HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/H2178    most recent 01292.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Kaufmann, P. A. Articles by Camici, P. G. Search for Related Content PubMed PubMed Citation Articles by Kaufmann, P. A. Articles by Camici, P. G.

Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses

¹Medical Research Council Clinical Sciences Center, Imperial College, Hammersmith Hospital, London, United Kingdom; ²Cardiovascular Center, Nuclear Cardiology, University Hospital, Zurich; and ³Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland

Submitted 26 November 2006 ; accepted in final form 27 July 2007

We studied the impact of systemic infusion of the nitric oxide synthase (NOS) inhibitor N^G-monomethyl-L-arginine (L-NMMA) on coronary flow reserve (CFR) in patients with coronary artery disease (CAD). We have previously demonstrated that CFR to adenosine was significantly increased after systemic infusion of L-NMMA in normal volunteers but not in recently transplanted denervated hearts. At baseline, myocardial blood flow (MBF; ml·min^–1·g^–1) was measured at rest and during intravenous administration of adenosine (140 µg·kg^–1·min^–1) in 10 controls (47 ± 5 yr) and 10 CAD patients (58 ± 8 yr; P < 0.01 vs. controls) using positron emission tomography and ¹⁵O-labeled water. Both MBF measurements were repeated during intravenous infusion of 10 mg/kg L-NMMA. CFR was calculated as the ratio of MBF during adenosine to MBF at rest. CFR was significantly higher in healthy volunteers than in CAD patients and increased significantly after L-NMMA in controls (4.00 ± 1.10 to 6.15 ± 1.35; P < 0.0001) and in patients, both in territories subtended by stenotic coronary arteries (>70% luminal diameter; 2.06 ± 1.13 to 3.21 ± 1.07; P < 0.01) and in remote segments (3.20 ± 1.23 to 3.92 ± 1.62; P < 0.05). In conclusion, CFR can be significantly increased in CAD by a systemic infusion of L-NMMA. Similarly to our previous findings in normal volunteers, this suggests that adenosine-induced hyperemia in CAD patients is constrained by a mechanism that can be relieved by systemic NOS inhibition with L-NMMA.

coronary circulation; autonomic nervous system; ischemic heart disease; cardiac imaging; positron emission tomography

This article has been cited by other articles:

				I. Heinonen, S. V. Nesterov, K. Liukko, J. Kemppainen, K. Nagren, M. Luotolahti, P. Virsu, V. Oikonen, P. Nuutila, U. M. Kujala, et al. Myocardial blood flow and adenosine A2A receptor density in endurance athletes and untrained men J. Physiol., November 1, 2008; 586(21): 5193 - 5202. [Abstract] [Full Text] [PDF]

				G. J. Crystal, M. El-Orbany, X. Zhou, M. R. Salem, and S.-J. Kim Hemodilution does not alter the coronary vasodilating effects of endogenous or exogenous nitric oxide: [L'hemodilution ne modifie pas les effets vasodilatateurs coronariens de l'oxyde nitrique endogene ou exogene] Can J Anesth, August 1, 2008; 55(8): 507 - 514. [Abstract] [Full Text] [PDF]