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Biomedical subjects

J J Friedman

Publications and source records attributed to J J Friedman.

At least 19 recordsLinked to original sources
PubMed1989

Vascular sensitivity and reactivity to norepinephrine in diabetes mellitus.

Vascular sensitivity (VS) and reactivity (VR) of hindquarters, totally isolated from rats made diabetic with 45 mg/kg of streptozotocin (STZ), were determined at 1, 2, 4, 8, and 12 wk post-STZ. Age-matched controls received saline injections and were followed for comparable periods. The hindquarters were perfused at constant flow (8-10 ml/min) with a Tyrode-perfluorocarbon (FC-43)albumin-alpha-globulin solution gassed with 95% O2-5% CO2. Tissues were continuously weighed and venous pressure adjusted to maintain an isogravimetric condition. VS and VR were determined from norepinephrine (NE) dose-response curves generated by infusing stock NE (1 mg/ml) at progressively increasing rates (0.004-0.025 ml/min) into a constant tissue perfusion rate (8-10 ml/min) for sufficient time to reach a plateau (2-3 min). Delivered doses ranged from 0.4 to 2.5 micrograms/ml. VR was established as the perfusion pressure reached in response to 2.5 micrograms/ml NE (Pmax). VS was defined as the delivered NE dose that increased perfusion pressure to 50% of Pmax (ED50). VS increased slightly but significantly (P less than 0.01) by 1 wk post-STZ and remained above control throughout the 12-wk post-STZ period. VR also increased significantly (P less than 0.05) by 1 wk post-STZ and remained above control throughout the 12-wk post-STZ period.

Animals↗
PubMed1986

The radial protein concentration profile in the interstitial space of the rat ileal mesentery.

The radial distribution of the protein concentration in the interstitium between arteriolar and venular vessels of the ileal mesentery of the rat was examined. Protein mass was determined by means of uv ultramicrospectrophotometry (UMS) and the relative volume distribution by means of fluorescence microscopy (FM) using the Na fluorescein and FITC-dextran (10,000 mol wt). UMS revealed gradients for protein mass from the vessels out into the interstitial space. FM showed a uniform distribution of fluorescence in the interstitium between the vessels. A gradient for protein mass without a gradient for volume distribution signifies the presence of a concentration gradient for protein in the interstitial space. The protein concentration across the arteriolar wall drops from 5.4 +/- 0.24 (SD) to 2.6 +/- 0.65% and across the venular wall from 5.4 +/- 0.24 to 3.3 +/- 0.43%. From the perivascular site the protein concentration declines exponentially reaching a minimum average interstitial concentration of 1.6 +/- 0.56%. Minimal protein concentration occurred at a point 37 +/- 6.4% of the 295 +/- 37 micron distance from the arteriolar to the venular vessels. In view of this distribution, it is unlikely that lymph or direct samples of interstitial fluid are representative of the perivascular protein concentration.

Animals↗
PubMed1985

Hyperosmolality and transcapillary fluid and protein movement in skeletal muscle.

The effect of hyperosmolal glucose infusion on the transcapillary transport of fluid and protein was examined in the isolated gracilis muscle of the dog. Volumes of 18, 36, and 72 microliter/min of 30% glucose were infused intraarterially for 30 min into blood flow held constant at 3-4 ml/min X 100 g, thereby increasing plasma osmolality from 21 to 126 mOsm/liter. Transcapillary fluid movement (Jv) was assessed plethysmographically and protein transport (Js) by direct monitoring of the rate of increase of tissue 125I-albumin radioactivity. Hyperosmolal perfusion reduced vascular resistance. Initially tissue volume declined and then while the infusion continued, reversed direction and rose, occasionally exceeding control volume within the 30-min infusion period. Js also declined transiently, then increased during infusion. The reversal of Js led the reversal of Jv, therefore the reversal of Jv during hyperosmolal infusion was attributed to development of a sufficient change in the oncotic gradient due to the increased Js. These changes were significantly dose dependent. Stopping the hyperosmolal infusion resulted in a marked increase in Jv at all dose levels and, except for the low dose, a maintained rate of increase of Js. Thus early during hyperosmolal exposure protein transport was enhanced by either diffusion or vesicular transport. During recovery, the maintained increase in Js was probably due to increased convection.

Analysis of Variance↗
PubMed1985

The effect of long-term intraarterial norepinephrine infusion on transcapillary fluid and protein transport.

The effect of long-term (4 hr) intraarterial norepinephrine (NOR) infusion on vascular resistance (R), transcapillary fluid movement (Jv), and protein transport (Js) was determined in the isolated hindlimb of the dog. The limb was isolated by an occluding tourniquet and perfused at constant pressure with blood from the opposite femoral artery. Tissue volume changes were detected with a Whitney (1953) mercury-in-rubber strain gauge and protein transport assessed by direct monitoring of the rate of accumulation of 125I-albumin in the tissue. Periodically venous pressure (Pv) was elevated 20 mm Hg in order to estimate the capillary filtration coefficient (Kf) and to determine whether or not prolonged NOR exposure modified the microcirculatory response to increased pressure. Infusing NOR at a delivered dose ranging from 0.026 to 0.13 micrograms/ml significantly elevated R for the entire infusion period. Tissue volume and radioactivity declined transiently and then returned to the control level within 15 min and remained at this level for the remainder of the infusion period. These changes were attributed to blood volume shifts. Elevating Pv during NOR infusion further increased R to an extent which exceeded that during control. Jv and Js were elevated to a greater extent than during control with the delta Js exceeding delta Jv. The changes in Jv are probably due to an increase in microvascular surface area as reflected in an elevated Kf. The greater increase in Js is due in part to an increase in convective transport across a greater microvascular surface area. However, since the ratio of Js/Jv increased with Pv elevation following NOR, the increased Js may represent a change in microvascular permeability produced by the increased Pv. It is also possible that due to myogenic activity or a venous-arteriolar reflex, the microvascular pressure profile was shifted toward the venous side where the reflection coefficient is lower.

Animals↗
PubMed1985

The mass balance method for estimating transcapillary protein transport in an extremity.

A 'clinical' procedure for applying the mass balance method to estimate transcapillary protein transport was compared with the 'experimental' procedure of direct tissue monitoring of the rate of 125I-albumin accumulation in the dog hindlimb under conditions of venous pressure (Pv) elevation, norepinephrine infusion, and hemorrhagic hypotension. Over a wide range of venous protein flux (0.2 to 4.6 mg/min X 100 gm), the two estimates correlated well. The correlation coefficients were 0.987, 0.962, and 0.993 for Pv elevation in the control state, during norepinephrine infusion, and following hemorrhage, respectively. Since the 'clinical' format requires only estimates of tissue blood flow, the change in tissue volume, and the change in protein concentration easily obtained with strain gauge plethysmography and venous blood sampling, it represents a relatively innocuous procedure for estimating protein transport which should be suitable for clinical application.

Animals↗
PubMed1984

Histamine and protein transport in canine muscle.

The effect of intraarterial histamine infusion on transcapillary protein transport was determined in the constant flow pump-perfused isolated gracilis muscle of the dog. Muscle vascular resistance (MVR), the rate of net transcapillary protein transport (Js), net transcapillary fluid transport (Jv), changes in protein-free transcapillary fluid movement (delta Jo) and rubidium extraction (ERb) were calculated following four experimental manipulations. First, as a control, venous pressure was elevated by 20 mmHg; next, histamine was infused intraarterially; then venous pressure was elevated by 20 mmHg during histamine infusion; and finally, the recovery of the tissue from histamine infusion was determined. Although elevation of venous pressure produced no change in MVR, it significantly increased Js, Jv and delta Jo. Histamine infusion caused a significant decline in MVR, and increases in Js and in Jv. delta Jo did not change significantly. When venous pressure elevation was superimposed upon histamine infusion, MVR did not change; Js, Jv, and delta Jo increased but only by increments similar to venous pressure elevation alone. None of the manipulations altered Rb extraction. At the constant flow used in this study, histamine does not appear to increase either capillary hydrostatic pressure or capillary surface area, so that the small intestine in Js was probably due to a slight increase in capillary permeability.

Animals↗
PubMed1982

Mass-balance approach for estimating transcapillary fluid and protein movement.

This study assesses the applicability of a procedure based on mass conservation to estimate transcapillary protein transport (PT) in patients. In a tissue that exhibits net transcapillary protein transport, total transcapillary fluid movement (FMT) is defined according to the law of mass conservation as: FMT = FA (CV - CA)/CV + PT/CV where FA is arterial plasma flow and CV and CA are respectively venous and arterial protein concentration. The first term above (FMO) was estimated from changes in venous plasma oncotic pressure. The second term was estimated both from the rate of tissue accumulation of 125I-albumin and from the mass-balance relationship as (FMT - FMO). FMT was determined in a jejunal segment as the sum of the changes in tissue weight, fluid secretion, and lymph flow. Increasing venous pressure by 10 and 20 mmHg produced changes in FMT and PT which, as estimated by the two methods, were not significantly different. Thus PT can be estimated from the mass-balance relationship without employing either radioactive labels or noxious tissue manipulation; such an approach should be suitable for clinical application.

Body Fluids↗
PubMed1980

Use of acetylacetone to prepare a prodrug of cycloserine.

Several derivatives of cycloserine (1) were prepared and it was found that (R)-4-[(1-methyl-3-oxo-1-butenyl)-amino]-3-isoxazolidinone (11), the condensation product of acetylacetone and cycloserine (1), was an efficacious prodrug of increased stability under aqueous conditions.

Animals↗
PubMed1978

The permeability of single capillaries to potassium ions.

This paper reports a description of methods for determining the diffusional permeability to potassium ions of single capillaries in the frog mesentery. By means of micropipettes, injections or infusions were delivered into a single capillary. The subsequent concentration variations in and about the capillary were followed with K(+)-sensitive microelectrodes. A theoretical analysis is provided which give a quantitative frame of reference for evaluating the observed time-concentration curves in terms of capillary permeability. The advantage of single capillary studies is that the surface area through which diffusion occurs is known as is the concentration difference across the capillary membrane. Three different techniques are: (a) the "single injection" method which represents an application of the indicator diffusion technique where a high-K(+) bolus is injected into a single capillary; (b) the "sack" method which determines the rate of K(+) disappearance from within and immediately outside an occluded capillary segment, after a brief increase in intracapillary K(+) concentration; and (c) the "interstitial diffusion" method which records time and spatial distribution of K(+) in the interstitial space after a step-change in intracapillary K(+) concentration. The methods gave an average potassium permeability of the capillary membrane of 67x10(-5) cm s(-1) (SD: 23, n=26) at room temperature. These figures are clearly higher than those previously reported in mammalian capillary studies using whole-organ techniques. In terms of the pappenheimer pore model, this estimate of capillary permeability is consistent with the behavior of a membrane with a thickness of 1.0 mum which possesses equivalent pores with a radius of 110 A, a fractional pore area of 0.3 percent, and a pore density of 8 mum(-2).

Animals↗
PubMed1978

Myocardial blood flow as measured by fractional uptake of rubidium-84 and microspheres.

Under conditions of varying flow rates, total myocardial blood flow, measured by fractional uptake of rubidium-84, using a coincidence counting system, was compared with myocardial flow measured by microspheres (15 +/- 5 micrometer). The methods were compared, open-chested, in 47 dogs: 17 during control, ten following 5 min of ligation of left anterior descending coronary artery, five following i.v. isoproterenol, six following ligation and isoproterenol, and nine after ligation plus dipyridamole. Regional flows by Rb-84 and by either Ce-141 or Cr-51 microspheres were also compared for left ventricle, as well as for nonischemic posterior wall, which served as a reference area, and for anterior wall with ligation of left anterior descending artery in the same preparations. There were no significant differences in total or regional flow measured by the two methods, nor in the estimate of ischemic area size. The data indicate that measurement of myocardial blood flow by fractional uptake of a potassium analog is a reliable method in the presence of ischemia and drug intervention. It is suggested that the inequalities of extraction ratio that occur with differing flow rates do not invalidate fractional-uptake methods over the flow ranges examined.

Animals↗