© 1995 by European Society of Cardiology
Copyright © 1995, European Society of Cardiology
Myocardial interstitial purine metabolites and lactate with increased work in swine
aSection of Cardiovascular Pharmacology, Institute of Pharmacology, Syntex Research, Palo Alto, CA 94303, USA
bDepartment of Human Biodynamics, University of California, Berkeley, CA 94720, USA
cDepartment of Biology, St. Olaf College, Northfield, MN 55057, USA
* Corresponding author: C.V. Therapeutics, 3172 Porter Drive, Palo Alto, CA 94304, USA.
1 Address for reprints: W.C. Stanley, C.V. Therapeutics, 3712 Porter Drive, Palo Alto, CA 94304, USA.
Objective: Dobutamine stimulates the β-receptors in the heart and increases myocardial blood flow and oxygen consumption 2–3-fold, similar to effects seen with exercise. The purpose of this study was to assess temporal changes in myocardial interstitial purine metabolites, adenosine monophosphate (AMP) and lactate during and following 30 min of dobutamine infusion. Methods: Dobutamine (15 µg/kg/min) was infused via the jugular vein into 9 anesthetized, open-chest, domestic swine. Interstitial fluid was sampled with microdialysis probes placed in the midmyocardium. The effluent from the probes, referred to as the dialysate, was used to estimate myocardial interstitial purine metabolites, AMP, and lactate levels before, during, and following a dobutamine-induced increased work state. Results: Dobutamine infusion resulted in a 77% increase in heart rate, a 258% increase in left ventricular dP/dt, a 208% increase in myocardial oxygen consumption, and a 155% increase in rate x pressure product. Myocardial blood flow was increased in the subepicardium, midmyocardium, and subendocardium by 207, 268, and 268%, respectively, compared to the control period. Neither coronary venous nor dialysate lactate concentrations changed throughout the protocol. Dialysate adenosine and AMP levels were both significantly elevated (P < 0.05) during the dobutamine period and fell back to control values during the recovery period. Conclusions: The dobutamine-induced increases in myocardial oxygen consumption, rate x pressure product, and blood flow, without an increase in coronary venous or interstitial lactate suggest that energy balance is maintained during dobutamine infusion. Thus an increase in myocardial work, in the absence of demand-induced ischemia, resulted in accumulation of adenosine and AMP in the interstitium.
KEYWORDS Coronary blood flow; Microdialysis; Cardiac metabolism; Purine metabolism; Dobutamine; Pig, anesthetized
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