Usefulness of pimobendan in the treatment of heart failure.
The effects of the benzimidazole-pyridazinone pimobendan (UD-CG 115 BS) on systemic haemodynamics, myocardial performance and the distribution of cardiac output were studied in open-chest anaesthetized pigs. After intravenous bolus injections (0.1-0.5 mg X kg-1, n = 7) increases in heart rate (up to 37%), LVdP/dtmax (up to 54%) and decreases in systemic vascular resistance (up to 33%) and left ventricular filling pressure (up to 50%) were observed, while cardiac output was unchanged. Vasodilation occurred in nearly all regional vascular beds, but was most pronounced in the adrenals (200%), followed by stomach (150%), small intestines (130%), heart (125%) and brain (110%). O2-consumption was not affected in spite of the increases in heart rate and myocardial inotropy. To evaluate the direct effects on the myocardial, pimobendan was also infused (1-5 micrograms X kg-1 X min-1, n = 7) directly into the left anterior descending coronary artery. In addition to a marked vasodilation of the coronary bed (140%), also a lowering of the left ventricular filling pressure (up to 20%) and cardiac output (15%) was observed, but no changes in regional myocardial function, LVdP/dtmax and systemic vascular resistance occurred. Immediately after intracoronary bolus injections (1 mg X kg-1, n = 4), vasodilation of the coronary vessels was apparent, but myocardial contractility was not affected. This may explain that cyclic AMP content, determined in biopsies excised 30 s after injection, was unaltered. It may be concluded that pimobendan exerts actions on the cardiovascular system which may be useful in the treatment of heart failure.
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011724:Pyridazines / Q000627:therapeutic use*; D013552:Swine
D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; D000242:Cyclic AMP; D006152:Cyclic GMP