Effects of nitric oxide synthase inhibition on Basal function and the force-frequency relationship in the normal and failing human heart in vivo.

2.50
Hdl Handle:
http://hdl.handle.net/2436/29435
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.
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.
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
Type:
Article
Language:
en
ISSN:
1524-4539
Appears in Collections:
Centre for Health and Social Care Improvement

Full metadata record

DC FieldValue Language
dc.contributor.authorCotton, James M.-
dc.contributor.authorKearney, Mark T.-
dc.contributor.authorMacCarthy, Philip A.-
dc.contributor.authorGrocott-Mason, Richard M.-
dc.contributor.authorMcClean, Dougal R.-
dc.contributor.authorHeymes, Christophe-
dc.contributor.authorRichardson, Peter J.-
dc.contributor.authorShah, Ajay M.-
dc.date.accessioned2008-06-04T09:02:29Z-
dc.date.available2008-06-04T09:02:29Z-
dc.date.issued2001-
dc.identifier.citationCirculation, 104(19): 2318-2323en
dc.identifier.issn1524-4539-
dc.identifier.pmid11696472-
dc.identifier.doi10.1161/hc4401.098515-
dc.identifier.urihttp://hdl.handle.net/2436/29435-
dc.description.abstractBACKGROUND: 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.en
dc.language.isoenen
dc.publisherAmerican Heart Association Incen
dc.relation.urlhttp://circ.ahajournals.org/cgi/content/full/104/19/2318en
dc.subjectContractilityen
dc.subjectHeart failureen
dc.subjectMyocardial contractionen
dc.subjectNitric oxideen
dc.subjectNitric oxide synthaseen
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshCardiac Pacing, Artificialen
dc.subject.meshCardiomyopathy, Dilateden
dc.subject.meshEnzyme Inhibitorsen
dc.subject.meshFemaleen
dc.subject.meshHearten
dc.subject.meshHeart Atriaen
dc.subject.meshHeart Catheterizationen
dc.subject.meshHemodynamicsen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshMyocardial Contractionen
dc.subject.meshMyocardiumen
dc.subject.meshNitric Oxideen
dc.subject.meshNitric Oxide Synthaseen
dc.subject.meshVentricular Function, Leften
dc.subject.meshomega-N-Methylarginineen
dc.titleEffects of nitric oxide synthase inhibition on Basal function and the force-frequency relationship in the normal and failing human heart in vivo.en
dc.typeArticleen
dc.identifier.journalCirculationen
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