November 6, 2001Circulation
Effects of Nitric Oxide Synthase Inhibition on Basal Function and the Force-Frequency Relationship in the Normal and Failing Human Heart In Vivo
Key result
Intracoronary L-NMMA reduced basal LV dP/dt(max) from 1826 to 1578 mm Hg/s in normal hearts (P<0.002) but had no effect in patients with dilated cardiomyopathy (1313 to 1337 mm Hg/s; P=NS).
Why the study?
Does intracoronary NO synthase inhibition with L-NMMA alter basal LV contractility and the force-frequency relationship in normal and failing human hearts?
Population
18 subjects: 11 patients with dilated cardiomyopathy and 7 control subjects with atypical chest pain and…
Comparison
Intracoronary NO synthase inhibition with… vs Baseline measurements prior to L-NMMA…
Design
Other
Authors
Discussion
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Implication
Endogenous NO supports basal contractility in normal hearts but not HF; leaves open NO pathway modulation in dilated cardiomyopathy.
Key Points
- This research aims to investigate how nitric oxide inhibition affects heart function and contractility in normal and failing hearts.
- Comparator study of nitric oxide synthase inhibition using L-NMMA in 11 patients with dilated cardiomyopathy and 7 control subjects.
- Assessments included left ventricular dP/dt(max) at baseline and during incremental atrial pacing.
- Comparisons made to determine the effect of L-NMMA on heart function between groups.
- In controls, L-NMMA significantly reduced left ventricular dP/dt(max) from 1826 to 1578 mm Hg/s (P<0.002).
- In dilated cardiomyopathy patients, L-NMMA had no significant effect on baseline dP/dt(max) (from 1313 to 1337 mm Hg/s; P=NS).
- The pacing-induced rise in left ventricular dP/dt(max) was unaltered by L-NMMA in both groups.
Structured PICO
Does intracoronary NO synthase inhibition with L-NMMA alter basal LV contractility and the force-frequency relationship in normal and failing human hearts?
P
Population
18 subjects, including 11 with dilated cardiomyopathy (mean age 51) and 7 controls with normal cardiac function (mean age 54), evaluated for the effects of intracoronary NO synthase inhibition.
I
Intervention
Intracoronary NO synthase inhibition with N(G)-monomethyl-L-arginine (L-NMMA; 25 micromol/min) during basal conditions and incremental atrial pacing.
C
Comparator
Baseline measurements prior to L-NMMA administration.
O
Outcome
Basal left ventricular (LV) dP/dt(max) and pacing-induced increases in LV dP/dt(max).surrogate
Main Result
Absolute Event Rate: 1578% vs 1826%
p-value: p=<0.002
Endogenous nitric oxide has a small baseline positive inotropic effect in the normal human heart that is lost in heart failure, but it does not significantly influence the force-frequency relationship in either state in vivo.
Limitations
- The study was performed in patients with moderate heart failure, so whether the findings apply to subjects with more severe heart failure requires further investigation.
- Study performed in patients with moderate heart failure, so findings may not apply to subjects with more severe heart failure
Cite This Study
Cotton et al. (2001) studied Dilated cardiomyopathy (n=18). N(G)-monomethyl-L-arginine (L-NMMA) vs. Baseline was evaluated on Basal LV dP/dt(max) (p=<0.002). Intracoronary L-NMMA reduced basal LV dP/dt(max) from 1826 to 1578 mm Hg/s in normal hearts (P<0.002) but had no effect in patients with dilated cardiomyopathy (1313 to 1337 mm Hg/s; P=NS).