IN VIVO MURINE CARDIAC ENERGY METABOLISM AND FUNCTION

高能磷酸(HEP)代谢为正常心脏提供能量 收缩功能，是心肌细胞生存所必需的。虽然 令人兴奋的心血管病理转基因小鼠模型现已问世 ，以前不可能对两者进行非侵入性评估 心脏能量代谢和收缩能力及其调节 生理状况，由于心脏尺寸较小(心脏重量 70-200毫克)和高心率(-600次/分钟)。我们在这里描述第一个 论证联合无创性手术可行性的研究 高分辨率磁共振(MR)图像引导心脏31P波谱I 老鼠。这项建议旨在进一步优化这些磁共振成像和光谱分析 技术，以便提供可靠、可靠的非侵入性检查 野生型和大鼠在体心脏能量代谢和功能的研究 转基因小鼠的生理心率。我们还建议使用这些 联合技术评估最近描述的两个转基因模型 高血压和正常血压肥厚。具体目标是：目标1： 优化31P和1H磁共振波谱联合成像方法 中国人心脏HEP和功能正常年龄相关范围的测定 生理条件下的小鼠，目标2：在体内开发和实施一种 负荷试验用于评估小鼠心脏代谢和收缩储备 3：检验由以下原因引起的初级代谢异常 切除GLUT4转运子导致心脏反常增加 并检验解释潜在机制的两个假说。 考虑到这一已证实的观察，目标4：检验以下假设 高血压肥厚与ATP利用率增加，原因是 消融内皮源性一氧化氮(ENOS)基因(与 正常血压的GLUT4核肥大)，随着时间的推移发展减少 能量储备和收缩功能障碍。这是第一个非侵入性工具 研究心脏结构、收缩功能和生物能量学 一次检查中的生理状况对心血管疾病将是无价的。 研究人员希望研究转基因的生理学意义 在老鼠身上的操控。它还将允许我们测试特定的新陈代谢 两种不同肥大模型的假说。

High-energy phosphate (HEP) metabolism fuels normal cardiac contractile function and is essential for myocellular viability. Although exciting transgenic murine models of cardiovascular pathology are now available, it has not been previously possible to noninvasively assess both cardiac energy metabolism and contractility or their regulation under physiologic conditions, due to the small cardiac dimensions (heart weights 70-200 mg) and high heart rates (-600/min) of mice. We describe here the first studies demonstrating the feasibility of doing combined non-invasive high-resolution magnetic resonance (MR) image-guided cardiac 31P spectroscopy I mice. This proposal aims to further optimize these MR imaging and spectroscopy techniques in order to provide a robust, reliable non-invasive exam for studying in vivo cardiac energy metabolism and function in wild-type and transgenic mice at physiologic heart rates. We also propose using these combined techniques to evaluate two recently described transgenic models of hypertenisve and normotensive hypertrophy. The specific aims are: Aim 1: To optimize combined 31P MR Spectroscopic and 1H MR imaging methods and to determine the normal age-associated ranges of cardiac HEP's and function in mice under physiologic conditions, Aim 2: To develop and implement an in vivo stress test for assessing murine cardiac metabolic and contractile reserve, Aim 3: To test the hypothesis that the primary metabolic abnormality resulting from ablation of the GLUT4 translocator results in a paradoxical increase in cardiac PCr/ATP ratio, and to test two hypotheses explaining potential mechanisms accounting for this confirmed observation, Aim 4: To test the hypothesis that hypertensive hypertrophy with increased ATP utilization, resulting from ablation of the endothelial-derived nitric oxide (eNOS) gene (in contrast to the normotensive hypertrophy of GLUT4 nulls), over time develops decreased energy reserve and contractile dysfunction. This first non-invasive tool for studying cardiac structure, contractile function, and bioenergetics under physiologic conditions in a single exam will be invaluable for cardiovascular investigators wishing to study the physiologic significance of transgenic manipulations in mice. It will also allow us to test specific metabolic hypotheses in two distinct hypertrophic models.