Regional expression of myocardial sheet dysfunction in dystrophin-deficient cardiomyopathy elucidated with diffusion ten
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Regional expression of myocardial sheet dysfunction in dystrophin-deficient cardiomyopathy elucidated with diffusion tensor MRI and optical calcium mapping Ya-Jian Cheng1,2*, Di Lang1, Shelton D Caruthers2, Gregory Lanza2, Igor Efimov1, Junjie Chen2, Samuel A Wickline2,1 From 15th Annual SCMR Scientific Sessions Orlando, FL, USA. 2-5 February 2012 Summary Duchene Muscular Dystrophy (DMD) is a lethal disease caused by ubiquitous lack of dystrophin, but the interaction with regional cardiac mechanical forces that may facilitate eventual expression of abnormal contractile function is unknown. Diffusion tensor MRI (DTI) was used to evaluate function in Langendorff perfused hearts in the mdx mouse model of DMD. Abnormal calcium kinetics (by optical mapping) and sheet mechanics (by DTMRI) occurred more prominently at the mid-upper ventricle, suggesting that regional mechanics influence the development of heart failure. Background The relationship between abnormal sarcoplasmic Ca2+ handling and cardiac structural mechanics in mdx mice has not been defined. DTI has been used to quantify the contribution of myocardial sheet architecture in ventricular wall thickening mechanics. In this study, DTI was employed to assess altered sheet mechanics that might be influenced by impaired calcium homeostasis. Furthermore, optical mapping of AP and CaT were employed to characterize local difference in ex vivo beating hearts. Methods Sixteen-month old mdx (n = 10) and age matched wildtype (WT, n = 10) mouse hearts were prepared for Langendorff perfusion by sequentially cardiac arrest in 1
Biomedical Engineering, Washington University in Saint Louis, Saint Louis, MO, USA Full list of author information is available at the end of the article
diastole and systole for DTI: The first group (WT-NC & mdx-NC) was perfused with regular St. Thomas’ cardioplegic solution containing normal [Ca2+] (1.2 mM) to arrest hearts in diastole. To assess the regulatory effect of [Ca2+] on diastolic sheet mechanics, the second group (WT-LC & mdx-LC) was perfused with modified cardioplegic solution containing low [Ca2+] (0.078 mM). All hearts were then reperfused with Krebs buffer to resume beating followed by 2.5mM barium-induced systolic arrest for DTI. Absolute values of sheet angles, |b| s, in each heart were calculated from the diffusion tensors. MANOVA was used for statistical analysis. Another set of Langendorff beating mouse hearts from WT (n=2) and mdx (n=3) mice were optically mapped. RH237 and Rhod-2 AM were used as membrane potential and calcium probes. Steady state restitution pacing protocol was applied to estimate the calcium dynamics at different heart rates.
Results In diastole, mdx hearts exhibited lower |b| in mid-upper ventricle than WT did. Reducing [Ca2+] in cardioplegic solution normalized the diastolic |b| in mdx hearts but had no detectable effect on WT hearts. No significant difference of systolic |b| was observed between mdx and WT hearts. (Fig. 1) Optical mapping of CaT showed a localized Ca alter
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