Increasing Heart Rate Decreased Actin-Myosin Interaction in Isolated Beating Rat Whole Heart

Background: Heart rate (HR) is one of the determinant factors of cardiac performance. Failing human myocardium shows negative force frequency relation, whereas normal one shows positive relation. Purpose: To test the effect of HR on actin-myosin interaction (AMI) in beating rat hearts those have negative force-frequency relation by X-ray diffraction (XRD) analysis at third-generation synchrotron facility. Methods: Seven isolated isovolumically contracting rat hearts were paced at 120, 240, and 300bpm after complete heart block, mounted so that the X-ray beam (15.0keV) passed the left ventricular (LV) free wall, and perfused with Tyrode solution bubbled with 100% O2. LV volume were adjusted through water filled thin latex balloon inserted into LV cavity so that end-diastolic LV pressure (LVP) was 0 mmHg. The amount of AMI was evaluated by the minimum value of the intensity ratio of inner (1,0) and outer (1,1) equatorial reflections (Imin) provided by anaysis of XRD. Between three different HRs, we compared the amount of AMI and LVP. We also measured frequency-dependent changes in Ca2+ transient in sliced myocardial preparations at 0.5, 1.0, and 2.0Hz. Results: In all hearts, we did not observe incomplete relaxations. As increasing HR at 120, 240, and 300bpm, LVP significantly decreased (66±18, 51±16, and 47±18mmHg, respectively) and Imin also significantly increased (0.93±0.16, 1.20±0.11, and 1.56±0.18, respectively), indicating a significant decrease of the amount of AMI. The durations of Ca2+ transient at 20% developed level at stimulating frequency of 0.5, 1.0, and 2.0Hz were significantly shortened (233±25, 206±34, and 171±28ms, respectively). Conclusion: Increasing HR reduces the AMI. Absence of incomplete relaxations indicates intact intracellular Ca2+ handling. These results may derive from shortening the period of Ca2+-myofilament interaction with increasing HR.