Mechanism of glucagon-induced intestinal secretion

1980 ◽  
Vol 239 (1) ◽  
pp. G30-G38
Author(s):  
D. N. Granger ◽  
P. R. Kvietys ◽  
W. H. Wilborn ◽  
N. A. Mortillaro ◽  
A. E. Taylor
Keyword(s):  
Capillary Pressure ◽  
Plasma Proteins ◽  
Fluid Pressure ◽  
Intestinal Secretion ◽  
Tissue Samples ◽  
Mucosal Membrane ◽  
Osmotic Reflection Coefficient ◽  
Capillary Fluid ◽  
Higher Doses ◽  
Flow Capillary

The effects of local intra-arterial glucagon infusion on transcapilary, lymphatic, and transmucosal fluid and protein fluxes were studied in autoperfused segments of cat ileum. The glucagon infusions resulted in a significant increase in intestinal blood flow, lymph flow, capillary filtration coefficient, capillary pressure, interstitial volume, and interstitial fluid pressure. Precapillary resistance and the pre-to-postcapillary resistance ratio decreased during the glucagon infusion. The transcapillary oncotic pressure gradient and the osmotic reflection coefficient were reduced, suggesting that capillary permeability is significantly increased with glucagon. Ultrastructural analysis of tissue samples acquired during the infusion of higher doses of glucagon indicates disruption of the mucosal membrane. An glucagon indicates disruption of the mucosal membrane. An alteration in mucosal structure is supported by the appearance of plasma proteins in the secreted fluid. The results of this study indicate that glucagon-induced intestinal secretion results from an alteration in capillary fluid balance, i.e., an increased capillary pressure and permeability.

PGE1-induced intestinal secretion: mechanism of enhanced transmucosal protein efflux.

1979 ◽  
Vol 236 (6) ◽  
pp. E788
Author(s):  
D N Granger ◽  
J S Shackleford ◽  
A E Taylor
Keyword(s):  
Blood Flow ◽  
Mesenteric Artery ◽  
Plasma Proteins ◽  
Structural Damage ◽  
Prostaglandin E1 ◽  
Intestinal Secretion ◽  
Fluid Exchange ◽  
Tissue Samples ◽  
Volume Absorption ◽  
Regional Hemodynamics

The effects of local intra-arterial prostaglandin E1 (PGE1) infusion on net transmucosal volume and protein fluxes, lymphatic volume and protein fluxes, and regional hemodynamics were ascertained in autoperfused segments of cat ileum. After acquiring control values (and tissue samples) for the various parameters, PGE1 (5.0 microgram/min) was infused directly into the superior mesenteric artery. The PGE1 infusions resulted in dramatic increases in ileal lymphatic volume and protein fluxes and blood flow. Infusion of PGE1 caused a reversion of net mucosal volume absorption to net secretion and an increased loss of plasma proteins into the lumen. Ultrastructural analysis of tissue samples taken during the PGE1 infusion indicate major structural damage to the mucosal membrane. The physiological and ultrastructural data acquired in this study suggest that 1) the increased transmucosal protein efflux during intra-arterial PGE1 infusions results from an alteration in mucosal transcapillary fluid exchange and 2) a significant portion of PGE1-induced ileal secretion is passively mediated.

Autoregulation of intestinal capillary filtration rate

1982 ◽  
Vol 243 (6) ◽  
pp. G475-G483
Author(s):  
D. N. Granger ◽  
N. A. Mortillaro ◽  
M. A. Perry ◽  
P. R. Kvietys
Keyword(s):  
Arterial Pressure ◽  
Capillary Pressure ◽  
Filtration Rate ◽  
Pressure Range ◽  
Fluid Pressure ◽  
Lymph Flow ◽  
Filtration Coefficient ◽  
Capillary Filtration ◽  
Capillary Filtration Coefficient ◽  
Flow Capillary

To determine whether intestinal capillary filtration rate, capillary pressure, or both are autoregulated in the cat ileum, the following parameters were measured under isovolumetric conditions: lymph flow, capillary pressure, capillary filtration coefficient, and lymph and plasma oncotic pressures. Superior mesenteric arterial pressure was reduced in 25-mmHg steps from 125 to 25 mmHg. As arterial pressure was reduced, lymph flow, capillary pressure, and the transcapillary oncotic pressure gradient decreased while the capillary filtration coefficient increased. Over the arterial pressure range of 75-125 mmHg, capillary pressure decreased in a fashion expected from a rigid system; however, capillary pressure was slightly autoregulated at lower arterial pressures. Lymph flow fell proportionately more than capillary pressure over the entire arterial pressure range. The results of this study indicate that intestinal capillary pressure and capillary filtration rate are poorly autoregulated in the cat when arterial pressure is reduced. Changes in interstitial fluid pressure play a major role in preventing interstitial dehydration in the cat ileum when arterial pressure is reduced.

Mechanical properties of the tracheal mucosal membrane in the rabbit. II. Morphometric analysis

2000 ◽  
Vol 88 (3) ◽  
pp. 1022-1028 ◽  
Author(s):  
Lu Wang ◽  
Kenneth L. Pinder ◽  
Joel L. Bert ◽  
Mitsushi Okazawa ◽  
Peter D. Paré
Keyword(s):  
Mechanical Properties ◽  
Volume Fraction ◽  
Mechanical Load ◽  
Morphological Structure ◽  
Longitudinal Direction ◽  
Smooth Muscle Contraction ◽  
Elastic Fibers ◽  
Tissue Samples ◽  
Mucosal Membrane ◽  
Simple Geometry

Folding of the airway mucosal membrane provides a mechanical load that impedes airway smooth muscle contraction. Mechanical testing of rabbit tracheal mucosal membrane showed that the membrane is stiffer in the longitudinal than in the circumferential direction of the airway. To explain this difference in the mechanical properties, we studied the morphological structure of the rabbit tracheal mucosal membrane in both longitudinal and circumferential directions. The collagen fibers were found to form a random meshwork, which would not account for differences in stiffness in the longitudinal and circumferential directions. The volume fraction of the elastic fibers was measured using a point-counting technique. The orientation of the elastic fibers in the tissue samples was measured using a new method based on simple geometry and probability. The results showed that the volume fraction of the elastic fibers in the rabbit tracheal mucosal membrane was ∼5% and that the elastic fibers were mainly oriented in the longitudinal direction. Age had no statistically significant effect on either the volume fraction or the orientation of the elastic fibers. Linear correlations were found between the steady-state stiffness and the quantity of the elastic fibers oriented in the direction of testing.

Starling’s Riddle of the Broken Heart

2011 ◽  
pp. 77-87
Author(s):  
James R. Munis
Keyword(s):  
Heart Failure ◽  
Arterial Pressure ◽  
Cardiac Tamponade ◽  
Capillary Pressure ◽  
Resting State ◽  
Fluid Pressure ◽  
Active Contraction

In 1897, Ernest Starling lectured on heart failure by inducing cardiac tamponade in an anesthetized dog. When the tamponade began to have an effect, the arterial pressure began to fall, but the venous pressures began to rise. In other words, heart failure didn't just decrease one type of pressure, it simultaneously increased another type of pressure. By the end of the experiment, all pressures had converged to the same value. The heart, like any pump, doesn't just raise fluid pressure on one side, it simultaneously lowers fluid pressure on the opposite side. The heart has a peculiar architecture that prefers a slightly filled resting state. Any smaller volume actually requires active contraction—it passively springs open during a part of diastole, suctioning blood into itself. Why then does heart failure cause capillary edema? We understand that the pressure in large veins will rise with heart failure, but capillary pressure is on the left side of the intersection of the curve and the Pms line. As such, capillary pressure should decrease with heart failure, and the tendency toward edema similarly should decrease.

Microvascular pressure, surface area, and permeability in isolated hindquarters of SHR

1985 ◽  
Vol 249 (3) ◽  
pp. H498-H504
Author(s):  
R. J. Korthuis ◽  
C. R. Kerr ◽  
M. I. Townsley ◽  
A. E. Taylor
Keyword(s):  
Skeletal Muscle ◽  
Capillary Pressure ◽  
Surface Area ◽  
Convective Transport ◽  
Microvascular Permeability ◽  
Spontaneously Hypertensive ◽  
Pressure Surface ◽  
Total Plasma Protein ◽  
Wistar Kyoto ◽  
Osmotic Reflection Coefficient

The transvascular escape rate (TER) of labeled albumin is reported to increase in essential hypertension. However, the mechanism for this augmented rate of protein efflux is uncertain and may be related to increased microvascular permeability, surface area, and/or pressure. To determine the possible contributions of these mechanisms to increased TER of protein, the osmotic reflection coefficient for total plasma protein, capillary filtration coefficient, and effective capillary pressure were estimated in isolated hindquarters of age-matched (12-13 wk) spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar (WR) rats. Estimates of the reflection and filtration coefficients were not significantly different in SHR, WKY, and WR. However, capillary pressure was significantly greater in SHR than in normotensive controls. These results indicate that 1) skeletal muscle microvascular permeability and surface area are similar in SHR, WKY, and WR; 2) effective capillary pressure is greater in SHR than WKY or WR; and 3) if TER for protein is elevated in hypertensive skeletal muscle, the primary mechanism for this process may be increased convective transport of protein secondary to elevated microvascular hydrostatic pressure.

2-Chlorodeoxyadenosine dose escalation in nonhematologic malignancies.

1993 ◽  
Vol 11 (4) ◽  
pp. 671-678 ◽  
Author(s):  
A Saven ◽  
H Kawasaki ◽  
C J Carrera ◽  
T Waltz ◽  
B Copeland ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Intravenous Infusion ◽  
Hematologic Malignancies ◽  
Maximum Tolerated Dose ◽  
Malignant Astrocytoma ◽  
Dose Escalation Study ◽  
Tissue Samples ◽  
Grade 3 ◽  
Higher Doses ◽  
Experienced Grade

PURPOSE We performed a dose-escalation study of 2-chlorodeoxyadenosine (2-CdA) in solid tumors to determine the maximum-tolerated dose (MTD) and define its toxicity profile at higher doses. PATIENTS AND METHODS Twenty-one patients, seven with malignant astrocytoma, twelve with metastatic melanoma, and two with metastatic hypernephroma, were enrolled onto the study. Patients were entered onto cohorts that received 0.10, 0.15, or 0.20 mg/kg/d of 2-CdA by continuous intravenous infusion for 7 days every 28 days. 2-CdA levels were determined by radioimmunoassay. In tumor tissue samples, deoxycytidine kinase (dCK) levels were measured by both enzyme activity and immunoreactive protein analysis. RESULTS Of seven patients treated with 2-CdA at 0.1 mg/kg/d, one experienced grade 3 or 4 myelotoxicity. Of 11 patients treated at 0.15 mg/kg/d, four experienced myelotoxicity, two after a single course of 2-CdA. All three patients who received 2-CdA at 0.2 mg/kg/d experienced myelosuppression. Neurologic events occurred in two patients, both with malignant melanoma. Two of seven patients (28.6%) with astrocytomas obtained partial responses with a median duration of 8 months. 2-CdA penetrated the blood-brain barrier. An association was found between dCK levels as measured by enzymatic activity and immunoreactive proteins, but this did not correlate with 2-CdA tumor responsiveness. CONCLUSION The MTD for 2-CdA delivered as a 7-day intravenous infusion in patients with nonhematologic malignancies was determined to be 0.1 mg/kg/d, the same as the MTD for patients with hematologic malignancies. There was no clinical correlation with dCK expression and response to 2-CdA. The responses noted in patients with malignant astrocytoma warrant further phase II study.

Effect of Gas/Oil Capillary Pressure on Minimum Miscibility Pressure for Tight Reservoirs

SPE Journal ◽  
2019 ◽  
Vol 25 (02) ◽  
pp. 820-831 ◽  
Author(s):  
Kaiyi Zhang ◽  
Bahareh Nojabaei ◽  
Kaveh Ahmadi ◽  
Russell T. Johns
Keyword(s):  
Capillary Pressure ◽  
Hyperbolic Equations ◽  
Fluid Pressure ◽  
Gas Oil ◽  
Minimum Miscibility Pressure ◽  
Tight Reservoir ◽  
Tie Lines ◽  
Tight Reservoirs ◽  
Shale Reservoirs ◽  
The Impact

Summary Shale and tight reservoir rocks have pore throats on the order of nanometers, and, subsequently, a large capillary pressure. When the permeability is ultralow (k < 200 nd), as in many shale reservoirs, diffusion might dominate over advection, so that the gas injection might no longer be controlled by the multicontact minimum miscibility pressure (MMP). For gasfloods in tight reservoirs, where k > 200 nd and capillary pressure is still large, however, advection likely dominates over diffusive transport, so that the MMP once again becomes important. This paper focuses on the latter case to demonstrate that the capillary pressure, which has an impact on the fluid pressure/volume/temperature (PVT) behavior, can also alter the MMP. The results show that the calculation of the MMP for reservoirs with nanopores is affected by the gas/oil capillary pressure, owing to alteration of the key tie lines in the displacement; however, the change in the MMP is not significant. The MMP is calculated using three methods: the method of characteristics (MOC); multiple mixing cells; and slimtube simulations. The MOC method relies on solving hyperbolic equations, so the gas/oil capillary pressure is assumed to be constant along all tie lines (saturation variations are not accounted for). Thus, the MOC method is not accurate away from the MMP but becomes accurate as the MMP is approached when one of the key tie lines first intersects a critical point (where the capillary pressure then becomes zero, making saturation variations immaterial there). Even though the capillary pressure is zero for this key tie line, its phase compositions (and, hence, the MMP) are impacted by the alteration of all other key tie lines in the composition space by the gas/oil capillary pressure. The reason for the change in the MMP is illustrated graphically for quaternary systems, in which the MMP values from the three methods agree well. The 1D simulations (typically slimtube simulations) show an agreement with these calculations as well. We also demonstrate the impact of capillary pressure on CO2-MMP for real reservoir fluids. The effect of large gas/oil capillary pressure on the characteristics of immiscible displacements, which occur at pressures well below the MMP, is discussed.

Transcapillary Starling forces using membrane osmometry

1980 ◽  
Vol 238 (6) ◽  
pp. H886-H888
Author(s):  
J. L. Christian ◽  
R. A. Brace
Keyword(s):  
Osmotic Pressure ◽  
Interstitial Fluid ◽  
Subcutaneous Tissue ◽  
Fluid Pressure ◽  
Colloid Osmotic Pressure ◽  
Interstitial Fluid Pressure ◽  
Tissue Samples ◽  
Small Pore ◽  
The Difference ◽  
Good Agreement

Membrane osmometry was used to estimate the four transcapillary Starling pressures in subcutaneous tissue of rats, guinea pigs, and dogs. Isolated subcutaneous tissue samples were either placed on a large-pore or small-pore osmometer that measured the interstitial fluid pressure (Pif) and the difference between the interstitial fluid pressure and the interstitial protein osmotic pressure (Pif-pi if), respectively. The colloid osmotic pressure of the interstitial fluid (pi if) was obtained from the difference in these two pressures. A plasma sample placed on the small-pore osmometer yielded the colloid osmotic pressure of the plasma proteins (pi c). Finally the capillary pressure (Pc) was calculated from the three other Starling forces. In the rat, guinea pig, and dog, respectively, the estimated Starling forces were as follows: Pif -2.2, -2.1, and -4.8 mmHg; pi if, 7.3, 4.8, and 4.4 mmHg; pi c, 21.3, 19.5, and 19.2 mmHg; and Pc, 11.8, 12.6, and 10.0 mmHg. A comparison with data obtained in other studies using different methods shows good agreement and strongly supports membrane osmometry as a method for measuring the Starling pressures in subcutaneous tissue.

Exclusion of plasma proteins in interstitium of tissues from the dog hind paw

1980 ◽  
Vol 239 (4) ◽  
pp. H532-H532 ◽  
Author(s):  
Donald R. Bell ◽  
Philip D. Watson ◽  
Eugene M. Renkin
Keyword(s):  
Plasma Proteins ◽  
Bolus Injection ◽  
Distribution Volume ◽  
Plasma Albumin ◽  
Tissue Samples ◽  
Vascular Volume ◽  
Protein Tracers ◽  
Composition And Structure ◽  
Anesthetized Dogs ◽  
Gel Phase

Exclusion of plasma albumin and fibrinogen from portions of the extravascular sucrose space in tissues of the hind paw of anesthetized dogs was studied by use of radioactive traces. Thirty hours after a bolus injection of the labeled proteins, tracer concentrations were measured in plasma, prenodal popliteal lymph, and samples of hind paw skin, tendon, muscle, and toe pad. In a few experiments, constant plasma levels of tracer sucrose were maintained for 2 h before terminal sampling. In all experiments a vascular volume marker was given 15 min before termination. A linear correlation was found between the amounts of extravascular protein tracers in the tissue samples and their concentrations in lymph from the same paw, as would be expected if their actual interstitial concentrations were closely related to their lymph concentrations. For albumin, the extravascular distribution volume calculated at lymph concentration was less than the sucrose space for all tissues except toe pad. For fibrinogen, the extravascular distribution volume was less than albumin and sucrose for all tissues except skin. Differences in pattern and degree of exclusion may reflect the differences in interstitial gel-phase composition and structure.

Intestinal capillary filtration in acute and chronic portal hypertension

1988 ◽  
Vol 254 (3) ◽  
pp. G339-G345 ◽  
Author(s):  
R. J. Korthuis ◽  
D. A. Kinden ◽  
G. E. Brimer ◽  
K. A. Slattery ◽  
P. Stogsdill ◽  
...  
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Capillary Pressure ◽  
Vascular Resistance ◽  
Interstitial Fluid ◽  
Venous Pressure ◽  
Fluid Pressure ◽  
Lymph Flow ◽  
Interstitial Fluid Pressure ◽  
Capillary Filtration

The impact of acute and chronic portal hypertension on the dynamics of intestinal microvascular fluid exchange was examined in anesthetized, fasted, sham-operated control rats with normal portal pressures (CON), during acute elevations in portal pressure (APH) in control rats, and in rats in which chronic portal hypertension (CPH) was produced by calibrated stenosis of the portal vein 10 days prior to the experiments. Although intestinal blood flow and vascular resistance were not altered by APH in control rats, CPH was associated with an increased intestinal blood flow and reduced intestinal vascular resistance when compared with CON and APH. Intestinal capillary pressure and lymph flow were elevated in APH and CPH relative to control values. However, the increase in both variables was greater in CPH. The capillary filtration coefficient was elevated only in CPH. The transcapillary oncotic pressure gradient was not altered by APH or CPH. Interstitial fluid pressure was increased from -1.1 mmHg in CON to 3.9 mmHg during APH and to 5.0 mmHg in CPH. The results of this study indicate that chronic elevations in portal venous pressure produce larger increments in intestinal capillary pressure and filtration rate than do acute elevations in portal venous pressure of the same magnitude. However, the potential edemagenic effects of elevated capillary pressure in both acute and chronic portal hypertension are opposed by increases in lymph flow and interstitial fluid pressure.

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