September 8, 2004Circulation
Systemic Inhibition of Nitric Oxide Synthase Unmasks Neural Constraint of Maximal Myocardial Blood Flow in Humans
Key result
Systemic NOS inhibition with 10 mg/kg L-NMMA increased hyperemic myocardial blood flow by 53% and coronary flow reserve by 52% (P<0.0001) in subjects with intact cardiac innervation.
Why the study?
Does systemic NOS inhibition with L-NMMA improve maximal myocardial blood flow and coronary flow reserve in humans?
Population
48 subjects, comprising volunteers and denervated heart transplant recipients.
Comparison
Intravenous infusion of N-monomethyl-L-arginine… vs Intravenous saline infusion and baseline…
Design
Other
Authors
Discussion
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Implication
May relieve neurally mediated coronary vasoconstriction; hypothesis-generating for NOS-targeted therapies before any clinical consideration.
Structured PICO
Does systemic NOS inhibition with L-NMMA improve maximal myocardial blood flow and coronary flow reserve in humans?
P
Population
48 volunteers and heart transplant recipients evaluated for myocardial blood flow and coronary flow reserve during systemic NOS inhibition.
I
Intervention
Intravenous infusion of N(G)-monomethyl-L-arginine (L-NMMA) at 3 mg/kg (Group 2) or 10 mg/kg (Groups 3 and 5), or phenylephrine titrated to simulate hemodynamic changes (Group 4).
C
Comparator
Intravenous saline infusion (Group 1) and baseline measurements.
O
Outcome
Myocardial blood flow (MBF) at rest and during adenosine-induced hyperemia, and coronary flow reserve (CFR) measured with positron emission tomography and 15O-labeled water.surrogate
Main Result
p-value: p=<0.0001
Maximal adenosine-induced hyperemia and coronary flow reserve in humans are constrained by neurally mediated vasoconstriction, which can be relieved by systemic NOS inhibition.
Cite This Study
Kaufmann et al. (2004) studied Healthy volunteers and heart transplant recipients (n=48). L-NMMA vs. Saline or phenylephrine was evaluated on Myocardial blood flow (MBF) and coronary flow reserve (CFR) (p=<0.0001). Systemic NOS inhibition with 10 mg/kg L-NMMA increased hyperemic myocardial blood flow by 53% and coronary flow reserve by 52% (P<0.0001) in subjects with intact cardiac innervation.