Effects of ivabradine on heart rate and left ventricular function in healthy cats and cats with hypertrophic cardiomyopathy

Sabine C. Riesen Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Karsten E. Schober Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Danielle N. Smith Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Cristiane C. Otoni Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Xiaobai Li Department of Biostatistics, College of Public Health, The Ohio State University, Columbus, OH 43210.

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John D. Bonagura Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Abstract

Objective—To evaluate the effects of the pacemaker funny current (If) inhibitor ivabradine on heart rate (HR), left ventricular (LV) systolic and diastolic function, and left atrial performance in healthy cats and cats with hypertrophic cardiomyopathy (HCM).

Animals—6 healthy cats and 6 cats with subclinical HCM.

Procedures—Anesthetized cats underwent cardiac catheterization and were studied over a range of hemodynamic states induced by treatment with esmolol (200 to 400 μg/kg/min, IV), esmolol and dobutamine (5 μg/kg/min, IV), ivabradine (0.3 mg/kg, IV), and ivabradine and dobutamine. Left ventricular systolic and diastolic function, cardiac output, and left atrial function were studied via catheter-based methods and echocardiography.

Results—Treatment with ivabradine resulted in a significant reduction of HR, rate-pressure product, and LV contractile function and a significant increase in LV end-diastolic pressure, LV end-diastolic wall stress, and LV relaxation time constant (tau) in cats with HCM. Concurrent administration of ivabradine and dobutamine resulted in a significant increase of LV contractility and lusitropy, with blunted chronotropic effects of the catecholamine. Left atrial performance was not significantly altered by ivabradine in cats with HCM. Regression analysis revealed an association between maximum rate of LV pressure rise and tau in cats with HCM.

Conclusions and Clinical Relevance—Ivabradine had significant effects on several cardiovascular variables in anesthetized cats with HCM. Studies in awake cats with HCM are needed to clinically validate these findings.

Abstract

Objective—To evaluate the effects of the pacemaker funny current (If) inhibitor ivabradine on heart rate (HR), left ventricular (LV) systolic and diastolic function, and left atrial performance in healthy cats and cats with hypertrophic cardiomyopathy (HCM).

Animals—6 healthy cats and 6 cats with subclinical HCM.

Procedures—Anesthetized cats underwent cardiac catheterization and were studied over a range of hemodynamic states induced by treatment with esmolol (200 to 400 μg/kg/min, IV), esmolol and dobutamine (5 μg/kg/min, IV), ivabradine (0.3 mg/kg, IV), and ivabradine and dobutamine. Left ventricular systolic and diastolic function, cardiac output, and left atrial function were studied via catheter-based methods and echocardiography.

Results—Treatment with ivabradine resulted in a significant reduction of HR, rate-pressure product, and LV contractile function and a significant increase in LV end-diastolic pressure, LV end-diastolic wall stress, and LV relaxation time constant (tau) in cats with HCM. Concurrent administration of ivabradine and dobutamine resulted in a significant increase of LV contractility and lusitropy, with blunted chronotropic effects of the catecholamine. Left atrial performance was not significantly altered by ivabradine in cats with HCM. Regression analysis revealed an association between maximum rate of LV pressure rise and tau in cats with HCM.

Conclusions and Clinical Relevance—Ivabradine had significant effects on several cardiovascular variables in anesthetized cats with HCM. Studies in awake cats with HCM are needed to clinically validate these findings.

Contributor Notes

Dr Riesen's present address is Section of Internal Medicine, Small Animal Clinic, University of Veterinary Medicine, 1210 Vienna, Austria.

Dr. Otoni's present address is Department of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060.

Supported by a grant from the American College of Veterinary Internal Medicine Foundation.

The authors thank Duane L. Hart, Mike Grigsby, Patricia T. Mueller, Laura J. Spayd, and Yukie Ueyama for technical assistance and Judith L. Stella and C. A. T. Buffington for their contributions.

Address correspondence to Dr. Schober (schober.4@osu.edu).
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