Glibenclamide does not abolish the protective effect of preconditioning on stunning in the isolated perfused rat heart

Teresa A. Fralix, Charles Steenbergen, Robert E. London, Elizabeth Murphy

Research output: Contribution to journalArticle

Abstract

Objective: The aim was to determine if the beneficial effects of preconditioning would be affected by inhibiting ATP sensitive potassium (KATP) channels in the isolated, perfused rat heart. Methods: The effects of inhibiting KATP channels with glibenclamide (10 μM) were evaluated on ionic alterations and recovery of function after 30 min ischaemia in non-preconditioned hearts and in hearts that had been preconditioned with four intermittent periods of 5 min ischaemia each separated by 5 min of reflow. [Ca2+]i, pHi, and high energy phosphate levels were measured using 19F and 31P nuclear magnetic resonance during the preconditioning periods of ischaemia, during 30 min of ischaemia, and during reflow, in the presence and absence of 10 μM glibenclamide. Results: High energy phosphate contents were decreased during the preconditioning period to a greater extent in glibenclamide treated hearts and the onset of contracture was hastened during the subsequent 30 min period of sustained ischaemia. However, glibenclamide (10 μM) did not abolish the protective effects of preconditioning on ion accumulation during ischaemia or on postischaemic recovery of contractile function. Recovery of left ventricular developed pressure (as % of initial value) following 30 min of ischaemia was 74(SEM 5)% in the preconditioned hearts without drug and 62(4)% in the preconditioned hearts with glibenclamide, while recovery was 25(5)% in the non-preconditioned hearts without drug and 19(2)% in the non-preconditioned hearts with drug. The alterations in [Ca2+]i and pHi during ischaemia were similar in the glibenclamide treated and untreated preconditioned hearts and in both cases were less marked than in the non-preconditioned untreated hearts. Conclusions: Thus, although inhibition of KATP channels accelerates high energy phosphate depletion during the preconditioning period, this does not result in accentuation of the ionic derangements during a subsequent sustained period of ischaemia and does not abolish the protective effect of preconditioning on stunning in the isolated rat heart.Cardiovascular Research 1993;27:630-637.

Original languageEnglish (US)
Pages (from-to)630-637
Number of pages8
JournalCardiovascular research
Volume27
Issue number4
DOIs
StatePublished - Apr 1993

Keywords

  • ATP sensitive K channel
  • Glibenclamide
  • Perfused heart
  • Preconditioning

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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