Ischemic preconditioning decreases the reperfusion-related formation of hydroxyl radicals in a rabbit model of regional myocardial ischemia and reperfusion: The role of KATP channels

Jacob Raphael, Benjamin Drenger, Julia Rivo, Edi Berenshtein, Mordechai Chevion, Yaacov Gozal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The objective of this study was to assess the effects of ischemic preconditioning (IP) on hydroxyl free radical production in an in vivo rabbit model of regional ischemia and reperfusion. Another goal was to determine whether KATP channels are involved in these effects. The hearts of anesthetized and mechanically ventilated New Zealand White rabbits were exposed through a left thoracotomy. After IV salicylate (100 mg/kg) administration, all animals underwent a 30-min stabilization period followed by 40 min of regional ischemia and 2 h of reperfusion. In the IP group, IP was elicited by 5 min of ischemia followed by 10 min of reperfusion (prior to the 40-min ischemia period). Glibenclamide, a KATP channel blocker, was administered prior to the preconditioning stimulus. Infarct size was measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. We quantified the hydroxyl-mediated conversion of salicylate to its 2,3 and 2,5-dihydroxybenzoate derivatives during reperfusion by high performance liquid chromatography coupled with electro-chemical detection. IP was evidenced by reduced infarct size compared to control animals: 22% vs. 58%, respectively. Glibenclamide inhibited this cardioprotective effect and infarct size was 53%. IP limited the increase in 2,3 and 2,5-dihydroxybenzoic acid to 24.3 and 23.8% above baseline, respectively. Glibenclamide abrogated this effect and the increase in 2,3 and 2,5-dihydroxybenzoic acid was 94.3 and 85% above baseline levels, respectively, similar to the increase in the control group. We demonstrated that IP decreased the formation of hydroxyl radicals during reperfusion. The fact that glibenclamide inhibited this effect, indicates that KATP channels play a key role in this cardioprotective effect of IP.

Original languageEnglish
Pages (from-to)747-754
Number of pages8
JournalFree Radical Research
Volume39
Issue number7
DOIs
StatePublished - Jul 2005
Externally publishedYes

Keywords

  • ATP sensitive potassium channels
  • Heart
  • Ischemic preconditioning
  • Myocardium
  • Oxygen free radicals

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