Abstract
Edrophonium, an anticholinesterase, exerts a biphasic effect on cardiovascular autonomic drive in humans (lower doses enhance; higher doses reduce). Twenty-five anesthetized, mechanically respired (10 breaths · min−1, constant tidal volume) patients were given either saline (n = 10) or edrophonium (0.01–1.0 mg · kg−1, n = 15) following surgery. ECG, radial arterial pressure, and respiratory rate were sampled at 250 Hz to obtain time series for consecutive R-R intervals (RRIs), and systolic (SBP) and diastolic blood pressure (DBP). A Wigner distribution was used for time frequency mapping of spectral powers at high (HFP, 0.15–0.5 Hz) and low (LFP, 0.0–0.05 Hz) frequency. Edrophonium produced a dose-dependent decrease in heart rate [baseline 66.8 ± 1.9 (S.E.M.) beats per minute; maximum decrease to 55.8 ± 1.4 beats per minute with 1.0 mg · kg−1, P < 0.01]. HFP of the RRI increased at low doses (0.2–0.4 mg · kg−1; maximum increase to 111.0 ± 58.2% baseline;P < 0.01) but decreased (−49.5 ± 35.5% baseline; P < 0.01) at higher (1.0 mg · kg−1) doses. Edrophonium had no effect on SBP and DBP. HFP of SBP decreased with increasing doses (maximal decrease to −26.2 ± 7.5% baseline, P < 0.01, 1.0 mg · kg−1). LFP of SBP was also decreased (−46.3 ± 10.9% baseline, P < 0.01, 1.0 mg · kg−1). Edrophonium may enhance (lower dose) or reduce (higher dose) cardiovascular autonomic drive in humans, as evidenced by the significant changes it evokes in HFP of the RRI (parasympathetic drive), and in the HFP and LFP of SBP (sympathetic drive). These observations may account for the modest autonomic side effects of edrophonium when this drug is used clinically.
Footnotes
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Supported by grants from La Foundation d'Anesthésiologie et Réanimation du Québec and Associated Anaesthetists Group, Royal Victoria Hospital. Preliminary results described in this paper were presented in part at the Society for Neuroscience 1999 Annual Meeting October 23–28, 1999, in Miami, FL (Soc Neurosci Abstr 25:877.1).
Abbreviations
- ACh
- acetylcholine
- HFP
- high frequency power
- LFP
- low frequency power
- RRI
- R-R interval
- SBP
- systolic blood pressure
- DBP
- diastolic blood pressure
- SA
- sinoatrial
- EDRO
- edrophonium-treated patients
- CONT
- control patients who received saline
- Received September 24, 2001.
- Accepted November 11, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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