Circulation, Vol 89, 818-826, Copyright © 1994 by American Heart Association
M Nagatsu, MR Zile, H Tsutsui, PG Schmid, G DeFreyte, G Cooper 4th and BA Carabello
BACKGROUND: It is generally accepted that the adrenergic nervous system
provides inotropic support for the failing heart. However, the magnitude of
this support has never been studied extensively. The present study was
performed to test the hypothesis that the adrenergic nervous system is
capable of maintaining indexes of pump and contractile function in the
normal range despite significant innate myocardial depression. METHODS AND
RESULTS: We used our model of experimental canine mitral regurgitation,
which produces left ventricular dysfunction after 3 months of volume
overload. We studied indexes of contractile function on and off
beta-blockade at baseline and again on and off beta-blockade 3 months after
chronic mitral regurgitation had induced significant contractile
dysfunction. At baseline, acute beta-blockade caused insignificant
reductions in the mass-corrected slope of the end-ejection stress-volume
relation (EESVR), the end-systolic stiffness constant, and the ejection
fraction- end-systolic stress and the mean velocity of circumferential
fiber shortening (VCF)-end-systolic stress relations. After 3 months of
chronic mitral regurgitation, all indexes of contractile function were
normal in the unblocked state except for the VCF-stress relation, which was
mildly reduced. However, after acute beta-blockade after 3 months of
chronic mitral regurgitation, the EESVR fell to 303 +/- 27 versus 443 +/-
24 during acute beta-blockade before mitral regurgitation was created (P
< .05), and the end-systolic stiffness constant was reduced to 2.54 +/-
0.15 versus 3.27 +/- 0.11 (P < .05). Only after beta- blockade was the
ejection fraction-stress relation significantly reduced for dogs with
chronic mitral regurgitation. The VCF-stress relation became markedly more
abnormal. The viscosity-velocity relation of myocytes isolated from the
ventricles of the dogs with mitral regurgitation confirmed that substantial
innate contractile depression was present. CONCLUSIONS: After 3 months of
chronic mitral regurgitation, the adrenergic nervous system was able to
maintain most indexes of contractile function in the normal range despite
significant depression in innate contractile function. Thus, in the absence
of beta- blockade, significant innate contractile depression may be
obscured by adrenergic support.
ARTICLES
Native beta-adrenergic support for left ventricular dysfunction in experimental mitral regurgitation normalizes indexes of pump and contractile function
Department of Medicine, Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston 29425-2221.
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