JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Oka, J.-i.
Right arrow Articles by Yasuda, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oka, J.-i.
Right arrow Articles by Yasuda, K.

Vol. 303, Issue 2, 681-687, November 2002

Carrier-Mediated Norepinephrine Release and Reperfusion Arrhythmias Induced by Protracted Ischemia in Isolated Perfused Guinea Pig Hearts: Effect of Presynaptic Modulation by alpha 2-Adrenoceptor in Mild Hypothermic Ischemia

Jun-ichi Oka, Michiaki Imamura, Eiichiro Hatta, Ryushi Maruyama, Mitsuhiro Isaka, Toshifumi Murashita and Keishu Yasuda

Department of Cardiovascular Surgery, Hokkaido University School of Medicine, Sapporo, Japan

Yohimbine, an alpha 2-adrenoceptor antagonist, has been reported to protect hypoxic myocardium and inhibit carrier-mediated norepinephrine (NE) release and reperfusion arrhythmias (ventricular fibrillation; VF) in normothermic ischemia. In heart surgery, mild hypothermic (tepid) cardioplegia has been reported to reduce metabolic demand and permit immediate recovery of cardiac function. Therefore, we determined the effect of yohimbine on NE release and reperfusion arrhythmias in isolated perfused guinea pig hearts of tepid temperature (32°C) ischemia model. Stepwise increase of global ischemia period (20, 40, and 60 min) induced a progressive increase of NE release and duration of VF. Neuronal uptake 1 inhibitor desipramine (100 nM) and Na+-H+ exchanger inhibitor 5-N-ethyl-N-isopropyl-amiloride (10 µM) decreased NE and VF in 60-min hypothermic ischemia. This indicated that NE release induced by protracted tepid ischemia was due to carrier-mediated release. Yohimbine (1 µM) markedly reduced NE release and VF (p < 0.01 versus control) and 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine [UK 14,304 (UK); 10 µM], an alpha 2-adrenoceptor agonist, increased NE release and VF (p < 0.01 versus control). Yohimbine (1 µM) prevented the potentiated effect of UK (10 µM) in hypothermia (p < 0.01 versus UK). Our findings indicate that presynaptic reduction of carrier-mediated NE release seems to be one of the most important factors controlling reperfusion arrhythmias, and alpha 2-adrenoceptor blockade by yohimbine (1 µM) in tepid ischemia may contribute to effective myocardial protection in terms of NE release and reperfusion arrhythmia.

0022-3565/02/3032-0681$07.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
C. Burgdorf, A. Dendorfer, T. Kurz, E. Schomig, I. Stolting, F. Schutte, and G. Richardt
Role of Neuronal KATP Channels and Extraneuronal Monoamine Transporter on Norepinephrine Overflow in a Model of Myocardial Low Flow Ischemia
J. Pharmacol. Exp. Ther., April 1, 2004; 309(1): 42 - 48.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.