Abstract
The aim of this study was to test the hypothesis that frequency‐dependent myofilament desensitization, a physiological response of healthy myocardium, is altered in hypertrophied myocardium. New Zealand White rabbits underwent pulmonary artery banding (PAB) and after 10 weeks animals were euthanized, and suitable trabeculae harvested from the right ventricle. Twitch contractions, calibrated bis‐fura‐2 calcium transients, and myofilament calcium sensitivity were measured at various frequencies. TnI and MLC2 phosphorylation status and expression levels of other proteins including titin isoforms were assessed. The force frequency response, relaxation frequency response, and calcium frequency relationships were significantly blunted, and diastolic tension increased with frequency in the PAB rabbits. Myofilament calcium sensitivity was identical at 1 Hz (pCa 6.11±0.03 vs. 6.11±0.06) but the frequency‐dependent desensitization that takes place in the sham group (delta pCa 0.14±0.06, p<0.05) was not observed in PAB animals (delta pCa 0.02±0.05). Frequency‐dependent phosphorylation of TnI occurred normally in the sham but not in PAB trabeculae. We conclude that frequency‐dependent myofilament desensitization is impaired in right ventricular hypertrophy, and may be associated with impaired TnI phosphorylation and contribute and/or be responsible for an elevation of diastolic tension.
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