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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).
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.
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.).
Ivabradine improves ventricular cardiomyocyte viability during simulated I/R, possibly by reduction of ROS formation.
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Anti-Ischemic Therapies
Abstract Category: 9. Chronic CAD/Stable Ischemic Heart Disease: Basic
Presentation Number: 1194-66
- 2013 American College of Cardiology Foundation