Effects of Dobutamine on Left Ventricular Performance, Coronary Dynamics, and Distribution of Cardiac Output in Conscious Dogs

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Abstract

The effects of dobutamine ([±]-4-[2-[[3-(p-hydroxyphenyl)-1-methyl propyl] amino] ethyl] pyrocatechol hydrochloride), a new synthetic cardioactive sympathomimetic amine, were examined on direct and continuous measurements of left ventricular (LV) diameter (D), pressures (P), velocity of shortening (V), dP/dt, dP/dt/P, arterial pressure, cardiac output, and regional blood flows in the left circumflex coronary, mesenteric, renal, and iliac beds in healthy, conscious dogs. At the highest dose of dobutamine examined, 40 μg/kg/min, the drug increased dP/dt/P from 65±3 to 128±4 s-1 and isolength velocity from 72±4 to 120±7 mm/s without affecting LV end diastolic D significantly. Mean arterial P rose from 92±2 to 104±3 mm Hg and heart rate from 78±3 to 111±7 beats/min, while LV end systolic D fell from 24.1±1.4 to 19.9±1.8 mm, reflecting a rise in stroke volume from 30±4 to 42±3 ml. Cardiac output rose from 2.41±0.23 to 4.35±0.28 liter/min, while calculated total peripheral resistance declined from 0.042±0.005 to 0.028±0.003 mm Hg/ml/min. The greatest increases in flow and decreases in calculated resistance occurred in the iliac and coronary beds, and the least occurred in the renal bed. Propranolol blocked the inotropic and beta2 dilator responses while vasoconstricting effects mediated by alpha adrenergic stimulation remained in each of the beds studied. When dobutamine was infused after a combination of practolol and phentolamine, dilatation occurred in each of the beds studied. These observations indicate that dobutamine is a potent positive inotropic agent with relatively slight effects on preload, afterload, or heart rate, and thus may be a potentially useful clinical agent. The one property of this drug which is not ideal is its tendency to cause a redistribution of cardiac output favoring the muscular beds at the expense of the kidney and visceral beds.

Authors

Stephen F. Vatner, Robert J. McRitchie, Eugene Braunwald