title: T-tubule disease: Relationship between t-tubule organization and regional contractile performance in human dilated cardiomyopathy.
abstract: Evidence from animal models suggest that t-tubule changes may play an important role in the contractile deficit associated with heart failure. However samples are usually taken at random with no regard as to regional variability present in failing hearts which leads to uncertainty in the relationship between contractile performance and possible t-tubule derangement. Regional contraction in human hearts was measured by tagged cine MRI and model fitting. At transplant, failing hearts were biopsy sampled in identified regions and immunocytochemistry was used to label t-tubules and sarcomeric z-lines. Computer image analysis was used to assess 5 different unbiased measures of t-tubule structure/organization. In regions of failing hearts that showed good contractile performance, t-tubule organization was similar to that seen in normal hearts, with worsening structure correlating with the loss of regional contractile performance. Statistical analysis showed that t-tubule direction was most highly correlated with local contractile performance, followed by the amplitude of the sarcomeric peak in the Fourier transform of the t-tubule image. Other area based measures were less well correlated. We conclude that regional contractile performance in failing human hearts is strongly correlated with the local t-tubule organization. Cluster tree analysis with a functional definition of failing contraction strength allowed a pathological definition of 't-tubule disease'. The regional variability in contractile performance and cellular structure is a confounding issue for analysis of samples taken from failing human hearts, although this may be overcome with regional analysis by using tagged cMRI and biopsy mapping.
authors.affiliation: Department of Physiology, University of Auckland, New Zealand.
authors.forename: David J
authors.initials: DJ
authors.lastname: Crossman
authors.affiliation: Department of Anatomy with Radiology, University of Auckland, New Zealand.
authors.forename: Alistair A
authors.initials: AA
authors.lastname: Young
authors.affiliation: Department of Cardiology, Auckland City Hospital, New Zealand.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Ruygrok
authors.affiliation: School of Mathematics, University of Bristol, UK.
authors.forename: Guy P
authors.initials: GP
authors.lastname: Nason
authors.affiliation: Department of Physiology, University of Auckland, New Zealand.
authors.forename: David
authors.initials: D
authors.lastname: Baddelely
authors.affiliation: Department of Physiology, University of Auckland, New Zealand.
authors.forename: Christian
authors.initials: C
authors.lastname: Soeller
authors.affiliation: Department of Physiology, University of Auckland, New Zealand; School of Physiology and Pharmacology, University of Bristol, UK. Electronic address: mark.cannell@bristol.ac.uk.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Cannell
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D012518:Sarcomeres / Q000378:metabolism; D014909:Wheat Germ Agglutinins / Q000378:metabolism; D055815:Young Adult
chemical_list: D014909:Wheat Germ Agglutinins
keywords: Contraction; Heart failure; Human; t-tubules