Disparate force-frequency effects of pimobendan and dobutamine in conscious dogs with tachycardia-induced cardiomyopathy.
BACKGROUND
This study was designed to examine how a calcium sensitizer, pimobendan, affected a force-frequency response (FFR) as compared to the beta-adrenergic agonist dobutamine.


RESULTS
Left ventricular (LV) contractility and relaxation were evaluated by the slope (Ees) of the LV end-systolic pressure-volume relation and the time constant (Tau) of LV pressure decay. Using 6 conscious dogs with tachycardia-induced heart failure, the FFR was examined before and after administration of dobutamine (6 microg/kg/min) or pimobendan (0.5 mg/kg). Despite the similar inotropic and lusitropic action at the baseline heart rate, pimobendan and dobutamine showed different FFR and relaxation-frequency responses. Before administration of these drugs, there was no significant increase in LV contractility and relaxation by increasing heart rate. However, dobutamine amplified FFR (Ees: +3.1 +/- 1.4, P <.05) as compared with Ees for a comparable increase in heart rate before administration of the drug. On the other hand, pimobendan showed relatively mild amplification of FFR compared with dobutamine (Ees: +1.9 +/- 1.1, P <.05). The relaxation-frequency response tended to increase with dobutamine but not with pimobendan.


CONCLUSIONS
Mild amplification of FFR observed in pimobendan suggests that this agent could be used more safely than beta-adrenergic agent when heart rate is increased, as seen with exercise.
Joho
Shuji
S
Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Asanoi
Hidetsugu
H
Ishizaka
Shinji
S
Kameyama
Tomoki
T
Inoue
Hiroshi
H
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002304:Cardiac Pacing, Artificial; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D006333:Heart Failure / Q000209:etiology* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011724:Pyridazines / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013318:Stroke Volume / Q000187:drug effects; D013610:Tachycardia / Q000150:complications* / Q000503:physiopathology*; D017725:Ventricular Pressure / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; D004280:Dobutamine