The β ₃ Adrenergic Receptor Antagonist L-748,337 Attenuates Dobutamine-Induced Cardiac Inefficiency While Preserving Inotropy in Anesthetized Pigs

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  Figure 1.. Hemodynamic data from healthy pigs. CO indicates cardiac output, measured using a flow probe on the pulmonary trunk; SVR, systemic vascular resistance, calculated from mean arterial pressure, central venous pressure in the vena cava and CO; MAP, mean arterial pressure measured using a vascular catheter in the abdominal aorta; HR, heart rate; SV, stroke volume calculated from CO and HR; EF, ejection fraction; End-systolic volume (ESV) and end-diastolic volume (EDV) calculated from sonomicrometric crystal signals calibrated by endocardial short axis diameter from epicardial echocardiography; EDPVR, end-diastolic pressure–volume relation given as the ratio of pressure divided by volume; dP/dt max, peak positive derivative of left ventricular pressure; PRSW, preload-recruitable stroke work, the slope of the relation between end-diastolic volume and stroke work; Tau, time constant of left ventricular isovolumetric relaxation calculated by Weiss method. Dob, dobutamine 5 μg/kg/min (n = 9); L, L-748,337 bolus 50 μg/kg (n = 5); Control, saline 0.9% (n = 7). Data were analyzed within groups using a two-way mixed ANOVA for repeated measures, and multiple comparisons were adjusted for by…

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  Figure 2.. Left ventricular work–myocardial oxygen consumption relationship from healthy pigs. Left panels show 95% confidence intervals for pooled scatterplots from all experiments. Right panels show example data from one individual pig in each group. All data was obtained by preload reductions by vena cava occlusions using a balloon catheter. Dobutamine (Dob, 5 μg/kg/min, n = 9) impairs cardiac efficiency over time as displayed by an increase in y-intercept from baseline and increased slope after 6 hours (upper panel). Combining Dob with L-748,337 (L, bolus 50 μg/kg, n = 5) shows an increase in y-intercept after ½ hour compared to 6 hours, but after 6 hours y-intercept and slope is unchanged from baseline (middle panel). In time-matched controls (Control, saline 0.9%, n = 7) there is no change in cardiac efficiency for 6 hours (lower panel). MVO2, myocardial oxygen consumption; PVA, pressure–volume area. * P < 0.05, 6 hours vs baseline and ½ hour for slope; † P < 0.05, baseline vs ½ hour and 6 hours for y-intercept; ‡ P < 0.05, ½ hour vs 6 hours for y-intercept (linear mixed model analysis).

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  Figure 3.. Metabolism data from healthy pigs. CPO, cardiac power output calculated as left ventricular developed pressure*cardiac output/451; MVO2, myocardial oxygen consumption; FFA, free fatty acid; Dob, dobutamine 5 μg/kg/min (n = 9); L, L-748,337 bolus 50 μg/kg (n = 5); Control, saline 0.9% (n = 7). Data were analyzed within groups using a two-way mixed ANOVA for repeated measures, and multiple comparisons were adjusted for by Bonferroni correction. Bars indicate mean values ± standard deviation. Brackets indicate statistically significant difference (P < 0.05).