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Title: The effects of vasoactive substances and calcium regulating hormones on bone blood flow and strontium clearance in the rat
Author: Cochrane, E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1990
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It is now believed that there is a significant association between skeletal blood flow and the movement of calcium and other ions in and out of bone. Bone is capable of regulation of this flow but this is affected by factors such as physiological stimuli, arterial blood pressure and humeral agents which can override this ability. The effects of vasoactive substances, noradrenaline and ATP and calcium regulating hormones, PGE2, PTH and calcitonin on bone blood flow and strontium clearance have been investigated in an experimental model in the rat. In order to proceed with this work smaller studies were undertaken to develop and validate the technique used to measure flow and clearance. These included;1. validation of choice of cannulation site,2. investigation of rat bone haematocrit,3. determination of an appropriate withdrawal rate. Cannulation of the carotid artery and insertion of the cannula into the ventricle provides adequate mixing of the microspheres, withdrawal at the caudal artery (0.197ml/min) an adequate reference sample. The haematocrit work suggests that a correction factor may be required when using this procedure as the haematocrit of rat bone is consistently less than that of the caudal artery. However the results in this study are too variable to incorporate this finding in the bone blood flow and clearance work. The main study involved the use of radioactive microspheres to estimate bone blood flow and strontium-85 for strontium clearance in rats weighing approximately 350 grammes. This involved cannulation of the carotid and caudal arteries with injection of the agent and microspheres vis the carotid and reference blood samples withdrawn from the caudal. For each animal blood flow and strontium clearance in bone, blood perfusion pressure and blood flow in muscle were measured and from these strontium extraction and vascular resistance in bone and muscle were calculated. Infusion of noradrenaline resulted in a significant decrease in blood flow and an increase in blood pressure, while ATP cuased a significant decrease in only blood pressure. Neither agent had any effect on strontium clearance. Parathyroid hormone produced a significant decrease in both strontium clearance and blood pressure with a general trend of decreasing blood flow with increasing concentration. While administration of PGE2 significantly reduced blood flow, pressure and strontium clearance. Calcitonin had no effect on any variable apart from strontium clearance. This was dependent on the degree of change at the 5OU. dose which represented an increase of 30% while at the other dose clearance remained relatively constant. With all groups, there was a significant relationship between blood flow and strontium clearance, but the slope of the regression was significantly different for PGE2 only. This shows that PGE2 was having a direct effect on bone independent of its effect on blood flow. In the normal untreated animal a change in flow is reflected by a change in clearance, indicating that some vascular mechanism is involved. The PTH, ATP, calcitonin and noradrenaline animals all demonstrate this same pattern suggesting that these also act through some vascular mechanism, either directly or indirectly. But PGE2 has a direct effect on strontium clearance suggesting indicating that some other mechanism may be involved, possibly through a non vascular effect. This would therefore invalidate the use of clearance measurements as estimtes of bone blood flow.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available