Mouse Cardiac Physiology Core

小鼠心脏生理学核心的长期目标是巩固科学和技术 专业知识和必要的专业设备，以提供：a）标准化，高质量，适当的， 用于在小鼠中诱导慢性心力衰竭的显微外科手术;和B）体内严谨、可靠和准确 小鼠心脏生理学的评估。本计划项目补助金中提出的所有四个项目都严重依赖于 在心力衰竭小鼠模型上测试关于心肌细胞钙调节机制的假设 健康和心脏病的渠道。兴奋-收缩偶联、收缩力和心脏重构 所有这些都需要心肌细胞钙通道亚单位及其 相互作用体即使研究人员专注于研究人类功能丧失变异，转基因 小鼠对于破译基因变异的调节功能是不可或缺的。考虑到，有时， 基因型-表型关联仅在胁迫条件下得到证明，因此必须检查 转基因小鼠在基线条件下和慢性心脏病后的心脏结构和功能 应力因此，小鼠心脏生理学核心将解决三个具体目标： 1.对小鼠进行生存显微手术，以诱导慢性压力超负荷或慢性 左心室缺血性应激。这将通过横向主动脉缩窄术完成 左冠状动脉结扎。 2.通过系列研究评估实验小鼠随时间推移的体内心脏结构和功能 超声心动图 3.应用在体有创电导测定左心室压力-容积关系 导管测量。 通过简化这些基本程序和分析，小鼠心脏生理学核心将加速 我们的研究人员获得对钙通道结构和功能的宝贵见解的速度 复杂的心脏生理学和疾病。因此，我们在小鼠心脏生理学核心的工作将是 与四个单独的计划项目和人类表型核心协同。我们预计 我们的累积研究结果将确定临床相关的调节机制和结构-功能 这种关系可以促进新的治疗发展和干预。

The long-term objective of the Mouse Cardiac Physiology Core is to consolidate the scientific and technical expertise and the specialized equipment necessary to provide: a) standardized, high-quality, and appropriate microsurgery for the induction of chronic heart failure in mice; and b) rigorous, reliable, and accurate in vivo assessment of mouse cardiac physiology. All four projects proposed in this Program Project Grant rely heavily on mouse models of heart failure to test hypotheses about regulatory mechanisms of cardiomyocyte calcium channels in health and cardiac disease. Excitation-contraction coupling, contractility, and cardiac remodeling all require the intricate regulation and coordination of cardiomyocyte calcium channel subunits and their interactomes. Even as investigators focus on studying human loss of function variants, genetically modified mice are indispensable to deciphering the regulatory function of the gene variants. Given that, at times, cardiac genotype-phenotype associations are evidenced only under stress conditions, it will be imperative to examine cardiac structure and function of transgenic mice under baseline conditions and following chronic cardiac stress. As such, the Mouse Cardiac Physiology Core will address three specific aims: 1. Performing survival microsurgeries on mice to induce either chronic pressure-overload or chronic ischemic stress upon the left ventricle. This will be accomplished through transverse aortic constriction and left coronary artery ligation, respectively. 2. Assessing in vivo cardiac structure and function of experimental mice over time via serial echocardiograms. 3. Determining the left ventricular pressure-volume relationship using in vivo invasive conductance catheter measurements. By streamlining these essential procedures and analyses, the Mouse Cardiac Physiology Core will accelerate the pace at which our Investigators obtain invaluable insights into the structure and function of calcium channel complexes in cardiac physiology and disease. Thus ,our work in the Mouse Cardiac Physiology Core will be synergistic with that of the four individual program projects and the Human Phenotyping Core. We expect that our cumulative findings will identify clinically relevant regulatory mechanisms and structure-function relationships that can then facilitate novel therapeutic developments and interventions.