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Biomedical subjects

D Mailman

Publications and source records attributed to D Mailman.

At least 37 records · Page 2Linked to original sources

Relationships between intestinal absorption and hemodynamics.

There are many interactions between intestinal blood flow and absorption. These include the support of transcellular transport by O2 delivery; the passive effects of Starling forces on absorption, secretion, and mucosal conductance; the washout of absorbed materials; and countercurrent exchange. Blood flow hemodynamics, and absorption interact. Regulatory mechanisms add a tertiary influence to these interactions. Further progress in this area would be greatly helped by techniques that could measure blood flow and hemodynamic factors at the absorptive and secretory sites more precisely.

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Blood flow an intestinal absorption.

Intestinal blood flow interacts with intestinal absorption at several levels and affects absorption through several mechanisms. The precise relationships are difficult to define because, at present, there is not an adequate technique available for measuring blood flow to the absorptive site. The absorption of certain nutrients requires O2 delivered through the blood for maintenance of carrier-mediated transcellular transport. Both altered capillary pressure, which may or may not accompany altered blood flow because of myogenic autoregulation, and changes in absorption can influence tissue hydrostatic and colloid osmotic pressure and also epithelial and interstitial space conductance. These latter, in turn, can change the rate of passive ultrafiltration for a constant driving force. Changes in blood flow can also influence the rate of washout of absorbed substances. Countercurrent exchange in the villous vasculature can buffer the rate of absorption of some substances and may also facilitate the absorption of water. Regulatory agents such as hormones or neurotransmitters can affect blood flow and absorption both independently and interactively. Agents that cause active intestinal secretion may have their effects modified by consequent changes in blood flow.

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Effects of morphine on canine intestinal absorption and blood flow.

1 Intestinal absorption and blood flow were determined in anaesthetized fed or fasted dogs following rapid intravenous injections of morphine (0.01, 0.1, 1 mg/kg). 2 3H2O and 22Na were used to determine the unidirectional fluxes of Na+ and H2O from saline perfused through the ileal lumen and the clearances of 3H2O were used to determine total and absorptive site blood flow. 3 Net Na+ and H2O absorption were increased at each dose of morphine in fed but not in fasted dogs, due primarily to increased absorptive fluxes. 4 Arterial pressure was decreased by morphine but mesenteric vein pressure was little affected. Absorptive site blood flow was increased by morphine due to decreased blood flow resistance but total blood flow resistance was little affected by morphine. 5 The absorptive fluxes of Na+ and H2O were correlated with absorpitve site blood flow in both fed and fasted animals. The secretory fluxes of Na+ and H2O were correlated with estimated capiliary pressure in fasted dogs but morphine decreased the the secretory fluxes at a given capillary pressure in dogs which had been fed. 6 Naloxone (0.12 mg, i.v.) reversed the effects of morphine. The effects of morphine on the gut were reversed more slowly than on systemic blood pressure. 7 It was concluded that morphine can increase net absorption in fed dogs by a selective increase in intestinal absorptive site blood flow and thus increase absorptive fluxes by a washout effect but that there is also an epithelial effect, sensitized by feeding, which reduces the secretory fluxes of Na+ and H2O.

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Effects of pentagastrin on intestinal absorption and blood flow in the anaesthetized dog.

1. Pentagastrin (1, 10 micrograms/min) was infused I.V. into fed and fasted anaesthetized dogs and the intestinal absorption of NaCl and H2O and blood flow were determined. The influence of pentagastrin-induced cardiovascular changes on absorption was investigated. 2. 22Na and 3H2O were used to determine the unidirectional Na and H2O fluxes from saline perfused through the ileal lumen and the clearances of 3H2O were used to calculate total and absorptive site blood flow. 3. Ileal absorption of Na and H2O was reduced by 10 micrograms/min pentagastrin due primarily to significant increases in the secretory flux of Na and decreases in the absorptive flux of H2O in both fed and fasted animals. 4. Neither total intestinal blood flow, arterial nor mesenteric vein pressure were changed by pentagastrin but absorptive site blood flow was decreased in fasted but not in fed dogs. 5. Pretreatment with atropine reduced the effects of pentagastrin but pretreatment with guanethidine potentiated the effects of pentagastrin. 6. Absorptive site blood flow was positively linearly correlated with the absorptive fluxes of both Na and H2O. The relationships between the secretory fluxes of Na and H2O and estimated capillary pressure were changed from a positive relationship in control periods to a less positive or negative relationship following pentagastrin. 7. It was concluded that pentagastrin reduces intestinal absorption through both a cardiovascular effect and an effect on the intestinal epithelium. Also, there is a strong autonomic component in the effects of pentagastrin on intestinal absorption.

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Intrinsic regulation of functional blood flow and water absorption in canine colon.

1. Autoregulation of total and absorptive site blood flow and H2O fluxes were studied in canine colon during arterial pressure decreases and venous pressure elevations. 2. Reductions in arterial pressure caused proportional decreases in total colonic blood flow indicating no autoregulatory ability. In contrast, absorptive site blood flow was constant over an arterial pressure range of 40-140 mmHg but decreased sharply below 40 mmHg. 3. Venous pressure elevation decreased total blood flow and increased resistance but had no effect on absorptive site blood flow over a range of 0-30 mmHg. 4. Net H2O absorption was unchanged by alteration of arterial or venous pressure but the unidirectional H2O fluxes decreased with arterial pressure reduction and were unchanged by venous pressure elevation. 5. Adenosine infusion increased total and absorptive site blood flow and the unidirectional H2O fluxes yet had no effect on net H2O flux. 6. It was concluded that absorptive site blood flow is very well autoregulated in the colon but total blood flow is not. Net H2O absorption is maintained during decreased blood flow by maintenance of blood flow to the mucosa and by decreasing the back flux of H2O across the mucosa.

Adenosine↗

Permeability characteristics of colonic capillaries.

Blood flow, lymph flow, lymph protein concentration (CL), lymph oncotic pressure, plasma protein concentration (CP), and plasma oncotic pressure were determined under steady-state conditions at venous pressures of 0, 10, 20, 30, and 40 mmHg in autoperfused segments of dog colon. Venous pressure elevation increased colonic vascular resistance, lymph flow, lymphatic protein flux, and the transcapillary oncotic pressure gradient, whereas the lymph-to-plasma protein concentration ratio (CL/CP) declined. The osmotic reflection coefficient (sigma d) was estimated using sigma d = 1-CL/CP when CL/CP is filtration independent (high lymph flows). For total protein sigma d = 0.85 +/- 0.02. Values of sigma d for plasma protein fractions with molecular radii ranging between 37 and 120 A increased as molecular radius increased. The results of this study suggest that 1) colonic capillaries selectively restrict macromolecules on the basis of molecular size, and 2) an increased lymph flow and transcapillary oncotic pressure gradient may play an important role in preventing interstitial edema subsequent to venous pressure elevation in the dog colon.

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Effects of vasoactive intestinal polypeptide on intestinal absorption and blood flow.

1. Intestinal absorption and blood flow in anaesthetized dogs was determined after I.V. infusion of vasoactive intestinal polypeptide (VIP) (1.75-175 ng/min) to determine the contribution of the cardiovascular changes to transport. 2. 22Na and 3H2O were utilized to determine the unidirectional fluxes of Na and H2O from saline perfused through the ileal lumen and the clearances of 3H2O were used to determine total and absorptive site blood flow. 3. Net Na and H2O absorption were reversed to secretion by VIP at 175 ng/min due to a significant decrease in unidirectional absorptive fluxes and smaller increases in secretory fluxes. 4. Arterial pressure and absorptive site blood flow were reduced in proportion to the changes in Na and H2O fluxes. 5. Total and absorptive site blood flow decreased and the blood flow resistances increased. 6. Prior treatment with guanethidine to suppress sympathetic effects did not greatly affect the responses to VIP. Prior treatment with atropine to suppress cholinergic effects inhibited most of the effects of VIP. 7. Absorptive site blood flow was linearly related to absorptive fluxes of Na and H2O but with different slopes for results from atropinized dogs as compared to those from dogs given VIP alone or VIP plus guanethidine. 8. It was concluded that VIP reduces gut absorption through a generalized cardiovascular effect and also through a mechanism which depends on the release of ACh by the gut.

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Effects of glucagon on canine intestinal sodium and water fluxes and regional blood flow.

1. Glucagon (0-05 or 0-5 microng/kg. min) was infused into a mesenteric artery of a canine ileal segment from which transport was measured (direct infusion) or into a mesenteric artery of an adjacent non-perfused segment (indirect infusion). Unidirectional Na and H2O fluxes and arterial and mesenteric vein pressures and total and absorptive site blood flows were measured. 2. Direct glucagon infusion increased the absorptive and secretory fluxes of Na and H2O and absorptive site blood flow, and decreased absorptive site resistance and arterial and mesenteric vein pressure. Indirect glucagon infusion had the opposite effects. 3. Neither the direct arterial infusion of histamine (0-1-53 microng/kg. min) nor the I.V. infusion of glucose (0-2 g/min) or insulin (0-1 micron/kg) or glucose plus insulin, mimicked the effects of glucagon. 4. The unidirectional secretory and absorptive fluxes of both Na and H2O were linearly related to the calculated capillary pressure during glucagon infusion. 5. It was concluded that the effects of glucagon on gut transport were due to effects exerted through the cardiovascular system.

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Cyclic nucleotide metabolism and vasodilation in canine mesenteric artery.

The uptake and extracellular and intracellular metabolism of radioisotopically labeled cyclic 3',5'-adenosine monophosphate (cAMP) and dibutyryl cAMP (DBcAMP) was determined in canine mesenteric arteries incubated in vitro. Intracellular tissue uptake was measured by radioisotope counting and labeled metabolites separated by thin-layer chromatography. Extracellularly, cAMP was extensively metabolized to AMP, adenosine, and Pi. DBcAMP was metabolized to monobutyryl cAMP (MBcAMP) intracellularly. Vasodilation of the mesenteric circulation in vivo was produced by cAMP, its metabolites and DBcAMP. DBcAMP caused greater vasodilation than cAMP but had a response time to its peak effect of 12 min versus 90 s for cAMP. The vasodilator properties of cAMP and DBcAMP were related to their metabolism. It was concluded that the vasodilation caused by cAMP was due to cAMP metabolites produced by extracellular metabolism.

Adenosine↗

Dopamine effects on the intestinal circulation.

The effects of intra-arterial infusion of dopamine on superior mesenteric artery blood flow, intestinal flow, intestinal oxygen consumption, and capillary density were studied in anesthetized dogs before and after blockade of dopamine receptors with haloperidol and after beta-adrenergic receptor blockade with propranolol. Mesenteric blood flow to a distal segment of the small intestine was measured with an electromagnetic blood flow-meter and intestinal oxygen consumption was calculated from the measured arteriovenous oxygen difference across the intestine and total blood flow. Intestinal capillary density was estimated from the clearance of 86Rb. In normal animals prior to dopaminergic or beta-adrenergic blockade, dopamine caused a dose-related decrease in mesenteric blood flow, intestinal oxygen consumption, and 86Rb clearance. Only the lowest dose of the drug, 1 mug/Kg.-min., did not significantly change the intestinal capillary density. In dogs pretreated with the dopamine receptor, antogonist, haloperidol, dopamine (20 mug/Kg.-min.) caused a significant increase in blood flow and oxygen consumption and did not significantly alter the number of perfused intestinal capillaries. These increases in haloperidol-blocked animals administered dopamine were reversed by propranolol. Our results indicate that dopamine caused smooth muscle contraction in mesenteric arterioles and precapillary sphincters, thereby producing intestinal ischemia and hypoxia. These findings with haloperidol and propranolol indicate that dopamine stimulates at least two different receptors in the canine mesenteric vascular bed: a constrictor receptor blocked by haloperidol and a dilator receptor blocked by propranolol.

Blood Pressure↗

Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction.

To delineate the mechanism through which vasoactive compounds alter intestinal oxygen consumption and to determine the pharmacological nature of the receptors involved, we quantitated the effects of vasoconstrictors on arteriovenous oxygen difference and on vascular resistance in isolated constant-flow perfused canine small bowel. Norepinephrine (NE) and sympathetic stimulation (SS) increased vascular resistance and depressed O2 extraction. These effects were not altered by beta-blockade, but were abolished by alpha-blockade. Since capillary filtration coefficients at constant-pressure perfusion and 86Rb extraction at constant flow are reported to diminish during NE and SS, it follows that these agents reduce O2 extraction by an alpha-adrenergic closure of precapillary sphincters. Vasopressin had similar effects which were not affected by adrenergic blocking agents. Epinephrine (Epi) in high doses or after propranolol produced the same effects as NE and SS. By contrast, Epi in low doses increased O2 and 86Rb extraction. This response to low doses of Epi was not affected by phentolamine, but was reversed by propranolol. We conclude that Epi in high doses or after propranolol depresses intestinal O2 extraction by the same mechanism as NE and SS, but the mechanism through which Epi increases intestinal O2 extraction is unclear.

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The effect of saline and hyperoncotic dextran infusion on canine ileal salt and water absorption and regional blood flow.

1. The unidirectional Na and H2O fluxes, vascular pressures and total and absorptive site blood flows in the canine ileum were determined before and during I.V. saline infusion and subsequent I.V. infusion of hyperoncotic dextran. The intestinal perfusion solutions were isotonic saline or isotonic saline and mannitol, but the effects of I.V. saline or I.V. hyperoncotic dextran infusion were generally the same for both luminal solutions. 2. Continuous I.V. infusion of saline caused a continuous increase in the unidirectional flux of Na and H2O into the ileal lumen, an increase in total blood flow, and an increase in venous pressure. 3. The net absorption of Na and H2O was decreased by I.V. saline infusion. 4. The unidirectional fluxes of Na and H2O out of the lumen, arterial pressure, and absorptive site blood flow were not affected by I.V. saline infusion. 5. I.V. hyperoncotic dextran infusion reversed most of the effects of saline infusion. 6. The unidirectional fluxes of Na and H2O into the lumen were significantly correlated with Starling forces during I.V. saline infusion. 7. It was concluded that intestinal transport of salt and water was subject to regulation by physical forces at the capillary level.

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