Failing canine ventricular myocytes exhibit prominent depletion of T-tubules and changes in the density of a variety of proteins in both surface and T-tubular sarcolemma but with preservation of the protein composition of junctional complexes. This subcellular remodeling contributes to abnormal excitation-contraction coupling in heart failure.
Background-Reduced sarcoplasmic reticulum (SR) Ca 2ϩ -ATPase (SERCA2a isoform) activity is a major determinant of reduced contractility in heart failure. Ca 2ϩ -ATPase inactivation can occur through SERCA2a nitration. We therefore investigated the role of SERCA2a nitration in heart failure. Methods and Results-We measured SERCA2a levels and nitrotyrosine levels in tissue from normal and failing human hearts using Western blots. We found that nitrotyrosine levels in idiopathic dilated cardiomyopathic (DCM) hearts were almost double those of control hearts in age-matched groups. Nitrotyrosine was dominantly present in a single protein with the molecular weight of SERCA2a, and immunoprecipitation confirmed that the protein recognized by the nitrotyrosine antibody was SERCA2a. There was a positive correlation between the time to half relaxation and the nitrotyrosine/SERCA2a content (PϽ0.01) in myocytes isolated from control and DCM hearts. In experiments with isolated SR vesicles from porcine hearts, we also showed that the Ca pump is inactivated by peroxynitrite exposure, and inactivation was prevented by protein kinase A pretreatment. Conclusions-We conclude that SERCA2a inactivation by nitration may contribute to Ca pump failure and hence heart failure in DCM.
Multidetector computed tomography (CT) is an excellent way to supplement the radiographic evaluation of problematic hip prostheses. Multidetector CT is well suited for assessing periprosthetic bone, determining precise acetabular cup position, and evaluating periprosthetic fluid collections or ossified masses. Metal implants pose a number of challenges in the performance and interpretation of CT examinations. However, metal artifacts can be minimized by decreasing the detector collimation and pitch, increasing the kilovolt peak and milliampere-seconds, and using appropriate reconstruction algorithms and section thickness. Image interpretation requires a basic understanding of hip reconstruction and hip implants, as well as use of a systematic method of analysis that incorporates prior radiographic findings and CT findings. Radiologists must be familiar with the normal and abnormal CT appearances of hip prostheses and be able to recognize common complications on CT scans.
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