Department of Medicine, Section of Cardiology, University of Illinois at Chicago, Chicago, Illinois, USA.
Am J Physiol Regul Integr Comp Physiol. 2011 Feb;300(2):R361-8. doi: 10.1152/ajpregu.00321.2010. Epub 2010 Nov 24.
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.
收缩功能障碍是许多心血管疾病的共同特征。在心力衰竭 (HF) 期间，针对肌丝水平增强心肌收缩力的方法可能提供改善整体心血管功能的手段。我们对心脏功能的性别差异以及增加收缩力的肌节激活剂的影响感兴趣。因此，我们研究了性别和时间对心肌梗死后整合的动静脉功能 (A-V 关系) 的影响。此外，还使用过度表达慢骨骼肌肌钙蛋白 I 同工型的转基因小鼠来确定 MI 后肌丝 Ca2+敏感性增加对心肌功能的影响。基于压力-容积 (P-V) 环测量，我们使用心血管功能的衍生参数来揭示 MI 后各组小鼠的性别、时间和增加的肌丝 Ca2+敏感性的影响。A-V 关系的分析表明，两性之间的初始增加相似，但心脏的血管卸载延迟了女性的代偿失调阶段。相反，MI 后 6 周和 10 周时男性的血管反应导致心血管功能持续下降。增加肌丝 Ca2+敏感性似乎为改善雄性和雌性转基因小鼠的收缩功能提供了足够的收缩支持。然而，改善的收缩功能在雄性中更为有益，因为血管反应的同时导致 MI 后雌性转基因小鼠的代偿失调阶段延迟。这项研究代表了一种整合血管-心室关系的定量方法，为 MI 后提供有意义和诊断价值。因此，这些数据为理解 A-V 关系如何在男性和女性之间耦合以及女性心血管系统耐受与 HF 相关的病理生理应激的增强能力提供了基础。
