Increasing Preload Reduced Actin-Myosin Interaction in Isolated Beating Rat Whole Heart Under Hypoxia

摘要

Background: Hypoxia reduces cardiac contrac-tile performance. However, there is no direct observation on how preload affects the actinmyosin-interaction (AMI) in beating hearts during hypoxia. Purpose: The aim of this study is to investigate this theme using X-ray-diffraction (XRD) analysis at a third-generation synchrotron radiation facility. Methods: Eight isolated isovolumically contracting rat hearts were paced at 120 bpm after complete heart block, mounted so that the X-ray beam (15.0 keV) passed the deeper layer of left ventricular (LV) free wall, and perfused with Tyrode solution bubbled with 100%O_2(Normo) or 100%N_2(Hypo). We record-ed XRD patterns and LV pressure (LVP) at end-diastolic LVP (EDP) of 0 and 20 mmHg. Results: Under Normo, increasing EDP significantly increased the developed-LVP (EDPO: 104±26mmHg vs. EDP20: 141±25mmHg, p<0.01). Under Hypo, developed LVP and its duration did not show significant dif-ferences compared with those in Normo. However, increasing EDP under Hypo significantly decreased developed LVP (72±13mmHg vs. 96±16mmHg, p<0.01). The minimum value of the (l,0)/(l,l) intensity ratio (Imin) provided by the XRD ana-lysis was used as an index of AMI. Imin showed a significantly negative correlation with developed LVP regardless of Normo or Hypo. The diastolic myosin filament lattice spacing (MFL) calculated from the diffraction angle of the (1,0) equatorial reflection would be reduced by increasing EDP. In contrast to a significantly positive MFL-lmin correlation under Normo, we observed the significantly negative MFL-lmin correlation under Hypo. We confirmed that the duration of Ca~2+ transient was slightly longer but the amplitude of Ca~2+ transient was unchanged under Hypo. Conclusion: These novel findings suggest that under Hypo the probability of AMI decreases even though the MFL was reduced with increasing preload. This is an underlyingmechanism for reduced cardiac contrac-tile performance under hypoxia.