The effects of midazolam and ephedrine on post-exercise autonomic chronotropic control of the heart in normal subjects.
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 degrees head-down position followed by a 70 degrees 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.
Lindqvist
A
A
Research Institute of Military Medicine, Central Military Hospital, Helsinki, Finland.
Jalonen
J
J
Laitinen
L A
LA
Seppälä
T
T
Strömberg
C
C
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004809:Ephedrine / Q000494:pharmacology; D005080:Exercise Test; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced*; D008874:Midazolam / Q000494:pharmacology; D012016:Reference Values; D018667:Tilt-Table Test
D000322:Adrenergic Agonists; D018686:Anesthetics, Intravenous; D014151:Anti-Anxiety Agents; D004809:Ephedrine; D008874:Midazolam