What is the clinical evidence from this study?

Study design: Observational. Population: Aging (n=56). Intervention: Pirenzepine vs. Age (Young vs. Older). Primary outcome: Correlation between right atrial muscarinic receptor density and age (r = -0.3946, p=0.0129).

What question did this study set out to answer?

To identify the physiological and biochemical mechanisms responsible for the age-dependent decline in heart rate reduction induced by the muscarinic antagonist pirenzepine.

January 15, 1998Journal of Clinical InvestigationOpen Access

Cardiac muscarinic receptors decrease with age. In vitro and in vivo studies.

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Key result

Right atrial M2 muscarinic receptor density and function decrease significantly with age, explaining the age-dependent decline in the heart rate-decreasing effect of pirenzepine.

Why the study?

Does age affect the heart rate response to pirenzepine and cardiac M2 muscarinic receptor density?

Key Points

To identify the physiological and biochemical mechanisms responsible for the age-dependent decline in heart rate reduction induced by the muscarinic antagonist pirenzepine.
Evaluated intravenous pirenzepine (0.32 and 0.64 mg) on isoprenaline-induced heart rate acceleration in 6 young volunteers (mean 26 years) and 6 older volunteers (mean 61 years).
Administered intravenous pirenzepine (0.05 to 10 mg) to 5 heart transplant recipients to measure resting heart rate responses in native versus transplanted sinus nodes.
Quantified M2 muscarinic receptor density and adenylyl cyclase activity using [3H]N-methyl-scopolamine binding in right atrial tissue from 39 surgical patients aged 5 days to 76 years.
Pirenzepine at both 0.32 mg and 0.64 mg doses decreased heart rate significantly more in young volunteers than in older volunteers.
Pirenzepine at doses under 1 mg decreased resting heart rate in the native sinus node but produced no rate changes in the denervated transplanted sinus node.
Right atrial M2 receptor density and carbachol-induced inhibition of adenylyl cyclase activity decreased significantly with advancing age across the 39-patient surgical cohort.

Study Design

Type

Observational (n=56)

Multicenter

Structured PICO

Does age affect the heart rate response to pirenzepine and cardiac M2 muscarinic receptor density?

Population

56 subjects total: 6 young (26 years old) and 6 older (61 years old) volunteers, 5 heart transplant recipients, and right atria from 39 patients (aged 5 days to 76 years) undergoing open heart surgery.

Intervention

Pirenzepine (0.32 and 0.64 mg i.v. bolus in volunteers; 0.05-10 mg i.v. bolus in transplant recipients) and in vitro assessment of M2 receptor density and adenylyl cyclase activity.

Comparator

Age groups (young vs older volunteers), sinus node type (native vs transplanted in heart transplant recipients), and age correlation in right atria samples.

Outcome

Changes in heart rate, M2 receptor density, and adenylyl cyclase activity.surrogate

Main Result

Effect estimate: r = -0.3946

p-value: p=0.0129

The heart rate-decreasing effect of acetylcholine declines with age due to a decrease in right atrial M2 receptor density and function.

Limitations

Cannot exclude the possibility that a diminished release of acetylcholine in the elderly might contribute to the effect
Cannot measure acetylcholine in the intact human heart
Loss of myocytes and fibrosis in the aging heart might contribute to the age-dependent decrease in muscarinic receptors

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Age may blunt pirenzepine response; leaves open whether M2 changes warrant targeted autonomic therapies in older adults.

Cite This Study

Brodde et al. (1998) conducted an observational in Aging (n=56). Pirenzepine vs. Age (Young vs. Older) was evaluated on Correlation between right atrial muscarinic receptor density and age (r = -0.3946, p=0.0129). Right atrial M2 muscarinic receptor density and function decrease significantly with age, explaining the age-dependent decline in the heart rate-decreasing effect of pirenzepine.

synapsesocial.com/papers/6a0d02c3a064aa35e1cc8ee2 https://doi.org/10.1172/jci1113

Topics

Heart transplantation

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Cardiac muscarinic receptors decrease with age. In vitro and in vivo studies.

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Topics

Cardiac muscarinic receptors decrease with age. In vitro and in vivo studies.

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Also Consider

Topics

Also Consider