HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Potassium channel openers and blockers: do they possess proarrhythmic or antiarrhythmic activity in ischemic and reperfused rat hearts?

Abstract
Cromakalim is a member of the new antihypertensive drug family possessing an action that involves an increased K efflux in vascular and cardiac muscle. We studied the contribution of opening of ATP-sensitive K channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na, K, Ca and Mg in isolated rat hearts. After 30 min of global ischemia, cromakalim (1 to 30 microM) failed to reduce reperfusion arrhythmias. On the postischemic-reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (duration of ischemia was reduced to 25 min), cromakalim treatment was associated with a higher incidence of reperfusion ventricular fibrillation (VF) and ventricular tachycardia (VT) as compared to the controls (100% VF and 100% VT in treated vs. 41% VF and 50% VT in controls, P < .05). Proarrhythmic effects of cromakalim were also reflected in a maldistribution of myocardial ions. At concentrations of 3, 10 and 30 microM of glibenclamide, a K channel blocker, a significant reduction in the incidence of reperfusion-induced VF and VT was observed, and an attenuation in the maldistribution of myocardial ion contents induced by ischemia/reperfusion was found. The reduction in myocardial contractility was detected at relatively high concentrations (10 and 30 microM) in both cromakalim- and glibenclamide-treated groups. The proarrhythmic effect of cromakalim (30 microM) was abolished by 3 microM of glibenclamide, suggesting that the increased tendency to develop reperfusion arrhythmias is associated with the cromakalim-induced K efflux.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsA Tosaki, P Szerdahelyi, R M Engelman, D K Das
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 267 Issue 3 Pg. 1355-62 (Dec 1993) ISSN: 0022-3565 [Print] UNITED STATES
PMID8263798 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Arrhythmia Agents
  • Antihypertensive Agents
  • Benzopyrans
  • Cations
  • Potassium Channels
  • Pyrroles
  • Cromakalim
  • Glyburide
Topics
  • Animals
  • Anti-Arrhythmia Agents (pharmacology)
  • Antihypertensive Agents (pharmacology)
  • Arrhythmias, Cardiac (chemically induced, etiology, physiopathology)
  • Benzopyrans (pharmacology)
  • Cations (metabolism)
  • Cromakalim
  • Glyburide (pharmacology)
  • Heart (drug effects, physiology)
  • Ion Channel Gating
  • Male
  • Myocardial Ischemia (metabolism, physiopathology)
  • Myocardial Reperfusion Injury (metabolism, physiopathology)
  • Potassium Channels (drug effects, physiology)
  • Pyrroles (pharmacology)
  • Rats
  • Rats, Sprague-Dawley

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: