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The Effects of Combined Versus Selective Adrenergic Blockade on Left Ventricular and Systemic Hemodynamics, Myocardial Substrate Preference, and Regional Perfusion in Conscious Dogs With Dilated Cardiomyopathy

Department of Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania

View larger version (23K): [in a new window]   Figure 1 Changes in left ventricular (LV) and systemic hemodynamics in conscious dogs with severe dilated cardiomyopathy (DCM) after treatment with carvedilol (n = 10) (open bars) versus metoprolol controlled release/extended release (CR/XL) (n = 8) (solid bars). Five dogs served as control subjects (gray bars) in which pacing was suspended after DCM developed but no therapy was initiated. LV dP/dt = maximal rate of left ventricular systolic pressure development; LVEDP = left ventricular end-diastolic pressure; MAP = mean arterial pressure; SVR = systemic vascular resistance. *p < 0.05 compared with carvedilol; p < 0.05 compared with metoprolol CR/XL.

View larger version (24K): [in a new window]   Figure 2 The heart rate response to isoproterenol infusion in dilated cardiomyopathy (DCM) before (A) and during carvedilol (n = 5) or metoprolol controlled release/extended release (CR/XL) (n = 5) treatment (B) and in five control dogs with cessation of pacing alone. *p < 0.05 compared with carvedilol and metoprolol. (C) The adenylyl cyclase response to guanine triphosphate/isoproterenol (GTP/Iso) and sodium flouride in sarcolemmal membrane preparations from these same dogs obtained after euthanasia. *p < 0.05 compared with baseline. p < 0.05 compared with DCM. Carv = carvedilol; Con = control subjects; Iso = isoproterenol; Met = metoprolol.

View larger version (23K): [in a new window]   Figure 3 Effects of carvedilol, metoprolol controlled release/extended release (CR/XL), and no treatment on left ventricular (LV) stroke work, myocardial oxygen consumption (MvO2), and LV mechanical efficiency. Although both treatments had comparable effects on MvO2, carvedilol was associated with greater increases in stroke work and mechanical efficiency. Cessation of pacing alone had no effect. The indicated p values represent the differences in the carvedilol response and metoprolol response. *p < 0.05 compared with before treatment. Open bars = before treatment; solid bars = after treatment. Carv = carvedilol; Con = control subjects; Met = metoprolol.

View larger version (16K): [in a new window]   Figure 4 Effects of carvedilol versus metoprolol controlled release/extended release (CR/XL) on renal, hepatic, and skeletal muscle blood flows. Carvedilol increased renal, hepatic, and skeletal muscle flow to a greater extent than metoprolol CR/XL (*p < 0.05 compared with before treatment). The indicated p values represent the differences in the carvedilol responses and the metoprolol responses by analysis of variance. Open bars = before treatment; solid bars = after treatment.

View larger version (33K): [in a new window]   Figure 5 The left ventricular (LV) and mean arterial pressure (MAP) response to exogenously administered norepinephrine (0.4 µg/kg/min) before (dilated cardiomyopathy [DCM]) and after 3 days of treatment with carvedilol (DCM+C) or metoprolol controlled release/extended release (DCM+M). The indicated p values represent the differences in the carvedilol responses and metoprolol responses by analysis of variance. LV dP/dt = maximal rate of left ventricular systolic pressure development; LVEDP = left ventricular end-diastolic pressure; LVP = left ventricular pressure.

View larger version (29K): [in a new window]   Figure 6 The effects of exogenously administered norepinephrine (0.4 µg/kg/min) before (dilated cardiomyopathy [DCM]) and after 3 days of treatment with carvedilol (DCM+C) or metoprolol controlled release/extended release (DCM+M) on cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), and characteristic aortic impedance. The indicated p values represent the differences in the carvedilol responses and metoprolol responses by analysis of variance.

View larger version (14K): [in a new window]   Figure 7 Effects of carvedilol versus metoprolol controlled release/extended release (CR/XL) on myocardial substrates, plasma insulin levels, and myocardial glucose uptake in severe dilated cardiomyopathy (DCM). Carvedilol was associated with decreased plasma nonesterified fatty acids (NEFAs) and with increased plasma insulin levels and myocardial glucose uptake compared with metoprolol CR/XL. The indicated p values represent the differences in the carvedilol responses and metoprolol or control responses by analysis of variance. DCM+Rx = DCM plus treatment.

View larger version (17K): [in a new window]   Figure 8 The effects of isoproterenol stimulation on myocardial nonesterified fatty acid (NEFA) uptake (A) and myocardial glucose uptake (B) in dogs with dilated cardiomyopathy (DCM) before and after treatment with selective ß1 or combined adrenergic blockade. The indicated p values represent the differences in the carvedilol response and metoprolol or response by analysis of variance. Iso = isoproterenol.