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Mitochondria are a target of cardioprotection by ivabradine
Author(s) -
Kleinbongard Petra,
Gedik Nilgün,
Heusch Gerd
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.954.6
Subject(s) - ivabradine , cardioprotection , mitochondrion , mitochondrial ros , reactive oxygen species , chemistry , respiration , biophysics , oxygen , pharmacology , ischemia , biochemistry , medicine , biology , heart rate , endocrinology , anatomy , organic chemistry , blood pressure
Background Ivabradine is a bradycardic agent, which inhibits the I f‐ current in the sinus node. In pigs, ivabradine reduced infarct size even when given only at reperfusion and in the absence of heart rate reduction. Ivabradine´s protective action at reperfusion, when a burst of reactive oxygen species (ROS) is released, suggests it might attenuate ROS formation. Mitochondria are a major source of ROS after ischemia/reperfusion (I/R). Thus, we wanted to analyze a potential effect of ivabradine on mitochondrial function during simulated I/R. Methods: Mitochondria were isolated from C57Bl/6J mouse hearts and subjected to simulated I/R (6 min hypoxia/3 min normoxia) in glutamate/malate‐ and ADP‐containing buffer ±3 µmol/l ivabradine at 30°C. After simulated I/R, mitochondrial complex I respiration (n=32,preparations), ROS concentration (n=9) and ATP production (n=15) were quantified. Results: After simulated I/R ivabradine did not affect mitochondrial complex I respiration, but reduced the ROS concentration (144±12 vs. 122±12 nmol H 2 O 2 /100 µg protein; p=0.01), and increased the ATP concentration (148±20 vs. 181±21 µmol/l; p=0.01). Conclusion Mitochondria seem to be a target of protection induced by ivabradine by reducing mitochondrial ROS formation and increasing mitochondrial ATP production. Further studies are necessary to identify such target structure/s of ivabradine on mitochondria.