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Evaluation of the Autonomic Nervous System in a Canine Model of Chronic Embolic Pulmonary Hypertension

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Abstract

Background

Sildenafil improves autonomic dysfunction caused by pulmonary hypertension (PH) in humans, but its effect is unknown in dogs with PH. This prospective study aimed to evaluate the autonomic nervous system function of a canine model of chronic embolic PH (CEPH) and the autonomic nervous system function of a canine model of CEPH in which sildenafil was administered.

Methods

This study used five clinically healthy female beagle dogs. Evaluation parameters included hemodynamic parameters, heart rate (HR) and heart rate variability (HRV). Each evaluation parameter was compared before and after creating the CEPH model (before, BL; after, CEPHBL) and between the CEPHBL model and after the administration of sildenafil (1 mg/kg, BID) in the CEPH model dogs (CEPHSil).

Results

In the CEPHBL model, the hemodynamic parameters indicated cardiac hypofunction, and HR was significantly increased and HRV was significantly decreased compared with BL. Further, in the CEPHSil model, the hemodynamic parameters suggested improvement in cardiac function, and HRV was significantly increased.

Conclusions

From the results of the CEPH model dogs, autonomic dysfunction was shown to occur in PH dogs. In addition, the administration of 1 mg/kg of sildenafil to CEPH model dogs may improve autonomic dysfunction.

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References

  • Acierno MJ, Brown S, Coleman AE, Jepson RE, Papich M, Stepien RL, Syme HM (2018) ACVIM consensus statement: guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med 32(6):1803–1822

    Article  Google Scholar 

  • Akabane R, Sato T, Sakatani A, Miyagawa Y, Tazaki H, Takemura N (2018) Pharmacokinetics of single-dose sildenafil administered orally in clinically healthy dogs: effect of feeding and dose proportionality. J Vet Pharmacol Ther 41(3):457–462

    Article  CAS  Google Scholar 

  • Bogucki S, Noszczyk-Nowak A (2015) Short-term heart rate variability (HRV) in healthy dogs. Pol J Vet Sci 18(2):307–312

    Article  Google Scholar 

  • Bragg RF, Bennett JS, Cummings A, Quimby JM (2015) Evaluation of the effects of hospital visit stress on physiologic variables in dogs. J Am Vet Med Assoc 246(2):212–215

    Article  Google Scholar 

  • Brown AJ, Davison E, Sleeper MM (2010) Clinical efficacy of sildenafil in treatment of pulmonary arterial hypertension in dogs. J Vet Intern Med 24(4):850–854

    Article  CAS  Google Scholar 

  • Ciarka A, Doan V, Velez-Roa S, Naeije R, van de Borne P (2010) Prognostic significance of sympathetic nervous system activation in pulmonary arterial hypertension. Am J Respir Crit Care Med 181(11):1269–1275

    Article  Google Scholar 

  • Fauchier L, Melin A, Eder V, Antier D, Bonnet P (2006) Heart rate variability in rats with chronic hypoxic pulmonary hypertension. Ann Cardiol Angeiol (Paris) 55(5):249–254

    Article  CAS  Google Scholar 

  • Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M (2016) 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Rev Esp Cardiol (Engl Ed) 69(2):177

    Article  Google Scholar 

  • Hori Y, Kondo C, Matsui M, Yamagishi M, Okano S, Chikazawa S, Kanai K, Hoshi F, Itoh N (2014) Effect of the phosphodiesterase type 5 inhibitor tadalafil on pulmonary hemodynamics in a canine model of pulmonary hypertension. Vet J 202(2):334–339

    Article  CAS  Google Scholar 

  • Hori Y, Uchide T, Saitoh R, Thoei D, Uchida M, Yoshioka K, Chikazawa S, Hoshi F (2012) Diagnostic utility of NT-proBNP and ANP in a canine model of chronic embolic pulmonary hypertension. Vet J 194(2):215–221

    Article  CAS  Google Scholar 

  • Kellihan HB, Stepien RL (2010) Pulmonary hypertension in dogs: diagnosis and therapy. Vet Clin North Am Small Anim Pract 40(4):623–641

    Article  Google Scholar 

  • Kellum HB, Stepien RL (2007) Sildenafil citrate therapy in 22 dogs with pulmonary hypertension. J Vet Intern Med 21(6):1258–1264

    Article  Google Scholar 

  • Malik M (1996) Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology Eur Heart J 17(3):354–381

    Google Scholar 

  • Matsunaga T, Harada T, Mitsui T, Inokuma M, Hashimoto M, Miyauchi M, Murano H, Shibutani Y (2001) Spectral analysis of circadian rhythms in heart rate variability of dogs. Am J Vet Res 62(1):37–42

    Article  CAS  Google Scholar 

  • McLaughlin VV, McGoon MD (2006) Pulmonary arterial hypertension. Circulation 114(13):1417–1431

    Article  Google Scholar 

  • Pyle R, Abbott J, Maclean H (2004) Pulmonary hypertension and cardiovascular sequelae in 54 dogs. J Appl Res Vet Med 2(2):99–109

  • Rothman A, Wiencek RG, Davidson S, Evans WN, Restrepo H, Sarukhanov V, Mann D (2017) Challenges in the development of chronic pulmonary hypertension models in large animals. Pulm Circ 7(1):156–166

    Article  Google Scholar 

  • Sayers BM (1973) Analysis of heart rate variability. Ergonomics 16(1):17–32

    Article  CAS  Google Scholar 

  • Schwartz BG, Levine LA, Comstock G, Stecher VJ, Kloner RA (2012) Cardiac uses of phosphodiesterase-5 inhibitors. J Am Coll Cardiol 59(1):9–15

    Article  CAS  Google Scholar 

  • Semen K, Yelisyeyeva O, Jarocka-Karpowicz I, Kaminskyy D, Solovey L, Skrzydlewska E, Yavorskyi O (2016) Sildenafil reduces signs of oxidative stress in pulmonary arterial hypertension: evaluation by fatty acid composition, level of hydroxynonenal and heart rate variability. Redox Biol 7:48–57

    Article  CAS  Google Scholar 

  • Toyoshima Y, Kanemoto I, Arai S, Toyoshima H (2007) A case of long-term sildenafil therapy in a young dog with pulmonary hypertension. J Vet Med Sci 69(10):1073–1075

    Article  CAS  Google Scholar 

  • Wensel R, Jilek C, Dörr M, Francis DP, Stadler H, Lange T, Blumberg F, Opitz C, Pfeifer M, Ewert R (2009) Impaired cardiac autonomic control relates to disease severity in pulmonary hypertension. Eur Respir J 34(4):895–901

    Article  CAS  Google Scholar 

  • Witte C, JU MZHGM-A, Andri R, Schrickel JW, Hammerstingl C, Schwab JO, Nickenig G, Skowasch D, Pizarro C (2016) Heart rate variability and arrhythmic burden in pulmonary hypertension. Adv Exp Med Biol 934:9–22

    Article  CAS  Google Scholar 

  • Yi HT, Hsieh YC, Wu TJ, Huang JL, Lin WW, Liang KW, Su CS, Tsai WJ, Wang KY (2014) Heart rate variability parameters and ventricular arrhythmia correlate with pulmonary arterial pressure in adult patients with idiopathic pulmonary arterial hypertension. Heart Lung 43(6):534–540

    Article  Google Scholar 

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Acknowledgements

We would like to thank the students of the Laboratory of Veterinary Internal Medicine II at Nippon Veterinary and Life Science University for supporting our study. In addition, we would also like to thank MARUZEN-YUSHODO Co., Ltd. (http://kw.maruzen.co.jp/kousei-honyaku/) for the English language editing.

Funding

This research did not receive any specific grants from funding agencies in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Laboratory of Veterinary Internal Medicine II, School of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan

    Mizuki Ogawa, Mio Ishizaka, Ryota Akabane, Atsushi Sakatani, Masayoshi Nagakawa, Hirosumi Miyakawa, Yuichi Miyagawa & Naoyuki Takemura

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  1. Mizuki Ogawa
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  2. Mio Ishizaka
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  3. Ryota Akabane
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  4. Atsushi Sakatani
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  5. Masayoshi Nagakawa
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  6. Hirosumi Miyakawa
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  7. Yuichi Miyagawa
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  8. Naoyuki Takemura
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Correspondence to Mizuki Ogawa.

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Ogawa, M., Ishizaka, M., Akabane, R. et al. Evaluation of the Autonomic Nervous System in a Canine Model of Chronic Embolic Pulmonary Hypertension. Vet Res Commun 44, 73–81 (2020). https://doi.org/10.1007/s11259-020-09774-z

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  • DOI: https://doi.org/10.1007/s11259-020-09774-z

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