What is the clinical evidence from this study?

Study design: Other. Population: Aging (n=24). Intervention: Norepinephrine vs. Baseline (unstimulated cells) and younger age groups. Primary outcome: Maximal effect of norepinephrine on twitch amplitude (percentage of control) (p=0.0001).

What question did this study set out to answer?

To examine how aging affects beta-adrenergic modulation of cardiac excitation-contraction coupling in rat myocytes.

November 1, 1994Journal of Clinical InvestigationOpen Access

Age-associated changes in beta-adrenergic modulation on rat cardiac excitation-contraction coupling.

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Key result

Beta-adrenergic stimulation with norepinephrine elicited a significantly diminished increase in twitch amplitude and cytosolic calcium transient in ventricular myocytes from older rats compared to younger rats.

Why the study?

Does beta-adrenergic stimulation by norepinephrine improve cardiac excitation-contraction coupling differently across age groups in rat ventricular myocytes?

Population

Single ventricular cardiac myocytes isolated from 2-4, 6-8, and 24-month-old male Wistar rats

Comparison

Beta-adrenergic stimulation by norepinephrine (NE) vs Baseline control conditions and comparison…

Design

Preclinical

Authors

RXR P XiaoJiangnan University HSHarold A. SpurgeonElectrophysiology FOF O'ConnorQueen's University Belfast

Discussion

Member takes

Implication

Caution against extrapolating beta-adrenergic effects by age to patients; leaves open calcium-handling mechanisms in human cardiac aging.

Key Points

To examine how aging affects beta-adrenergic modulation of cardiac excitation-contraction coupling in rat myocytes.
Isolated ventricular myocytes from rat hearts aged 2, 6-8, and 24 months were used.
Calcium current (ICa), calcium transient (Cai2+), and contraction responses to norepinephrine were measured.
Responses to beta-adrenergic stimulation were quantified and compared across age groups.
The response to beta-adrenergic stimulation decreased significantly with age, with increased threshold concentration and ED50 for contraction.
Maximum contraction and Cai2+ transient responses diminished with aging.
The efficacy of beta AR stimulation to enhance ICa was reduced, correlating with decreased contraction and Cai2+ responses.

Structured PICO

Does beta-adrenergic stimulation by norepinephrine improve cardiac excitation-contraction coupling differently across age groups in rat ventricular myocytes?

Population

Ventricular myocytes isolated from 24 male Wistar rats aged 2 to 24 months to study age-associated changes in beta-adrenergic modulation.

Intervention

Beta-adrenergic stimulation by norepinephrine (NE)

Comparator

Baseline control conditions (cells before NE exposure) and comparison across age groups

Outcome

Responses of calcium current (ICa), cytosolic Ca2+ (Cai2+) transient, and contraction to beta-adrenergic stimulationsurrogate

Main Result

Absolute Event Rate: 199.9% vs 266.7%

p-value: p=0.0001

The age-associated reduction in beta-adrenergic modulation of cardiac contraction is partly due to a deficit in the modulation of cytosolic calcium, specifically L-type calcium channel activity.

Limitations

Age differences in SR Ca2+ release in response to beta-AR stimulation may also relate to changes in SR Ca2+ release channel properties which could not be measured in this study.

Cite This Study

Xiao et al. (1994) studied Aging (n=24). Norepinephrine vs. Baseline (unstimulated cells) and younger age groups was evaluated on Maximal effect of norepinephrine on twitch amplitude (percentage of control) (p=0.0001). Beta-adrenergic stimulation with norepinephrine elicited a significantly diminished increase in twitch amplitude and cytosolic calcium transient in ventricular myocytes from older rats compared to younger rats.

synapsesocial.com/papers/6a204a2d6504ae8788d1e210 https://doi.org/10.1172/jci117559

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