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Evidence for pleiotropic cardioprotection by the bradycardic agent ivabradine
Author(s) -
Kleinbongard Petra,
Heusch Gerd
Publication year - 2013
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.27.1_supplement.1130.5
Subject(s) - ivabradine , cardioprotection , ischemia , cardiology , medicine , chemistry , heart rate , viability assay , sinoatrial node , pharmacology , biochemistry , apoptosis , blood pressure
Background In prior studies in pigs, ivabradine reduced infarct size even when given only at reperfusion and in the absence of heart rate reduction (atrial pacing). Methods Ventricular cardiomyocytes were isolated enzymatically from C57Bl/6J mouse hearts (n=15), aliquoted and incubated in Tyrode buffer ± ivabradine (3 μM) for 30 min, respectively. Simulated ischemia ± ivabradine was induced (hypoxia, pH 6.5, 310 mOsm/l, 60 min) and followed by reperfusion ± ivabradine (normoxia, pH 7.4, 250 mOsm/l, 5 min). Viability (trypan blue exclusion) was quantified in >; 200 cells/per preparation. In a subset of hearts (n=5), cardiomyocytes were loaded with CM‐H2DCFDA (5 μM) as an indicator for reactive oxygen species (ROS) formation. Intracellular fluorescence was detected before and after simulated ischemia ± ivabradine. Results Viability was comparable at baseline (control, 73±4%; ivabradine, 73±2%), and it remained relatively stable with 60 min normoxia (53±2%). Simulated I/R reduced cardiomyocyte viability (9±3%), whereas it was better preserved with ivabradine (27±2%, p=0.026 versus I/R). Preliminary data indicate a reduction of ischemia‐induced ROS formation (3.1±0.4 a.u.) by ivabradine (2.0±0.4 a.u.). Conclusion Ivabradine improves ventricular cardiomyocyte viability during simulated I/R, possibly by reduction of ROS formation.