Abstract
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
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Abbreviations
- dP/dt max :
-
maximum rate of change of left-ventricular pressure
- EF:
-
ejection fraction
- FLASH:
-
fast low-angle shot
- LV:
-
left ventricle, left-ventricular
- LVEDD:
-
left-ventricular end-diastolic diameter
- LVEDP:
-
left-ventricular end-diastolic pressure
- LVEDV:
-
left-ventricular end-diastolic volume
- LVESD:
-
left-ventricular end-systolic diameter
- LVESV:
-
left-ventricular end-systolic volume
- LVH:
-
left-ventricular hypertrophy
- LVW:
-
left-ventricular weight
- LVW/TL:
-
left-ventricular weight normalised to tibial length
- LVWS:
-
left-ventricular wall stress
- MR(I):
-
magnetic resonance (imaging)
- PS:
-
left-ventricular peak systolic pressure
- PWTD :
-
posterior wall thickness (diastolic)
- PWTS :
-
posterior wall thickness (systolic)
- SWTD :
-
end-diastolic septal thickness
- SV:
-
stroke volume
- TL:
-
tibial length
- WS:
-
wall stress
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This work was supported in part by a grant of the Ministry of Health (ICS 030.6/RF00-49)
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Marano, G., Palazzesi, S., Vergari, A. et al. Inhibition of left ventricular remodelling preserves chamber systolic function in pressure-overloaded mice. Pflugers Arch - Eur J Physiol 446, 429–436 (2003). https://doi.org/10.1007/s00424-003-1059-2
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DOI: https://doi.org/10.1007/s00424-003-1059-2