Submitted on November 26, 2006
Accepted on July 27, 2007
Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses
Philipp A Kaufmann1, Ornella Rimoldi2, Tomaso Gnecchi-Ruscone2, Thomas F Luscher1, and Paolo G Camici2*
1 Nuclear Cardiology, University of Zurich, Zurich, Zurich, Switzerland
2 MRC CSC, Imperial College, Hammersmith Hospital, London, United Kingdom
* To whom correspondence should be addressed. E-mail: paolo.camici{at}csc.mrc.ac.uk.
We studied the impact of systemic infusion of the nitric oxide synthase (NOS) inhibitor NG-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 freshly transplanted denervated hearts. At baseline, myocardial blood flow (MBF, ml/min/g) was measured at rest and during iv adenosine (140 µg/kg/min) in 10 controls (47±5 years) and 10 CAD patients (58±8 years; p<0.01 vs. controls) using positron emission tomography and oxygen-15 labeled water. Both MBF measurements were repeated during iv infusion of 10 mg/kg L-NMMA. CFR was calculated as adenosine-MBF/rest-MBF. 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 neurally-mediated vasoconstriction which can be relieved by systemic NOS inhibition by L-NMMA.
