Hypertrophy of existing myocytes occurs with cardiac enlargement in the adult mammal. Although a variety of structural changes have been found with cardiac hypertrophy, changes in myocyte geometry have been difficult to determine in whole sectioned tissue.
The specific aim of this project is to determine if changes in myocyte geometry reflect the type of cardiac workload. The hypothesis is that cell length is primarily affected with volume overload, whereas changes in cell diameter are more evident in pressure overload. Isolated myocytes will be used to compare differences in cell length, width and volume from hyperthyroid, propranolol treated hyperthyroid, control, propranolol treated, hypertensive (DOCA-salt), volume overloaded (arteriovenous fistula) and exercised rat hearts. Cell length will be measured directly from isolated myocytes. Cell volume will be determined with a Coulter Chanelyzer system. To validate this technique, myocyte cross-sectional areas obtained from the quotient of isolated cell volume (Coulter Channelyzer) and isolated cell length will be compared to corrected cross-sectional area values obtained from tissue sections. Hyperthyroidism produces an increased cardiac output due primarily to tachycardia. Normalization of heart rate in hyperthyroid rats with propranolol should produce a model of increased stroke volume for comparison with the hyperthyroid, volume overloaded (a-v fistula), and hypertensive groups. These models of pathological hypertrophy will be compared to physiological hypertrophy induced by swimming exercise in another group of animals. Additionally, the cellular changes after reversal of hypertension, volume overload (a-v fistula), and hyperthyroidism will be evaluated to determine if myocytes are reduced to a normal size, or if they remain enlarged (normal heart size with larger myocytes would indicate cell death). Hearts from each group will also be perfusion fixed for morphometric evaluation of capillary supply, cellular composition, and myocyte mitochondrial/myofibril ratio. In addition, hydroxyproline concentrations will be measured in each group to determine the effects of this protocol on connective tissue content. The results of this study should provide important new information regarding the effects of different types of workload on the structural reorganization of the heart.
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