Effects of toborinone on myocardial oxygen consumption in pacing-induced heart failure dogs. 1996

S Itoh, and T Mori, and H Fujiki, and M Tominaga
2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Japan.

The effects of a novel positive inotropic agent, toborinone ((+/-)-1-[3,4-dimethoxy-benzylamino)-2-hydroxypropoxy]-2(1H)-quinolinone , CAS 128667-95-8, OPC-18790, on myocardial oxygen consumption were examined in pacing-induced heart failure dogs. Ten dogs were ventricularly paced at 260 beats/min for 10 days to induce heart failure. Five of them were controls and the remaining five were given toborinone. Dogs were anesthetized with halothane, and cardiac functions, hemodynamics and myocardial oxygen consumption were measured. The peak of the first derivative of left ventricular pressure (LV dP/dtmax), cardiac output (CO) and mean blood pressure (mBP) were significantly decreased, and left ventricular end-diastolic pressure (LVEDP), mean right atrial pressure (mRAP), pulmonary capillary wedge pressure (PCWP) and mean pulmonary arterial pressure (mPAP) were also significantly increased after 10 days of rapid ventricular pacing. Toborinone (5 and 10 micrograms/kg/min) dose-dependently increased LV dP/dtmax, coronary blood flow (CBF) and CO and decreased LVEDP and systemic vascular resistance (SVR) without increasing myocardial oxygen consumption in the pacing-induced heart failure dogs. These results suggest that toborinone may be useful for the management of chronic and congestive heart failure.

UI MeSH Term Description Entries
D008297 Male Males
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010101 Oxygen Consumption The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346) Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D002304 Cardiac Pacing, Artificial Regulation of the rate of contraction of the heart muscles by an artificial pacemaker. Pacing, Cardiac, Artificial,Artificial Cardiac Pacing,Artificial Cardiac Pacings,Cardiac Pacings, Artificial,Pacing, Artificial Cardiac,Pacings, Artificial Cardiac
D002316 Cardiotonic Agents Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE). Cardiac Stimulant,Cardiac Stimulants,Cardioprotective Agent,Cardioprotective Agents,Cardiotonic,Cardiotonic Agent,Cardiotonic Drug,Inotropic Agents, Positive Cardiac,Myocardial Stimulant,Myocardial Stimulants,Cardiotonic Drugs,Cardiotonics,Agent, Cardioprotective,Agent, Cardiotonic,Drug, Cardiotonic,Stimulant, Cardiac,Stimulant, Myocardial
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006333 Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION. Cardiac Failure,Heart Decompensation,Congestive Heart Failure,Heart Failure, Congestive,Heart Failure, Left-Sided,Heart Failure, Right-Sided,Left-Sided Heart Failure,Myocardial Failure,Right-Sided Heart Failure,Decompensation, Heart,Heart Failure, Left Sided,Heart Failure, Right Sided,Left Sided Heart Failure,Right Sided Heart Failure

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