The length-dependent activation of contraction is attenuated in the failing myocardium of adult male rats. This pathological change is not seen in adult female rats, possibly because of a protective effect of sex hormones. The present study evaluated length-dependent changes in isometric twitch, Ca(2+) transient (CaT) and action potential (AP) in the right ventricular myocardium of impuberal healthy male and female rats (control) and in rats treated with a single injection of 50 mg/kg monocrotaline (MCT). Compared with sex-matched control rats, MCT-treated male and female rats exhibited increased right ventricular weight (134% and 142% of control, respectively), decreased left ventricular weight (72% and 79%), twitch attenuation (48.8 ± 2.7% and 57.5 ± 1.2%) and prolongation (125 ± 3% and 127 ± 2%), CaT attenuation (37.8 ± 0.4% and 39.1 ± 1.1%) and prolongation (114 ± 1% and 116 ± 1%) and AP prolongation at 90% repolarization (195 ± 2% and 203 ± 1%). The MCT-treated male rats exhibited a 50% lower integral magnitude and an approximately 25% larger time-to-peak 'bump' compared with control male rats. These parameters in MCT-treated female rats tended to show similar changes to those seen in the control female rats, with no significant difference between the two groups. In all groups, integral magnitude and time-to-peak 'bump' increased with length. In conclusion, the length-dependent activation of contraction was equally blunted in the failing right ventricular myocardium of impuberal male and female rats. This was related to changes in CaT and AP, which were similar between male and female rats. Therefore, puberty is necessary for manifestation of the protective effects of sex hormones on this remodelling.

We aim to compare the effects of stretch on isometric tension/Ca(2+) transient in the right ventricular trabeculae of control (CONT) and hypertensive (MCT, monocrotaline application) adult male and female rats. The treatment with MCT resulted in RV hypertrophy in males only. Blunted active force-length relation and substantially prolonged twitch were found in MCT-males but not MCT-females (vs same-sex CONT). Ca(2+) transient was prolonged in both MCT-treated groups but extremely so in the MCT-males. The gradual stretch resulted in a distinct "bump" on Ca(2+) transient decline in CONT and MCT-treated groups. The integral magnitude of the "bump" was unaffected by the treatment with MCT in males or females but was larger in males vs females. The rate of "bump" development was significantly slower in MCT-males. In conclusion, the sex-specific differences in the stretch-dependent regulation of [Ca(2+)] i may underlie preservation of the Frank-Starling mechanism in female rat myocardium in monocrotaline-induced pulmonary hypertension.

Heart failure is a widespread cardiac pathology with high mortality rates in humans. The therapy of heart failure offers treatment by β-receptor blockers, inhibitors of angiotensin-converting enzymes, and aldosterone antagonists, which affect systolic function.However, the use of these compounds has at least two side effects: an increased Ca 2+ concentration in the cytosol of cardiomyocytes and increased demand for oxygen. 1,2 To overcome these problems, the novel therapy is based on a selective activation of myosin. [3][4][5][6][7][8] The activator is a low-molecular substance omecamtiv mecarbil (OM) which is currently under clinical trial phase 3. 9 It specifically binds to the heavy chain of cardiac β-myosin and enhances cardiac contractility by prolongation of actomyosin interaction. [10][11][12][13] The therapeutic

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Effect of different Ca concentrations in the bathing solution [Ca] on the parameters of single isometric contraction and slow force response to stretching was studied in isolated preparations of healthy and hypertrophied myocardium of male and female Wistar rats. In all groups of experimental animals, the increase in calcium concentration was followed by a decrease in the myocardium slow response intensity. We revealed a complementary relationship between the current and medium-term systems of myocardial contractility regulation by the length of the myocardium aimed at the maintenance of the constant level during adaptation to the load. Slow responses of the hypertrophied rat heart myocardium were suppressed in comparison with those in the healthy myocardium and their intensity did not depend on animal sex.

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Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO–NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex.

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