The length‐dependent activation of contraction is equally impaired in impuberal male and female rats in monocrotaline‐induced right ventricular failure

Abstract

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.

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae

“…; Lookin et al . ). We note that comparable results of normal active stress production have been reported in isolated RV trabeculae (Kogler et al .…”

“…; Lookin et al . ), and higher active stress in isolated permeabilised cardiomyocytes of RV tissue from PAH patients (Rain et al . ).…”

“…; Lookin et al . ), and (iv) decreased expression of the sarcoplasmic reticulum Ca 2+ ‐ATPase (Kogler et al . ; Hardziyenka et al .…”

Length-Dependent Activation of Contractility and Ca-Transient Kinetics in Auxotonically Contracting Isolated Rat Ventricular Cardiomyocytes

“…In contrast to length-dependent prolongation of the isometric twitch in healthy rat myocardium (Kentish and Wrzosek, 1998;Janssen et al, 2002;Lookin et al, 2015), the timing characteristics of auxotonic twitch/Ca-transient revealed moderate or minor SL-dependence (for SL = 1.8-1.95 μm) under any experimental condition. This might be closely related to the progressively increased amplitude of auxotonic shortening in a stretched cell and the enhanced shorteninginduced attenuation and acceleration of the twitch (Hanft et al, 2008;Iribe et al, 2014).…”

“…For instance, if a putative Ca-TnC interaction is evaluated during a complete twitch, the integral magnitude of the bump is more reliable vs. the bump amplitude, which reflects a momentary Ca-TnC interaction. A promising finding of this study is that a rate of Ca 2+ utilization by TnC in auxotonically contracting cells, indirectly obtained from the bump time-to-peak value, shows rather the opposite length-dependence compared to isometrically contracting muscles (Lookin et al, 2015;Lookin and Protsenko, 2019). This is very likely attributed to the shortening-induced inactivation of contraction: increased amplitude of auxotonic shortening in a pre-stretched cell induces more inactivation and faster release of Ca 2+ from TnC.…”