What question did this study set out to answer?

To determine the presynaptic modulation of noradrenaline release from sympathetic nerve terminals in isolated human papillary muscle.

May 1, 1994Cardiovascular Research

Receptor mediated presynaptic modulation of the release of noradrenaline in human papillary muscle

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Population

Human isolated papillary muscle and right atrial appendage obtained from operations on 22 patients

Comparison

Pharmacological modulation with alpha-2… vs Baseline or unmodulated release

Design

Preclinical

Authors

IMI MatkóSomogy Megyei Kaposi Mór Oktató Kórház ÉFÉ FehérSemmelweis University EVE. Sylvester ViziSemmelweis University

Discussion

Member takes

Implication

No immediate change to sympathetic modulation strategies in HF; hypothesis-generating for alpha-2/M3 targeting and requires translational validation.

Key Points

To determine the presynaptic modulation of noradrenaline release from sympathetic nerve terminals in isolated human papillary muscle.
Obtained papillary muscle and right atrial appendage specimens from cardiac operations in 22 patients (10 men and 12 women).
Preincubated papillary muscle preparations with [3H]noradrenaline to measure [3H] release at rest and during electrical field stimulation, accompanied by dopamine-beta-hydroxylase immunohistochemistry.
Identified dopamine-beta-hydroxylase-positive neurons throughout both papillary muscle and right atrial appendage specimens.
Observed that noradrenaline release was enhanced by the selective alpha-2 antagonist CH-38083 and inhibited by the alpha-2 agonist xylazine, verifying active autoinhibitory feedback.
Found that noradrenaline release increased with muscarinic antagonists (atropine, pancuronium, 4-DAMP) and decreased with the muscarinic agonist oxotremorine, demonstrating inhibitory M3 heteroreceptor regulation.

Structured PICO

Population

Human isolated papillary muscle and right atrial appendage obtained from operations on 22 patients (10 men and 12 women)

Intervention

Pharmacological modulation with alpha-2 adrenoceptor agents (CH-38083, xylazine) and muscarinic receptor agents (atropine, pancuronium, 4-DAMP, oxotremorine)

Comparator

Baseline or unmodulated release

Outcome

Release of [3H]noradrenaline at rest and in response to field stimulationsurrogate

This study provides the first evidence in human papillary muscle that noradrenaline release is presynaptically modulated by alpha-2 autoreceptors and M3 muscarinic heteroreceptors.

Cite This Study

Matkó et al. (1994) studied this question.

synapsesocial.com/papers/69f17a19b6126e0e7a7282ff https://doi.org/10.1093/cvr/28.5.700

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Implication

No immediate change to sympathetic modulation strategies in HF; hypothesis-generating for alpha-2/M3 targeting and requires translational validation.

Receptor mediated presynaptic modulation of the release of noradrenaline in human papillary muscle

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Receptor mediated presynaptic modulation of the release of noradrenaline in human papillary muscle

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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