Distribution Of Intestinal Blood Flow Research Articles

Regional Blood Flow Distribution and Oxygen Metabolism During Mesenteric Ischemia and Congestion

Acute mesenteric ischemia is a potentially fatal vascular emergency with mortality rates ranging between 60% and 80%. Several studies have extensively examined the hemodynamic and metabolic effects of superior mesenteric artery occlusion. On the other hand, the cardiocirculatory derangement and the tissue damage induced by intestinal outflow obstruction have not been investigated systematically. For these reasons we decided to assess the initial impact of venous mesenteric occlusion on intestinal blood flow distribution, and correlate these findings with other systemic and regional perfusion markers. Fourteen mongrel dogs were subjected to 45 min of superior mesenteric artery (SMAO) or vein occlusion (SMVO), and observed for 120 min after reperfusion. Systemic hemodynamics were evaluated using Swan-Ganz and arterial catheters. Regional blood flow (ultrasonic flow probes), intestinal O(2)-derived variables, and mesenteric-arterial and tonometric-arterial pCO(2) gradients (D(mv-a)pCO(2) and D(t-a)pCO(2)) were also calculated. SMVO was associated with hypotension and low cardiac output. A significant increase in the regional pCO(2) gradients was also observed in both groups during the ischemic period. After reperfusion, a progressive reduction in D(mv-a)pCO(2) occurred in the SMVO group; however, no improvement in D(t-a)pCO(2) was observed. The histopathologic injury scores were 2.7 +/- 0.5 and 4.8 +/- 0.2 for SMAO and SMVO, respectively. SMV occlusion promoted early and significant hemodynamic and metabolic derangement at systemic and regional levels. Additionally, systemic pCO(2) gradient is not a reliable parameter to evaluate the local intestinal oxygenation. Finally, the D(t-a)pCO(2) correlates with histologic changes during intestinal congestion or ischemia. However, minor histologic changes cannot be detected using this methodology.

Perfusion pressure manipulation in porcine sepsis: effects on intestinal hemodynamics

Limited information is available about selection of the threshold for arterial blood pressure in critically ill patients, particularly in sepsis when normal organ blood flow autoregulation may be altered. The present experimental study investigated whether increasing perfusion pressure using norepinephrine in normotensive hyperdynamic porcine bacteremia affects intestinal macro- and microcirculation. Nine pigs received continuous i.v. administration of Pseudomonas aeruginosa (PSAE) to develop hyperdynamic, normotensive (mean arterial pressure [MAP] 65 mm Hg) sepsis. Norepinephrine was used to achieve 10-15 % increase in MAP. Mesenteric arterial blood flow (Q(gut)), ileal mucosal microvascular perfusion (LDF(gut)) and ileal-end-tidal PCO(2) gap (PCO(2) gap) were measured before norepinephrine, after 60 min of norepinephrine infusion and 60 min after norepinephrine infusion had been discontinued. During a 12 h period of PSAE infusion all pigs developed hyperdynamic circulation with significantly decreased MAP. Although the mesenteric blood flow remained unchanged, infusion of PSAE resulted in a gradual fall of ileal microvascular perfusion, which was associated with progressively rising PCO(2) gap. Norepinephrine which induced a 10-15 % increase in perfusion pressure (i.e. titrated to attain near baseline values of MAP) affected neither Q(gut) nor the intestinal blood flow distribution (Q(gut)/CO). Similarly, norepinephrine did not change either LDF(gut) or PCO(2) gap. In this hyperdynamic, normotensive porcine bacteremia, norepinephrine-induced increase in perfusion pressure exhibited neither beneficial nor deleterious effects on intestinal macrocirculatory blood flow and ileal mucosal microcirculation. The lack of changes suggests that the gut perfusion was within its autoregulatory range.

Effects of norepinephrine on the distribution of intestinal blood flow and tissue adenosine triphosphate content in endotoxic shock.

To investigate, during endotoxic shock, the effect of a treatment of norepinephrine (NE) administration on the distribution of blood flow and adenosine triphosphate (ATP) content in the intestinal wall. Randomized controlled trial. Animal laboratory. Domestic pigs. A total of 18 pigs were anesthetized with ketamine and pentobarbital, mechanically ventilated, hemodynamically monitored, and then challenged with a continuous infusion of Escherichia coli endotoxin (ET) (15 microg/kg) for 2 hrs. Three groups of six animals were studied; one served as time control, one group received ET and fluid resuscitation, and a third group received ET, fluid resuscitation, and a perfusion of NE to maintain constant mean arterial pressure (MAP). Cardiac output, mesenteric arterial blood flow, MAP, pulmonary pressure, and portal pressure were measured. Intestinal mucosal intracellular pH (pHi) was determined with saline-filled balloon tonometers. Tissue blood flows to the intestinal mucosa and to the muscular layer were independently measured with fluorescent microspheres, using the arterial reference sample method. Measurements were performed before and 3 hrs after the start of the ET challenge. At the end of the experiments, muscularis and mucosal samples were quickly frozen for further enzymatic ATP measurements. ET administration with fluid resuscitation induced a distributive shock with increased mucosal blood flow and decreased muscularis blood flow, whereas pHi decreased and mucosal ATP content was significantly lower than in the control group. In the group receiving ET plus NE, MAP remained constant, mucosal blood flow did not increase, and mucosal ATP content was equal to the time control group. Meanwhile, mucosal acidosis was not prevented. Normodynamic endotoxic shock may induce an alteration in mucosal oxygenation, despite an increased tissue blood flow. A treatment of NE combined with fluid resuscitation has complex effects on tissue blood flow, ATP content, and pHi.

Nitric oxide modulates regional blood flow differences in the fetal gastrointestinal tract.

We studied the role of endogenous nitric oxide (NO) in the regulation of gastrointestinal (GI) circulation in 11 chronically instrumented and unanesthetized late-gestation fetal sheep. Systemic and GI blood flows were measured by the radiolabeled microsphere technique. Mean arterial pressure (MAP), heart rate, blood flows, oxygen delivery, and vascular resistance were determined before and after infusion of the specific NO synthase inhibitor, N omega-nitro-L-arginine (L-NNA), to cumulative doses of 10 and 25 mg/kg. At both L-NNA doses, MAP increased, and combined ventricular output and heart rate decreased. GI blood flow and oxygen delivery decreased and vascular resistance increased for the stomach, all segments of the small intestine, and proximal colon and cecum but were unchanged in the middle and distal colon and rectum. Because blood flow reduction in the small intestine was pronounced (from 176 to 107 ml.min-1.100 g-1, P < 0.001) and blood flow in the large intestine was unchanged, distribution of intestinal blood flow became more uniform. Overall, blood flow reduction was proportionally greater in GI circulation than in the remainder of fetal circulation. In three additional animals we established that L-NNA reduced blood flow to the mucosal-submucosal layer (P < 0.02) but not to the muscularis serosa of the small intestine. In the same animals, L-arginine (250 mg/kg) restored systemic hemodynamics and partially restored small intestinal blood flow. Our results suggest that NO is an important differential regulator of vascular tone in the developing GI circulation.

Effects of peptide YY on intestinal blood flow distribution and motility in the dog

Previous investigators in our laboratory have demonstrated that peptide YY (PYY), a putative gut hormone, exerts a potent emetic effect when administered intravenously to conscious dogs. The current study was carried out to examine the effects of an emetic dose of PYY on cardiovascular status, splanchnic blood flow distribution (estimated using 15 μm microspheres) and small intestinal motility in anesthetized dogs. PYY, infused i.v. at a dose of 25 pmol/kg/min led to a localized significant reduction in small intestinal muscularis externa blood flow both 15 and 30 min after the start of PYY infusion in both jejunum and ileum. This decreased muscularis perfusion was not accompanied by any significant change in whole gut wall blood flow and was explained on the basis of an observed significant redistribution of blood flow away from the muscularis towards the mucosa/submucosa. Similar, although non-significant, effects of PYY on colonic blood flow distribution were also observed. Despite the effects on jejunum and ileum, PYY exerted minimal effects on duodenal blood flow. The decrease in ileal and jejunal muscularis blood flows was accompanied by a significant increase in the amplitude of intestinal contractions in these regions. Frequency of contractions was unaltered however. These results demonstrate that PYY infusion leads to concurrent changes in small intestinal blood flow and motility.

Intestinal absorption of glandular kallikrein in the rat.

We studied the possibility of intestinal absorption of glandular kallikrein in unanesthetized rats after administration of 5 mg of active or phenylmethylsulfonyl fluoride-inactivated pig pancreatic kallikrein (PPK). Immunoreactive PPK was measured in plasma and urine by radioimmunoassay using an antiserum to PPK that does not cross-react with rat glandular kallikrein. In addition, we studied the effect of intestinally administered active PPK on the intestinal blood flow distribution. Although immunoreactive PPK could not be detected (less than 10 ng/ml) in plasma after active PPK was administered, very small amounts were found in urine (20-40 ng/3 h). In the urine most of the PPK was in active form because over 75% could be bound to aprotinin-Sepharose. After inactive PPK was administered, immunoreactive PPK was detectable in the plasma of all rats, and urinary excretion was higher than after administration of active PPK. Blood flow distribution to the small intestine as a percentage of cardiac output was significantly greater 30 min after intestinal application of active PPK (5 mg) than after administration of the vehicle alone (1 ml of 0.9% saline). These results suggest that active and inactive PPK is absorbed from the gut in very small amounts. The finding of higher amounts of immunoreactive PPK in plasma and urine after inactive PPK was administered is probably due to the fact that the inactive form of the enzyme is not bound by the plasma inhibitors. These small amounts of kallikrein absorbed appear to have some effect on intestinal blood flow distribution.

Vasodilation or altered perfusion pressure moves 15-micrometers spheres trapped in the gut wall.

To determine whether the microsphere method for measuring the intramural distribution of intestinal blood flow is affected by perfusion pressure or vasodilation, we infused radioactive 9- and 15-micrometers spheres into adjacent segments of isolated canine small bowel. After sphere infusion the blood supply of the control loop was occluded, and the vasculature of the experimental loop was either dilated by infusing isoproterenol or was subjected to increased perfusion pressure. Intestinal segments were dissected into mucosal, submucosal, and muscularis samples. Venous blood was collected during sphere infusions and experimental perturbations. Accumulations of spheres in tissue samples and venous blood were assessed in a gamma radioactivity counter. Isoproterenol caused previously infused spheres to leave submucosa and redistributed them primarily to mucosa with few additional spheres reaching venous blood. An increase in perfusion pressure also dislodged spheres from submucosa, but these did reach venous blood. The combined estimate of mucosal plus submucosal blood flow was relatively unaffected by isoproterenol infusion but was significantly altered by increased perfusion pressure. These results have the following implications for microsphere studies of the intramural distribution of intestinal blood flow: 1) tissue must be sampled after each sphere infusion unless the possibility of sphere migration has been experimentally eliminated and 2) even a two-compartment fractionation of blood flow into muscularis and mucosal-plus-submucosal compartments is not valid under some experimental conditions.

Role of capillary recruitment in the regulation of intestinal oxygenation

Increasing evidence indicates that capillary recruitment plays a significant role in regulating the oxygenation of intestinal tissue. Measurements of permeability-surface area product (PS) and capillary filtration coefficients (Kf) in isolated perfused gut loops indicate that changes in capillary density modulate oxygen extraction in a variety of experimental circumstances. Moreover, the intestinal microvasculature seems capable of independently regulating resistance and capillary exchange. Although "precapillary sphincters" have been identified in the intestine, the capillary density changes have not yet been confirmed by intravital microscopy, as they have been in skeletal muscle. Nevertheless, these changes in capillary density have quantitatively significant effects on oxygen extraction. For example, sympathetic stimulation depresses oxygen uptake in gut loops perfused at constant blood flow, presumably by reducing capillary density to such an extent that oxygen extraction becomes diffusion limited. The microvascular elements that control intestinal capillary density (presumably precapillary sphincters) are apparently under the control of neurogenic, myogenic, and local metabolic mechanisms, but the interaction among these mechanisms is poorly understood. In addition, the PS and Kf data, although well documented, could result from a redistribution of blood flow or an alteration in capillary permeability rather than a change in capillary density. Thus, the physiological mechanisms regulating capillary permeability and the intramural distribution of intestinal blood flow will have to be better understood before the role of capillary recruitment in regulating intestinal oxygenation will be firmly established.

Effect of microsphere size on apparent intramural distribution of intestinal blood flow.

Microspheres were used in earlier studies to determine the distribution of blood flow within the intestinal wall, but the selection of microsphere size was not systematic. In one study, a 5-micrometers difference in mean diameter markedly altered the submucosal vs. mucosal distribution of microspheres. Therefore, we examined the effect of size on microsphere distribution within the gut wall. Loops of canine small bowel were perfused at constant pressure, and microspheres were injected in the following order: 9 +/- 1, 15 +/- 1, and 26 +/- 2 micrometers. Gut segments were separated into mucosal, submucosal, and muscularis tissues. The microspheres were recovered from digested tissues and venous blood. The number and diameter of spheres in an aliquot of resuspended spheres were determined by digital image analysis. The ratio of mucosal to submucosal accumulation varied 60-fold for sphere diameters from 8 to 20 micrometers. The muscularis' share did not vary systematically with sphere size. Approximately 20% of spheres less than 11 micrometers reached venous blood, whereas few (less than 1%) of larger sizes did. We conclude: 1) sphere distribution within the gut wall is size dependent, 2) correction for microsphere shunting will be difficult, because the route taken by untrapped spheres is unknown, and 3) fractionating intramural flow among the three layers is not practical with commercially available spheres. However, under control conditions 15-micrometers spheres seem to distribute independently of size between muscularis and a lumped mucosal-submucosal compartment.