What question did this study set out to answer?

This research explores the effects of a neutral endopeptidase inhibitor on heart failure symptoms in dogs.

June 1, 1993Cardiovascular Research

Inhibition of neutral endopeptidase 3.4.24.11 in conscious dogs with pacing induced heart failure

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Why the study?

Does the neutral endopeptidase inhibitor SQ 28,603 improve natriuresis and increase atrial natriuretic peptide levels in dogs with pacing-induced heart failure?

Population

Conscious dogs with heart failure induced by rapid ventricular pacing for one or three weeks, and normal…

Comparison

SQ 28,603 10, 30, or 100 mumol.kg-1 given… vs Normal conscious dogs and baseline measurements…

Design

Preclinical

Authors

ASAndrea A. SeymourMerck & Co., Inc., Rahway, NJ, USA (United States)MAMagdi M. AsaadBristol-Myers Squibb (Germany)VLV LanoceBristol-Myers Squibb (Germany)

Discussion

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Implication

NEP inhibition augments natriuresis in established canine HF; hypothesis-generating and requires human trials before clinical consideration.

Key Points

This research explores the effects of a neutral endopeptidase inhibitor on heart failure symptoms in dogs.
Induced heart failure in dogs by rapid ventricular pacing for one or three weeks.
Measured atrial pressures, mean arterial pressure, cardiac output, and renal blood flow.
Administered SQ 28,603 at doses of 10, 30, or 100 mumol.kg-1 intravenously.
Inhibition increased sodium excretion from 0.1% to 2.0% after one week, and from 0.5% to 3.7% after three weeks.
Plasma concentrations of atrial natriuretic peptide were significantly higher in paced dogs compared to normal dogs.
No significant effects on renal or hemodynamic variables were observed in normal dogs.

Structured PICO

Does the neutral endopeptidase inhibitor SQ 28,603 improve natriuresis and increase atrial natriuretic peptide levels in dogs with pacing-induced heart failure?

Population

Conscious dogs with heart failure induced by rapid ventricular pacing for one or three weeks, and normal conscious dogs

Intervention

SQ 28,603 (neutral endopeptidase inhibitor) 10, 30, or 100 mumol.kg-1 given intravenously

Comparator

Normal conscious dogs and baseline measurements prior to intervention

Outcome

Sodium excretion, cyclic GMP excretion, and plasma concentrations of atrial natriuretic peptidesurrogate

Inhibition of neutral endopeptidase with SQ 28,603 in a canine model of pacing-induced heart failure protects endogenous atrial natriuretic peptide from degradation and stimulates sustained natriuresis.

Cite This Study

Seymour et al. (1993) studied this question.

synapsesocial.com/papers/6a2115ae23521dddf4c3bf04 https://doi.org/10.1093/cvr/27.6.1015

Topics

HFrEF treatment Heart failure

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Implication

NEP inhibition augments natriuresis in established canine HF; hypothesis-generating and requires human trials before clinical consideration.

Inhibition of neutral endopeptidase 3.4.24.11 in conscious dogs with pacing induced heart failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Inhibition of neutral endopeptidase 3.4.24.11 in conscious dogs with pacing induced heart failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

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