Angiotensin II receptor blockade does not improve left ventricular function and remodeling in subacute mitral regurgitation in the dog

We hypothesized that angiotensin II type-1 (AT(1)) receptor blocker (AT(1)RB) would prevent adverse left ventricular (LV) remodeling and LV dysfunction when started at the outset of mitral regurgitation (MR). Little is known regarding the efficacy of AT(1)RB treatment of MR. Mitral regurgitation was...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American College of Cardiology 2002-04, Vol.39 (8), p.1374-1379
Main Authors: Perry, Gilbert J, Wei, Chih-Chang, Hankes, Gerald H, Dillon, S Ray, Rynders, Patricia, Mukherjee, Rupak, Spinale, Francis G, Dell'Italia, Louis J
Format: Article
Language:English
Subjects:
Alabama
Angiotensin I - blood
Angiotensin II - blood
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors - blood
Animals
Body Weight - drug effects
Chymases
Disease Models, Animal
Dogs
Female
Heart Ventricles - enzymology
Hemodynamics - drug effects
Male
Mitral Valve Insufficiency - drug therapy
Receptor, Angiotensin, Type 1
Renin - blood
Renin - drug effects
Serine Endopeptidases - blood
Treatment Outcome
Ventricular Function, Left - drug effects
Ventricular Remodeling - drug effects
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We hypothesized that angiotensin II type-1 (AT(1)) receptor blocker (AT(1)RB) would prevent adverse left ventricular (LV) remodeling and LV dysfunction when started at the outset of mitral regurgitation (MR). Little is known regarding the efficacy of AT(1)RB treatment of MR. Mitral regurgitation was induced by chordal disruption in adult mongrel dogs. Six normal dogs (NLs) were compared to six untreated MR dogs (MR) and seven dogs treated with the receptor blocker irbesartan (MR+AT(1)RB) started 24 h after induction of MR (60 mg/kg p.o. b.i.d.) and continued for three months. Treatment with AT(1)RB decreased systemic vascular resistance but did not significantly improve cardiac output, LV end-diastolic dimension (LVEDD) or LVEDD/wall thickness compared to untreated MR dogs. Resting isolated cardiomyocyte length increased in MR versus NLs and was further increased in AT(1)RB dogs. Left ventricular end-systolic dimension increased to a greater extent from baseline in AT(1)RB dogs versus untreated MR dogs (29 +/- 9% vs. 12 +/- 6%, p < 0.05), despite a significantly lower LV peak systolic pressure in AT(1)RB dogs. Plasma-angiotensin (ANG) II was elevated greater than threefold in both MR and MR+AT(1)RB versus NLs. In contrast, intracardiac ANG II was increased greater than twofold in MR dogs versus NLs, but was normalized by AT(1)RB. The use of AT(1)RB decreased systemic vascular resistance and attenuated local expression of the renin-angiotensin system but did not prevent adverse LV chamber and cardiomyocyte remodeling. These results suggest that blockade of the AT(1) receptor does not improve LV remodeling and function in the early myocardial adaptive phase of MR.
ISSN:0735-1097
1558-3597
DOI:10.1016/S0735-1097(02)01763-1