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

Academic Article

Abstract

  • OBJECTIVES: We hypothesized that angiotensin II type-1 (AT1) receptor blocker (AT1RB) would prevent adverse left ventricular (LV) remodeling and LV dysfunction when started at the outset of mitral regurgitation (MR). BACKGROUND: Little is known regarding the efficacy of AT1RB treatment of MR. METHODS: 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+AT1RB) started 24 h after induction of MR (60 mg/kg p.o. b.i.d.) and continued for three months. RESULTS: Treatment with AT1RB 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 AT1RB dogs. Left ventricular end-systolic dimension increased to a greater extent from baseline in AT1RB dogs versus untreated MR dogs (29 ± 9% vs. 12 ± 6%, p < 0.05), despite a significantly lower LV peak systolic pressure in AT1RB dogs. Plasma-angiotensin (ANG) II was elevated greater than threefold in both MR and MR+AT1RB versus NLs. In contrast, intracardiac ANG II was increased greater than twofold in MR dogs versus NLs, but was normalized by AT1RB. CONCLUSIONS: The use of AT1RB 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 AT1 receptor does not improve LV remodeling and tuncnon in the early myocardial adaptive phase of MR. © 2002 by the American College of Cardiology Foundation.
  • Digital Object Identifier (doi)

    Author List

  • Perry GJ; Wei CC; Hankes GH; Dillon SR; Rynders P; Mukherjee R; Spinale FG; Dell'Italia LJ
  • Start Page

  • 1374
  • End Page

  • 1379
  • Volume

  • 39
  • Issue

  • 8