© 2002 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Catecholamine stimulation is associated with impaired myocardial O2 utilization in heart failure
aDepartment of Medicine, Allegheny General Hospital, MCP-Hahneman University School of Medicine, 320 E. North Avenue, Pittsburgh, PA 15212, USA
bMerck Research Laboratories, West Point, PA, USA
* Corresponding author. Tel.: +1-412-359-3022; fax: +1-412-359-8152 rshannon{at}wpahs.org
Objectives: To investigate the effect of 
, β1 and β2 adrenergic receptor (AR) stimulation on coronary hemodynamics, myocardial oxygen consumption (MvO2) and metabolic substrate preference in advanced dilated cardiomyopathy (DCM). Methods: We studied 19 conscious, instrumented dogs with pacing-induced DCM. We evaluated systemic, coronary hemodynamics and MvO2 in response to norepinephrine (NOR, 0.05–0.4 µg/kg per min), dobutamine (DOB, 1–10 µg/kg per min), phenylephrine (PHE, 1–5 µg/kg per min) and isoproterenol (ISO, 0.05–0.4 µg/kg per min) alone or in the presence of metoprolol (ISO+MET). Experiments were conducted in control state and in advanced DCM, 4–5 weeks after the initiation of pacing. Results: Contractile responses (LV dP/dt) to catecholamines were desensitized and accompanied by a parallel decrease in heart rate-adjusted myocardial O2 consumption (MvO2/beat), when (PHE) or β1 (DOB) or both /β1 (NOR) AR were stimulated in DCM. This was due to impaired transmyocardial (Ao–Cs) O2 extraction rather than limitations in CBF responses. There was an associated shift in myocardial metabolism, evidenced by an increased preference for glycolytic substrates (
Respiratory Quotient) following administration of any of these three adrenergic agonists in DCM. Combined β1/β2 stimulation with ISO or β2-AR stimulation (ISO+MET) in DCM resulted in greater MvO2/beat, [(Ao–Cs) O2] extraction, and decreases in myocardial RQ consistent with a shift toward oxidation of FFA. Conclusions: The impairment in contractile responses to dobutamine and norepinephrine in DCM is associated with impaired myocardial O2 extraction, and a shift toward a preference for glycolysis. A different myocardial metabolic pattern suggestive of increased oxidation of FFA with increased myocardial O2 extraction was observed in the presence of combined β1/β2 stimulation with isoproterenol or β2 stimulation (ISO+MET). These data suggest that β2-AR stimulation in DCM shifts substrate preference toward FFA oxidation associated with greater MvO2 requirements. These findings identify a putative metabolic effect of β2 –AR in DCM that may be deleterious.
KEYWORDS Cardiomyopathy; Adrenergic (ant)agonists; Heart failure; Oxygen consumption; Energy metabolism; Hemodynamics
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