Bumetanide limits changes in myocardial NAJ and PH| during Ischemia after preconditioning

S. E. Anderson, Hong Liu, Peter M Cala

Research output: Contribution to journalArticle

Abstract

To test the hypothesis that ischémie preconditioning (PC) stimulates Na+K+2Cl cotransport we measured intracellular Na (Naj) and pH (pHj) in isolated perfused newborn rabbit hearts during ischemia±PC±bumetanide (Bum - 20 (xM - cotransport inhibitor). We further postulate that ion flux via the cotransporter is functionally coupled with the C1/HCO3 anion exchanger such that CI is recycled. Thus, for example, Cl entry via the cotransporter increases Cl efflux and HCO3 uptake via the anion exchanger and results in increased pHj. NMR was used to measure pHj and Naj, in newborn (4-7 days) rabbit hearts Langendorff-perfused with Krebs-Henseleit solution at pH 7.4±0.5 equilibrated with 95%O2/5%CC-2 at 37'C . Control hearts were perfused for 30 min before 40 min of global ischemia followed by 40 min of reperfusion. PC hearts were treated the same except four 5 min intervals of ischemia each followed by 10 min of perfusion preceded global ischemia. Data are meanlSEM. p<0.05 vs. PC Group(n) Pre-ischemia End Ischemia End Reperfusion pHj control (4) 7.0740.01 5.86±0.05 7.0910.01 control +Bum(3) 7.0910.01 5.7810.07 7.12±0.01 PC (4) 7.14±0.03 6.3410.04 7.0810.01 PC+Bum(3) 7.0640.01 6.5540.03 7.0940.03 Nai control (4) 1240.9 114116 55±12 (mEo/kg/dry) PC (4) 29.219.1 62±9 2516.8 PC+Bum (3) 23.713.3 29.711.7 29,714.3 The results support the hypothesis that PC stimulates Na+K+2Cl cotransport which is functionally coupled with C1/HCU3 exchange. The data are further consistent with the postulate that Bum inhibition of Na+K+2Cl uptake early during ischemia decreases Cl efflux and HCC>3 uptake via Cl/HCOg exchange whereas later during ischemia, after Naj has risen, the opposite occurs.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996

    Fingerprint

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this