Molecular and Cellular Biochemistry

, Volume 450, Issue 1–2, pp 175–185 | Cite as

Comparative effects of calcium and potassium channel modulators on ischemia/reperfusion injury in the isolated rat heart

  • Nina Simonovic
  • Vladimir JakovljevicEmail author
  • Jovana Jeremic
  • Zarko Finderle
  • Ivan Srejovic
  • Tamara Nikolic Turnic
  • Isidora Milosavljevic
  • Vladimir Zivkovic


The aim of this study was to examine and compare the effects of the acute administration of verapamil or amlodipine as representatives of the calcium channel blockers or nicorandil as a representative of the mitochondrial ATP-dependent potassium (KATP) channel opener to cardiac contractility, coronary flow, and oxidative stress markers on ischemia/reperfusion injury in the isolated rat heart. The hearts of adult male Wistar albino rats (n = 60 total, 12 per group) were divided into five groups, two controls (preconditioning with Krebs–Henseleit solution) and three experimental depending on acute administrated pharmacological agents (0,63 µmol/L of verapamil, 0,1 µmol/L of amlodipine, and 200 µmol/L of nicorandil). After stabilization and 5 min of preconditioning in experimental groups, hearts from I/R control and all experimental groups underwent global ischemia (20 min) and reperfusion (30 min). Hearts from sham group were continuously followed for 50 min, after stabilization period. Cardiodynamic parameters and coronary flow were recorded at the end of stabilization (S), at the last minute of pharmacological preconditioning (P) and at intervals of 5 min after global ischemia, during reperfusion, or in case of sham group during 20–50 min after stabilization. At the same intervals, we collected coronary venous effluent from which we spectrophotometrically measured the parameters of oxidative stress: the index of lipid peroxidation, superoxide anion radical, hydrogen peroxide, and nitrite. In summary, our findings clearly indicate that the blocking of the calcium channel or the activation of KATP may mediate the protective effect of myocardial preconditioning. The ex vivo results showed that all examined drugs after ischemia and reperfusion have beneficial cardioprotective properties associated with lower values of major pro-oxidative molecules. Obtained effects seem to be the most convincible in case of nicorandil.


Verapamil Amlodipine Nicorandil Ischemia/reperfusion Pharmacological preconditioning 


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Nina Simonovic
    • 1
  • Vladimir Jakovljevic
    • 2
    • 3
    Email author
  • Jovana Jeremic
    • 4
  • Zarko Finderle
    • 5
  • Ivan Srejovic
    • 2
  • Tamara Nikolic Turnic
    • 4
  • Isidora Milosavljevic
    • 4
  • Vladimir Zivkovic
    • 2
  1. 1.Health Center ”Vozdovac”BelgradeSerbia
  2. 2.Department of Physiology, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia
  3. 3.Department of Human Pathology1st Moscow State Medical University IM SechenovMoscowRussia
  4. 4.Department of Pharmacy, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia
  5. 5.Department of Physiology, Medical FacultyUniversity of LjubljanaLjubljanaSlovenia

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