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The effects of midazolam and ephedrine on post-exercise autonomic chronotropic control of the heart in normal subjects

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Abstract

Benzodiazepines may induce hypotension by inhibiting the pressor response. Ephedrine has adrenergic effects on the circulation. After exercise, changes in cardiovascular control impair orthostatic tolerance. The impaired pressure response can be compensated for by chronotropic control of the heart. We studied the effect of midazolam and ephedrine on post-exercise cardiac autonomic chronotropic control in six 21-year-old female volunteers, who received single doses of 15 mg midazolam, 50 mg ephedrine, or placebo orally according to a placebo-controlled, double-blind, crossover design. After exercise, the subjects assumed the supine position for rest, then a−10° head-down position followed by a 70° head-up position. Power spectral analysis of heart rate variability for 7 min and steady-state brachial arterial blood pressure were measured in each position. After administration of midazolam, three subjects had an abnormal fall in their arterial blood pressure (with one presyncope) as a response to head-up tilt. Changes in heart rate variability exceeded those seen during placebo treatment (p<0.01) and involved oscillations, suggesting activation of both sympathetic and parasympathetic dynamics. After ephedrine administration, arterial blood pressure increased during head-down tilt, but parasympathetic dynamics to the heart were dampened. Head-up tilt induced increased sympathetic stimulation of the heart and a sympathicotonic cardiovascular response (p<0.01). In conclusion, midazolam induced unexpectedly great changes in dynamic cardiac control during cardiovascular stimulation. Ephedrine increased tonic sympathetic activity and stabilized the neural circulatory control of the heart by immobilizing dynamic parasympathetic activation.

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Authors and Affiliations

  1. Research Institute of Military Medicine, Central Military Hospital, Helsinki, Finland

    A. Lindqvist MD & L. A. Laitinen

  2. Research Unit of Pulmonary Medicine, Department of Medicine, Helsinki University Central Hospital, Finland

    A. Lindqvist MD

  3. Cardiorespiratory Research Unit, University of Turku, Turku, Finland

    J. Jalonen MSc

  4. Division of Mental Health, National Public Health Institute, Helsinki, Finland

    T. Seppälä MD

  5. National Agency for Medicines, Helsinki, Finland

    C. Strömberg MD

Authors
  1. A. Lindqvist MD
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  2. J. Jalonen MSc
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  3. L. A. Laitinen
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  4. T. Seppälä MD
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  5. C. Strömberg MD
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Lindqvist, A., Jalonen, J., Laitinen, L.A. et al. The effects of midazolam and ephedrine on post-exercise autonomic chronotropic control of the heart in normal subjects. Clinical Autonomic Research 6, 343–349 (1996). https://doi.org/10.1007/BF02556305

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  • DOI: https://doi.org/10.1007/BF02556305

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