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Biomedical subjects

E D Jacobson

Publications and source records attributed to E D Jacobson.

At least 73 records · Page 4Linked to original sources
PubMed1982

A model of the mesenteric circulation.

A model of the mesenteric microcirculation is proposed that explains three observed variations in the hyperemic response of the small intestine to different dilator stimuli. The model assumes a two-component circulation in which one component delivers more than enough blood flow and oxygen to meet the metabolic demands of the resting tissue served by this "flow-independent component." The second portion, known as the "flow-limited component" delivers an insufficient blood supply for tissue needs and, therefore, restricts the metabolism of the parenchyma it serves. The three types of reported hyperemic responses are a) hyperemia induced by certain drugs, such as nifedipine and acetylcholine, in which case only the flow-limited component is dilated and one observes an increase in blood flow to the gut without any increase in intestinal oxygen consumption; b) hyperemia induced by stimulating active cotransport of nutrients from the intestinal lumen, in which case the tissue served by the flow-independent component increases its metabolism and oxygen demand, resulting in an increase in oxygen consumption that exceeds proportionately the increase in blood flow; and c) hyperemia induced by other vasodilator drugs, such as adenosine, in which case both vascular components are dilated and both blood flow and oxygen uptake are increased, but the increase in blood flow is proportionately greater than the increase in oxygen consumption.

Acetylcholine↗
PubMed1982

Na+, K+-ATPase of the canine mesenteric artery.

Na+,K+-ATPase, the enzymatic moiety that operates as the electrogenic sodium-potassium pump of the cell plasma membrane, is inhibited by cardiac glycosides, and this specific interaction of a drug with an enzyme has been considered to be responsible for digitalis-induced vascular smooth muscle contraction. Although studies aimed at localization, isolation, and measurement of the Na+,K+-ATPase activity (or Na+, K- pump activity) indicate its presence in vascular smooth muscle sarcolemma, its characterization as the putative vasopressor receptor site for cardiac glycosides has depended on pharmacological studies of vascular response in vivo and on isolated artery contractile responses in vitro. More recently, radioligand-binding studies using [3H]ouabain have aided in the characterization of drug-enzyme interaction. Such studies indicate that in canine superior mesenteric artery (SMA), Na+,K+-ATPase is the only specific site of interaction of ouabain with resultant inhibition of the enzyme. The characteristics of [3H]ouabain binding to this site are similar to those of purified or partially purified Na+,K+-ATPase of other tissues, which suggests that if Na+,K+-ATPase inhibition is causally related to digitalis-mediated effects on vascular smooth muscle contraction, then therapeutic concentrations of cardiac glycosides could act to cause SMA vasoconstriction. The additional finding from radioligand-binding studies that Na+,K+-ATPase exists in much smaller quantities (density of sites per cell) in SMA than in either heart or kidney may have implications concerning its physiological, biochemical or pharmacological role in modulating vascular muscle tone.

Animals↗
PubMed1981

Hemodynamic and metabolic changes during stimulation of ileal motility.

Hemodynamic and metabolic responses of the mesenteric circulation were studied during infusion of agents known to stimulate intestinal motility. Agents were infused intraarterially in graded doses and included acetylcholine, angiotensin II, prostaglandin D2, prostaglandin F2-alpha, methionine-enkephalin, and morphine. Measurements were made of blood flow to the ileal portion of the small intestine, arteriovenous oxygen content difference, fractional distribution of radiolabeled microspheres to the muscularis, and intraluminal pressure. The clearance of 86Rb was determined in some experiments. From these measurements we calculated oxygen consumption, fractional blood flow to the muscularis, permeability and surface area product (PS-product), and the mean motility index. All agents increased mean motility index to varying degrees. At comparable levels of increased mean motility index with each drug, there were variable degrees of increase or decrease or no change in the other parameters between drugs. Mesenteric hemodynamic and metabolic responses to these dissimilar stimuli of motor activity reflected mainly the vasoactive properties of each agent. This suggests that increased motor activity has little influence on the mesenteric circulation.

Acetylcholine↗
PubMed1981

Hemodynamic effects of rapid injection into the canine superior mesenteric artery.

We explored the hemodynamic effects of rapid injection of 0.9% saline and arterial blood into the canine superior mesenteric artery in anesthetized animals. Mesenteric artery blood flow and pressure were measured in the vessel distal to the site of injection. Injection rates were at or below the rate of blood flow in the mesenteric artery. Rapid injection of saline caused increases in blood flow and decreases in pressure in the mesenteric artery, with responses to saline occurring during or shortly after the period of injection. Injection of arterialized blood into the artery prompted changes resembling those with saline. Injection of blood for up to 16 sec at a rate which was equal to the resting blood flow in the vessel increased both flow and pressure during the period of injection. Blood flow continued at an elevated level for many seconds after cessation of injection. During this time, pressure in the artery fell to a level below the control value. Calculated mesenteric vascular resistance exhibited a decrease during and following injection. Our findings suggest that the hemodynamic response of the superior mesenteric artery to a pulsation of blood or saline is vasodilation.

Animals↗
PubMed1981

Mesenteric vascular reactivity to histamine receptor agonists and antagonists.

Response patterns of intestinal blood flow, oxygen extraction and consumption, blood flow distribution, and motility were assessed during intraarterial infusions of histamine, histamine after H1 or H2 blockade, dimaprit or dimaprit after H2 blockade. Histamine produced an initial peak response of blood flow with a slow decrease thereafter. Oxygen extraction was evenly depressed throughout the infusion, and oxygen consumption increased at the beginning. All initial responses were blocked by tripelennamine. Ranitidine, a new H2 antagonist, accelerated the decay of all responses. Dimaprit produced effects identical to those of histamine after tripelennamine. Distribution of blood flow was unchanged at the beginning of histamine infusion, but subsequently showed a shift to muscularis which was blocked by tripelennamine. Histamine usually stimulated intestinal contractions and this effect was abolished by tripelennamine. Thus, H1 stimulation, besides producing an initial vasodilation, increases oxygen uptake and redistributes flow to the muscularis.

Adrenergic Agonists↗
PubMed1981

The role of prostacyclin (PGI2) in metabolic hyperemia.

We explored the possibility that prostacyclin might be the dilator metabolite of postprandial hyperemia. In canine free-flow preparations, effects of prostacyclin were compared with effects of actively absorbed nutrients on hemodynamic and metabolic parameters in the small intestine. Prostacyclin was infused directly into the superior mesenteric artery for 10 minutes at 1.0 nanograms/kg-min. In absorptive study an isosmotic solution of glucose (1.0 g/l) dissolved in 0.9% NaCl was perfused through the gut lumen for 20 minutes. Prostacyclin increased total blood flow to the intestinal segment and decreased oxygen extraction, while not significantly changing either oxygen consumption or PS-product. Active cotransport of glucose and sodium increased total blood flow, oxygen extraction, oxygen consumption and PS-product. In constant flow canine gut preparations, intraarterial prostacyclin infusion decreased arterial pressure, oxygen extraction, oxygen consumption and mesenteric vascular resistance but increased venous pressure. Absorption of glucose and sodium increased oxygen extraction but decreased mesenteric vascular resistance while not affecting other parameters significantly. Since responses to prostacyclin did not coincide with responses to metabolically dependent transport of glucose and sodium, we conclude that the dilator metabolite of postprandial hyperemia is probably not prostacyclin.

Animals↗
PubMed1981

Ultraviolet light action spectra for neoplastic transformation and lethality of Syrian hamster embryo cells correlate with spectrum for pyrimidine dimer formation in cellular DNA.

Action spectra were determined for neoplastic transformation, production of pyrimidine dimers, and lethality in Syrian hamster embryo cells. Of wavelengths between 240 and 313 nm, the most effective were 265 and 270. The relative sensitivities per quantum for transformation, pyrimidine dimer production, and lethality were essentially the same at each of the wavelengths tested. This action spectrum for transformation, which is relevant to carcinogenesis, is similar to spectra obtained previously by measuring other cellular responses in either microbial or mammalian systems. Because the action spectra for cytotoxicity and transformation are the same as the spectrum for dimer production, DNA is suggested as the target for all these processes.

Animals↗
PubMed1981

Relation between small intestinal motility and circulation.

Effects of muscular activity on local blood flow have been delineated in other muscular organs but are part of a complex relationship in the small intestine. Some of our inability to provide a clear picture of the circulatory events surrounding intestinal motility relates to the variety of imprecise techniques that have been used to explore the relationship. Distension of the gut impedes blood flow through the intestinal wall, especially in the mucosa. Stimulation of motility evokes more variable responses in the intestinal circulation, including increases in blood flow; however, the circulatory response reflects mostly the nature of the intervention used to activate motility. Many motor stimuli in the gut have intrinsic vasoactive properties. Spontaneous motor events seem to have only small effects on total blood flow to the small intestine. Reduction in blood flow to the gut evokes initial increases in motility followed by inhibition of motor activity. Products of metabolism in the intestine influence both motor and vascular reactivity. More sensitive methods need to be developed to separate the types of intestinal motor activity, to localize mechanical events in specific sites in the wall of the gut, to better record electrical correlates of motility, and to measure local tissue blood flow. These technical developments will permit delineation of the linkage between motor and vascular events and should identify the regulatory factors.

Animals↗
PubMed1981

Effects of calcium and its antagonists on the canine mesenteric circulation.

We studied circulatory and metabolic responses of the intestinal circulation to intraarterial infusions of solutions containing calcium chloride or calcium antagonists in anesthetized dogs. Measurements included blood flow to the terminal ileum, arteriovenous oxygen content difference, distribution of radiolabeled microspheres to the mucosal-submucosal compartment and intraluminal pressure. Calculated parameters included oxygen consumption and fractional mucosal-submucosal blood flow. Both calcium antagonists, nifedipine and diltiazem, increased intestinal blood flow, mainly to the mucosa-submucosa, depressed intestinal motility, and did not change oxygen consumption. Thus, both agents appear to act mainly on resistance vessels without increasing the nutrient circulation. Calcium chloride (1.0-500.0 microgram/kg per min) had a mild constrictor effect; at a dose of 1000.0 microgram/kg per min, calcium chloride became a dilator agent in the mesenteric circulation. The dilator effect of the highest dose of calcium was reversed by digoxin, suggesting the involvement of Na+,K+-ATPase. Nifedipine completely blocked calcium-induced constriction of the intestinal circulation and partly inhibited norepinephrine-induced constriction. Studies on isolated mesenteric arterial smooth muscle revealed that nifedipine relaxed KCl-contracted strips in the presence of external calcium and relaxed norepinephrine-contracted strips in both the presence and absence of external calcium. These in vitro findings suggest that calcium antagonists interfere with the release of calcium from intracellular sites as well as with the slow inward current of calcium.

Animals↗
PubMed1981

Effects of adenosine and its derivatives on the canine intestinal vasculature.

The effects of adenosine and two of its structural analogs on small intestinal blood flow, flow distribution, oxygen extraction, and uptake were studied in anesthetized dogs. Adenosine induced dose-dependent increases in intestinal blood flow and oxygen consumption but decreased oxygen extraction. These effects were significantly attenuated by theophylline, an adenosine antagonist. Propranolol did not influence the responses of the intestinal circulation to adenosine suggesting that beta-adrenergic receptors are not involved in the action of adenosine. 2-Chloroadenosine, one of the most potent adenosine analogs, produced changes very similar to adenosine but was about six times more potent on a molar basis. Effects of 2-chloroadenosine were attenuated by a 10-fold smaller dose of theophylline. Adenosine-9 beta-D-arabinofuranoside, another analog, was ineffective in the mesenteric circulation. Characteristic activity of both analogs and the antagonism of the effects of adenosine and 2-chloroadenosine by theophylline suggest the presence of adenosine-sensitive binding sites in precapillary resistance vessels of the intestinal circulation. The presence of adenosine receptors in intestinal vascular smooth muscle is further supported by our in vitro results in which all three agents induce patterns of response similar to those noted under in vivo conditions. However, concentrations necessary to obtain relaxation of isolated muscle strips were much greater than those sufficient to produce mesenteric vasodilation in vivo. It was also noted that strips obtained from branches of the superior mesenteric artery were more reactive to adenosine and its analogs than were strips prepared from the main trunk of the vessel.

Adenosine↗
PubMed1980

Sunlight-induced mutagenesis and toxicity in L5178Y mouse cells: determination and comparison with other light sources.

Compared to the basis of equal exposure, in joules per square meter (J/m2) the mutagenic and toxic effects in L5178Y mouse lymphoma cells of radiation emitted by some fluorescent lamps and a sunlamp are quantitatively similar to solar radiation effects at the earth's surface. When the relative intensities of radiation are taken into account, the artificial light sources range from 8 to 1/222 times as mutagenic and 4.1 to less than 1/99 times as toxic as sunlight.

Animals↗
PubMed1980

Effects of a rapid injection into the canine superior mesenteric artery of diatrizoate meglumine and diatrizoate sodium (Renografin-76).

In an effort to evaluate the "spillover method" of measuring blood flow during angiography, we explored the effects of rapid injection of diatrizoate meglumine and diatrizoate sodium (Renografin-76) at rates no greater than resting blood flow in the superior mesenteric artery of anesthetized dogs. An increase in mesenteric blood flow and a decrease in mesenteric arterial pressure occurred many seconds after cessation of the injection. The dilation effected by the contrast agent was less marked at elevated blood flow values than at resting flows. The pattern of response to diatrizoate meglumine and diatrizoate sodium resembled that observed with vasodilator drugs. Our findings also suggest that the initial vascular response to a pulsation of the diatrizoate medium is vasodilation.

Animals↗