Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
OtherCARDIOVASCULAR PHARMACOLOGY

Extracellular Mg++ Manipulation Prevents the Proarrhythmic Activity of Cromakalim in Ischemic/Reperfused Diabetic Hearts

Arpad Tosaki and Dipak K. Das
Journal of Pharmacology and Experimental Therapeutics July 1997, 282 (1) 309-317;
Arpad Tosaki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dipak K. Das
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Cromakalim, an adenosine triphosphate-sensitive potassium channel opener, shows proarrhythmic activity at moderate doses (1–10 μmol/liter) in the ischemic and reperfused myocardium. We studied the effects of extracellular Mg++ ([Mg++]◦) on the incidence of reperfusion-induced ventricular fibrillation and ventricular tachycardia in isolated working hearts (n = 12 in each group) subjected to 20 min of global ischemia followed by 30 min of reperfusion, a model eliciting a low incidence of reperfusion arrhythmias, obtained from 8-wk streptozotocin-induced diabetic rats. Cromakalim, at a concentration of 3 μmol/liter, perfused 5 min before the induction of ischemia and throughout reperfusion increased the incidence of ventricular fibrillation and ventricular tachycardia from their drug-free diabetic control values of 25 and 42% ([Mg++]◦ = 1.2 mmol/liter) to 92% (P < .05) and 100% (P < .05), respectively. Glibenclamide at a concentration of 3 μmol/liter prevented the proarrhythmiac activity of cromakalim. Increasing concentration of [Mg++]◦ to 2.4, 3.6 and 4.8 mmol/liter in the perfusion buffer, the arrhythmogenic effect of cromakalim was also abolished. Thus, with 2.4, 3.6 and 4.8 mmol/liter of [Mg++]◦ perfused before the administration of cromakalim and the onset of ischemia, the incidence of reperfusion-induced ventricular tachycardia was reduced from 92% (in cromakalim treated group) to 67%, 42% (P < .05), and 25% (P < .05), respectively. The incidence of reperfusion-induced ventricular tachycardia showed the same pattern. Elevated [Mg++]◦ prevented the cromakalim-induced cellular Na+ gain and K+ loss, measured by atomic absorption spectrophotometer. [Mg++]◦ could prevent the proarrhythmic activity of cromakalim, and the use of cromakalim as an antihypertensive or antiischemic agent may be of particular concern in the population of postischemic diabetic subjects who are known to be at high risk of sudden coronary death.

Footnotes

  • Send reprint requests to: Dr. A. Tosaki, University of Connecticut Health Center, School of Medicine, Farmington, CT 06032-1110.

  • ↵1 This work was supported by United States Public Health Service Grant NIH HL 225590.

  • Abbreviations:
    KATP channel
    ATP-sensitive potassium channel
    [Mg++]◦
    extracellular magnesium
    VF
    ventricular fibrillation
    VT
    ventricular tachycardia
    HR
    heart rate
    CF
    coronary flow
    AF
    aortic flow
    LVDP
    left ventricular developed pressure
    LVdp/dt
    first derivative of left ventricular developed pressure
    T3 serum triiodothyronine
    T4, serum thyroxine
    ECG
    electrocardiogram
    • Received October 25, 1996.
    • Accepted March 5, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 1
1 Jul 1997
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Extracellular Mg++ Manipulation Prevents the Proarrhythmic Activity of Cromakalim in Ischemic/Reperfused Diabetic Hearts
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherCARDIOVASCULAR PHARMACOLOGY

Extracellular Mg++ Manipulation Prevents the Proarrhythmic Activity of Cromakalim in Ischemic/Reperfused Diabetic Hearts

Arpad Tosaki and Dipak K. Das
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 309-317;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
OtherCARDIOVASCULAR PHARMACOLOGY

Extracellular Mg++ Manipulation Prevents the Proarrhythmic Activity of Cromakalim in Ischemic/Reperfused Diabetic Hearts

Arpad Tosaki and Dipak K. Das
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 309-317;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Preconditioning of Rat Heart with Monophosphoryl Lipid A: A Role for Nitric Oxide
  • TAS-301, an Inhibitor of Smooth Muscle Cell Migration and Proliferation, Inhibits Intimal Thickening after Balloon Injury to Rat Carotid Arteries
  • Identification of Low Molecular Weight GP IIb/IIIa Antagonists That Bind Preferentially to Activated Platelets
Show more CARDIOVASCULAR PHARMACOLOGY

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics