CARDIAC ATROPHY--STUDIES IN THE TRANSPLANTED HEART

心脏功是心脏大小的主要决定因素。 高血压、主动脉瓣狭窄和 甲状腺功能亢进增加心肌的工作，并导致 肥大的发展。 心脏的快速变化 RNA和蛋白质的合成介导了心脏的这种增加， 增长已经得到很好的描述。 相反，心脏萎缩， 这可能发生在心脏工作减少，热量剥夺， 甲状腺功能减退症和阿狄森氏病还没有得到很好的研究。 本研究旨在描述 大小、蛋白质含量、蛋白质合成、RNA含量和RNA 在移植心脏的新模型系统中合成。 大鼠异位心脏移植是一种血管灌注的器官 可以保持结构和功能的完整性， 长时间的。 当放置在肾下位置时 移植的心脏会自发地跳动， 外部工作。 心肌对血流动力学的反应 与移植相关的卸载是一个迅速减少， 肌肉质量. 为了进一步表征这种萎缩反应， 心肌质量变化率、总蛋白含量、肌球蛋白 含量和肌球蛋白同工酶分布。 到 探讨蛋白质含量下降的机理， 体内和体外总心脏蛋白合成率将 在移植后的不同时间进行。 的 移植的心脏模型使其具有独特的能力， 同时测量蛋白质合成参数， 原位（工作）心脏和异位（非工作）心脏。 为了确定蛋白质合成的变化是否是 改变核酸合成或内容，RNA代谢将是 研究了 在移植细胞中蛋白质合成的时间点， 心脏减少，总RNA含量，总RNA合成，总 信使RNA含量和特定mRNA种类，包括 将测量肌球蛋白mRNA，并与 工作的心。 由于成人心肌，类似于高度 中枢神经系统的分化组织不能 经历细胞分裂，它只能对压力或伤害做出反应， 细胞大小和蛋白质合成速率的变化。 的结果 这些研究我们希望能够了解 心肌对心脏收缩力变化的反应机制 工作量和调节其收缩蛋白的含量

Cardiac work is the major determinant of cardiac size. Conditions such as hypertension, aortic stenosis, and hyperthyroidism increase the work of the myocardium and lead to the development of hypertrophy. The rapid changes in cardiac RNA and protein synthesis that mediate this increase in cardiac growth have been well described. In contrast, cardiac atrophy, which can occur with decreased cardiac work, caloric deprivation, hypothyroidism and Addison's disease has not been well studied. The present studies are designed to characterize the changes in size, protein content, protein synthesis, RNA content and RNA synthesis in the novel model system of the transplanted heart. Heterotopic rat cardiac isografts are vasculary perfused organs that can maintain structural and functional integrity for prolonged periods of time. When placed in an infrarenal position the transplanted heart beats spontaneously but does essentially no external work. The myocardial response to the hemodynamic unloading associated with transplantation is a prompt decrease in muscle mass. To further characterize this atrophy response the rate of change of cardiac mass, total protein content, myosin content and myosin isoenzyme distribution will be measured. To probe the mechanism of decreased protein content, studies of in vivo and in vitro rates of total cardiac protein synthesis will be performed at various times after transplantation. The transplanted heart model allows the unique ability to simultaneously measure protein synthetic parameters in the in situ (working) heart and in the heterotopic (non-working) heart. To determine if changes in protein synthesis are a result of altered nucleic acid synthesis or content, RNA metabolism will be studied. At time points when protein synthesis in the transplanted heart is decreased, total RNA content, total RNA synthesis, total messenger RNA content and specific mRNA species including myosin mRNA will be measured and compared to the levels in the working heart. Since adult cardiac muscle, similar to the highly differentiated tissue of the central nervous system is unable to undergo cell division, it can only respond to stress or injury by changes in cell size and rates of protein synthesis. As a result of these studies we hope to be able to understand the basic mechanisms by which cardiac muscle responds to changes in workload and regulates its content of contractile proteins