Heart, Lung and Circulation

In Situ Measurements of Cross-bridge Dynamics and Lattice Spacing in Diabetic Rat Hearts using X-ray Diffraction

      Independent of hypertension and coronary artery disease diabetes is associated with a specific diabetic cardiomyopathy. The use of synchrotron radiation (SR) as a source for small-angle X-ray diffraction allows the assessment of myocyte cross-bridge dynamics in situ and in real time. This study aimed to investigate cross-bridge dynamics and myosin interfilament lattice spacing, in situ, in diabetic rat hearts using SR.
      Experiments were conducted at the Japanese Synchrotron, SPring-8 using anaesthetised Sprague–Dawley rats three weeks after treatment with either vehicle (control) or streptozotocin (diabetic; 65 mg/kg i.p.). Rats were thoracotomised and myocardial diffraction patterns were digitally recorded. Cardiac function was assessed simultaneously via cardiac catheterisation of the left ventricle (LV).
      Preliminary analysis of our data shows that cross-bridge cycling in the beating hearts of diabetic rats is abnormal in the diastolic phase. Furthermore, recordings obtained from the anterior and posterior walls of the LV in diabetic rats at different depths within the myocardium reveals a transmural gradient of contractile depression not observed in controls. At progressively deeper layers within the diabetic heart wall (subepicardium and endocardial layers) diastolic intensity ratio (I1,0/I1,1) is elevated 4.0–8.0 versus 2.0–3.0 in controls, and is higher than that previously reported for resting muscle or arrested hearts 3.0–3.5. This suggests that in diabetic hearts myosin heads are forced further from actin filaments during diastole than normal.
      Using synchrotron X-ray diffraction in situ, this preliminary analysis uncovers for the first time a significant impairment in the regulation of myosin head order in diabetic hearts during relaxation.