The effects of amrinone versus dobutamine on myocardial mechanics and energetics after hypothermic global ischemia. 1993

W Ko, and J A Zelano, and A L Fahey, and K Berman, and D Lang, and O W Isom, and K H Krieger
Cardiothoracic Surgery Research Laboratory, New York Hospital-Cornell University Medical College, NY 10021.

The effects on the postischemic myocardium of amrinone and dobutamine were studied in canine hearts that underwent 90 minutes of hypothermic (10 degrees C) arrested ischemia. In an isolated heart preparation cross-circulated by a support dog, left ventricular pressure-volume loops were collected under a constant afterload based on a mock circulatory system and a range of preload conditions controlled by a computerized servo volume pump. Dobutamine (0, 5, 10, 15 micrograms/kg per minute) and amrinone (0, 0.75, 1.5, 3.0 mg/kg) were tested in this order based on the weights of the support dogs in eight experiments. Changes in intrinsic myocardial contractility were analyzed as percent increases in the preload recruitable stroke work area from baselines. Dobutamine exhibited significant dose-related increases in the preload recruitable stroke work area. Amrinone did not produce significant increases in preload recruitable stroke work area at 0.75 mg/kg; amrinone's inotropic effect was equivalent to dobutamine, 5 micrograms/kg per minute at 1.5 mg/kg, and at the maximum dose (3.0 mg/kg) it was equivalent to dobutamine, 10 micrograms/kg per minute. The myocardial energetic efficiency was determined from the analysis of the myocardial oxygen consumption-pressure volume area relationship. The y intercept represents the basal metabolic oxygen requirement of the unloaded beating heart, and the slope is inversely proportional to the rate of energy conversion for increasing loading conditions. Dobutamine significantly increased the y intercepts, but it had no effects on the slopes. These changes demonstrate reduced myocardial efficiencies that are consistent with previous reports. Amrinone (0.75 and 1.50 mg/kg) did not result in change of the y intercepts and the slopes of myocardial oxygen consumption-pressure-volume area relationship from baseline conditions. The y intercept was increased with amrinone (3.0 mg/kg), although still not significantly higher than baseline and not to the extents of the dobutamine group. Dobutamine did not have any primary effect on coronary resistance, while amrinone significantly reduced coronary resistance in all loading conditions at 1.5 and 3.0 mg/kg. This study demonstrates that the inotropic effects of amrinone tested under this constant afterload preparation were lower than those of dobutamine. Amrinone has a superior profile of myocardial efficiency on the postischemic myocardium since it does not produce the oxygen-wasting effects of the traditional inotropic agents such as the beta agonists. This benefit, together with amrinone's coronary dilating effects, critically improves the supply/demand ratio that may be of importance in certain clinical situations.

UI MeSH Term Description Entries
D007036 Hypothermia, Induced Abnormally low BODY TEMPERATURE that is intentionally induced in warm-blooded animals by artificial means. In humans, mild or moderate hypothermia has been used to reduce tissue damages, particularly after cardiac or spinal cord injuries and during subsequent surgeries. Induced Hypothermia,Mild Hypothermia, Induced,Moderate Hypothermia, Induced,Targeted Temperature Management,Therapeutic Hypothermia,Hypothermia, Therapeutic,Induced Mild Hypothermia,Induced Mild Hypothermias,Induced Moderate Hypothermia,Induced Moderate Hypothermias,Mild Hypothermias, Induced,Moderate Hypothermias, Induced,Targeted Temperature Managements
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
D003331 Coronary Vessels The veins and arteries of the HEART. Coronary Arteries,Sinus Node Artery,Coronary Veins,Arteries, Coronary,Arteries, Sinus Node,Artery, Coronary,Artery, Sinus Node,Coronary Artery,Coronary Vein,Coronary Vessel,Sinus Node Arteries,Vein, Coronary,Veins, Coronary,Vessel, Coronary,Vessels, Coronary
D004280 Dobutamine A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY. Dobucor,Dobuject,Dobutamin Fresenius,Dobutamin Hexal,Dobutamin Solvay,Dobutamin-ratiopharm,Dobutamina Inibsa,Dobutamina Rovi,Dobutamine (+)-Isomer,Dobutamine Hydrobromide,Dobutamine Hydrochloride,Dobutamine Lactobionate,Dobutamine Phosphate (1:1) Salt, (-)-Isomer,Dobutamine Tartrate,Dobutamine Tartrate (1:1), (R-(R*,R*))-Isomer,Dobutamine Tartrate (1:1), (S-(R*,R*))-Isomer,Dobutamine, (-)-Isomer,Dobutamine, Phosphate (1:1) Salt (+)-Isomer,Dobutrex,Lilly 81929,Oxiken,Posiject,Dobutamin ratiopharm,Hydrobromide, Dobutamine,Hydrochloride, Dobutamine,Lactobionate, Dobutamine,Tartrate, Dobutamine
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
D000676 Amrinone A positive inotropic cardiotonic (CARDIOTONIC AGENTS) with vasodilator properties, phosphodiesterase 3 inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell. 5-Amino-(3,4'-bipyridine)-6(1H)-one,Amrinon,Cordemcura,Inocor,Win-40680,Wincoram,Win 40680,Win40680
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013268 Stimulation, Chemical The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Stimulation,Chemical Stimulations,Stimulations, Chemical

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