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Biomedical subjects

A J Paskins-Hurlburt

Publications and source records attributed to A J Paskins-Hurlburt.

10 recordsLinked to original sources

"Tissue need" and limb collateral arterial growth. Skeletal contractile power and perfusion during collateral development in the rat.

Among the factors that might influence collateral arterial growth after arterial occlusion, the capacity to deliver blood flow in relation to metabolic need and work performance are obvious candidates. In this study in rats after superficial femoral artery ligation, we assessed collateral arterial growth (by arteriography), basal and peak limb blood flow during acetylcholine-induced vasodilation (by electronic drop counting), pressure-flow relations, and contractile power of the gastrocnemius muscle (force transduction during sciatic nerve stimulation) at intervals over 3 months after superficial femoral artery ligation. Basal and peak blood flow and muscle contractile power were clearly reduced 1 week after ligation but had returned to normal by 3 weeks. Major collateral arterial growth, however, progressed between 3 weeks and 3 months. The limb perfusion pressure-blood flow relation was still altered at 3 weeks, with blunting of the normal autoregulation, and became more normal by 3 months after superficial femoral artery ligation. Collateral arterial growth continues after blood flow adequate to maintain work performance has been restored and may reflect a response to more subtle abnormalities involving distal pressure delivery, evident in altered pressure-flow relations.

Angiography↗

Autonomy extends to the arterial supply of rapidly growing tumors. Studies on the feeder vessel to carcinoma in rat testis.

There has been longstanding interest in the characteristics of "feeder vessels" to tumors. To develop a convenient model for assessing the determinants of the responsiveness of the arterial blood supply to tumors, we assessed by arteriography the response of the spermatic artery to norepinephrine, vasopressin, and ergonovine after implantation of Walker carcinoma in the testis of the rat. Loss of response to norepinephrine of the spermatic artery supply to the tumor occurred by the fourth day of tumor growth in this model, along the entire length of the spermatic artery. As expected, there was sustained vasoconstriction of the contralateral spermatic artery to the normal testis in response to norepinephrine. Vasopressin and ergonovine exerted no effect, so that the specificity of the loss of response to norepinephrine remains unclear. The spermatic artery provides an accessible and convenient model for studying the blood supply to tumors.

Animals↗

Centripetal spread of endothelial cell mitotic activity in the artery leading to a rapidly growing tumor.

Vascular proliferation and growth have been attributed either to biophysical forces in the vessel lumen or to chemical mediators. In this study growth and endothelial cell tritiated thymidine uptake in the spermatic artery of the rat during early growth of the Walker 256 carcinoma in the testicle were examined. Testicular blood flow was measured with radioactive microspheres; radioautography following administration of tritiated thymidine was employed to define the endothelial cell labeling index; angiography was employed to assess the diameter of the spermatic artery lumen; and the mass of the artery was determined directly. Endothelial proliferation in the spermatic artery was increased on the second day, simultaneous with rather than subsequent to a significant increase in blood flow to the testicle. Moreover, endothelial cell thymidine uptake began to decline well before the blood flow through the artery reached a maximum. A gradient in endothelial cell proliferation and in lumen diameter of the spermatic artery became apparent during tumor growth; the increase in both lumen diameter and endothelial cell thymidine uptake in the spermatic artery occurred first in the portions nearest the testicle and spread centripetally throughout the length of the artery over several days. Because the spermatic artery is an end artery, without branches and without a normal change in internal diameter, and because the increase in blood flow must have occurred throughout the length of the artery at the same time, we conclude that factors other than those related to an increase in blood flow were primarily responsible for the increase in endothelial cell turnover. These observations make a chemical messenger, perhaps moving retrogradely through cell-to-cell contact, the most likely candidate as the responsible mediator.

Animals↗

Hepatic contrast agents for computed tomography: high atomic number particulate material.

We used a stepwise approach to identify, design, synthesize, and test new high atomic number particulate contrast agents that would be especially well suited for use with computed tomography (CT). Our goal was to produce extremely radiopaque compounds with highly selective biodistribution to the normal liver. In this way, dose requirements could be lessened and toxicity minimized. Suspensions of cerium, gadolinium, and dysprosium oxide particles and silver iodide colloid were tested and compared with standard agents. All four experimental agents were selectively concentrated in the reticuloendothelial systems of rats and rabbits. These compounds produced greater and longer opacification of normal livers and larger liver-to-tumor differences in rabbits with hepatic tumors than did equivalent amounts of standard, iodinated agents. Lesions as small as 5 mm were visible with CT. These experimental materials have favorable characteristics as hepatic contrast agents, but their toxicity and long term retention may limit clinical use.

Animals↗

Influence of fucoidan on the intestinal absorption of iron, cobalt, manganese and zinc in rats.

Fucoidan was extracted from the seaweed Ascophyllum nodosum with boiling water and purified by repeated precipitation steps. Increasing doses of fucoidan (1.2--200 mg) were injected together with 360 nmol 59Fe-(FeCl3) or 60Co-(CoCl2) into tied-off jejunal segments of two groups of rats fed either a normal (160 mg Fe/kg) or a low iron diet (5 mg/kg). Fucoidan together with 360 nmol 54Mn-(MnCl2) or 65Zn-(ZnCl2) was administered in the same manner in rats fed a normal diet only. Fucoidan administered in doses above 30 mg decreased the absorption of iron, cobalt, manganese and zinc in normal rats, and the absorption of iron and cobalt in iron-deficient rats. This inhibitory effect of fucoidan on the absorption of heavy metals is apparently the consequence of the formation of metal complexes which are poorly absorbed from the intestinal lumen.

Animals↗

Heavy metal particulate contrast materials for computed tomography of the liver.

Silver iodide colloid was used as a model of a particulate hepatic contrast agent for computed tomography (CT). Following intravenous administration to rabbits, approximately 90% of the injected dose was phagocytized by the liver's reticuloendothelial system, resulting in a four- to five-fold increase in the liver CT number. Suspensions of CeO2, Dy2O3, and Gd2O3 were prepared using stabilizers to prevent clumping. Particles of appropriate size for reticuloendothelial cell uptake were selected by centrifugation. Intravenous injections of the three suspensions increased the CT number of rabbit liver by approximately 30 Hounsfield units (HU: 1,000 scale) for each experimental contrast agent resulted in a minimum addition of 250 HU to the liver CT number. A linear relationship was found between the CT number and its contrast material concentration. This relationship was also tested in vitro by ashing samples of livers containing various amounts of contrast material. Standard curves of CT number versus contrast material concentration in the liver were plotted, which predicted the amount of liver enhancement obtained after contrast material injection. There may be a use for heavy metal-containing particulate materials as hepatic contrast agents, since they opacify the liver more selectively, to a higher degree, and for longer periods than the conventional biliary and urographic iodinated contrast materials.

Animals↗

The microvascular response to growth factors in the hamster cheek pouch.

Implicit in attempts to characterize and purify biologically active factors is the premise that the bioassay system employed will show a progressive increase in the response as the concentration of the responsible factor increases. We employed the hamster cheek pouch to assay the neovascularization potential of growth factors, including endothelial cell growth supplement (ECGS), epidermal growth factor (EGF), fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF). Each growth factor was applied to the system in graded concentration and two approaches used to assess neovascularization: first, direct serial inspection of the cheek pouches at 40 power; second, tritiated thymidine incorporation into endothelial cells, assessed by radioautography. PDGF induced a dose-related increase in neovascularization, with a threshold dose of 17.5 micrograms/ml and a peak, 56% response, at a PDGF concentration of 175 micrograms/ml. Progressive increases in PDGF concentration, thereafter, induced progressive reductions in the neovascularization rate. Under some conditions optimal bioassay requires serial dilutions of the assay material over a wide range.

Animals↗

Collateral arterial formation. Lymph draining ischemic kidneys contains a neovascular stimulating agent of high molecular weight.

An agent has been identified in lymph from rat kidneys rendered ischemic by partial renal artery occlusion that induces a striking neovascular response in a hamster cheek-pouch assay system. The factor has a high molecular weight, cannot be identified in lymph from normal kidneys, and is associated with a marked increase in vascularity and in endothelial cell turnover in the cheek pouch employed for assay. This factor may play an important role in the production of the collateral arterial circulation found in the presence of renal artery stenosis and renal ischemia.

Angiogenesis Inducing Agents↗