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Biomedical subjects

M A Perry

Publications and source records attributed to M A Perry.

At least 55 records · Page 3Linked to original sources

Effect of hypoxia on feline intestinal capillary permeability.

The multiple-indicator dilution technique was used to investigate the permeability characteristics of capillaries in the cat small intestine during hypoxia. Reducing the arterial oxygen tension from 108 to 35 mmHg for 10 min increased the calculated equivalent pore radius of intestinal capillaries from 59 to 67 A. This effect was sustained for at least 15 min after the hypoxic episode. Hypoxia did not alter intestinal lymphatic protein clearance. Thus, the dimensions of the large pores did not change. This study demonstrates that 10 min of severe hypoxia increases vascular permeability in the small intestine and that this change occurs only in the small pores and is sustained, at least briefly, after restoration of normoxia. Hypoxia does not significantly change the permeability to macromolecules.

Animals↗

Regulation of capillary exchange capacity in the dog stomach.

The capillary exchange capacity of the isolated, perfused dog stomach was investigated during vasoconstriction (norepinephrine) and vasodilation (isoproterenol) and compared with values obtained when blood flow to the stomach was decreased or increased mechanically. The capillary filtration coefficient (Kf,c) was used as an index of capillary exchange capacity. Under resting conditions, Kf,c in the isolated stomach was 0.20 +/- 0.02 ml . min-1 . mmHg-1 . 100 g-1. Vasoconstriction and mechanical reduction in blood flow caused Kf,c to fall to 68 and 58% of control, while vasodilation and mechanical increase in blood flow caused Kf,c to rise to 176 and 231% of control, respectively. Pentagastrin produced an increase in gastric oxygen consumption and a 50% increase in Kf,c. In all instances, capillary exchange capacity appeared to be correlated with gastric blood flow. The data suggest there is little local control of precapillary sphincter tone in the stomach and that capillary exchange capacity may be governed by local pressure within the microvasculature.

Animals↗

Capillary and interstitial forces during fluid absorption in the cat small intestine.

A systematic steady-state analysis of the forces and membrane coefficients governing transcapillary and lymphatic fluid fluxes was performed in the cat ileum under absorptive and nonabsorptive conditions. Net transmucosal fluid flux, lymph flow, capillary pressure, blood flow, capillary filtration coefficient, and lymph and plasma oncotic pressures were measured before and during perfusion of the ileal lumen with a glucose (20 mM)--Tyrode's solution. Interstitial fluid pressure was calculated for the two conditions from measured parameters. Stimulation of mucosal fluid absorption resulted in an increase in lymph flow (which tripled), capillary filtration coefficient (which doubled), capillary pressure (which increased by 9%), interstitial fluid pressure (which doubled), and blood flow (which increased by 16%), whereas interstitial (lymph) oncotic pressure fell (by 20%). These changes converted filtering capillaries to absorbing capillaries, thereby allowing 82% of the absorbed fluid to be removed from the mucosal interstitium via the capillaries, while the lymphatics removed the remaining 18%. The results of this study indicate that hydrostatic and oncotic forces within the interstitium are primarily responsible for preventing interstitial fluid accumulation during periods of net fluid absorption in the small bowel.

Animals↗

A new method for estimating intestinal capillary pressure.

The purpose of this study was to compare the venous occlusion method for measuring capillary pressure with the stop-flow isovolumetric method in the cat small intestine. Venous occlusion pressures were determined from the inflection point of the venous pressure tracing after sudden occlusion of the venous outflow cannula. Venous occlusion pressure was highly correlated (r = 0.98, P less than 0.01) with stop-flow capillary pressure. This finding indicates that the major sites of fluid filtration and vascular capacitance reside at the same segment of the intestinal microcirculation. The venous occlusion method is a relatively simple technique for measuring whole-organ capillary pressure that is not constrained by the technical difficulties associated with volumetric/gravimetric techniques.

Animals↗

Effects of cardiac tamponade on colonic hemodynamics and oxygen uptake.

The local hemodynamic response of the innervated but vascularly isolated colon to decreased systemic perfusion induced by cardiac tamponade was studied in anesthesized dogs as a model of nonocclusive mesenteric ischemia. Increasing levels of pericardial pressure caused progressive decreases in colonic blood flow associated with substantial increases in colonic vascular resistance. These increases in local colonic resistance were proportionately larger than concurrent increases in systemic resistance. The disproportionate response of the colonic resistance vessels was not diminished by colonic (sympathetic) denervation. Reductions of blood flow to 30 ml . min-1 . 100 g-1 resulted in compensatory increases in colonic oxygen extraction such that colonic oxygen consumption remained constant (flow independent) at about 1.5 ml . min-1 . 100 g-1. At blood flows below 30 ml . min-1 . 100 g-1 colonic oxygen consumption was markedly dependent on blood flow. This fundamental relation of colonic oxygen consumption to blood flow was the same whether ischemia was induced by cardiac tamponade, partial mechanical arterial occlusion, or vasoconstrictor (norepinephrine or digoxin) infusion. Furthermore, this relationship was not altered by vasodilation with isoproterenol after the induction of ischemia by any of the above means.

Animals↗

Permeability of pancreatic capillaries to small molecules.

The permeability of capillaries in the isolated, blood-perfused canine pancreas was studied with the double-indicator dilution technique. The permeability-surface area products (PS) for inulin and beta-lactoglobulin A were determined at different plasma flows (attained by pump perfusion). The PS for inulin increased with increasing plasma flow, while the PS for beta-lactoglobulin A was relatively independent of plasma flow. At the highest plasma flow acquired, PS for inulin and beta-lactoglobulin A were approximately 23 and 3.5 ml X min-1 X 100 g-1, respectively. The ratio of the PS values for these two solutes was greater than the ratio of their free diffusion coefficients, indicating restricted diffusion of beta-lactoglobulin A relative to inulin. The degree of restriction was consistent with a maximum equivalent pore radius of 67 A for pancreatic capillaries. An ultrastructural analysis revealed that ductal as well as acinar and islet capillaries were fenestrated. The permeability characteristics of fenestrated pancreatic capillaries are similar to those previously reported for the small intestine.

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Restricted transport of cationic macromolecules across intestinal capillaries.

The charge-selective properties of intestinal capillaries were investigated by measuring steady-state lymph-to-plasma concentration ratios (L/P) of endogenous and exogenous macromolecules of comparable molecular size but different charge. The steady-state L/P values for endogenous lactate dehydrogenase isoenzymes (LD1-LD5) decreased with increasing isoelectric point. The osmotic reflection coefficient for LD1, the most negative isoenzyme studied, was 0.71 +/- 0.01; that for the most positive isoenzyme (LD5) was 0.95 +/- 0.01. The steady-state L/P for an exogenous molecule, neutral dextran, was 0.51 +/- 0.04; the L/P for the positively charged dextran of similar size was 0.25 +/- 0.04. The results indicate that intestinal capillaries behave as a positively charged barrier that reduces blood-lymph exchange of cationic macromolecules and enhances the exchange of anionic molecules.

Animals↗

Intestinal capillary exchange capacity and oxygen delivery-to-demand ratio.

The relations between intestinal capillary exchange capacity and various determinants of tissue oxygenation were characterized in autoperfused, denervated preparations of the canine ileum. Ileal metabolic demand was either increased (intraluminal glucose) or decreased (graded reductions in intraluminal temperature) while measuring blood flow, arterial oxygen content, arteriovenous oxygen difference, and the capillary filtration coefficient (an index of capillary exchange capacity). No significant correlations were obtained between the capillary filtration coefficient and 1) blood flow), 2) oxygen delivery, or 3) oxygen demand. The capillary filtration coefficient was directly related to the arteriovenous oxygen difference and inversely related to the oxygen delivery-to-demand ratio. These observations support the hypothesis that intrinsic modulation of oxygen extraction is mediated by vascular elements which govern capillary exchange capacity and that capillary exchange capacity is inversely related to the oxygen delivery-to-demand ratio.

Animals↗

Computer registration of radioactive indicator-dilution curves.

A system is described for recording indicator-dilution curves produced by gamma radiation-emitting tracers. The system consists of a flow-through cuvette in a well counter, appropriate commercially available gamma radiation-detecting equipment, an Apple II computer, and a two-channel pulse-counting interface of our own design. With the counting interface and the software described here, an investigator can simultaneously record two indicator-dilution curves produced by gamma emitters. Instead of having to wait hours or days for results, the investigator can watch the data being recorded and display the results in graphic form almost immediately after each injection.

Animals↗

Effects of the constituents of a corticosteroid enema preparation on colonic blood flow and oxygen uptake in the dog.

A number of currently available therapeutic agents for the management of idiopathic inflammatory bowel disease were studied with respect to their influence on blood flow and oxygen extraction in the dog colon. Some commercially available corticosteroid enemas including Cortenema and its vehicle and sulfasalazine and its split products were delivered intraluminally while arterial pressure, blood flow and oxygen extraction in autoperfused segments of the colon were continuously monitored. Of the agents studied, only Cortenema and its vehicle exerted any appreciable effect on colonic blood flow, producing a sustained 50% increase; this increase in blood flow was confined to the mucosa-submucosal layer. Of the constituents of Cortenema, methylparaben was responsible for 72% of the hyperemia whereas the remainder was due to carboxypolymethylene. The corticosteroid itself had no effect. Oxygen uptake by the colon was reduced by approximately 10% with Cortenema, this reduction being due entirely to polysorbate 80. In vitro analysis of the oxygen uptake effect indicates that the enema exerts a direct metabolic action.

Acrylic Resins↗

The microcirculation and fluid transport in digestive organs.

The microcirculation of digestive organs is responsible for providing the fluid required for salivary, gastric, pancreatic, and biliary secretions and plays a major role in removing fluid from the interstitium of the intestines during absorption. Data from the literature suggest that hydrostatic and oncotic pressures within the interstitium are important in modulating fluid movement between the microcirculation and transporting epithelia in most digestive organs. Changes in capillary hydrostatic pressure appear to play a more important role in some organs, i.e., salivary glands. Alterations in the density of perfused capillaries and capillary permeability also enhance capillary fluid exchange during transport. These factors, coupled to the high capillary hydraulic conductivity, allow the digestive organs to move large amounts of fluid between the blood and transporting epithelia.

Digestive System Physiological Phenomena↗

Relationship between acid secretion and blood flow in the canine stomach: role of oxygen consumption.

The relationship of acid secretion to blood flow and oxygen consumption was investigated in the isolated canine stomach during intraarterial infusion of pentagastrin. Blood flows above and below control values were achieved by pump perfusion and partial arterial occlusion, respectively. When blood flow was increased from a control value of 38 ml X min-1 X 100 g-1 to 85 ml X min-1 X 100 g-1, both acid secretion and oxygen consumption remained constant at 0.08 mEq X min-1 X 100 g-1 and 2.1 ml X min-1 X 100 g-1, respectively. A reduction in blood flow to 9.0 ml X min-1 X 100 g-1 caused acid secretion and oxygen consumption to decrease to 26% and 44% of control values, respectively. The results indicate that acid secretion is independent of blood flow at flow rates above 38 ml X min-1 X 100 g-1. A model of the interrelationships between blood flow, oxygen consumption, and acid secretion is proposed that may explain much of the conflict in the literature concerning these three parameters.

Animals↗

Relationship between intestinal volume secretion and oxygen uptake.

The effects of net volume secretion on blood flow, oxygen extraction, and oxygen extraction, and oxygen uptake were analyzed in autoperfused segments of cat ileum. Intestinal secretion was induced by local intraarterial infusion of glucagon, histamine, theophylline, prostaglandin E1, or vasoactive intestinal peptide, and, by intraluminal placement of cholera toxin or ricinoleic acid. Net volume secretion rates were determined using a volume recovery method. Intestinal oxygen uptake was increased by all secretagogues. The increases oxygen uptake by the screening intestine resulted from an increased blood flow or oxygen extraction or both. Significant positive correlations between intestinal oxygen uptake and secretion rate were acquired only during cholera toxin, theophylline, and prostaglandin E1, secretion. The results indicate that the metabolic work incurred in the small bowel during secretory states greatly exceeds that reported for the absorptive state.

Alprostadil↗

Oxygen uptake as a determinant of gastric blood flow autoregulation.

Autoregulation of blood flow in the denervated, autoperfused dog stomach was studied before and during local intraarterial infusion of histamine. Histamine caused an increase in gastric blood flow and oxygen uptake. The increased oxygen uptake was due entirely to an increased blood flow, ie, oxygen extraction was not altered by histamine infusion. When oxygen uptake by the stomach was less than 2.0 ml/min/100 g, there was no evidence of blood flow autoregulation, while an oxygen uptake greater than 4.0 ml/min/100 g was consistently associated with blood flow autoregulation. The data indicate that histamine enhances the ability of the stomach to autoregulate its blood flow. This effect appears to be due to histamine's influence on gastric oxygen uptake.

Animals↗

The pulmonary interstitium in capillary exchange.

When capillaries filter excessive fluid, tissue fluid pressure increases, tissue colloid osmotic pressure decreases, and lymph flow increases. The change in tissue forces and flows have been termed edema safety factors since they act to oppose alterations in pulmonary capillary pressure. It is well known that pulmonary capillary pressure can be acutely increased by approximately 20 mm Hg before fluid enters the alveoli, and that the changes in the tissue forces are responsible for this phenomenon. The decrease in interstitial colloid osmotic pressure appears to account for approximately 50% of the tissue's ability to oppose increases in pulmonary capillary pressure. The tissue colloids change because the capillaries filter a protein-poor fluid, and the exclusion of plasma proteins decreases with increasing interstitial volume. Tissue pressure, at least in the perivascular regions, increases with tissue hydration and provides another major tissue force opposing capillary filtration. The contribution of lymph flow to the overall edema safety factor is difficult to estimate at the present time. However, it is possible that the pressure drop associated with the flow of interstitial fluid between the alveolar septal interstitium and the larger perivascular spaces could serve as an edema safety factor, rather than the standard lymphatic flow pressure drop across the capillary membrane. To calculate the standard lymph flow contribution to the total edema safety factor, total lymph flow [LF] and the filtration coefficient of the capillaries [Kf,c] must be known, i.e., Capillary Wall Drop = LF/Kf,c. For normal lung lymph flows and Kf,c's, it would appear that this factor is small. However, if the total pressure drop for fluid movement through the entire lung tissue is used to estimate the lymphatic factor, then it may represent a major portion of the edema safety factor, i.e., Total Pressure Drop = LF/[Kf,cKf,t]/Kf,c + Kf,t] where Kf,t is the filtration coefficient of the tissues. Tissue forces at different site within the lung tissue are presently under intense investigation in serveral laboratories. The next years should provide the necessary information to discuss fluid accumulation in lung tissue in terms of local transcapillary forces rather than the average forces that are now the "present state of the art."

Blood Pressure↗

Permeability of intestinal capillaries: effects of fat absorption and gastrointestinal hormones.

The purpose of this study was to determine whether the postprandial increase of intestinal lymphatic protein flux is due to an increased capillary permeability. Intestinal lymph flow and lymph (L) and plasma (P) protein concentrations were measured at various venous pressures under control conditions, after cream feeding, and during intraluminal perfusion with a bile-oleic acid solution. The osmotic reflection coefficient (sigma d), a measure of capillary permeability that is independent of surface area, was estimated under all conditions, assuming sigma d = 1 - L/P at high capillary filtration rates. The results acquired indicate that cream feeding and intraluminal perfusion with bile-oleic acid significantly increases intestinal capillary permeability. Pretreatment with indomethacin and antihistamines did not alter the permeability increase induced by intraluminal bile-oleic acid. Intra-arterial infusion of cholecystokinin and secretin did not increase intestinal capillary permeability. These studies indicate that the postprandial increase in intestinal lymphatic protein flux is due at least in part, to an increase in capillary permeability. Cholecystokinin, secretin, histamine, and prostaglandins do not appear to mediate the increased intestinal capillary permeability during fat absorption.

Animals↗

Regulation of oxygen uptake in resting and pentagastrin-stimulated canine stomach.

The relation between oxygen uptake and blood flow in the isolated dog stomach was investigated under resting conditions and during intra-arterial infusion of isoproterenol or pentagastrin. Blood flows above and below control values were achieved by pump perfusion and partial arterial occlusion, respectively. In the resting stomach oxygen uptake increased from 0.4 to 1.5 ml.min-1.100 g-1 as blood flow increased from 4 to 40 ml.min-1.100 g-1 and then remained constant for blood flows up to 100 ml.min-1.100 g-1. Isoproterenol did not significantly alter the relation between oxygen uptake and blood flow. In pentagastrin-stimulated stomachs oxygen uptake was maintained at 2.5 ml.min-1.100 g-1 at blood flows between 40 and 100 ml.min-1.100 g-1 and decreased at blood flows below 40 ml.min-1.100 g-1. The results indicate that pentagastrin increases oxidative metabolism in the stomach. Despite this increase in oxygen consumption with pentagastrin, the general shape of the relation between blood flow and oxygen uptake remained the same and was simply displaced vertically above the control data.

Animals↗