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Effects of adenosine on autonomic control of heart rate in man
T B Conradson1, B Clarke, C M Dixon
1Department of Clinical Pharmacology, Brompton Hospital, London, UK.
Insights
Adenosine increases heart rate in humans, potentially by reducing vagal tone. This effect was observed in a study investigating autonomic mechanisms, with results suggesting a role for parasympathetic inhibition.
Area of Science:
- Cardiovascular Physiology
- Autonomic Nervous System Function
Background:
- Adenosine is known to affect heart rate.
- The precise autonomic mechanisms underlying adenosine's chronotropic effects in humans require further elucidation.
Purpose of the Study:
- To investigate the autonomic mechanisms responsible for the positive chronotropic effect of adenosine in conscious individuals.
- To determine the role of cardiac vagal tone and sympathetic activity in mediating adenosine's effects on heart rate.
Main Methods:
- A double-blind, randomized cross-over study involving six healthy subjects.
- Adenosine infusion at increasing doses was administered following placebo, propranolol, or propranolol plus atropine.
- Measurements included heart rate, blood pressure, and plasma catecholamines during various maneuvers (supine, standing, Valsalva).
Main Results:
- Adenosine caused a dose-related increase in heart rate after saline infusion (18 ± 8 bpm).
- This effect was attenuated by propranolol but abolished by propranolol plus atropine, which induced a decrease in heart rate (-5 ± 3 bpm).
- Adenosine augmented the heart rate increase upon standing and increased plasma noradrenaline levels.
Conclusions:
- The positive chronotropic effect of infused adenosine in conscious humans is, in part, mediated by the inhibition of cardiac vagal tone.
- Sympathetic activation may also contribute to adenosine's heart rate-increasing effects.
Abstract:
Six healthy subjects (two female) aged 23-40 years participated in a double-blind randomized cross-over study to investigate autonomic mechanisms involved in the chronotropic effect of adenosine in conscious man. Adenosine was infused in increasing doses following saline, propranolol (0.2 mg kg-1 body weight) or propranolol (0.2 mg kg-1 plus atropine (0.04 mg kg-1). Heart rate and blood pressure were measured supine, on standing and during a Valsalva manoeuvre. Plasma catecholamines were measured in the supine and standing positions. Following saline, adenosine (up to 120 micrograms kg-1 min-1) caused a dose-related increase in heart rate (mean +/- SD maximum increase 18 +/- 8 bpm; P less than 0.01). The change in heart rate with adenosine after propranolol (12 +/- 9 bpm; P less than 0.05) did not differ significantly from the corresponding change following saline but was abolished by propranolol plus atropine, which, in turn, was associated with a mean maximum decrease in heart rate of 5 +/- 3 bpm (P less than 0.01). The increase in heart rate during the initial 30 s on standing was augmented with adenosine compared with saline (16 +/- 5 bpm; P less than 0.01). A significant increase in plasma noradrenaline on standing was also found with adenosine compared with saline (6.37 +/- 2.86 vs. 4.77 +/- 1.79 nmol 1(-1); P less than 0.05). The heart rate response to the Valsalva manoeuvre was not affected by adenosine. These results suggest that the positive chronotropic effect of infused adenosine in conscious man may in part be caused by an inhibition of cardiac vagal tone.(ABSTRACT TRUNCATED AT 250 WORDS)