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CARDIOVASCULAR ANESTHESIA

The Sympathomimetic Actions of l-Ephedrine and d-Pseudoephedrine: Direct Receptor Activation or Norepinephrine Release?

Shigeaki Kobayashi, MD^*, Masayuki Endou, MD PhD, Fumika Sakuraya, MD^*, Naoyuki Matsuda, MD PhD^*, Xiao-Hong Zhang, MD^*, Mitsue Azuma, Mphar^*, Noriyuki Echigo, MD, Osamu Kemmotsu, MD PhD^*, Yuichi Hattori, MD PhD, and Satoshi Gando, MD PhD^*

From the Departments of *Anesthesiology & Critical Care Medicine and Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan; and the Department of Anesthesiology, Yokohama City University School of Medicine, Yokohama, Japan

Address correspondence and reprint requests to Yuichi Hattori, MD, PhD, Department of Pharmacology, Hokkaido University School of Medicine, Sapporo 060–8638, Japan. Address e-mail to yhattori{at}med.hokudai.ac.jp

The basic mechanisms by which ephedrine is preferred over other vasopressors in obstetric anesthesia have not been clearly defined. We examined the sympathomimetic effects of l-ephedrine, currently used as a vasopressor, and d-pseudoephedrine, currently used as a decongestant. In anesthetized rats, l-ephedrine and d-pseudoephedrine caused dose-dependent increases in arterial blood pressure and heart rate, and these effects disappeared after destruction of the sympathetic nerve terminals with 6-hydroxydopamine (6-OHDA) pretreatment. The two ephedrine isomers produced concentration-dependent increases in tension of anococcygeal muscle and sinus rate of right atrium from rats. However, the anococcygeal and atrial responses to d-pseudoephedrine were abolished after 6-OHDA pretreatment, whereas approximately 50% of the responses to l-ephedrine were 6-OHDA-resistant. In human umbilical artery and vein, the two isomers failed to generate any contraction when given at the concentration that is capable of producing significant effects on anococcygeal and atrial tissues. Although direct adrenoceptor activation with l-ephedrine was detectable at tissue levels, the pressor response in vivo was entirely attributable to norepinephrine release from sympathetic nerves. This indirect mechanism could partly explain why l-ephedrine is better at increasing maternal arterial blood pressure while preserving the uteroplacental blood flow that is devoid of the involvement of the sympathetic innervation.

IMPLICATIONS: The indirectly sympathomimetic property of l-ephedrine may be one of the mechanisms to explain why ephedrine is preferred over -adrenergic agonists as a vasopressor for treatment of intraspinal anesthesia-induced hypotension in obstetrics.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999