Effects of the Anticholinesterase Edrophonium on Spectral Analysis of Heart Rate and Blood Pressure Variability in Humans

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 ⅐ min Ϫ1 , constant tidal volume) patients were given either saline (n ϭ 10) or edrophonium (0.01-1.0 mg ⅐ kg Ϫ1 , n ϭ 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 Ϯ 1.9 (S.E.M.) beats per minute; maximum decrease to 55.8 Ϯ 1.4 beats per minute with 1.0 mg ⅐ kg Ϫ1 , P Ͻ 0.01]. HFP of the RRI increased at low doses (0.2-0.4 mg ⅐ kg Ϫ1 ; maximum increase to 111.0 Ϯ 58.2% baseline; P Ͻ 0.01) but decreased (Ϫ49.5 Ϯ 35.5% baseline; P Ͻ 0.01) at higher (1.0 mg ⅐ kg Ϫ1 ) doses. Edrophonium had no effect on SBP and DBP. HFP of SBP decreased with increasing doses (maximal decrease to Ϫ26.2 Ϯ 7.5% baseline, P Ͻ 0.01, 1.0 mg ⅐ kg Ϫ1 ). LFP of SBP was also decreased (Ϫ46.3 Ϯ 10.9% baseline, P Ͻ 0.01, 1.0 mg ⅐ kg Ϫ1 ). 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.

Changes in Heart Rate Variability in Patients under Local Anesthesia

“…Spectral analysis techniques have been used to show the effect of anticholinesterase edrophonium on heart rate and blood pressure variability [3]. Changes in HRV due to atropine administration have also been studied using spectral analysis techniques [4].…”

Sick Sinus Syndrome Observed in a Patient with Cholinesterase Deficiency

“…Given that observed AF is suspected to be mediated vagally, enhanced cholinergic transmission may influence the sinus node and atria in this case. Indeed, potent cholinesterase inhibition induced by intravenous edrophonium is reported to decrease the HR in anesthetized patients dose-dependently (7).…”

Fixation stability of the upward gaze in patients with myasthenia gravis: an eye-tracker study

“… 7 Electromyography demonstrates the fatigue phenomena electrophysiologically and the edrophonium test shows the pharmacological condition of the fatigue phenomenon. However, these tests are diagnostic invasive methods (ie, electromyography is painful 26 ; edrophonium has effect on cardiovascular system 27 ), and therefore, ophthalmologists avoid repeated use of these tests if alternative, non-invasive methods are available. The ice pack test, which involves cooling the orbital cavity through the application of ice over closed eyelids for 2 min, is less invasive for diagnosing myasthenic ptosis.…”