Effects of single bolus injection of pimobendan on cardiac function, hemodynamics, and heart rate variability in healthy dogs

Abstract

In veterinary medicine, pimobendan has been recommended for management of dogs with congestive heart failure for decades. Recently, an intravenous injectable solution of this drug has been launched. However, the effects of this preparation on electrocardiography, cardiac functions, hemodynamics, heart rate variability (HRV), and the pharmacokinetics (PK) in dogs are still limited. Therefore, the objective of this investigation is to investigate the hemodynamics, cardiac functions, electrocardiographic parameters, the PK profiles and its active metabolite, O-desmethyl pimobendan (ODMP), as well as its effect on HRV of a single bolus pimobendan in healthy dogs. Nine dogs were anesthetized and instrumented to obtained parameters of left ventricular functions, hemodynamics, and electrocardiograms. Bolus pimobendan (0.15 mg/kg, IV) was given to all dogs and the effects were monitored for 2 h. Plasma concentrations of pimobendan and ODMP were quantified using LC-MS/MS. Seven of those dogs were instrumented with Holter monitoring for obtaining heart rate variability while they were conscious and clam. Bolus pimobendan (0.15 mg/kg, IV) was given to all dogs and the effects were monitored for 3 h. The results revealed that single bolus pimobendan fastened the heart rate while the PQ interval was shortened. Furthermore, the results also indicated that pimobendan significantly improves both cardiac contraction and relaxation within 10 to 20 mins after injection. In addition, pimobendan significantly reduced both systemic- and pulmonic-vascular resistances. The Cmax of pimobendan and ODMP were 83.7 and 30 ug/L, respectively, while the Tmax of ODMP was 0.33 h. The volume of distribution of pimobendan and ODMP were 8.9 and 7.1 L/kg, respectively. The half-life of pimobendan and ODMP were 1 h and 2.8 h, respectively. The clearance of pimobendan and ODMP were 5.8 and 2.2 L/kg/h, respectively. In conscious dogs, single bolus pimobendan augmented the cardiac autonomic nervous activity inferred from an increasing of heart rate variability. Moreover, the results also suggested that pimobendan tended to intensify parasympathetic activity more than the sympathetic branch. In conclusion, intravenous pimobendan improves cardiac functions and hemodynamics shortly after injection and enhances a cardiac autonomic nervous activity, which may be a great benefit for dogs with congestive heart failure.