Journal
BIOPHYSICAL JOURNAL
Volume 104, Issue 5, Pages 1065-1072Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2013.01.037
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Funding
- Access to Major Research Facilities Programme (Australian Nuclear Science and Technology Organisation, AMRFP) [AS-IA101]
- Ministry of Health, Labour and Welfare
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20590242, 23650213, 23249038]
- National Health and Medical Research Council (NHMRC) Program [546272]
- Grants-in-Aid for Scientific Research [23249038, 23650213, 20590242] Funding Source: KAKEN
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Diabetes is independently associated with a specific cardiomyopathy, characterized by impaired cardiac muscle relaxation and force development. Using synchrotron radiation small-angle x-ray scattering, this study investigated in the in situ heart and in real-time whether changes in cross-bridge disposition and myosin interfilament spacing underlie the early development of diabetic cardiomyopathy. Experiments were conducted using anesthetized Sprague-Dawley rats 3 weeks after treatment with either vehicle (control) or streptozotocin (diabetic). Diffraction patterns were recorded during baseline and dobutamine infusions simultaneous with ventricular pressure-volumetry. From these diffraction patterns myosin mass transfer to actin filaments was assessed as the change in intensity ratio (I-1,I-0/I-1,I-1). In diabetic hearts cross-bridge disposition was most notably abnormal in the diastolic phase (p < 0.05) and to a lesser extent the systolic phase (p < 0.05). In diabetic rats only, there was a transmural gradient of contractile depression. Elevated diabetic end-diastolic intensity ratios were correlated with the suppression of diastolic function (p < 0.05). Furthermore, the expected increase in myosin head transfer by dobutamine was significantly blunted in diabetic animals (p < 0.05). Interfilament spacing did not differ between groups. We reveal that impaired cross-bridge disposition and radial transfer may thus underlie the early decline in ventricular function observed in diabetic cardiomyopathy.
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