Myocardial interstitial purine metabolites and lactate with increased work in swine.
OBJECTIVE
Dobutamine stimulates the beta-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 micrograms/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.
Hall
J L
JL
Section of Cardiovascular Pharmacology, Syntex Research, Palo Alto, CA 94303, USA.
Van Wylen
D G
DG
Pizzurro
R D
RD
Hamilton
C D
CD
Reiling
C M
CM
Stanley
W C
WC
D000241:Adenosine / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation; D004280:Dobutamine / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D017551:Microdialysis; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011687:Purines / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine / Q000378:metabolism*; D017725:Ventricular Pressure / Q000187:drug effects
D007773:Lactates; D011687:Purines; D011943:Receptors, Adrenergic, beta; D019344:Lactic Acid; D004280:Dobutamine; D000249:Adenosine Monophosphate; D000241:Adenosine