Background: Glucose is the preferred myocardial metabolic substrate in heart failure due to its efficiency in generating high-energy phosphates. Catecholamines are potent counter-regulatory hormones to the action of insulin and can contribute to decreased glucose uptake. β-adrenergic antagonists are established treatment in dilated cardiomyopathy (DCM). However, the benefits of combined versus selective adrenergic blockade on myocardial glucose and non-esterified fatty acid (NEFA) uptake in DCM remain to be determined.

Methods: We studied 11 conscious dogs, instrumented to measure coronary blood flow (CBF) and arterial and coronary sinus catheters to measure myocardial substrate balance, at 29±3 days following RV pacing at 240 min^-1 which induced severe DCM. Dogs received either carvedilol (CARV: 25 mg po BID, n=6) or metoprolol succinate (MET: 50 mg po QD, n=5) for 3 days, designed to reduce heart rate similarly (-33±6 from 124±7 min^-1). Myocardial substrate uptake and plasma hormones governing glucose homeostasis were measured before and after treatment.

Results: CARV treatment was associated with significant (*p≦0.05) increase in plasma insulin (64±8 to 151±38 pmol/L*) compared to MET (58±12 to 44±17 pmol/L), and significant decrease in plasma NEFA (CARV: 476±56 to 212±41 μmol/L*) compared to MET (513±61 to 476±81 μmol/L) while plasma glucose levels did not differ. CARV decreased plasma norepinephrine levels (322±67 to 212±48 pg/ml*) to a greater extent than MET (376±26 to 342±71 pg/ml). CARV was associated with significant increase in myocardial glucose uptake (6.7±2.1 to16.8±3.5 μmol/min*) compared to MET (7.2±2.2 to 6.6±2.7 μmol/min) in association with the increase in plasma insulin. Myocardial nitric oxide (NO_x) production increased with CARV (9.6±0.3 to 18.9±1.9 nmol/min*), but not with MET (8.7±0.4 to 9.4±0.6 nmol/min). These metabolic improvements were associated with increased LV contractility in CARV group (LV dP/dt; CARV: +756±92 from 1,470±89 mmHg/sec; MET: +389±111 from 1,330±102 mmHg/sec).

Conclusion: Combined adrenergic blockade with CARV was associated with significant insulinotropic and lipostatic effects and improvement in myocardial glucose uptake compared to β-blockade alone.