Parathyroid perfusion

They obtained a prompt systemic hypocalcemic response, while cross-transfusion of the parathyroid venous plasma to another sheep was followed by a sharp fall in its systemic blood calcium also. These authors considered that the negative results obtained by Copp and Henze (C16) and by Foster et al. (F4) in their parathyroid perfusions might have arisen because there was insuflScient functional parathyroid tissue to give a measurable response, perhaps from effects of anesthesia and of surgical trauma. 

Clinical signs of chronic renal failure primarily include (1) edema due to reduced renal perfusion leading to stimulation of the renin-angiotensin system, which stimulates aldosterone secretion leading to retention of sodium and water, (2) hypocalcemia with compensatory parathyroid activity and osteodystrophy, and (3) reduced red blood cell counts due to decreased synthesis of erythropoietin as a result of damage to the juxtaglomerular cells. 

Daugaard H, Eg ord M, Olgaard K. Influence of calcium on the metabolism of intact parathyroid hormone by isolated perfused rat kidney and Ever. Endocrinology 1990 126 1813-20. 

Recently, Care et al. (C6) have completed a more extensive investigation into the possible parathyroid origin of calcitonin. Hypercalcemic perfusion of one superior parathyroid gland in seven conscious sheep... 

Fig. 1. The effect on the systemic plasma calcium concentration of hypercalcemic perfusion of a parathyroid gland in a conscious, thyroidectomized sheep, followed by drainage (D) of the perfused parathyroid venous blood from the animal. The vertical lines represent the standard error. [From Care et al. (C6).]...

The extraction procedures used for thyrocalcitonin preparation have been applied to many other tissues, in a search for further hypocalcemic agents. Hirsch et al. (H4) were unable to demonstrate hypocalcemic activity in extracts of ox thymus, rat pituitary, or rat parathyroid. Rat liver, kidney, and salivary gland likewise yielded inactive extracts on assay in the rat. Gudmundsson et al. (G4) found no significant activity in pig liver, bovine parathyroid, or kidney. Extracts of dog lung, kidney, myocardium, skeletal muscle, spleen, brain, liver, and pancreas, when prepared by methods that yield potent extracts from the thyroid, failed to demonstrate hypocalcemic activity (CIO). Extracts of sheep liver and of gluteal muscle showed no activity in the sheep, and high-calcium perfusion of the thymus, isolated from parathyroid tissue, produced no... 

The earlier evidence for a second parathyroid hormone (calcitonin) cannot be said to have been either satisfactorily established or finally disproved. Conflicting reports on the systemic effects of separate perfusions of thyroid and of parathyroid glands, and on the presence or otherwise of consistent biphasic effects on plasma calcium when extracts of the parathyroid gland are injected, have contributed to the atmosphere of uncertainty. There are, however, some observations that cannot be readily explained solely on the basis of a thyroid origin for the hypocalcemic principle, notably the effects of cross-transfusion of parathyroid venous plasma in the sheep and the impaired tolerance to infused calcium that follows parathyroidectomy without thyroidectomy. 

Care et al. (C9) have demonstrated that perfusion of the isolated goat parathyroid gland with blood containing an elevated magnesium concentration suppresses the secretion of parathormone in a manner similar to perfusion with hypercalcemic blood. Extension of these studies to the perfusion of pig thyroid with hypermagnesemic blood, however, did not affect the systemic plasma calcium level. It was also shown that per-... 

Hypocalcemic perfusion of the pig thyroid in situ results in a slight rise in the systemic blood calcium level, which might be caused by a shutting-off of thyrocalcitonin secretion (C5). The normal level of thyrocalcitonin output might depend on the prevailing level of secretion of parathyroid hormone this possibility is supported by the observation that hypocalcemic perfusion of the thyroid in parathyroidectomized pigs was unaccompanied by the rise in systemic plasma calcium observed in intact animals. Until sensitive immunoassay procedures become more widely available, however, it is difficult to be sure whether or not thyrocalcitonin is secreted under resting conditions in the intact animal. A preliminary report of a radioimmunoassay technique for thyrocalcitonin, by Arnaud and Littledyke (A5), indicates that all plasma samples examined contained detectable thyrocalcitonin, and that thyroidectomy resulted in a decrease in thyrocalcitonin levels below those found in normal animals. 

Apart from variations in the response of different animal species to thyrocalcitonin injections or infusions, already described, different species might vary widely in the degree of hypercalcemia necessary to stimulate secretion of thyrocalcitonin. Care et al. (C6) reported that hypercal-cemic perfusion of the sheep thyroid produced a hypocalcemic response similar in magnitude to that obtained by Foster et al. (F4) during hyper-calcemic perfusion of the thyroid and superior parathyroid in a goat of... 

C16. Copp, D. H., and Henze, K. G., Parathyroid origin of calcitonin—evidence from perfusion of sheep glands. Endocrinology 76, 49-55 (1964). 

The secretion of the parathyroid glands is probably controUed by die concentration of ionic calcium concentration in the tissue fluid. Artificial elevation of plasma calcium suppresses the parathyroids (H12, K5, N5), and parathyroid size varies inversely with the level of plasma calcium (HI, S6). Part and Luckhardt (P3) demonstrated an increase in parathyroid hormone secretion in response to the perfusion of parathyroid glands with fluids of low calcium concentration. Talmage s osteoclast count, which is believed to measure parathyroid activity, rises in response to rapid removal of calcium from the extracellular fluid of intact rats (T2). The precise ionic calcium levels which stimulate and suppress the parathyroids are not known, but calcium infusions suggest that parathyroid suppression occurs when total plasma calcium rises above about 11 mg/100 ml. Stimulation probably occurs when the concentration falls below about 9 mg/100 ml. 

The addition of heparin to the isolated rat diaphragm previously loaded with rubidium 86 results in change of the inflow of rubidium . Heparin has a permeabilizing action which appears to be due to mobilization of bound potassium and this can be related to a reduction of calcium in the perfusion solution. Karasek and Mourek.i conclude that heparin depresses oxidative processes through an effect on cell permeability it is possible that it adsorbs certain substances such as potassium chloride or acetylcholine. In extracorporeal dialysis , heparin causes an apparent decrease of 60 per cent in plasma calcium concentration. Heparin also forms a chelate-like compound with calcium ions " . This process is usually unimportant as heparin absorbs a maximum of only 5 per cent of its weight of calcium, but with intradermal, intramuscular or subcutaneous administration, heparin may deplete the capillary walls of calcium and cause them to become fragile. Heparin alsc decreases wound strength 6-14 days after operation in some experiments and may delay the union of fractures in bone repair . Heparin, but not chondroitin sulphate or hyaluronic acid, in tissue culture increases the amount of bone resorption in the presence of suboptimal concentrations of parathyroid extracts, and thus may be a cofactor in bone metabolism. ... 

Fig. 342. Lipogenic pigmentation in the parathyroid gland parenchymal cells (block 1911) of an unmedicated old Wistar rat (No.l breeder S.Ivanovas, Kissleg/Allgau). Under pentobarbital anaesthesia (30 mg/kg), the animal was perfused from the abdominal aorta with 2.5 % glutaraldehyde in 0.1 M sodium cacodylate buffer (pH 7.4). Postfixation with 1 % osmium tetroxide in sodium cacodylate buffer. Embedded in Epon 812 and sectioned at 50 nm. Lead citrate and uranyl acetate. Film 639-37...

Conclusive evidence for the control mechanism of parathormone secretion has been obtained by experiments done on the thyroid-parathyroid preparation of the dog. In these experiments, the thyroid-parathyroid preparation is first perfused with calcium deficient blood, then the perfusate is injected intravenously to parathyroidectomized dogs. The injected dogs develop hypercalcemia and phosphaturia, indicating that perfusion of the parathyroids with low calcium levels stimulates parathormone secretion. It is not known whether the stimulated parathyroid synthesizes new hormone or releases existing parathormone. However, the crude parathyroid extracts of parathyroid-thyroid perfused with low calcium levels contained a new factor separable from the classical parathormone. The reciprocal experiment in which calcium-rich blood is used to perfuse the thyroid-parathyroid preparation leads to hypocalcemia in the animals injected with the perfusate. 

---