Mesenteric blood system

Figure 38 Correlations between appearance permeability coefficients for a related series of peptides measured in mesenteric blood draining perfused rat ileal segments and Caco-2 cell monolayers in the Transwell system. See Table 14 for identification of the peptides. The Pe for the rat ileum was not corrected for the aqueous boundary layer and blood flow effects. [Redrawn from Kim et al. (1993) with permission from the publisher.]...

Absorption evaluation from luminal disappearance of drugs has been widely employed as a simple and easy method. Although the appearance of drugs in the mesenteric blood can provide a more sensitive way that enables to detect lower levels of absorption, it is technically more complicated, especially due to the colon s anatomical and morphological configuration. Another alternative for absorption evaluation is to measure drugs that appear in the systemic circulation, although this method cannot provide a direct measure of membrane permeability. 

A more direct approach for analyzing absorption characteristics than the sampling of systemic or excreted body fluids entails the sampling of portal blood [24] or the collection of the mesenteric blood draining the sites of absorption of the test substance. Such a procedure requires considerably more complicated surgical techniques than that of sampling systemic blood, urine, or breath. Furthermore, transfusions of blood into the animal may be required. An important advantage of this procedure is the... 

Because of its large size (200-800 pm), the chylomicron cannot permeate the blood capillaries, and as a result, is absorbed into a porous mesenteric lymph vessel called lacteal, and travels with the lymph until drainage into the systemic blood circulation. 

Lipids, unlike many excipients, whether present in food or as discreet pharmaceutical additives, are processed both chemically and physically within the GIT before absorption and transport into the portal blood (or mesenteric lymph). Indeed, most of the effects mediated by formulation-based lipids or the lipid content of food are mediated by means of the products of lipid digestion—molecules that may exhibit very different physicochemical and physiological properties when compared with the initial excipient or food constituent. Therefore, although administered lipids have formulation properties in their own right, many of their effects are mediated by species that are produced after transformation or activation in the GIT. An understanding of the luminal and/or enterocyte-based processing pathways of lipids and lipid systems is therefore critical to the effective design of lipid-based delivery systems. 

Stimulated lymphocytes are transported via lymphatic cells to the nearest mesenteric lymph nodes, and next to systemic immunological organs, and via the blood stream to other tissues. Stimulation or expiration of immunological responses occurs. Some lymphocytes return to the intestines, thanks to integrin a4p7 and CCR9 chemokine receptors. 

In the rabbit, delta opioid receptors may have a role in protecting the enterohepatic system from ischemic injury [151]. This effect may be related to the presynaptic inhibition of mesenteric arteriolar constriction and consequent preservation of blood flow by delta opioid agonists [152], However, vasoactive effects of opioids mediated by delta opioid receptors are not observed in the rat [153,154]. Delta-opioid receptors have a similar protective action in the myocardium, which is described in detail elsewhere in this volume. 

Various modifications are reported with respect to the experimental setup (single pass or recirculated intestinal perfusion) as well as the site of blood collection, e.g. mesenteric vessels for estimation of the intestinal absorption rate (DeGraw RT, Anderson BD 2004). vs. peripheral veins for estimation of systemic availability of the candidate compound. This method is widely used for investigation of intestinal absorption of nutrients by using radioactive tracers (e.g. cholesterol, glucose) and their interference with the candidate compound (Arts et al. 2004). In addition the secretion of the candidate compound into the intestine can be studied by peripheral administration of the compound into a peripheral vein and subsequent determination of the appearance of the candidate compound in the intestinal perfusate (Merino et al. 2003 Berggren et al. 2004). Also variations are reported using chronically isolated intestinal loops in rats (Poelma et al. 1992). 

Blood from the haemorrhoidal venous plexus passes via the azygous superior rectal vein into the inferior mesenteric vein and thereafter into the portal vein. By contrast, the paired middle rectal vein and inferior rectal vein discharge their blood via the iliac vein into the inferior vena cava. In portal hypertension, anorectal varices are found in the region of the rectum, the anal canal and the external anal region. Haemorrhoids are distended and dislocated cavernous bodies in the rectum, which have no connection to the portal venous system. Although haemorrhoids and anorectal varices are two different clinical pictures, it is quite possible for them to occur simultaneously. The frequency of anorectal varices (40-80%) is dependent upon the extent and duration of portal hypertension. The bleeding tendency is low (7-14%). However, there have also been reports of massive haemorrhages. (21,45,55,66,83,105,156) (s. tab. 14.10)... 

Previous shunt operations and TIPS need to be removed in order to guarantee that the transplanted liver is sufficiently supplied with portovenous blood. In these cases, the portal system is checked preoperatively for thromboses by means of colour-encoded duplex sonography and X-ray techniques. In any case, the confluence of superior mesenteric vein and splenic vein must be free. (391) The main advantage of portacaval end-to-side anastomosis is its low thrombosis rate of < 5% in addition, there is no need for a distal shunt ligature. In shunts distal to the hilus (mesocaval, distal splenorenal), no preparation of the liver hilus is required however, in 10% of cases, these shunts show portal vein thrombosis (in TIPS, up to 15%). Usually, all surgical shunts are disconnected or ligated before the liver transplantation is completed in order to... 

Although a1B-knockout mice showed significantly reduced blood pressure, they displayed reduced, instead of increased, systemic arterial blood pressure compared to WT (39) and a normal contractile response of mesenteric segments to a,-agonists (39). The mechanism of the hypotension is likely the autonomic failure that characterizes the a1B-transgenic mice, indicating that a1B-ARs are not significant players in vasoconstriction. 

Effects of cannabinoids on the sympathetic nervous system have been studied in isolated tissues and in pithed animals (Table 4). Sympathetic neurons were usually activated by electrical stimulation. Activation of CBi receptors led to inhibition of noradrenaline and/or ATP release and, consequently, to inhibition of the effector responses in the heart, in mesenteric and renal blood vessels and in the vas deferens. Figure 5A shows that cannabinoids inhibit sympathetic neuroeffector transmission in the heart. Sympathetically mediated vasoconstriction was inhibited in many tissues of pithed rats and rabbits. Sympathetic tone is depressed during long-term A -tetrahydrocannabinol administration in humans the presynaptic inhibitory effect of cannabinoids on sympathetic axon endings maybe the basis of this effect. 

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