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Wolverhampton Intellectual Repository and E-Theses > School of Health & Wellbeing > Centre for Health and Social Care Improvement > Effects of nitric oxide synthase inhibition on Basal function and the force-frequency relationship in the normal and failing human heart in vivo.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/29435
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Title: Effects of nitric oxide synthase inhibition on Basal function and the force-frequency relationship in the normal and failing human heart in vivo.
Authors: Cotton, James M.
Kearney, Mark T.
MacCarthy, Philip A.
Grocott-Mason, Richard M.
McClean, Dougal R.
Heymes, Christophe
Richardson, Peter J.
Shah, Ajay M.
Citation: Circulation, 104(19): 2318-2323
Publisher: American Heart Association Inc
Journal: Circulation
Issue Date: 2001
URI: http://hdl.handle.net/2436/29435
DOI: 10.1161/hc4401.098515
PubMed ID: 11696472
Additional Links: http://circ.ahajournals.org/cgi/content/full/104/19/2318
Abstract: BACKGROUND: Nitric oxide (NO) exerts autocrine/paracrine effects on cardiac function, including alterations of the inotropic state. In vitro studies suggest that NO modulates the myocardial force-frequency relationship. Basal left ventricular (LV) contractility is depressed and the force-frequency relationship is blunted in human heart failure, and it is speculated that an increase in NO production is involved. METHODS AND RESULTS: We compared the effects of intracoronary NO synthase inhibition with N(G)-monomethyl-L-arginine (L-NMMA; 25 micromol/min) on basal LV function and the response to incremental atrial pacing in patients with dilated cardiomyopathy (n=11; mean age, 51 years) and in control subjects with atypical chest pain and normal cardiac function (n=7; mean age, 54 years). In controls, L-NMMA significantly reduced basal LV dP/dt(max) (from 1826 to 1578 mm Hg/s; P<0.002), but had no effect on heart rate, mean aortic pressure, or right atrial pressure. Pacing-induced increases in LV dP/dt(max) were unaltered by L-NMMA. In patients with dilated cardiomyopathy, L-NMMA had no effect on baseline LV dP/dt(max) (from 1313 to 1337 mm Hg/s; P=NS). The blunted pacing-induced rise in LV dP/dt(max) in these patients was unaltered by L-NMMA. CONCLUSION: Endogenous NO has a small baseline positive inotropic effect in the normal human heart, which is lost in heart failure patients. NO does not significantly influence the force-frequency relationship in either the normal or failing human heart in vivo. Because this study was performed in patients with moderate heart failure, whether the findings apply to subjects with more severe heart failure requires further investigation.
Type: Article
Language: en
Keywords: Contractility
Heart failure
Myocardial contraction
Nitric oxide
Nitric oxide synthase
MeSH: Adult
Aged
Cardiac Pacing, Artificial
Cardiomyopathy, Dilated
Enzyme Inhibitors
Female
Heart
Heart Atria
Heart Catheterization
Hemodynamics
Humans
Male
Middle Aged
Myocardial Contraction
Myocardium
Nitric Oxide
Nitric Oxide Synthase
Ventricular Function, Left
omega-N-Methylarginine
ISSN: 1524-4539
Appears in Collections: Centre for Health and Social Care Improvement

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