title: Myofilament calcium sensitization delays decompensated hypertrophy differently between the sexes following myocardial infarction.
abstract: Contractile dysfunction is common to many forms of cardiovascular disease. Approaches directed at enhancing cardiac contractility at the level of the myofilaments during heart failure (HF) may provide a means to improve overall cardiovascular function. We are interested in gender-based differences in cardiac function and the effect of sarcomere activation agents that increase contractility. Thus, we studied the effect of gender and time on integrated arterial-ventricular function (A-V relationship) following myocardial infarction (MI). In addition, transgenic mice that overexpress the slow skeletal troponin I isoform were used to determine the impact of increased myofilament Ca(2+) sensitivity following MI. Based on pressure-volume (P-V) loop measurements, we used derived parameters of cardiovascular function to reveal the effects of sex, time, and increased myofilament Ca(2+) sensitivity among groups of post-MI mice. Analysis of the A-V relationship revealed that the initial increase was similar between the sexes, but the vascular unloading of the heart served to delay the decompensated stage in females. Conversely, the vascular response at 6 and 10 wk post-MI in males contributed to the continuous decline in cardiovascular function. Increasing the myofilament Ca(2+) sensitivity appeared to provide sufficient contractile support to improve contractile function in both male and female transgenic mice. However, the improved contractile function was more beneficial in males as the concurrent vascular response contributed to a delayed decompensated stage in female transgenic mice post-MI. This study represents a quantitative approach to integrating the vascular-ventricular relationship to provide meaningful and diagnostic value following MI. Consequently, the data provide a basis for understanding how the A-V relationship is coupled between males and females and the enhanced ability of the cardiovascular system to tolerate pathophysiological stresses associated with HF in females.
authors.affiliation: Department of Medicine, Section of Cardiology, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Krystyna M
authors.initials: KM
authors.lastname: Shioura
authors.forename: Mariam
authors.initials: M
authors.lastname: Farjah
authors.forename: David L
authors.initials: DL
authors.lastname: Geenen
authors.forename: R John
authors.initials: RJ
authors.lastname: Solaro
authors.forename: Paul H
authors.initials: PH
authors.lastname: Goldspink
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002302:Cardiac Output / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D012727:Sex Characteristics; D013318:Stroke Volume / Q000502:physiology; D019210:Troponin I / Q000235:genetics; D014655:Vascular Resistance / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D020033:Protein Isoforms; D019210:Troponin I; D002118:Calcium