In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 7 ( 1997-10-07), p. 2397-2406
Abstract:
Background The goal of this study was to determine the effects of ACE inhibition alone, AT 1 angiotensin (Ang) II receptor blockade alone, and combined ACEI and AT 1 Ang II receptor blockade in a model of congestive heart failure (CHF) on isolated LV myocyte function and fundamental components of the excitation-contraction coupling process. Methods and Results Pigs were randomly assigned to one of five groups: (1) rapid atrial pacing (240 bpm) for 3 weeks (n=9), (2) concomitant ACEI (benazeprilat, 0.187 mg · kg −1 · d −1 ) and rapid pacing (n=9), (3) concomitant AT 1 Ang II receptor blockade (valsartan, 3 mg/kg/d) and rapid pacing (n=9), (4) concomitant ACEI and AT 1 Ang II receptor blockade (benazeprilat/valsartan, 0.05/3 mg · kg −1 · d −1 ) and rapid pacing (n=9), and (5) sham controls (n=10). LV myocyte shortening velocity was reduced with chronic rapid pacing compared with control (27.2±0.6 versus 58.6±1.2 μm/s, P 〈 .05) and remained reduced with AT 1 Ang II receptor blockade and rapid pacing (28.0±0.5 μm/s, P 〈 .05). Myocyte shortening velocity increased with ACEI or combination treatment compared with rapid pacing only (36.9±0.7 and 42.3±0.8 μm/s, respectively, P 〈 .05). Myocyte β-adrenergic response was reduced by 〉 50% in both the rapid pacing group and the AT 1 Ang II blockade group and improved by 25% with ACEI and increased by 54% with combined treatment. Both L-type Ca 2+ channel density and the relative abundance of sarcoplasmic reticulum Ca 2+ ATPase density were reduced with rapid pacing and returned to control levels in the combined ACEI and AT 1 Ang II blockade group. Conclusions The unique findings of this study were twofold. First, basic defects in specific components of the myocyte excitation-contraction coupling process that occur with CHF are reversible. Second, combined ACEI and AT 1 Ang II blockade may provide unique benefits on myocyte contractile processes in the setting of CHF.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.96.7.2397
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1997
detail.hit.zdb_id:
1466401-X
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