Abstract 3387: Contractile Reserve Revealed by β1-Adrenergic Stimulation as a Predictor of Altered Myocardial Expression of Contractile Regulatory Proteins in Mildly Symptomatic Patients with Idiopathic Dilated Cardiomyopathy
Objectives: To determine whether reduced myocardial contractile reserve revealed with dobutamine might predict altered myocardial expression of contractile regulatory proteins in mildly symptomatic patients with idiopathic dilated cardiomyopathy (DCM).
Methods: The maximal first derivative of left ventricular pressure (LV dP/dtmax) during infusion of dobutamine (10 μg kg-1 min-1) was determined in 42 mildly symptomatic (NYHA functional class I or II) patients with DCM. The abundance of mRNAs for the β1-adrenergic receptor, β-adrenergic receptor kinase, α subunits of Gs and Gi proteins, sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban, ryanodine receptor-2, calsequestrin, and the Na+/Ca2+ exchanger in endomyocardial biopsy specimens was quantified by reverse transcription and real-time polymerase chain reaction analysis.
Results: Patients were classified into two groups: those who showed an increase of ≤100% (group A, n = 24) and those who showed an increase of 3>100% (group B, n = 18) in LV dP/dtmax during dobutamine infusion. The abundance of mRNAs for the β1-adrenergic receptor (0.37 ± 0.17 vs. 0.84 ± 0.43, P < 0.01), SERCA2a (0.33 ± 0.16 vs. 0.54 ± 0.27, P < 0.05), and phospholamban (0.54 ± 0.19 vs. 0.75 ± 0.26, P < 0.05) was significantly smaller in group A than in group B. The plasma concentration of norepinephrine at baseline was significantly higher in group A than in group B (630 ± 253 vs. 411 ± 148 pg/mL, P < 0.05).
Conclusions: These results suggest that the myocardial contractile reserve revealed by β1-adrenergic stimulation with dobutamine is a potential predictor of down-regulation of contractile regulatory proteins even in mildly symptomatic patients with DCM.