caa a22 4500 475833104 CHVBK 20180406123846.0 cr unu---uuuuu 170329e20000201xx s 000 0 eng 10.1023/A:1007899307128 doi (NATIONALLICENCE)springer-10.1023/A:1007899307128 Hemodynamic Effects of a Novel Sodium Channel Activator in Dogs With Chronic Heart Failure [Elektronische Daten] [Mitsuhiro Tanimura, Takayuki Mishima, Mitchell Steinberg, Steven Borzak, Sidney Goldstein, Hani Sabbah] The use of positive inotropic agents, such as sympathomimetics and phosphodiesterase inhibitors, in heart failure (HF) is limited by proarrhythmic and positive chronotropic effects. In the present study, we compared the hemodynamic effects of intravenous LY366634 (LY), a Na+ channel enhancer, with dobutamine (DOB), in eight dogs with HF produced by intracoronary microembolizations. We also determined whether intravenous LY has synergistic effects when combined with digoxin. After baseline measurements, infusion of DOB was initiated at a dose of 2 µg/kg/min and increased until an increase of heart rate (HR) >30% of baseline or ventricular arrhythmias developed. Once hemodynamics returned to baseline, LY was infused at a dose of 2 µg/kg/min and increased until the LV fractional area of shortening (FAS), determined echocardiographically, reached a similar level as with DOB. Both drugs increased FAS equivalently compared to baseline (DOB, 24 ± 3 to 47 ± 2; LY, 27 ± 2 to 46 ± 2%). DOB increased HR from 78 ± 4 min-1 at baseline to 107 ± 7 min-1 at maximal dose (p < 0.05) and provoked serious arrhythmias in one dog. In contrast, LY infusion did not increase HR (82 ± 7 vs. 80 ± 8 min-1) or elicit arrhythmias. After 1 week of oral digoxin, dogs were infused again with LY. A lower dose of LY was needed to achieve the same increase in FAS compared to LY alone, but this was not statistically significant. The combination of LY with digoxin did not increase HR or evoke arrhythmias. We conclude that in dogs with HF, intravenous LY improves LV function to the same extent as DOB without increasing HR or evoking ventricular arrhythmias. The combination of LY with digoxin elicits a safe positive inotropic response. Kluwer Academic Publishers, 2000 congestive heart failure nationallicence sodium channel nationallicence ventricular function nationallicence inotropic agents nationallicence animal models nationallicence Tanimura Mitsuhiro Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan aut Mishima Takayuki Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan aut Steinberg Mitchell Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana aut Borzak Steven Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan aut Goldstein Sidney Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan aut Sabbah Hani Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/1(2000-02-01), 77-82 0920-3206 14:1<77 2000 14 10557 https://doi.org/10.1023/A:1007899307128 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007899307128 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tanimura Mitsuhiro Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan aut NATIONALLICENCE 700 1- Mishima Takayuki Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan aut NATIONALLICENCE 700 1- Steinberg Mitchell Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana aut NATIONALLICENCE 700 1- Borzak Steven Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan aut NATIONALLICENCE 700 1- Goldstein Sidney Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan aut NATIONALLICENCE 700 1- Sabbah Hani Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/1(2000-02-01), 77-82 0920-3206 14:1<77 2000 14 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer