NMR STUDIES OF PHYSIOLOGY AND BIOCHEMISTRY IN CELLS, ORGANS AND ANIMALS
细胞、器官和动物生理学和生物化学的核磁共振研究
基本信息
- 批准号:6097823
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Summary of Work: We have used 31-P NMR
spectroscopy to indirectly assess angiogenesis in muscle by
evaluating tissue bioenergetic status. We have found that these
measurements are much more sensitive to tissue perfusion than are
blood pressure measurements. In addition, because they are
non-invasive, the methods can be used for human subjects, as well
as applied to longitudinal studies in experimental animals. Although
the bioenergetic state of muscle is not a direct measurement of
blood flow, increased myocellular energy charge correlates with
greater muscular endurance, and clearly represents a desirable
therapeutic endpoint. Further, direct comparisons have
demonstrated a high degree of correlation between bioenergetic
status, as determined by 31-P NMR, and blood flow as determined
by microsphere measurements. We have constructed an
experimental apparatus which permits 31-P spectra to be obtained
in electrically stimulated muscle in animals. Our experimental
protocol consists of measurement of intracellular phosphates in the
gastrocnemius muscle of the anesthetized rat at rest, during a
period of intense muscle stimulation, and during recovery from
stimulation. Initial investigations focused on the hypothesis that
neovascularization takes place more slowly and less completely in
aged animals as compared to young animals. We found that the
declines in phosphocreatine and in contraction force with exercise
are significantly more pronounced, and their recovery significantly
slower, in the older than in the younger rats. This strongly suggests
the loss of angiogenic potential with age. To study the effect of
modulators of angiogenesis, we have employed protocols for
delivery of vascular endothelial growth factor (VEGF) to the
ischemic limb. One set of experiments involved application of
VEGF three weeks prior to femoral artery resection. This was
followed by assessment of intracellular energy charge in the
gastrocnemius muscle over a period of weeks. Once again, all 31-P
NMR measurements incorporated physiologic stress in order to
probe vascular reserve. We found that VEGF acted essentially
immediately and profoundly to normalize the pattern of
bioenergetic response to muscle stimulation and recovery,
suggesting a marked increase in the rate of development of
perfusing vessels. We are in the process of correlating our NMR
spectroscopy data with direct measurement of blood flow as
derived from microsphere measurements. Protocols for MRI-based
blood flow measurements are also being developed. Neocartilage
studies by NMR imaging and spectroscopy We have also
investigated neocartilage tissue grown in a hollow fiber bioreactor
(HFBR) system which permits chondrocytes and the
three-dimensional matrix which they elaborate to be studied
longitudinally for several weeks in a non-invasive manner. We have
used this to assess the development of neocartilage from embryonic
chick chondrocytes as well as from human articular cartilage. We
have carried out detailed correlations between histology and NMR
microimages in cartilage derived from chick chondrocytes,
correlating NMR-measurable parameters with cartilage
microstructure. We have also successfully developed detailed
correlations between NMR-derived tissue properties and the results
of biochemical assays. Finally, we are currently incorporating EPR
imaging and spectroscopy into these studies, investigating
mitochondrial metabolism and local oxygen content in the
developing tissue.
工作总结:我们使用了31-P NMR
光谱学间接评估肌肉中血管生成
评估组织生物能量状态。我们发现,
测量结果对组织灌注的敏感性比
血压测量。此外,由于它们是
非侵入性,该方法也可用于人类受试者,
适用于实验动物的纵向研究。 虽然
肌肉的生物能状态不是直接测量
血流量,增加肌细胞能荷与
更大的肌肉耐力,显然代表了一个理想的
治疗终点此外,直接比较
证明了生物能量和
通过31-P NMR测定的状态和通过31-P NMR测定的血流量
通过微球测量。 我们建立了一个
能获得31-P谱的实验装置
在动物的电刺激肌肉中。我们的实验
方案由测量细胞内磷酸盐组成,
腓肠肌的麻醉大鼠在休息,在一个
强烈的肌肉刺激期,以及从
刺激. 最初的调查集中在假设,
新生血管化发生得更慢,
与年轻动物相比,老年动物。我们发现
运动时磷酸肌酸和收缩力下降
明显更明显,他们的恢复显着
老年大鼠比年轻大鼠慢。这有力地表明
随着年龄的增长血管生成能力的丧失。 探讨蛋白酶体抑制剂
血管生成的调节剂,我们已经采用了协议,
将血管内皮生长因子(VEGF)递送至
缺血肢体一组实验涉及应用
VEGF在股动脉切除术前三周。这是
然后评估细胞内的能量电荷,
几周内的腓肠肌。再一次,所有31-P
NMR测量结合了生理应力,
探测血管储备。我们发现VEGF的作用本质上是
立即和深刻地规范模式,
对肌肉刺激和恢复的生物能响应,
这表明,
灌注血管 我们正在把核磁共振
直接测量血流的光谱数据,
来自微球测量。基于MRI的协议
血流测量也正在开发中。新软骨
通过核磁共振成像和光谱学的研究,
研究了在中空纤维生物反应器中生长的新软骨组织
(HFBR)系统,其允许软骨细胞和软骨细胞之间的相互作用。
他们精心设计的三维矩阵
以非侵入性方式纵向地持续几周。我们有
用它来评估胚胎软骨的发育,
鸡软骨细胞以及人关节软骨。 我们
进行了组织学和核磁共振之间的详细关联
来自鸡软骨细胞的软骨的显微图像,
将NMR可测量参数与软骨相关联
微观结构我们还成功地开发了详细的
NMR衍生的组织性质与结果之间的相关性
生物化学分析。最后,我们目前正在纳入EPR
成像和光谱学到这些研究中,调查
线粒体代谢和局部氧含量
正在发育的组织。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Richard Spencer其他文献
Richard Spencer的其他文献
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{{ truncateString('Richard Spencer', 18)}}的其他基金
Accurate Quantification in Physiologic Phosphorus MR Spectroscopy
生理磷 MR 光谱的准确定量
- 批准号:
7964093 - 财政年份:
- 资助金额:
-- - 项目类别:
Improving Sensitivity and Specificity of Parametric MRI Assessment of Cartilage
提高软骨参数 MRI 评估的灵敏度和特异性
- 批准号:
7964089 - 财政年份:
- 资助金额:
-- - 项目类别:
Anabolic Interventions in Engineered Cartilage and Degenerative Joint Disease
工程软骨和退行性关节疾病的合成代谢干预
- 批准号:
7964090 - 财政年份:
- 资助金额:
-- - 项目类别:
Accurate Quantification in Physiologic Phosphorus MR Spectroscopy
生理磷 MR 光谱的准确定量
- 批准号:
8736647 - 财政年份:
- 资助金额:
-- - 项目类别:
Magnetic Resonance Analysis of Connective Tissue and Muscle
结缔组织和肌肉的磁共振分析
- 批准号:
8335965 - 财政年份:
- 资助金额:
-- - 项目类别:
Advanced magnetic resonance imaging of the human brain in normative aging, cognitive impairment, and dementia
人类大脑在正常衰老、认知障碍和痴呆症中的先进磁共振成像
- 批准号:
10913064 - 财政年份:
- 资助金额:
-- - 项目类别:
Magnetic Resonance Analysis of Connective Tissue and Muscle
结缔组织和肌肉的磁共振分析
- 批准号:
7732353 - 财政年份:
- 资助金额:
-- - 项目类别:
Advanced magnetic resonance imaging of the human brain in normative aging, cognitive impairment, and dementia
人类大脑在正常衰老、认知障碍和痴呆症中的先进磁共振成像
- 批准号:
10688802 - 财政年份:
- 资助金额:
-- - 项目类别:
Accurate Quantification in Physiologic Phosphorus MR Spectroscopy
生理磷 MR 光谱的准确定量
- 批准号:
10688868 - 财政年份:
- 资助金额:
-- - 项目类别:
Multicompartment quantification of tissue in vitro and in vivo with magnetic resonance imaging and spectroscopy
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- 批准号:
10252565 - 财政年份:
- 资助金额:
-- - 项目类别:
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