Inhibitors of ischemic preconditioning do not attenuate Na+/H+ exchange inhibitor mediated cardioprotection

Richard J. Gumina, Norbert Beier, Pierre Schelling, Garrett J. Gross

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Pharmacologic inhibition of the K(ATP) channel with sulfonylureas or the adenosine receptor with methylxanthines has been shown to attenuate ischemic preconditioning (IPC). Both classes of compounds are widely used clinically, and several reports have demonstrated adverse outcomes in patients taking sulfonylureas. Recently inhibition of the sodium/hydrogen exchanger isozyme-1 (NHE-1) has been shown to be equal to IPC at providing myocardial protection in dogs and may be an alternative to IPC in patients taking sulfonylureas or methylxanthines. However, no experiments have examined the pharmacologic overlap between IPC and NHE-1 inhibitor-mediated cardioprotection in dogs. With an in vivo canine infarct model in which the left anterior descending coronary artery was occluded for 60 min and reperfused for 3 h, neither the K(ATP) channel antagonist glibenclamide nor the adenosine-receptor antagonist PD 115199 attenuated NHE-1 inhibitor-mediated reduction in infarct size expressed as a percentage of the area at risk produced by EMD 85131 (Control, 24.2 ± 3.6%; EMD 85131, 6.4 ± 2.3%; PD 115199 + EMD 85131, 626 ± 2.4%; glibenclamide + EMD 85131, 3.5 ± 1.2%). NHE-1 inhibition and IPC do not overlap pharmacologically, and NHE-1 inhibition may be an alternative for cardioprotection in patients taking sulfonylureas or methylaxanthines.

Original languageEnglish (US)
Pages (from-to)949-953
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume35
Issue number6
DOIs
StatePublished - Jun 13 2000

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Ischemic Preconditioning
Glyburide
Adenosine Triphosphate
Dogs
Purinergic P1 Receptor Antagonists
Sodium-Hydrogen Antiporter
Purinergic P1 Receptors
Isoenzymes
Canidae
Coronary Vessels
hydrochloride N-diaminomethylene-2-methyl-5-methylsulfonyl-4-pyrrolobenzamide

Keywords

  • Adenosine
  • Ischemic preconditioning
  • K(ATP) channels
  • Sodium/hydrogen antiport

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Inhibitors of ischemic preconditioning do not attenuate Na+/H+ exchange inhibitor mediated cardioprotection. / Gumina, Richard J.; Beier, Norbert; Schelling, Pierre; Gross, Garrett J.

In: Journal of Cardiovascular Pharmacology, Vol. 35, No. 6, 13.06.2000, p. 949-953.

Research output: Contribution to journalArticle

Gumina, Richard J. ; Beier, Norbert ; Schelling, Pierre ; Gross, Garrett J. / Inhibitors of ischemic preconditioning do not attenuate Na+/H+ exchange inhibitor mediated cardioprotection. In: Journal of Cardiovascular Pharmacology. 2000 ; Vol. 35, No. 6. pp. 949-953.
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