.jp
Machida
Noboru
N
Mitsuishi
Megumi
M
Yamane
Yoshihisa
Y
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D005355:Fibrosis / Q000503:physiopathology / Q000517:prevention & control; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D020303:Rats, Inbred Dahl; D013318:Stroke Volume / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000517:prevention & control; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol