Preconditioning with hyperbaric oxygen and calcium and potassium channel modulators in the rat heart
Authors:   University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacy, Kragujevac, Serbia, Bradic Jovana , Petkovic Anica ,   University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacy, Kragujevac, Serbia, Simonovic Nina ,   Health Center “Vozdovac,” Belgrade, Serbia, Radovanovic Milan ,   Clinical Center Kragujevac, Department of Emergency Medicine, Kragujevac, Serbia, Jeremic Jovana ,   University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacy, Kragujevac, Serbia, Zivkovic Vladimir ,   University of Kragujevac, Faculty of Medical Sciences, Department of Physiology, Kragujevac, Serbia, Mitrovic Slobodanka ,   University of Kragujevac, Faculty of Medical Sciences, Department of Pathology, Kragujevac, Serbia, Bolevich Sergey ,   1st Moscow State Medical University IM Sechenov, Department of Human Pathology, Moscow, Russia, Jakovljevic Vladimir ,   University of Kragujevac, Faculty of Medical Sciences, Department of Physiology, Kragujevac, Serbia,   1st Moscow State Medical University IM Sechenov, Department of Human Pathology, Moscow, Russia, Sretenovic Jasmina ,   University of Kragujevac, Faculty of Medical Sciences, Department of Physiology, Kragujevac, Serbia, Srejovic Ivan ,   University of Kragujevac, Faculty of Medical Sciences, Department of Physiology, Kragujevac, Serbia
Published: October 2022

The aim of this study was to establish the effect of combined therapy with hyperbaric oxygen (HBO2) therapy and verapamil, amlodipine or nicorandil on functional recovery and oxidative stress markers after ischemia in the isolated rat heart. The study included 48 rats (Wistar albino, male gender, eight weeks old, body weight 200Å}50g). All animals were exposed to HBO2 treatment over 14 days. Isolated heart rats were perfused by the Langendorff retrograde method at a constant coronary pressure of 70 cm H2O. After stabilization period the hearts were divided into the following groups: HBO2 group (animals exposed to only HBO2 preconditioning); HBO2 + verapamil; HBO2 + amlodipine; and HBO2 + nicorandil (animals pretreated with HBO2 and appropriate pharmacological agent). Afterward, the hearts in all groups were subjected to 20-minute global ischemia and 30-minute reperfusion. Parameters of heart function were registered, including maximum and minimum rate of pressure development, systolic and diastolic left ventricular pressure, heart rate and coronary flow. Levels of pro-oxidants such as index of lipid peroxidation, measured as thiobarbituric acid-reactive substances, nitrites, levels of superoxide anion radicals and hydrogen peroxide were determined in coronary venous effluent. Changes in cardiac tissue were evaluated by hematoxylin and eosin staining. Obtained results clearly indicate that blockage of calcium channel or the activation of adenosine triphosphate-sensitive potassium (KATP) in combination with HBO2 prevented ischemia/reperfusion-induced cardiac deleterious effects, thus contributing to improvement of functional recovery of the heart. However, future studies are certainly necessary for better understanding the mechanisms through which combination of these two maneuvers of preconditioning triggers cardioprotection.