Abstract 19788: Unloading With Left Ventricular Assist Devices Protects Heart Function by Normalizing Alterations of Calcium Handling Proteins after Myocardium Infarction
Introduction: The mechanism of chronic heart failure after myocardial infarction (MI) is unclear. Sarcoplasmic reticulum calcium ATPase-2α (SERCA-2α), Na+-Ca2+ exchanger-1 (NCX-1), and phospholamban (PLB) are a group of calcium handling proteins (CHPs), which are vital to the contraction and relaxation of myocardium.
Hypothesis: The alterations of CHPs after MI were caused by increased mechanical stress and could be ameliorated by unloading with left ventricular assist devices (LVAD).
Methods: Twenty-four adult sheep underwent 25% MI and were terminated at 2 days, 2 weeks, or 12 weeks (n=6, respectively). Six sheep with MI were unloaded with an axial LVAD in first 2 weeks and were terminated at 12 weeks. Four sheep were used as sham control. Strain was defined as the deformation of the end-diastolic geometry of LV and determined using 16 sonomicrometry transducers implanted in free wall of LV. Echocardiography was used to evaluate the dilation and function of LV. Western blotting was used to measure the regional expression of CHPs in non-ischemic adjacent zone (AZ) and remote zone (RZ) of MI.
Results: Dilation and dysfunction of LV were present 12 weeks after MI (LVEDV: 75.0±7.3 ml vs 106.1±14.3 ml; EF: 52.5±4.3% vs 40.7±3.4%, P<0.05). Strain in AZ increased after MI (5.1±0.8% vs 78.2±2.6%, P<0.05) and was 3.4±0.7 times higher than in RZ after 12 weeks. In AZ, after 2 days, SERCA-2α decreased compared with in RZ; in 2 weeks, PLB decreased and NCX-1 increased. By 12 weeks post-MI, SERCA-2α and PLB in AZ further decreased compared with in RZ (1.9±0.3 vs 1.4±0.3; 2.6±0.7 vs 1.6±0.7, respectively, P<0.05) and NCX-1 in AZ increased (0.9±0.2 vs 1.2±0.3, P<0.05). There were no statistical differences between RZ and control. Regional and temporal correlation showed that the alteration of CHPs was strain-related (SERCA-2α: r2=0.44; PLB: r2=0.45; NCX-1: r2=0.52, P<0.05). In unloading group, heart function improved (LVEDV: 80.1±9.1 ml vs 106.1±14.3 ml; EF: 47.1±4.2% vs 40.7±3.4%, P<0.05). Unloading with the LVAD decreased 61.6±10.3% strain in AZ, and CHPs expression in AZ was normalized compared with in RZ and sham control.
Conclusions: The strain is the main cause of the alteration of CHPs after MI and LVAD could protect heart function by normalizing the alteration of CHPs.
- © 2010 by American Heart Association, Inc.