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W J Angerson

Publications and source records attributed to W J Angerson.

At least 55 records · Page 3Linked to original sources
PubMed1992

Is there a relationship between regional microsphere distribution and hepatic arterial blood flow?

The relationship between hepatic arterial albumin microsphere distribution and hepatic arterial blood flow and the effects of regional angiotensin II were studied in a rat liver metastases model. Hooded-Lister rats were inoculated subcapsularly with 2 x 10(6) HSN sarcoma cells. At 20 days, hepatic arterial blood flow was measured using the reference microsphere technique. Animals then randomly received 50 microliters hepatic arterial saline or albumin microspheres (40 microns, 20 mg ml-1). Hepatic arterial blood flow measurements were then repeated at 5 min. After 5 min, animals were killed and tissues were weighed and counted in a gamma well counter. There were no significant differences between the hepatic blood flow measurements recorded before and after the control hepatic arterial saline infusion. However, regional albumin microspheres produced a significant reduction in tumour and normal liver blood flow and an 80% reduction in mean T/N blood flow ratio. Regional albumin microspheres were delivered to tumour in greater proportions (mean T/N ratio 3.89, SE 0.49) than would be expected from baseline hepatic arterial blood flow (mean T/N ratio 1.28, SE 0.22. P = 0.006). There was no correlation between T/N for baseline blood flow and albumin microsphere distribution.

Animals↗
PubMed1992

Monitoring blood flow to colorectal liver metastases using laser Doppler flowmetry: the effect of angiotensin II.

Many colorectal liver metastases are hypovascular, and their low level of perfusion is associated with limited drug uptake and poor response rates with regional chemotherapy. We have previously shown that hepatic arterial vasoconstrictors may increase drug delivery to liver tumours, but the underlying haemodynamic changes have not been defined. Using intraoperative laser Doppler flowmetry (LDF) we have assessed the effect of intraarterial angiotensin II (AI) on tumour blood flow in ten patients with colorectal liver metastases. Measurements were performed during placement of infusion catheters for regional chemotherapy. Blood flow was recorded continuously with a Periflux PF3 perfusion monitor via a probe held on the tumour surface, following hepatic arterial infusion of 15 micrograms AII over 90 s. Six patients with isolated small metastases (< 5 cm in diameter) showed increases in flow, which reached a peak at 170-240 s from the start of AII infusion, and which were closely correlated with the corresponding increase in arterial pressure (r = 0.92, P = 0.009). Of the four patients with large confluent tumour deposits, two showed smaller transient increases in flow over the first 60 s of AII infusion and two had no measurable flow response. Increased blood flow following AII infusion may increase the exposure of tumour to therapeutic agents. This study suggests that both tumour size and the effect upon systemic arterial pressure may be important determinants of the blood flow response to AII. LDF may provide useful information about the potential of AII and other vasoconstrictors to enhance targeting precision.

Angiotensin II↗
PubMed1992

Flow measurement using duplex Doppler ultrasound: haemodynamic changes in patients with colorectal liver metastases.

Duplex Doppler ultrasound has been used to make measurements of liver blood flow. The relationship between time average velocity as measured using pulsed Doppler and the true mean velocity was determined using a flow phantom. Correction factors were applied to measured time average velocities of blood in the hepatic artery and portal vein. Blood flow was calculated from the product of corrected velocities and the cross-sectional area of the vessels. There was no significant difference in total liver blood flow for patients with colorectal liver metastases when compared with controls. However, the ratio of the hepatic arterial flow to the sum of the portal and hepatic arterial flows (Doppler perfusion index, DPI) was markedly elevated (P < 0.0001) in the patients with metastases when compared with the controls. The DPI values for a third group of subjects who had undergone resection for colonic cancer but who had no proven liver metastases overlapped the values for the other two groups. When attention is paid to technique, the procedure can detect and quantify the changes in liver blood flow which occur in the presence of metastases.

Blood Flow Velocity↗
PubMed1992

Taurocholate induced gastric mucosal injuries in experimental portal hypertension.

The susceptibility of the gastric mucosa to injury by topical sodium taurocholate (40 mmol/l) in hydrochloric acid (150 mmol/l) was studied in prehepatic and cirrhotic rat models of portal hypertension. Portal venous pressure was increased in rats who had undergone partial portal vein ligation compared with rats that had undergone sham operation on days 3, 7, and 28 after operation (20.6 (0.9), 14.8 (0.8), and 11.3 (0.5) mm Hg v 7.3 (0.7), 7.3 (0.6), and 8.2 (0.2) mmHg respectively (mean (SEM)). At day 3 gastric mucosal injuries were increased in rats with partial portal vein ligation compared with sham operated rats (55.3 (9.4) vs 22.3 (10.5) mm2, p = 0.006), but at the later time intervals there was no significant difference in injuries between the two groups. In rats with carbon tetrachloride induced hepatic cirrhosis, portal pressure was increased (15.6 (1.0) v 6.7 (0.6) mmHg), but again there was no significant difference in mucosal injuries relative to control animals. We conclude that gastric mucosal defence mechanisms are impaired in acute but not chronic experimental portal hypertension.

Acute Disease↗
PubMed1992

A study of regional gastric mucosal blood flow in a rat model of hepatic cirrhosis.

There is controversy surrounding the effects of portal hypertension on the level of perfusion to the gastric wall. This study maps the regional distribution of gastric mucosal and muscle blood flow measured using quantitative autoradiography in a carbon tetrachloride-induced rat model of hepatic cirrhosis. There was a significant increase in both corpus mucosal (124.3 +/- 13.8 vs. 84.8 +/- 4.2 ml.100 g-1.min-1) and muscle blood flow (50.9 +/- 3.6 vs. 33.4 +/- 2.3 ml.100 g-1.min-1) in animals with experimental cirrhosis compared with controls. There was no significant difference in the ratio of blood tracer concentration between the basal and luminal aspects of corpus mucosa in cirrhotic and control groups. We conclude that experimental cirrhosis is associated with gastric mucosal hyperperfusion and that "active" rather than "passive" congestion of the stomach wall may be a more appropriate description of the basic hemodynamic change in this model.

Animals↗
PubMed1992

A study of regional distribution of renal blood flow using quantitative autoradiography.

Quantitative autoradiography utilizing [14C]iodoantipyrine was used to measure regional renal blood flow in anesthetized rats. This technique allowed blood flow in any region of the kidney to be measured with a resolution of 100 microns. There was no significant difference between flow to polar and middle regions of the renal cortex [875 +/- 57 vs. 926 +/- 71 (SE) ml.100 g-1 x mm-1]. Areas of high optical density in renal cortex corresponded to peritubular capillaries. Mean cortical blood flow was three times greater than mean medullary blood flow. Outer medullary blood flow was uniform but significantly higher than inner medullary blood flow (272 +/- 16 vs. 45 +/- 7 ml.100 g-1 x mm-1; P < 0.001).

Animals↗
PubMed1992

Erosive gastritis and portal hypertension.

There is conflicting evidence concerning the effects of portal hypertension on the gastric mucosa. This paper summarises the histological and haemodynamic alterations which are present in both human and experimental portal hypertension. Despite the fact that histological studies suggests that the gastric mucosa is an oedematous plethoric structure in portal hypertension, haemodynamic studies show that gastric mucosal blood glow is at least maintained if not increased in portal hypertension. The term "active" rather than "passive" congestion is a more appropriate description of the basic change present in the gastric mucosa in portal hypertension.

Animals↗
PubMed1991

Regional chemotherapy for inoperable renal carcinoma: a method of targeting therapeutic microspheres to tumour.

Regionally-administered, drug-loaded microspheres have a potential role in the treatment of renal tumours. Vasoactive agents, for example, angiotensin II, may allow selective delivery of microspheres to tumour. The present study defines the regional advantage that may be obtained from angiotensin II by quantifying tumour and normal kidney blood flow using radiolabelled microsphere renal perfusion studies and per-operative laser-doppler flow measurements. Angiotensin II increased microsphere distribution to tumour, relative to normal kidney, by a factor of four. This enhancement was associated with an absolute increase in tumour blood flow.

Angiotensin II↗
PubMed1991

Regional delivery of microspheres to liver metastases: the effects of particle size and concentration on intrahepatic distribution.

There is increasing interest in the use of microspheres, loaded with chemotherapeutic agents, for regional therapy to hepatic metastases. It is necessary to deliver these particles predominately to tumour rather than to normal liver. This study investigates factors influencing the distribution of regionally injected microspheres. Discreet tumour was induced in rats by subcapsular hepatic inoculations of HSN cells. At 20 days, 12.5 microns, 25 microns or 40 microns diameter, radiolabelled albumin microspheres were administered, in various concentrations, via the gastroduodenal artery. Tumour to normal liver microsphere distribution ratios were determined and median values ranged from 0.1 (0.2 mg ml-1 12.5 microns microspheres) to 1.8 (20 mg ml 40 microns microspheres). Concentrated suspensions (20 mg ml-1) of large microspheres (40 microns) produced the most favourable tumour to normal liver distribution ratios. These results not only have implications for the therapeutic administration of microspheres but also for their use in blood-flow studies.

Albumins↗
PubMed1991

Differential penetration of targeting agents into multicellular spheroids derived from human neuroblastoma.

We have used a multicellular tumour spheroid model for determination of the penetration of various targeting agents of potential use in the treatment of neuroblastoma. Both the radiopharmaceutical meta-iodobenzylguanidine (mIBG) and the beta subunit of nerve growth factor (beta-NGF) distributed uniformly throughout spheroids, though the latter was poorly concentrated relative to mIBG. In contrast, the anti-neuroectodermal monoclonal antibody. UJ13A bound only to peripheral cell layers with little accumulation in the spheroid interior. Differential penetration of targeting agents may influence the choice of conjugated radionuclide which is likely to achieve maximum therapeutic benefit.

3-Iodobenzylguanidine↗
PubMed1990

Responses of bone and joint blood vessels in cats and rabbits to electrical stimulation of nerves supplying the knee.

1. Experiments were performed to assess the extent to which knee joint blood flow in cats and rabbits is affected by electrical stimulation of the nerve supply to the knee. 2. Absolute changes in blood flow were measured using the radiolabelled microsphere (approximately 15 microns) technique whilst relative changes in blood flow were assessed using laser Doppler flowmetry. 3. Despite deep general anaesthesia, sympathetic nerve fibres innervating cat knee joint blood vessels showed marked 'tone'. 4. Blood flow to the joint capsule (synovium and overlying fibrous and areolar tissues) was substantially reduced (by approximately 90% in the cat and approximately 45% in the rabbit) during electrical stimulation of the articular nerve supply. 5. The percentage change in the laser Doppler flowmeter signal did not differ significantly from the percentage change in blood flow measured by microsphere technique. 6. Blood vessels in the cancellous bone of the distal femur (condyles) and proximal tibia (plateau) appear to be innervated by vasoconstrictor fibres which reach their effectors via the articular nerves. However, the cortical bone and red marrow of the diaphysis of the femur do not receive such innervation. 7. The potency of the vasoconstrictor influences acting on joint blood vessels could be of relevance in the pathogenesis of inflammatory joint diseases.

Anesthesia, General↗
PubMed1989

Autoradiographic study of the regional distribution of gastric blood flow in portal hypertensive rats.

This study measures regional gastric blood flow in portal hypertensive rats at three separate periods after portal vein ligation using quantitative autoradiography with 14C-labeled iodoantipyrine. The level of corpus mucosal blood flow was significantly reduced in 3-day portal vein-ligated animals compared with sham-operated control animals (30.4 +/- 2.3 vs. 47.1 +/- 5.6 ml/100 g.min). There was no significant difference in corpus mucosal blood flow between portal vein-ligated and sham-operated animals at 7- and 28-day periods, although the level of perfusion was higher in the 28-day portal vein-ligated group. There was no significant difference in antral mucosal or muscle blood flow between portal hypertensive and control animals at any of the study periods. We conclude that the acute period after portal vein ligation is associated with a reduced corpus mucosal microcirculation but that this effect is not sustained in portal hypertensive animals studied at later intervals after portal vein ligation.

Animals↗
PubMed1989

Portal venous pressure and portasystemic shunting in experimental portal hypertension.

The relationship between portal venous pressure and the degree of portasystemic shunting was studied in portal vein-ligated and cirrhotic rats anesthetized with halothane. One day after partial portal vein ligation there was a strong positive correlation (r = 0.80, n = 7) between portal pressure and shunting of mesenteric venous blood as measured by injection of radioactive microspheres. The relationship subsequently underwent rapid change but stabilized by 14 days postligation, when higher levels of shunting were again associated with higher portal pressures up to a limit of approximately 70% shunting, above which pressures did not increase further. This relationship was well described by a quadratic function (r = 0.75, n = 17). In cirrhotic rats there was no relationship between portal pressure and shunting (r = -0.01, n = 10). The results suggest that in the prehepatic model there is little inherent variability in capacity to develop shunts, which open to a degree directly related to portal pressure, but that this relationship may be altered in cirrhotic portal hypertension.

Animals↗
PubMed1988

An autoradiographic study of regional distribution of gastric mucosal blood flow.

Iodo[14C]antipyrine autoradiography was used to measure gastric mucosal blood flow in anesthetized rats and to study regional distribution. Blood flows of 61 +/- 8 ml.100 g-1.min-1 (means +/- SE) in corpus and 84 +/- 9 ml.100 g-1.min-1 in antral mucosa compared well with previously reported measurements by hydrogen clearance. Blood flow in the crests of corpus mucosal folds was significantly higher than in the valleys between folds, indicating that the greater susceptibility of the former areas to acute injury, documented in several studies, is not associated with a perfusion defect in the resting stomach. Corpus mucosal blood flow was also higher in the side walls of the stomach than in the greater curvature region, and in distal than in proximal locations. No systematic regional variations within antral mucosa were demonstrated.

Animals↗
PubMed1985

The uniformity of liver perfusion as measured by krypton-85 clearance.

The uniformity of regional liver perfusion was studied in eight anaesthetised dogs by measuring the clearance of 85Kr with three beta detectors, and the results were compared with independent measurements of mean perfusion by electromagnetic flowmetry. The intra-hepatic flow distribution was found to be heterogeneous, with a coefficient of variation between locations which averaged 17%. The pattern of flow varied from liver to liver, and there was no consistent tendency for any one of a limited number of locations to be better or less well perfused than any other. Discrepancies between 85Kr clearance and flowmeter measurements were of a similar magnitude to inter-regional variations in flow, and there was no evidence of a systematic difference between the two measurement techniques. Individual 85Kr clearance measurements can misrepresent the perfusion of the liver as a whole, and averaging several measurements performed in different locations is likely to yield a better estimate of mean flow.

Animals↗
PubMed1982

Intra-arterial histamine increases blood-brain transport in rats.

The neurotransmitter histamine is located in multiple compartments in the brain and may influence cerebral vessels during some conditions. We made measurements of cerebrovascular transport of labeled sucrose, alpha-aminoisobutyric acid (AIB), and horseradish peroxidase during sustained infusion of histamine into the internal carotid artery of anesthetized rats. Histamine increased the rates of transport of sucrose and AIB up to 237% in several brain regions and in different areas of cerebral cortex. The effect was dose dependent, was reversible within 2 h, and was mediated primarily by histamine H2-receptors. An increase in cortical water content occurred, and electron microscopic examination revealed that perivascular astroglial processes were swollen. There was a twofold increase in the number of endothelial pits and vesicles in cortical capillaries perfused by histamine. We conclude that histamine can influence the function of the blood-brain barrier.

Animals↗