This thesis is a report of a study on bone blood flow in adult dogs and rabbits. The effects of epinephrine and some other factors were investigated: (1) by direct observation of bone bleeding through drill holes and in the medullary cavity; (2) by measurement of changes in intramedullary pressure of long bones; and (3) by quantitative estimation of bone blood flow by the Fick principle. A technique was developed for measurement of the initial Sr⁸⁵ clearance by bone by dividing the bone uptake of Sr⁸⁵ by the integrated average concentration of Sr⁸⁵ in the systemic arterial blood. This clearance will represent at least a minimum bone blood flow. It should be equivalent to effective bone blood flow on the assumption that bone clears Sr⁸⁵ rapidly and almost completely from blood circulating through bone by exchange with calcium in bone, just as PAH clearance gives a measure of effective renal blood flow. The normal rate of bone blood flow in adult rabbits by the rate of initial Sr⁸⁵ clearance appeared to be at least 16 ml. per minute per 100 gm. of fresh bone which would represent about 5-10% of the resting cardiac output. The average intramedullary pressure of the femur in dogs was about 55 mm Hg, about 1/2 of the systolic systemic arterial blood pressure. Epinephrine caused a profound reduction in bone blood flow as indicated by reduced bone bleeding, a marked (65%) reduction in intramedullary pressure of bone marrow in the presence of persistently increased systemic blood pressure, and a significant (75%) reduction in Sr⁸⁵ clearance by bone. The changes in intramedullary pressure and in Sr⁸⁵ clearance by bone thus appear to correlate very well with changes in bone blood flow. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Hormonal regulation of growth and of macromolecular synthesis in a variety of tissues is now well established. This dissertation addresses the role of circulating hormones, particularly epinephrine, in the physiological regulation of myocardial mass. Following hemodynamic overload of the right ventricle, the circulating epinephrine concentration increased significantly, and blood epinephrine exhibited a significant positive correlation with myocardial mass. Further, a nonspecific β-antagonist, propranolol, blocked the usual myocardial hypertrophy that occurs in response to hemodynamic overload. These studies strongly implicate β-adrenoceptors in the regulation of myocardial mass. Theoretically, a circulating myocardial trophic hormone should result in biventricular hypertrophy. We found that a selective hemodynamic overload of the right ventricle produced significant hypertrophy of both the right and the left ventricles. A biochemical marker of β-receptor activity, ornithine decarboxylase, a key regulatory enzyme in growth, showed elevated activity in both the right and left ventricles following hemodynamic overload of the left ventricle. To further evaluate possible circulating myocardial trophic hormones, we studied hypertrophy in a donor heart transplanted into the abdomen of a recipient animal. Myocardial hypertrophy of the donor heart occurred independently of innervation and of any hemodynamic parameters. Alteration in myocardial mass paralleled the extent of β-receptor activity as assessed by the administration of exogenous β-agonists or by the modulation of β-receptor number by denervation. β-Receptor activity was assessed by the ability of isoproterenol to elevate ornithine decarboxylase activity in either the donor or the recipient heart. Finally, alterations in the levels of circulating endogenous hormones in response to pulmonary artery banding of the recipient rat heart resulted in concomitant hypertrophy of both recipient and donor hearts. These studies suggest that myocardial mass is regulated by the concentration of circulating epinephrine through its effect on myocardial β-adrenoceptors. This effect may be modified by the level of other hormones such as thyroid hormone, but does not appear to be altered to any extent by myocardial innervation or by the alteration of hemodynamic parameters except as they affect the circulating level of catecholamines.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

The effect of intravenous injection of epinephrine on blood volume, red cell volume, and hematocrit was studied. The effects of such a challenge on anesthetized intact, awake intact, and awake splenectomized rats were compared.The epinephrine challenge caused significant increases in the hematocrits of anesthetized animals and highly significant increases in the awake intact animals. No other statistically significant changes occurred in the parameters studied.The results indicate that the rat sequesters red blood cells in the spleen which are released with an appropriate challenge. This release response is attenuated by sodium pentobarbital anesthesia. It was not possible to detect an increase in blood volume or in red cell volume by using Cr51 tagged cells as tracers.Ball State UniversityMuncie, IN 47306

The extreme elevation in plasma levels of norepinephrine (NE) and epinephrine (EP) which occurs during forced diving of ducks (Anas platyrhynchos) was studied before and after denervation of the adrenal glands. Elevated PaCO₂, decreased arterial pH, decreased blood glucose as well as low PaO₂ have been described as causal factors in this response. These variables, as well as blood pressure, heart rate and breathing frequency were measured in ducks dived after breathing air or pure 0₂ to clarify and quantify the mechanism involved and its physiological function. Both NE and EP concentration increased by up to 2 orders of magnitude in the 4 minute dive period, but by a significantly lesser amount if the duck breathed 0₂, before the dive. While pH and PaCO₂ were well correlated with the changes in plasma NE and EP levels during both air and 0₂ dives, both pH and PaCO₂ changed more in the 0₂ trials, indicating that they are not the primary cause of the response. Plasma glucose levels were variable. PaO₂ values less than normal correlated well with increasing NE and EP concentrations, but at high PaO₂s, there was no correlation, suggesting that hypoxia is the permissive state for the full response. Compared with breathing air, breathing O₂ before the dive attenuated the diving bradycardia, eliminated the decrease in blood pressure normally observed during dives, and caused more extreme changes in pH, PaC0₂, and of course, PaO₂. Denervating the adrenals decreased the amounts of both catecholamines released during dives after breathing air and 0₂, EP significantly more than NE. Adrenal denervation per se did not cause a significant change in heart rate, blood pressure, arterial gas tensions, pH, or plasma glucose changes during dives although the operation caused increased variation in some of the parameters. In ducks, the cause for the catecholamine release is decreasing PaO₂ and full expression of the response is dependent on intact innervation of the adrenal gland, although there is a component that is unaffected by denervation. While possible roles for this response are discussed, the true physiological function of this response remains cast in shadows. / Science, Faculty of / Zoology, Department of / Graduate