Inhibition of left ventricular remodelling preserves chamber systolic function in pressure-overloaded mice.
Controversy exists whether the development of left-ventricular hypertrophy (LVH) is a mechanism able to prevent cardiac dysfunction under conditions of pressure overload. In the present study we re-assessed the long-term effects of attenuating LVH by using L- and D-propranolol, which are equally able to inhibit the development of LVH induced by aortic banding. The aortic arch was banded proximal to the left common carotid artery in 71 CD-1 mice that were then assigned randomly to receive L-propranolol, D-propranolol (both 80 mg/kg per day) or vehicle. Concurrently, sham-operated mice were given L-propranolol, D-propranolol or vehicle. LV dimension and performance were evaluated under isoflurane anaesthesia by cine-magnetic resonance imaging, echocardiography and cardiac catheterization up to 8 weeks after surgery. After 2 weeks of pressure overload, the vehicle-treated banded mice had enhanced LV weight, normal chamber size and increased relative wall thickness (concentric hypertrophy), whereas L-propranolol- or D-propranolol-banded mice showed a markedly blunted hypertrophic response, i.e. normal chamber size and normal relative wall thickness, as well as preserved systolic LV chamber function. After 4 weeks, the vehicle-treated banded mice showed LV enlargement with a reduced relative wall thickness (eccentric remodelling) and a clear-cut deterioration in LV systolic function. In contrast, L-propranolol- or D-propranolol-treated banded mice showed normal chamber size with a normal relative wall thickness and preserved systolic function. A distinct histological feature was that in banded mice, L-or D-propranolol attenuated the development of cardiomyocyte hypertrophy but not the attendant myocardial fibrosis. At the 8-week stage, LV dysfunction was present in propranolol-treated banded mice although it was much less severe than in vehicle-treated banded mice. It is concluded that (i) deterioration of LV systolic performance is delayed if LV hypertrophy is inhibited, (ii) banding-induced deterioration of LV systolic function is associated with LV eccentric remodelling and (iii) the antihypertrophic effect of propranolol is due to a selective action on cardiomyocytes rather than on collagen accumulation
Marano
Giuseppe
G
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. gmarano@iss.it
Palazzesi
Sergio
S
Vergari
Alessandro
A
Catalano
Liviana
L
Gaudi
Simona
S
Testa
Claudia
C
Canese
Rossella
R
Carpinelli
Giulia
G
Podo
Franca
F
Ferrari
Alberto U
AU
D000818:Animals; D001011:Aorta / Q000503:physiopathology; D004452:Echocardiography; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011433:Propranolol / Q000494:pharmacology; D013599:Systole / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
D014665:Vasodilator Agents; D011433:Propranolol