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Effects of anesthesia and K+ ATP channel blockade on interstitial adenosine accumulation in ischemic rabbit myocardium

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Abstract

Glibenclamide, a K+ ATP channel antagonist, blocks the anti-infarct effect of ischemic preconditioning in rabbits, but only when the latter are anesthetized with ketamine-xylazine. Furthermore, the protection triggered by pinacidil, a K+ ATP channel opener, can be aborted by treatment with the adenosine antagonist 8-(P-sulfo-phenyl) theophylline. This study tests whether either the anesthetic regimen or glibenclamide affects infarct size by modulating interstitial adenosine levels. Interstitial adenosine and total purine concentrations were assessed in open-chest rabbits by the microdialysis technique. Dialysis fibers were inserted into myocardium served by a coronary artery branch surrounded by a snare. All animals sustained a 30-min coronary occlusion and then 120-min reperfusion. Rabbits were anesthetized with either sodium pentobarbital or a ketamine-xylazine mixture. Half of the latter animals also received glibenclamide. The control levels of adenosine in the dialysate were comparable in the three groups, as were those of total purines, and the infusion of glibenclamide caused no change. Ischemia led to 10- to 20-fold increases in interstitial adenosine and 10-to-40-fold rises in total purine concentrations. These increase were equivalent in all groups. Furthermore, infarct size as a percentage of the myocardium at risk was also comparable in the three groups. Neither the anesthetic agent nor glibenclamide appears to modulate interstitial adenosine release from ischemic tissue.

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Authors and Affiliations

  1. Department of Physiology, University of South Alabama College of Medicine, MDB 3050, 36688, Mobile, Alabama, USA

    M. V. Cohen, K. S. Snell, A. Tsuchida & J. M. Downey

  2. Department of Biology, St. Olaf College, 55057, Northfield, Minnesota, USA

    D. G. L. Van Wylen

Authors
  1. M. V. Cohen
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  2. K. S. Snell
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  3. A. Tsuchida
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  4. D. G. L. Van Wylen
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  5. J. M. Downey
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Additional information

This work was supported in part by grants from the National Institutes of Healt, Heart, Lung, and Blood Institute, HL-20468, HL-46027, and HL-50688 and Bristol Myers Squibb, and was performed during the tenure of an Established Investigator Award from the American Heart Association (DGLVW).

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Cohen, M.V., Snell, K.S., Tsuchida, A. et al. Effects of anesthesia and K+ ATP channel blockade on interstitial adenosine accumulation in ischemic rabbit myocardium. Basic Res Cardiol 90, 410–417 (1995). https://doi.org/10.1007/BF00788503

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  • DOI: https://doi.org/10.1007/BF00788503

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