October 15, 1995Circulation
Nitric Oxide Inhibits the Positive Inotropic Response to β-Adrenergic Stimulation in Humans With Left Ventricular Dysfunction
Key result
Intracoronary infusion of the NO synthase inhibitor L-NMMA potentiated the LV peak +dP/dt response to dobutamine by 30 ± 10% (P<0.04), indicating NO attenuates beta-adrenergic inotropy.
Why the study?
Does NO synthase inhibition with L-NMMA improve the positive inotropic response to dobutamine in patients with left ventricular dysfunction?
Population
14 patients with various degrees of left ventricular dysfunction and free from epicardial coronary artery…
Comparison
Intracoronary infusion of NO synthase inhibitor… vs Dobutamine infusion alone.
Design
Other
Follow-up
10 minutes (acute infusion)
Authors
Discussion
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Implication
NO may contribute to beta-adrenergic hyporesponsiveness in LV dysfunction; leaves open therapeutic NOS inhibition.
Key Points
- To determine whether endogenous nitric oxide produced in the heart inhibits the positive inotropic response to beta-adrenergic stimulation in patients with left ventricular dysfunction.
- Assessed cardiac mechanics using a left main coronary artery infusion catheter and an LV micromanometer-tipped catheter in patients with left ventricular dysfunction free from coronary artery disease.
- Administered dobutamine via intracoronary infusion (n = 8; 25 or 50 µg/min) or peripheral vein (n = 6; 6, 10, or 15 µg·kg⁻¹·min⁻¹) before and during intracoronary nitric oxide synthase inhibition with L-NMMA (20 µmol/min).
- Intracoronary dobutamine alone increased LV peak +dP/dt by 33 ± 3%, whereas intracoronary L-NMMA alone did not alter baseline LV pressures, aortic pressure, or heart rate.
- Concurrent intracoronary L-NMMA potentiated the LV peak +dP/dt response to intracoronary dobutamine by 30 ± 10% (P < 0.04 vs dobutamine alone) and to peripheral dobutamine by 37 ± 18%.
Structured PICO
Does NO synthase inhibition with L-NMMA improve the positive inotropic response to dobutamine in patients with left ventricular dysfunction?
P
Population
14 patients with various degrees of left ventricular (LV) dysfunction and free from epicardial coronary artery disease.
I
Intervention
Intracoronary infusion of NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 20 mumol/min for 10 minutes) concurrent with dobutamine infusion (intracoronary or peripheral).
C
Comparator
Dobutamine infusion alone.
O
Outcome
Left ventricular (LV) peak +dP/dt.surrogate
Main Result
Effect estimate: 30 +/- 10% potentiation
p-value: p=<0.04
Nitric oxide produced in the heart attenuates the positive inotropic response to beta-adrenergic stimulation in patients with LV dysfunction, suggesting NO contributes to beta-adrenergic hyporesponsiveness.
Cite This Study
Hare et al. (1995) studied Left ventricular dysfunction (n=14). L-NMMA (NO synthase inhibitor) concurrent with dobutamine vs. Dobutamine alone was evaluated on LV peak +dP/dt response (30 +/- 10% potentiation, p=<0.04). Intracoronary infusion of the NO synthase inhibitor L-NMMA potentiated the LV peak +dP/dt response to dobutamine by 30 ± 10% (P<0.04), indicating NO attenuates beta-adrenergic inotropy.