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Anesth Analg 2005;100:33-37
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000139357.87358.94


CARDIOVASCULAR ANESTHESIA

Protamine After Heparin Produces Hypotension Resulting from Decreased Sympathetic Outflow Secondary to Increased Nitric Oxide in the Central Nervous System

Yoshikazu Hamada, MD*, Yoshiyuki Kameyama, MD*, Hideyuki Narita, MD*, Kirk T. Benson, MD{dagger}, and Hiroshi Goto, MD{dagger}

*Department of Anesthesiology, Tokyo Medical University, Shinjuku, Tokyo, Japan; {dagger}Department of Anesthesiology, University of Kansas Medical Center, Kansas City, Kansas.

Address correspondence and reprint requests to Yoshikazu Hamada, MD, Department of Anesthesiology, Tokyo Medical University, 6–7–1 Nishi-shinjuku, Shinjuku, Tokyo, 160–0023 Japan. Address e-mail to yhamada{at}mbg.ocn.ne.jp

To elucidate whether there are linkages among protamine-induced hypotension, nitric oxide (NO), and sympathetic nerve activity, we administered 3 mg/kg protamine sulfate after 300 U/kg heparin after 20 mg/kg of NG-nitro-D-arginine methyl ester (D-NAME) or NG-nitro-L-arginine methyl ester (L-NAME) as a pretreatment to baroreceptor-denervated rabbits and compared changes in hemodynamic variables and renal sympathetic nerve activity (RSNA). In the D-NAME group, heart rate (HR), mean arterial blood pressure (MAP), and RSNA significantly decreased to 93.7% ± 0.7%, 75.0% ± 5.1% and 65.2% ± 4.6% (mean ± SE), respectively. In the L-NAME group, the pretreatment of L-NAME significantly inhibited the depressant effects of protamine on these variables. Because the animals were totally baroreceptor-denervated, decreased RSNA was attributable to the central depressant effect of protamine, and decreased sympathetic outflow could have contributed to the reduction of HR and MAP. The depressant effect of protamine on sympathetic outflow was inhibited by the pretreatment with L-NAME, a NO synthase inhibitor, suggesting that decreased sympathetic outflow secondary to a protamine-induced increase in NO concentration in the central nervous system may contribute to protamine-induced cardiovascular depression.

IMPLICATIONS: Using baroreceptor-denervated rabbits it was shown that decreased sympathetic outflow resulting from increased nitric oxide is one mechanism of protamine-induced hypotension.







Lippincott, Williams & Wilkins 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 HighWire Press
Copyright © 2005 by the International Anesthesia Research Society.