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(Circulation. 1999;99:3009-3016.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Endomyocardial Nitric Oxide Synthase and Left Ventricular Preload Reserve in Dilated Cardiomyopathy
From the Cardiovascular Center, O.L.V. Ziekenhuis, Aalst, Belgium (C.H., M.V., W.J.P.); Inserm U127, IFR Circulation, Université D. Diderot, Paris, France (C.H.); Department of Cardiology, Free University Hospital, Amsterdam, the Netherlands (J.G.F.B.); and Department of Cardiology, University of Wales College of Medicine, Cardiff, UK (A.M.S.).
Correspondence to Dr Walter J. Paulus, MD, PhD, Cardiovascular Center, O.L.V. Ziekenhuis, Moorselbaan 164, B 9300 Aalst, Belgium. E-mail Walter.Paulus{at}ping.be
Background—Patients with heart failure have modified myocardial expression of nitric oxide synthase (NOS), as is evident from induction of calcium-insensitive NOS isoforms. The functional significance of this modified NOS gene expression for left ventricular (LV) contractile performance was investigated in patients with dilated nonischemic cardiomyopathy.
Methods and Results—In patients with dilated, nonischemic cardiomyopathy, invasive measures of LV contractile performance were derived from LV microtip pressure recordings and angiograms and correlated with intensity of gene expression of inducible (NOS2) and constitutive (NOS3) NOS isoforms in simultaneously procured LV endomyocardial biopsies (n=20). LV endomyocardial expression of NOS2 was linearly correlated with LV stroke volume (P=0.001; r=0.66), LV ejection fraction (P=0.007; r=0.58), and LV stroke work (P=0.003; r=0.62). In patients with elevated LV end-diastolic pressure (>16 mm Hg), a closer correlation was observed between endomyocardial expression of NOS2 and LV stroke volume (P=0.001; r=0.74), LV ejection fraction (P=0.0007; r=0.77), and LV stroke work (r=0.82; P=0.0002). LV endomyocardial expression of NOS3 was linearly correlated with LV stroke volume (P=0.01; r=0.53) and LV stroke work (P=0.01; r=0.52). To establish the role of nitric oxide (NO) as a mediator of the observed correlations, substance P (which causes endothelial release of NO) was infused intracoronarily (n=12). In patients with elevated LV end-diastolic pressure, an intracoronary infusion of substance P increased LV stroke volume from 72±13 to 91±16 mL (P=0.06) and LV stroke work from 67±11 to 90±15 g · m (P=0.03) and shifted the LV end-diastolic pressure–volume relation to the right.
Conclusions—In patients with dilated cardiomyopathy, an increase in endomyocardial NOS2 or NOS3 gene expression augments LV stroke volume and LV stroke work because of a NO-mediated rightward shift of the diastolic LV pressure-volume relation and a concomitant increase in LV preload reserve.
Key Words: nitric oxide • cardiomyopathy • ventricles • diastole
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|
|
|
|
|
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|
|
|
|
|
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|
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|
|
|
|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
W. Grossman Defining Diastolic Dysfunction Circulation, May 2, 2000; 101(17): 2020 - 2021. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
J. Heger, A. Godecke, U. Flogel, M. W. Merx, A. Molojavyi, W. N. Kuhn-Velten, and J. Schrader Cardiac-Specific Overexpression of Inducible Nitric Oxide Synthase Does Not Result in Severe Cardiac Dysfunction Circ. Res., January 11, 2002; 90(1): 93 - 99. [Abstract] [Full Text] [PDF]
|
|