Graduate Thesis Or Dissertation

 

Inotropic and Chronotropic Effects of Sotalol in Healthy Dogs Public Deposited

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/hh63t2314

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  • Sotalol is a class III anti-arrhythmic drug with class II properties that is commonly used in the treatment of ventricular tachyarrhythmias in dogs. The anti-arrhythmic effects of sotalol are mediated by an increase in action potential duration and prolongation of atrial and ventricular repolarization via antagonism of the delayed rectifier potassium current. These effects have been demonstrated to be independent of sotalol’s beta-blocking properties. However, beta blockade may result in reduced myocardial contractility and also contribute to slowing of the sinus rate. A cardiodepressant effect is of clinical importance when sotalol is used in patients with existing heart disease, yet the inotropic properties of sotalol are not well characterized. The aim of this study was to investigate the inotropic and chronotropic effects of sotalol on healthy, awake dogs. Ten healthy dogs were recruited from the faculty, staff, and students of the Oregon State University College of Veterinary Medicine. Eligible dogs were between one and six years of age and weighed over 20 kilograms (kg). Dogs were considered healthy based on history, physical exam, oscillometric blood pressure measurement, transthoracic echocardiography, and a 10-lead electrocardiogram. Each dog was also evaluated with a 24-hour baseline Holter monitor. Sotalol at a dose of 1-2 mg/kg was then administered for 12-16 days, followed by a second evaluation including the same diagnostics tests. Physical exam parameters, heart rate (HR) and arrhythmias on Holter recording, blood pressure, standard echocardiographic measurements, three-dimensional (3D) left ventricular (LV) volumes, and 3D strain were measured at each evaluation. Measurements from before and after treatment were compared with paired t-tests for normally distributed data and Wilcoxon signed rank tests for non-normally distributed data. 3D data were available for 7/10 dogs. No correction was made for multiple comparisons. Ten dogs were included in the study, with a mean age of 3.4 years (range, 1.1-6.4 years) and mean weight of 26.14 kg (range, 21-35.8 kg). Each dog received 40 mg sotalol orally every 12 hours, resulting in a mean dose of 1.56 ± 0.23 mg/kg. HR on exam was significantly (p = 0.036) lower post-treatment (81 ± 23 bpm) than pre-treatment (101 ± 26 bpm). Maximum HR on Holter monitor was also significantly (p = 0.002) lower post-treatment (195 ± 14 bpm) than pre-treatment (215 ± 13 bpm). Fractional shortening (FS) using two-dimensional (2D) and M-mode (MM) measurements was significantly reduced post-treatment (2D 27.4 ± 4; MM 24.9 ± 5.7%) compared to pre-treatment (2D 30.7%, IQR 28.7-33.8; MM 32.5 ± 2.6%) with p = 0.01 and p = 0.004 for 2D and M-mode measurements, respectively. Similarly, ejection fraction (EF) via Simpson’s method of disks (SMOD) was significantly (p = 0.002) lower post-treatment (48 ± 6.8%) than pre-treatment (53.8 ± 4.4%). Post-treatment there was also a 12.3% (95% CI: 6.4-18.2%) increase in LV end-systolic dimension on 2D and a 12.6% (95% CI: 3.7-21.5%) increase on M-mode measurements (p = 0.001, p = 0.01, respectively). There was no significant difference between pre- and post-treatment in the 3D left ventricular volumes, nor in global longitudinal or circumferential strain, twist, or torsion. The results of this study indicate that sotalol has a negative inotropic and chronotropic effect in healthy dogs. Standard 2D and M-mode echocardiographic measurements used to assess systolic function showed a small but statistically significant decrease after sotalol treatment, with a mean reduction in EF (SMOD) of 5.8%. The lack of significance based on 3D imaging may reflect the variability in measurement and the small sample size. The effect of sotalol should be assessed in dogs with heart disease to further elucidate the clinical significance of the reduction in systolic function, and the implications of this reduction in patients at risk for heart failure.
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  • Seattle, WA, USA
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  • OSU Department of Clinical Sciences Resident Research
  • ACVIM Cardiology Resident Research Grant
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  • Ongoing Research
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  • 2018-06-07 to 2019-07-07

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