Search

BACKGROUND Portal vein resection and reconstruction in locally advanced pancreatic cancer represents a potentially curative treatment in selected patients without increasing surgical mortality. However, vascular reconstruction after segmental venous resection is challenging. The parietal peritoneum has emerged as a venous substitute but few reports include its use as a tubular graft. We report a retrospective series of portal vein reconstruction using a falciform ligament tubular graft during pancreaticoduodenectomy. MATERIAL AND METHODS Technical aspects and short-term morbidity and mortality after pancreaticoduodenectomy with falciform ligament tubular graft interposition were analyzed. RESULTS Among 21 patients who used parietal peritoneum for venous substitution between 2015 and 2019, eight underwent pancreaticoduodenectomy with venous resection and reconstruction using interposition of falciform ligament tubular graft. The mean duration of surgery and clamping time were 350 and 27 min, respectively. No perioperative blood transfusion was required. All the grafts were patent the day after surgery. No complication related to venous obstruction was detected during the hospital stay. Two patients had postoperative pancreatic fistula. No further intervention was needed. The 90-day mortality was null. CONCLUSIONS The use of interposition of falciform ligament tubular graft for portal venous reconstruction during pancreaticoduodenectomy seems to be a reliable, inexpensive, and safe procedure.

Aim The aim of this study was to evaluate the arterial collateral vasculature between the superior mesenteric artery and the inferior mesenteric artery (IMA) from a surgical perspective. Method A total of 107 fresh adult cadavers (94 male) were studied with emphasis on the vascular anatomy of the left colon. Dissections were carried out mimicking the anterior resection technique. The vasculature of the left mesocolon and the collaterals between the superior mesenteric artery and the IMA with respect to their relationship to the inferior mesenteric vein (IMV) were assessed and classified. Collaterals were classified into three different groups: marginal anastomoses (via the marginal = pericolic artery), intermediate mesocolic anastomoses (parallel to the marginal artery but neither adjacent to the IMV nor close to the duodenum) and central mesocolic anastomoses (next to the IMV at the level of the duodenojejunal junction and the lower border of the pancreas). Results All patients had a marginal anastomosis. However, the marginal anastomosis, as the only anastomosis between the superior and inferior mesenteric arteries at the splenic flexure, was observed in 41 cases (38%). In addition to the marginal artery, intermediate mesocolic anastomoses were found in 49 (46%) and a central mesocolic anastomosis was observed in 17 (16%) of the 107 cases in the splenic flexure mesocolon. It is in this latter variant that collateral vessels can be compromised during ligation/transection of the IMV. Conclusion This new classification can contribute to a precise mesocolic dissection technique and splenic flexure mobilization and help prevent ischaemic damage to the descending colon.

Aim Recently, the accessory middle colic artery (AMCA) has been recognized as the vessel that supplies blood to the splenic flexure. However, the positional relationship between the AMCA and inferior mesenteric vein (IMV) has not been evaluated. Herein, we aimed to evaluate the anatomy of the AMCA and the splenic flexure vein (SFV). Method Two hundred and five patients with colorectal cancer who underwent enhanced CT preoperatively were enrolled in the present study. The locations of the AMCA and IMV were evaluated, focusing on the positional relationship between the vessels and pancreas - below the pancreas or to the dorsal side of the pancreas. Results The AMCA was observed in 74 (36.1%) patients whereas the SFV was found in 177 (86.3%) patients. The left colic artery (LCA) was the major artery accompanying the SFV in 87 (42.4%) of patients. The AMCA accompanied the SFV in 65 (32.7%) patients. In 15 (7.8%) patients, no artery accompanied the SFV. The origin of the AMCA was located on the dorsal side of the pancreas in 15 (20.3%) of these 74 patients. Similarly, the destination of the IMV was located on the dorsal side of the pancreas in 65 (31.7%) of patients. Conclusion The SFV was observed in most patients, and the LCA or AMCA was the common accompanying artery. In some patients these vessels were located on the dorsal side of the pancreas and not below it. Preoperative evaluation of this anatomy may be beneficial for lymph node dissection during left-sided hemicolectomy.

Aim Complete mesocolic excision (CME) with central vascular ligation (CVL) has been advocated for right colon adenocarcinoma (RC), but the radicality of vascular dissection remains controversial. Our aim is to report outcomes of selective CVL (D3 lymphadenectomy) during minimally invasive CME for RC. Method A prospective database identified patients who were treated for RC between 2009 and 2016. Minimally invasive CME was standard. The radicality of lymphadenectomy was defined as high ligation (HL) versus CVL based on operative reports and videos. Two blinded radiologists independently evaluated the pre- and postoperative CT scans for radiographically abnormal nodes. Results Of 197 patients who underwent CME, HL was performed in 56 (28%) and CVL in 141 (72%). There were no baseline differences in age, sex, body mass index, American Society of Anesthesiologists score or pathological staging, and there were no major intra-operative complications in either group (including no major vascular injuries). The median total number of nodes retrieved was 27 and 31 (P = 0.011) in HL and CVL groups, resepctively, with pathologically positive nodes identified in 33.9% and 39.8% (P = 0.704), respectively. Preoperative imaging identified abnormal cN3 nodes in 1.5% of patients; all of whom underwent CVL. No abnormal cN2 or cN3 nodes remained on postoperative imaging. The 60-day mortality was 0.5%, and major morbidity was 4%. One patient (0.5%) had an anastomotic recurrence after a median follow-up of 22 months. Conclusion With imperfect preoperative clinical nodal staging, and in the absence of randomized data, the low morbidity and oncological outcomes observed support the approach of CME with HL as a minimum standard, with CVL (D3 lymphadenectomy) in selected cases.

AIM Colon ischaemia (CI) is most commonly an acute and reversible manifestation of a transient, non-occlusive decrease of blood flow in the colonic microvasculature. Irreversible complications are uncommon and the progression to chronic CI remains controversial. Our objective was to identify cases of chronic CI and assess for distinct clinicopathological features. METHOD A retrospective review was performed of CI patients having symptom chronicity of ≥ 1 month and ischaemic histology at our institution from 1994 to 2015. Demographic, clinical, endoscopic, radiological, pathological and outcome variables were abstracted. Histological evaluation was performed by two gastrointestinal pathologists. RESULTS Fifteen patients (n = 9; 67% men) with a median age of 65 years (range 22-88) were identified. The most common presenting symptoms were diarrhoea and abdominal pain (n = 6, 86%; n = 5, 71%, respectively). The typical endoscopic appearance was segmental ulceration of the sigmoid colon (n = 6, 75%). Vascular imaging showed patent mesenteric vessels in all patients. Histopathological evaluation revealed venous intimal hyperplasia consistent with idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) in eight patients; the remainder showed non-specific ulceration and fibrosis. Surgical resection was performed in seven IMHMV patients, resulting in symptom resolution. On re-review of pre-resection biopsies, all IMHMV patients had characteristic changes of hyperplastic, thick-walled, hyalinized vessels in the lamina propria. CONCLUSIONS IMHMV is a unique histopathological entity causing chronic CI. The small vessel histological changes in IMHMV are distinctive in colonic resections and undetectable by routine vascular imaging. Preoperative diagnosis of IMHMV is possible with endoscopic biopsy and segmental colon resection is curative.

Background and aims: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. Methods: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008-2018). Recursive partition analysis (RPA) was performed to evaluate interactions between MaVI, clinical variables and treatment, exploring the inter-relationship determining overall survival. Results: MaVI prevalence was 11.1%, and median survival of these patients was 6.0months (95% CI, 5.1-7.1). MaVI was associated with younger age at diagnosis, presence of symptoms, worse Performance Status (PS) and liver function, high alphafetoprotein levels and large HCCs. MaVI extension was associated with worse PS, ascites and greater impairment in liver function. RPA identified patients' categories with different treatment indications and survival, ranging from 2.4months in those with PS>1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1months in patients with PS 0-1, no ascites and Vp1-Vp2 MaVI (treated with surgery in 19.1% of cases). Conclusions: MaVI presence and extension, together with PS and ascites, significantly affect patients' survival and treatment selection. The decision tree based on these parameters may help assess patients' prognosis and inform therapeutic decisions.

This case report describes a 13-year 10-month-old girl who underwent a deceased-donor split LT for primary diagnosis of biliary atresia at the age of 12 months, who presented with a lower GI bleed. Ultrasound and CT revealed a venous vascular anomaly involving the cecum and ascending colon, with communication of the SMV and pelvic veins consistent with a CEPS. Associated varices were noted in the pelvis along the uterus and urinary bladder. These findings were confirmed by trans-hepatic porto-venography, which was diagnostic and therapeutic as a successful embolization of the CEPS was performed using micro-coils. There were no complications following the procedure and no further GI bleeding occurred, illustrating the efficacy of this treatment option for CEPS. We discuss the literature regarding the presenting complaint of GI bleeding post-LT, CEPS as a rare cause of GI bleeding and its association with PV, and the classification and treatment of CEPS.

This study was conducted in an attempt to quantify the impact of N load on splanchnic tissues metabolism of sheep. The trial was conducted with four male sheep (45 ± 2.5 kg body weight (BW)) surgically implanted with chronic indwelling catheters into the portal, hepatic and mesenteric veins. Blood flow and metabolic flux through portal-drained viscera (PDV), liver and total splanchnic tissues (ST) were measured daily following a 4 × 4 Latin Square experimental design, where sheep were continually infused into the mesenteric vein with a physiological saline (0.15 m NaCl) solution during 90 min followed by the infusion, during more 120 min, of either solution: physiological saline (control), 0.250 mNH4 HCO3 , 0.250 m L-alanine or 0.125 m L-arginine, all of them infused at a rate of 1.5 ml/min to provide 375 μmol N/min. During the treatment infusion period, the net removal of ammonia N and the net production of urea N by liver were higher (p

AIM Data on risk factors for portomesenteric venous thrombosis (PMVT) following abdominal surgery for ulcerative colitis (UC) are limited. The aim of this study was to investigate factors associated with PMVT after surgical treatment for UC. METHOD Patients who underwent restorative proctocolectomy (RPC) and ileal pouch-anal anastomosis (IPAA) including diverting ileostomy closure for medically refractory UC were identified from a prospectively maintained database. Patient-related, disease-related and treatment-related variables were collected. Univariable and multivariable analyses were performed to assess factors associated with PMVT. RESULTS Of the 521 patients completing surgical treatment for UC between 2006 and 2012, symptomatic PMVT occurred in 36 (7%), which resulted in a significantly increased hospital stay (P < 0.001). Patients developing PMVT were younger (P = 0.014), had a lower preoperative albumin level (P = 0.037) and were more likely to have been taking steroids within 1 month before surgery (P = 0.006). The combined incidence of PMVT was comparable between patients having a three-stage and two-stage management (6% vs. 8%, P = 0.43), but the relative incidence of PMVT after RPC + IPAA was 8%, significantly higher than the 4% after total abdominal colectomy (TAC) (P = 0.005) and the 2% after subsequent completion proctectomy (CP) + IPAA (P = 0.038). Multivariate analysis confirmed that RPC + IPAA was associated with a significantly greater risk of PMVT than CP + IPAA (OR = 4.9, P = 0.003) or TAC (OR = 3.5, P = 0.011). Preoperative steroid use was an independent factor for PMVT (OR = 5.8, P = 0.006). CONCLUSION Steroid use 1 month before surgery is associated with an increased risk of PMVT. A staged restorative proctocolectomy does not increase the overall incidence of PMVT.

Due to a lack of a standardized surgical approach in splenic flexure cancer, we consider useful to present a how to do it material on laparoscopic high left colectomy with complete mesocolic excision and central vascular ligation for this type of tumours.

Aim The primary aim of this study was to determine whether the in-hospital mortality for acute mesenteric infarction has reduced in the last decade. The secondary aim was to determine if there was a statistical difference in mortality between patients having acute primary mesenteric infarction due to different causes. Method A literature search was performed of PubMed, Ovid (Embase) and Google Scholar databases. Studies on acute mesenteric infarction of primary vascular pathology were included for pooled analyses while studies that had reported comparative mortality between arterial, venous and non-occlusive mesenteric infarction (NOMI) were included in meta-analyses. Their quality was assessed using the National Institute for Health and Care Excellence assessment scale. Odds ratios (ORs) of mortality were calculated using a Mantel−Haenszel random effect model. Results The total number of patients was 4527 and the male/female ratio was 1912/2247. The pooled in-hospital mortality was 63%. There was no significant reduction of in-hospital mortality rate in the last decade (P = 0.78). There was a significant difference in in-hospital mortality between acute arterial mesenteric infarction (73.9%) compared with acute venous mesenteric infarction (41.7%) [OR 3.47, confidence interval (CI) 2.43−4.96, P

Disturbance of T-cell homeostasis could lead to intestinal inflammation. Naive CD4 T cells undergoing spontaneous proliferation, a robust proliferative response that occurs under severe lymphopenic conditions, differentiate into effector cells producing Th1- and/or Th17-type cytokines and induce a chronic inflammation in the intestine that resembles human inflammatory bowel disease. In this study, we investigated the key properties of CD4 T cells necessary to induce experimental colitis. α4β7 upregulation was primarily induced by mesenteric lymph node (mLN) resident CD11b(+) dendritic cell subsets via transforming growth factor beta (TGFβ)/retinoic acid-dependent mechanism. Interestingly, α4β7 expression was essential but not sufficient to induce inflammation. In addition to gut-homing specificity, expression of gut Ag specificity was also crucial. T-cell acquisition of the specificity was dramatically enhanced by the presence of γδ T cells, a population previously shown to exacerbate T-cell-mediated colitis. Importantly, interleukin (IL)-23-mediated γδ T cell stimulation was necessary to enhance colitogenicity but not gut antigen reactivity of proliferating CD4 T cells. These findings demonstrate that T-cell colitogenicity is achieved through multiple processes, offering a therapeutic rationale by intervening these pathways.

In laparoscopic colorectal resection, the medial-to-lateral approach has been largely adopted. This approach can be initiated by the division of either the inferior mesenteric artery (IMA) or the inferior mesenteric vein (IMV). This cadaveric study aimed to establish the feasibility of IMV dissection as the initial landmark of medial-to-lateral left colonic mobilization for evaluating the size of the peritoneal window between the IMV at the lower part of the pancreas and the origin of the IMA (IMA-IMV distance) and the point of origin of the IMA compared to the lower edge of the third part of the duodenum (IMA-D3 distance). These distances were recorded on 30 fresh cadavers. The IMA-D3 distance was 0.4 ± 2.2 cm (mean ± SD). The IMA originated from the aorta at the level of or below the D3 in 21 cases (70%). The IMA-IMV distance was 5.5 ± 1.8 cm and was greater or equal to 5 cm (large window) in 21 cases (70%). IMA-IMV distance was correlated with IMA-D3 showing that a large window was inversely correlated with a low IMA origin (P < 0.001). IMA-D3 distance was not correlated with weight, height and sex. IMA-IMV distance was largerin male (6.7 ± 0.9 vs. 4.9 ± 1.8, P = 0.001) and correlated with weight, (r = 0.60, 95%CI = 0.03-0.10, P < 0.001) and height (r = 0.54, 95%CI = 0.05-0.21, P = 0.002). IMV can be used as the initial landmark for laparoscopic medial-to-lateral dissection in two-thirds of cases. A too-small window can require first IMA division. The choice between the two different medial-to-lateral approaches could be made by evaluating the anatomical relationship between IMA, IMV, and D3.

Summary Background Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease, characterised by thickening of the wall of the right hemicolon with calcification of mesenteric veins. However, the aetiology remains unknown. Aim To investigate the possible association of herbal medicines with IMP. Method The clinical data of four of our own patients were collected. Furthermore, we searched for previous reports about similar patients with detailed descriptions of herbal prescriptions that they had taken. We compared herbal ingredients to identify the toxic agent as a possible aetiological factor. Results Clinical data on a total of 25 patients were summarised. Mean age was 61.8 years and there was female predominance (6 men and 19 women). The used Kampo prescription, the number of cases, and the mean duration of use were as follows: kamisyoyosan in 12 cases for 12.8 years, inshin-iseihaito in 5 cases for 13.4 years, orengedokuto in 4 cases for 14.3 years, inchinkoto in 1 case for 20 years, kamikihitou in 1 case for 19 years, seijobofuto in 1 case for 10 years and gorinsan in 1 case for an unknown duration. Only one ingredient, sansisi, was common to the herbal medicines of all 25 patients. This crude drug called geniposide in English is a major constituent of the Gardenia fruits. Conclusion The long-term use of geniposide in herbal medicines appears to be associated with mesenteric phlebosclerosis.

A simple, rapid and sensitive method was developed for determination of bicyclol, a new synthetic anti-hepatitis drug, in rat plasma from the mesenteric vein using a high-performance liquid chromatography system coupled to a positive ion electrospray-mass spectrometric analysis. Bicyclol and internal standard (biphenyldicarboxylate, DDB) were isolated from plasma by liquid-liquid extraction, then separated on a Zorbax SB-C(18) column (3.5 microm, 2.1 x 100 mm) with mobile phase of methanol-water (60:40, v/v) at a flow rate of 0.2 mL/min. Detection was performed on a Trap XCT mass spectrometer equipped with an electrospray ionization (ESI) source operated in selected ion monitoring mode. Positive ion ESI was used to form sodium adduct molecular ions at m/z 413 for bicyclol and m/z 441 for DDB, respectively. A linear detection response was obtained for bicyclol ranging from 3.3 to 333.3 ng/mL and the lower limit of quantitation was 3.3 ng/mL. The coefficients of variation for intra- and inter-day precisions were 1.1-7.7 and 2.0-6.6%, respectively. The percentage of absolute recovery of bicyclol was 85.3-94.6%. All analytes proved to be stable during all sample storage, preparation and analytic procedures. The method was successfully applied to determine the plasma concentration of bicyclol in mesenteric vein after intestinal perfusion.

OBJECTIVE A new ultrasonographic technique for detecting parenchymal stiffness of the pancreas is proposed. This technique measures changes in the diameter of the origin of the superior mesenteric vein (SMV) induced by deep inspiration. The origin of the SMV has extensive attachments to the pancreatic parenchyma; therefore, both physiologic enlargement and shrinkage of the venous lumen cannot occur without changes in the shape of the surrounding parenchyma. Therefore, increased parenchymal stiffness due to chronic pancreatitis (CP) may result in impaired changes in the venous diameter. To confirm this hypothesis, patients with CP and those with a normal pancreas were examined in this study. METHODS Twelve patients in each group were examined. Images of the origin of the SMV were obtained with a commercial ultrasound system. The smallest diameter of the SMV was measured during normal breathing. The patients were then asked to take a deep breath to increase the portal blood pressure followed immediately by the same measurements as performed during normal breathing, and the ratio of the change was calculated. RESULTS In the normal group, the diameter of the SMV changed by 79.5% +/- 43.8% (mean +/- SD), whereas a change of 1.4% +/- 7.3% was observed in the CP group. The difference between the two groups was statistically significant (P < .0001). CONCLUSIONS The physiologic change in the diameter of the origin of the SMV enhanced by deep inspiration may reflect the stiffness of the pancreatic parenchyma. Therefore, detection of an impaired diameter change may be useful for screening of CP.

Acute mesenteric venous thrombosis is a rare and potentially fatal disease, which often occurs in medically compromised elderly patients. Isolated mesenteric venous thrombosis may be encountered in young women who have underlying hypercoagulable disease. We report a case of mesenteric venous thrombosis in a young pregnant woman in whom protein S deficiency was diagnosed at a later stage. The patient underwent extensive bowel resection. On follow-up she had developed an obstruction on the intestinal anastomosis. The anastomosis was revised, but the patient died of intervening complications 3 months after the operation. Early management of acute mesenteric venous thrombosis relies on early diagnosis, which requires a high index of suspicion. The condition must be considered during evaluation of persistent abdominal pain in pregnant women with hypercoagulable disorder.

Immune heparin-induced thrombocytopenia (HIT) is a life-threatening adverse effect of heparin. It can result from any type of heparin exposure and by any route of administration; however only a few cases are reported after exposures to small quantities of heparin from catheter flushes. The major clinical problem associated with HIT is thrombosis. Early detection and institution of alternative, non-heparin anticoagulation are important. We report a patient with HIT associated with use of therapeutic-dose unfractionated heparin in whom immune sensitization to heparin was triggered by two 500-unit exposure to UFH associated with intravascular catheter flushing for antineoplastic chemotherapy in a patient with colon adenocarcinoma.

An increasing number of reports have demonstrated the presence of tumor-specific DNA in cancer patients' plasma/serum. These findings offer the prospective of serologic tumor markers that may aide in early disease detection, predict subclinical disease progression, and monitor treatment responses. However, for patients with colorectal cancer (CRC), there are few reports using this approach, with most revealing poor sensitivity. In contrast to tumors of other organ systems, CRCs drain predominantly via the mesenteric/portal veins (MV) to the liver. We hypothesize that because of this unique relation, tumor DNA may be less abundant in CRC patients' systemic circulation as compared to the mesenteric/portal system. At the time of surgery, paired blood was collected from both the peripheral vein (PV) and MV from 33 CRC patients. DNA was isolated from serum, quantified and assessed for loss of heterozygosity (LOH) using a panel of 11 microsatellite markers corresponding to regions on six chromosomes frequent for LOH in CRC. In addition, 16 samples were assessed for the presence of hypermethylated DNA for tumor suppressor genes: MGMT, P16, RAR-beta2, RASSF1A, and APC. Circulating tumor DNA associated with LOH or methylation was more frequently detected in the MV of patients, 11 (33%) and 6 (38%), as compared to PV, 9 (27%) and 1 (6%), respectively. This study is the first to identify the presence of increased tumor DNA in the direct efferent venous drainage system of CRC and its variation as compared to systemic circulation. The findings provide important evidence supporting the origin of tumor-associated DNA in circulation, which merits consideration when devising blood-based nucleic acid assays for the assessment of CRC.

Summary 1 In the rat, a fructose-enriched diet induces hyperglycaemia, hypertriglyceridaemia, insulin resistance and hypertension; a model which resembles the human metabolic syndrome. 2 Prostanoids, metabolites of arachidonic acid, include vasoactive substances synthesized and released from the vascular wall that have been implicated in the increase of peripheral resistance, one of the mechanisms involved in the fructose-induced hypertension. 3 The aim of the present study was to: (i) analyse the effects of the in vitro incubation with fructose on the production and release of prostanoids in rat thoracic aorta and in rat mesenteric bed and (ii) compare the effects of incubation with those of the in vivo acute and chronic treatment of rats with fructose and with the combination of both in vivo and in vitro procedures. 4 Blood pressure, glycaemia and triglyceridaemia were significantly elevated in both 4- and 22-week fructose-treated groups. Meanwhile, body and heart weight as well as insulinaemia were similar between experimental animals and controls. 5 In aortae, 4 weeks of Fructose treatment did not modify the prostanoid pattern release, but in vitro incubation decreased prostacyclin (PGI2) production. However, after 22 weeks, fructose treatment and incubation exerted the same effect. 6 In mesenteric bed, after 4 weeks, the incubation and the combination of both procedures reduced the release of the vasodilators PGI2 and PGE2, while fructose treatment only diminished the PGE2 release. On the contrary, the production of the vasoconstrictor thromboxane A2 (TXA2) was enhanced by incubation and both the procedures. After 22 weeks, fructose treatment increased PGI2 release, while it was reduced by incubation. The combination of both did not modify this peripheral resistance when compared with controls. Finally, incubation of tissues from treated rats increased the release of the vasoconstrictors, PGF2α and TXA2. 7 In conclusion, the mesenteric bed, a resistance vascular bed, seems to be more sensitive than the aorta, a conductance vessel, to the effects of fructose on prostanoid production. This difference could be related to a more relevant role of resistance vessels in the regulation of peripheral resistance and consequently of blood pressure. The observed effects should contribute to a shift in the balance of the release of prostanoid in favour of vasoconstrictor metabolites. This phenomenon could be related to an increase in the peripheral resistance and the mild hypertension observed in the fructose-treated rats.

AIM Rat mesenteric resistance vessels (RV) were characterized with respect to concentration of individual alpha-subunit isoforms of Na,K-ATPase. METHODS Total vessel homogenates were used to avoid any loss or subfractionation of membranes. They were applied to sodium dodecyl sulphate gels and, for calibration, in parallel lanes were run purified rat Na,K-ATPase preparations with known isoform distribution and content. The capacity per mg protein for Na+-dependent 32P-phosphorylation of Na,K-ATPase isolated from rat kidney was used for alpha1 calibration and that for high-affinity (3H)ouabain binding of Na,K-ATPase isolated from rat brain was used for (alpha2 + alpha3) calibration. Western blots containing homogenate proteins and reference enzyme were incubated with isoform-specific antibodies and radiolabelled secondary antibodies. The signals from adjacent alpha spots were used for qualitative and quantitative characterization of rat vessels. RESULTS A concentration of 100.7 +/- 14.4 pmol (n = 11) per g wet weight of the alpha1-isoform containing Na,K-ATPase was found in RV from 12-14-week rats. A much lower and more unreliable content of alpha2- and alpha3-isoforms was found. These ouabain-sensitive isoforms seem to represent a maximum of 5-10% each compared with the ouabain-insensitive rat alpha1-isoform. CONCLUSIONS The isoform pattern in RV, in which the isoform with high/intermediate Na+-affinity is the absolutely dominating one representing nearly all sodium pumps in this tissue, is very different from that seen in rat skeletal muscles. Due to the high content of the ouabain-insensitive alpha1-isoform in rat RV this species would seem a less relevant model in studies addressing a role of cardiac glycosides and putative endogenous ouabain-like factors in hypertension.

A visual analog scale and a numeric scoring scale were designed for the assessment of dynamic intraoperative mesenteric portovenography in the dog and cat. Two independent observers evaluated both scoring scales for reproducibility (differences between observers) and repeatability (within-observer differences) in the assessment of 60 trial portovenograms. Agreement (interchangeability) of both scales was evaluated by comparing the scores obtained in the assessment of 200 portovenograms obtained from 100 dogs and cats. There was no statistical difference between the two observers when scoring the same portovenogram for either the visual analog scale (p = .730, reproducibility coefficient = 17.85 units) or the numeric scoring scale (scores identical, reproducibility coefficient = 0). There was no statistical difference, for either of the observers, when the same portovenogram was assessed on two separate occasions using the visual analog scale (observer 1, p = .35, repeatability coefficient = 17.93 units; observer 2, p = .42, repeatability coefficient = 8.27 units) or the numeric scoring scale (scores given by both observers were identical, repeatability coefficient = 0 for both observers). The results of comparison between the visual analog scale and numeric scoring scale confirmed that the two scoring systems were not directly interchangeable. Although both scoring systems demonstrated good reproducibility and repeatability, the numeric scoring scale possessed a number of inherent deficiencies that suggested it was not the method of choice for the assessment of the subjective data obtained from dynamic intraoperative mesenteric portovenography.

1. The modulatory effects of agonists and antagonists of prejunctional alpha2-adrenoceptors on the electrical field stimulation (EFS, 0.3 ms, 12 V)-induced release of endogenous noradrenaline (NA) and the cotransmitter adenosine 5' triphosphate (ATP) were measured in endothelium-denuded segments of canine inferior mesenteric artery and compared with effects in mesenteric vein. The overflow of NA and ATP was evoked by long-duration (2 min) EFS at low frequency (4 Hz) and high frequency (16 Hz) of stimulation and was analysed using HPLC techniques with electrochemical detection and fluorescence detection, respectively. 2. The EFS-evoked overflow of both NA and ATP was significantly reduced by tetrodotoxin (1 microM) and guanethidine (10 microM) in the artery and vein. Desipramine (10 microM), a blocker of neuronal uptake of NA, increased the EFS (4 and 16 Hz)-evoked overflow of NA in both artery and vein. EFS-evoked overflow of NA in vein exceeded the NA overflow in artery at both 4 and 16 Hz in control preparations as well as in the presence of desipramine. However, the EFS-evoked overflow of ATP was equal in the artery and vein. 3. Stimulation of alpha2-adrenoceptors with clonidine (0.1 microM) and oxymethazoline (0.3 microM) reduced the EFS evoked overflow of NA in both artery and vein at 4 Hz, whereas the NA overflow at 16 Hz remained unchanged in both blood vessels. The overflow of ATP as well as of ADP (and hence ATP:ADP ratio) was unaffected by the alpha2-adrenoceptor agonists in the artery and vein. 4. In artery, blockade of alpha2-adrenoceptors with yohimbine at a concentration of 0.1 microM caused no effect on the NA overflow neither at 4 Hz nor at 16 Hz of EFS. Yohimbine at a concentration of 1 microM increased the overflow of NA at 4 Hz but not 16 Hz of EFS. In vein, however, yohimbine (0.1 and 1 microM) increased NA overflow at both 4 and 16 Hz of stimulation. Idazoxan (1 microM) increased the NA overflow in artery only at 4 Hz, whereas in vein idazoxan increased the NA overflow at both 4 and 16 Hz. No changes of EFS-evoked ATP overflow were observed in the presence of 0.1 microM yohimbine in both artery and vein. Greater concentration of yohimbine (i.e. 1 microM) increased the overflow of ATP in both the artery and vein only at 4 Hz EFS. Idazoxan (1 microM) enhanced the ATP overflow only at 16 Hz in vein. The overflow of ADP was affected by both yohimbine and idazoxan in a similar manner to the ATP overflow so that the ATP:ADP ratios were not changed. 5. In conclusion, sympathetic nerves in both mesenteric arteries and veins appear to release ATP along with NA. Release of NA in veins exceeds release of NA in arteries, whereas both the canine artery and vein release equal amount of ATP. At long-duration nerve stimulation (as might occur during stress) the alpha2-adrenoceptors appear to rather modulate release of NA than release of the cotransmitter ATP. The prejunctional autoinhibition of NA release is more effective at lower frequencies of nerve stimulation. The alpha2-adrenoceptor-mediated neuromodulation plays a greater role in veins than arteries. Quantitative differences in alpha2-adrenoceptor-mediated neuromodulation in the arteries and veins may participate to differing contributions of mesenteric blood vessels to the control of blood flow and volume distribution in splanchnic circulation.

Background and Objective To study the impact of laser pulses on animal microvasculature as a model for laser treatment of port wine stains. Study Design/Materials and Methods Rat mesenteric blood vessels were irradiated with a laser pulse (585 nm, 0.2–0.6 ms pulse duration, 0.5–30 J/cm2 radiant exposure). Video microscopy was used to assess vessel dilation, formation of intravascular thrombi, bubble formation, and vessel rupture. Changes in reflection during a laser pulse were measured by simultaneously recording the temporal behavior of the incident and reflected signals. Results A threshold radiant exposure of approximately 3 J/cm2 was found for changes in optical properties of blood in vivo, confirming previous in vitro results. Often, laser exposure induced a significant increase in vessel diameter, up to three times the initial diameter for venules and four times for arterioles, within 200 ms after laser exposure. Arterioles were more likely to dilate than venules. Sometimes, immediately after the pulse, round structures, interpreted as being gas bubbles, were seen within the vessel lumen. Conclusions A variety of phenomena can occur when blood vessels of sizes comparable to those in port wine stains are irradiated with laser pulses as used in port wine stain treatment. Thrombus formation and vessel rupture have been described before from histological sections of laser-irradiated port wine stains. However, vessel dilation and formation of non-transient gas bubbles as found in this study have not been described before. Lasers Surg. Med. 39:461–468, 2001. © 2001 Wiley-Liss, Inc.

In this study, plasma time-activity curves of 99mTc-mebrofenin were used to quantify hepatic function in dogs before and after induction of hepatic damage using a hepatotoxic agent. Nine dogs were determined to be healthy on the basis of physical examination, laboratory data and hepatic imaging. Plasma samples were collected 1, 3, 5, 7, 9, 15, 20, 30, 40, 50, and 60 minutes following a peripheral venous injection of 111-222 MBq (3-6 mCi) of 99mTc-mebrofenin. The area under the plasma time-activity curve (AUC) was calculated using two different methods and compared to direct measurement of the hepatic extraction efficiency. First pass hepatic extraction efficiency of 99mTc-mebrofenin was calculated from differential equation analysis of a two-compartment model following mesenteric venous injection of the radiopharmaceutical. In 7 of the original 9 dogs and 2 additional healthy dogs, plasma clearance and hepatic extraction efficiency determination were repeated following induction of hepatic injury by thiacetarsamide (3 mg/kg IV twice daily for 1 day). In one additional dog, hepatic injury was induced using carbon tetrachloride (0.3 ml/kg IP). Plasma time-activity curves of 99mTc-mebrofenin had kinetics of a two compartment model. Area under the curve was highly correlated with hepatic extraction efficiency. The AUC integrated from 1-60 minutes (AUC60) had the best correlation with hepatic extraction efficiency (r2 = 0.978, p < 0.001). A formula for calculation of hepatic extraction efficiency was derived using linear regression analysis: hepatic extraction efficiency = 105.583 - 3.099 x 10(5) x AUC60. Plasma clearance of a peripheral venous injection of 99mTc-mebrofenin is a simple, non-invasive, convenient method to quantify hepatic function which can be performed without a gamma camera.

The rate of delivery of molecules to a tissue depends on microvascular blood flow, the surface area of the walls of microvessels, and microvascular permeability. In the conventional analysis of blood tissue exchange (e.g. Renkin, 1959, 1984), it is assumed that the permeability is constant and independent of blood flow, and that transport is regulated by changes in flow and surface area. Recently, however, the interesting possibility has arisen that microvascular permeability might increase with microvascular flow. The evidence for this has been reported in studies carried out on the isolated perfused vessels (Yuan et al. 1992; Pallone et al. 1995) and cultured monolayers of endothelium (Jo et al. 1991; Sill et al. 1995; Waters, 1996). Recently, we have been able to demonstrate rapid and reversible changes in the potassium ion permeability (PK) following the changes in the flow velocity (U) of the single perfused capillaries of frog mesentery (Kajimura et al. 1998; Kajimura & Michel, 1999). Our development of the single bolus microperfusion technique of Crone et al. (1978) for measuring the PK allows not only rapid and repeated estimates of the permeability coefficient to K+ but also estimates of the transit time of the single bolus from which the flow velocity is accurately estimated. Using this method, we have shown that the flow-dependent component of microvascular permeability to K+ is independent of both microvascular pressure and the direction of gradient of [K+] across the vessel wall (Kajimura et al. 1998). Furthermore it can be abolished by the agents which raise intracellular levels of cAMP (Kajimura & Michel, 1999). In this paper, we apply the technique to mammalian microvessels in situ. Our results suggest: (i) that permeability itself increases with blood flow on single mesenteric venules perfused in situ in anaesthetised rats; and (ii) that in these vessels the phenomenon can be abolished by inhibitors of nitric oxide synthase (NOS). Preliminary reports of our findings have been presented to the Japanese Society for Microcirculation (Kajimura & Michel, 1998a), the Microcirculatory Society (Kajimura & Michel, 1998b) and the British Microcirculation Society (Kajimura & Michel, 1998c).

Elucidation of the hepatic hemodynamics in acute ethanol administration is an issue of clinical importance for better understanding of alcoholic liver diseases. The purpose of this study is to clarify the mechanism of hepatic microcirculatory disturbances after acute ethanol administration, especially regarding the effects of ethanol on alterations of sinusoidal endothelial fenestrae (SEF) and the involvement of endothelin-1 (ET-1) in the mechanism of portal hypertension induced by ethanol. Ethanol was administrated into the portal vein via the mesenteric vein branch of rats as a continuous infusion (4 and 8 mg/min of ethanol) for 60 min. Hepatic tissue blood flow measured with a laser Doppler blood flowmeter was found to be remarkably decreased with time, whereas portal pressure began to increase at 10 min and showed a significant increase by approximately 1.5 cm H2O at 60 min. Ethanol concentrations in blood at 60 min after 4 and 8 mg/min of ethanol infusion were 0.75 mg/ml and 1.77 mg/ml, respectively. At this point, scanning electron microscopy revealed significant decreases in number and diameter of SEF both in zone 1 and zone 3, with the increase in ethanol level. These findings suggested that decreases in number and diameter of SEF, whether primary or secondary, may lead to the impairment of the transport of plasma substances from sinusoids to hepatocytes in acute ethanol administration. Furthermore, the pretreatment of BQ-123 inhibited a decrease in hepatic tissue blood flow and an increase in portal pressure caused by ethanol, indicating that ET-1 may be involved in the mechanism of hepatic circulatory disturbances in acute ethanol administration.

Protein C deficiency is a known underlying risk factor for thromboembolic disease. Most commonly it presents as thrombophlebitis, deep venous thrombosis or pulmonary embolism. Less common presentations are becoming increasingly recognized now that assays for protein C are more widely available. We present two cases of mesenteric venous thrombosis who were found to have protein C deficiency.

Small-bowel infarction resulting from mesenteric venous thrombosis is a rare but life-threatening complication to which young women taking oral contraceptives are liable. The patient characteristically presents with an "acute abdomen" after a variable prodromal period of vague abdominal pain. The correct diagnosis can be made from the macroscopic appearance at laparotomy, provided the surgeon is alert to the condition. An accurate diagnosis is important, as anticoagulation measures must be instituted early to counter the commonly associated thromboembolic phenomena.A case report of mesenteric venous thrombosis with small bowel infarction in a 38-year-old woman who had been taking oral contraceptives is reported. The patient was admitted complaining of severe abdominal pain and vomiting for 36 hours. On admission, temperature was 37.5 degrees C and pulse 120/minute. Abdominal rigidity and left-sided abdominal tenderness were present. X-ray of the abdomen showed 2 distended loops of small bowel and 3 fluid levels. Serum amylase was normal. White cell count was 10,000/cu mm. There was a history of abdominal pain and diarrhea over a period of several years. For 6 months she had been taking Ovulen (mestranol .1 mg and ethynodiol diacetate .5 mg) for menstrual irregularity. 2 weeks earlier she had suffered an influenzalike illness with pleuristic chest pain, loin pain, urinary frequency, and dysuria. Chest X-ray and intravenous pylography were then reported as normal. At immediate operation, a 15 cm segment of ileum was found to be infarcted. Semipurulent fluid was present in the abdomen and areas of fibrinous peritonitis were observed. The involved segment of ileum was resected. A small thrombus was extracted from a mesenteric vein. Initial postoperative course was good but 3 days after operation chest pain, dyspnea, and giddiness developed and cardiac arrest followed. Resuscitation was successful. Pulmonary angiography then showed thrombi in all branches of the pulmonary artery. After heparin therapy symptoms improved and the patient left the hospital in 2 weeks, her condition being stabilized with warfarin and dipyridamole (Persantin). The diagnosis was confirmed by histological examination. Early recanalization of a mesenteric vein was noted. Other reported cases have shown an average prodromal phase of 4 or 5 days. The long-term diarrhea was considered as not connected with the present illness but the presumed influenza illness 2 weeks earlier may have been due to a pulmonary embolism. Of reported cases, 5 of 13 have died. Early diagnosis, prompt surgery, and heparin therpay are considered important.

Intestinal ischaemia resulting from shock is particularly hazardous because it can cause loss of barrier function, which could contribute to the development of sepsis (Pinsky & Matuschak, 1989). The oxygenation of the microcirculation can show deterioration in advance of changes in global parameters of oxygenation (Gutierrez, 1986; Stein et al. 1993; Lam et al. 1994; Kerger et al. 1996). However, the behaviour of microcirculatory oxygenation in shock and resuscitation remains largely unknown. Therefore methods are needed to assess the microvascular PO2 (μPO2). The application of the quenching of Pd-porphyrin phosphorescence by oxygen provides a new promising optical method. This method of oxygen measurement has been applied to measure the PO2 of the microcirculation of the eye (Shonat et al. 1992), the isolated rat heart (Ince et al. 1993; Rumsey et al. 1994), brain (Wilson et al. 1991; Pastuszko et al. 1993), muscle (Poole et al. 1995; Kerger et al. 1996) and tumour (Helmlinger et al. 1997). However, it has not as yet been applied to the intestines. The quenching of phosphorescence technique provides a quantitative measure of the amount of oxygen in the microcirculation. In this technique, the decay time of the phosphorescence is measured after pulsed excitation. The Pd-porphyrin is bound to albumin and when this molecular complex is injected intravascularly the dye is confined to the circulation and enables measurement of the PO2 of this compartment (Shonat et al. 1992). We recently calibrated and characterized the use of Pd-porphyrin phosphorescence for measurement of PO2 with a newly developed phosphorimeter (Sinaasappel & Ince, 1996). The main purpose of this study was to investigate the relation between the microvascular oxygenation of the pig ileum, measured by the quenched phosphorescence of Pd-porphyrin, and regional and global parameters of oxygenation, during haemorrhagic shock and resuscitation. Pd-porphyrin phosphorescence quenching by oxygen was validated for measurement of μPO2 in the intestine by comparison with surface electrode measurements. The results presented in this study show that μPO2 becomes lower than the venous PO2 during haemorrhagic shock, indicating that oxygen bypasses the microcirculation. This indicates that venous PO2 is not a good measure of the oxygenation of the intestine under all circumstances.

Gastric mucosal inflammation causes hypergastrinemia, and gastrin receptors have been detected in several leukocyte types. We have analyzed whether gastrin affects the leukocyte-endothelial cell interactions in vivo by monitoring leukocyte rolling, adhesion, and emigration in rat mesenteric venules using intravital microscopy. Mesenteric superfusion with exogenous gastrin increased these processes in a concentration- and time-dependent manner, effects prevented by the cholecystokinin (CCK)-2 receptor antagonists (proglumide, L-365,260) but not by the CCK-1 receptor antagonist devazepide. A similar response was induced by exogenous CCK or endogenously released gastrin. CCK-2 receptors were localized in mesenteric macrophages and polymorphonuclear leukocytes. This effect of gastrin is not modulated by somatostatin and is independent of the endogenous release of histamine. To analyze whether hypergastrinemia elicited by Helicobacter pylori (HP) modulates the inflammation induced by the germ, rats were chronically administered with an extract of a CagA+/VacA+ strain of HP. This protocol increased gastrinemia and induced an inflammatory response in the rat mesentery. Blockade of CCK-2 receptors attenuated this response and induced a qualitative change in the leukocyte infiltrate suggestive of a receding inflammatory process. Our results reveal a new proinflammatory role of gastrin that seems to contribute to the maintenance of the inflammation elicited by HP components.

BACKGROUND. There is considerable evidence that blood returning from different abdominal organs does not mix completely but maintains streamline flow in the portal vein. This study tested the hypothesis that the location of primary colorectal carcinoma affects the intrahepatic distribution of liver metastases according to streamline flow in the portal vein. METHODS. Eighty-five patients with histologically verified liver metastases from colorectal carcinoma underwent potentially curative hepatectomy. Primary tumor location was the right-sided colon in 18 patients and the left-sided colon in 67. The liver was divided into two lobes by Cantlie's line. RESULTS. A total of 195 metastatic deposits were resected : 135 in the right lobe and 60 in the left. In the right-sided colon carcinoma group, 29 deposits were in the right lobe and 3 in the left. In the left-sided colon carcinoma group, 106 deposits were in the right lobe and 57 in the left. The pattern of lobar distribution was significantly different in the two groups (P = 0.003). CONCLUSIONS. Right-sided colon cancers selectively involve the right lobe, while left-sided tumors involve the entire liver, considering the ratio of weights of the right to left lobe is 2 :1. This difference suggests that primary tumor location affects the pattern of lobar distribution of colorectal carcinoma liver metastases according to streamline flow in the portal vein.

As patients with glycogen storage disease type I survive longer, cases with hepatic tumor have been increasingly documented. A 16 year old boy with glycogen storage disease type I was evaluated for multiple liver tumors. He was diagnosed on clinical features at 9 months of age and underwent a mesocaval shunt operation at 5 years of age. The biopsy of one of the masses showed focal nodular hyperplasia. This is uncommon in patients with glycogen storage disease type I, compared to those with adenoma or malignant hepatic tumor. The association of a portacaval shunt with focal nodular hyperplasia is significant compared to other tumors. An environment of high estrogen concentration or sex hormone binding globulin accompanied by shunt operation may cause focal nodular hyperplasia to develop in the liver of patients with glycogen storage disease type I.

1. We investigated the nature of the adrenoceptors in the dog saphenous vein (DSV) and dog mesenteric vein (DMV) to determine the nature of the unexpected interactions of phenylephrine and methoxamine with rauwolscine in the DSV, i.e. the ability of the putative alpha 2-adrenoceptor antagonist to inhibit competitively contractions to these alpha 1-agonists. Radioligand binding studies were performed in parallel with contractility studies. 2. Functionally, in the DSV, phenylephrine and methoxamine-induced, contractions were antagonized by rauwolscine with Schild slopes of -0.52 and -0.46, respectively and apparent pA2 values of 8.5 and 9.2, respectively. Such antagonism was not observed in the DMV. In the DSV, prazosin competes for [3H]-rauwolscine binding sites with a high and a low affinity binding site (Ki of 1.49 +/- 0.65 and 94.7 +/- 51 microM, n = 6, respectively). 3. Pretreatment with 100 microM chloroethylclonidine (CEC) for 15 min abolished [3H]-prazosin binding in microsomes from both veins and reduced binding (Bmax) of [3H]-rauwolscine in microsomes by 55.1 +/- 0.8% (n = 3) in the DSV but did not affect the Bmax in the DMV. CEC pretreatment in the venular rings denuded of endothelium caused persistent contraction in the DSV but not in the DMV. In the DSV, CEC appeared to interact with a single [3H]-rauwolscine binding site. In both the DSV and the DMV, CEC (100 microM) caused a significant shift in the EC50 values for phenylephrine and methoxamine. Maximum responses in the DMV were significantly attenuated while those in the DSV were unaffected when total tension was considered. 4. Studies of the functional interactions of the DSV and the DMV with WB 4101 or 5-methylurapidil (5-MU) suggested the presence of alpha 1D-adrenoceptors in the DSV and alpha 1A-adrenoceptors in the DMV. The receptors inactivated by CEC in the DMV and DSV may represent some or all of the receptors with properties of alpha 1D and alpha 1A-receptors present in the two veins. Studies of radioligand binding interactions of these two antagonists with [3H]-prazosin, were consistent with the presence of some alpha 1D-receptors in DSV and alpha 1A-receptors in DMV. These findings raise questions about the selectivity of CEC in differentiating alpha 1-adrenoceptor subtypes. 5. B-HT 920 caused contractions in the DSV smaller than those to the alpha 1-agonists but the maximum was not affected by CEC pretreatment. The EC50 values were shifted to the left after CEC. In radioligand binding studies, B-HT 920 competition for [3H]-rauwolscine binding was not significantly affected by CEC pretreatment. 6. These results suggest the presence of unusual alpha-adrenoceptors in the DSV. In addition to alpha 2-adrenoceptors, receptors recognizing rauwolscine as well as prazosin, WB 4101, phenylephrine and methoxamine and susceptible to inactivation by CEC are present. They appear to be, in part, unusual alpha 1D-adrenoceptors.

The consequential implications of the leukocyte-endothelial cell adhesion reaction, as well as the subsequent migratory activity of the leukocytes within the interstitium proper, are currently known only in general phenomenological terms. Our objective was to carry out a detailed quantitative analysis of transendothelial and interstitial migration.We incorporated several new features, such as the video recording of time-lapse photography in conjunction with the time history of individual leukocytes under the influence of representative stimulators and inhibitors. The mesentery was suffused with the chemical activator N-formyl-met-leu-phe (fMLP, 5 x 10(-8) M) and histamine (10(-6) M) for periods up to 3 h. This leads to an attachment of neutrophils preferentially to the walls of small postcapillary venules followed by migration into the adjacent interstitium.The time interval between the initial neutrophil adhesion to the luminal side of the venules and their first appearance on the abluminal side of the venule wall was about 25 min. The time interval for the actual physical migration across the endothelium was only about 1-2 min. There was an initial increase in the number of neutrophils migrating across the wall per unit time after the application of fMLP. However, this effect then gradually decreased over the course of 1 h. In the extravascular tissue, the neutrophils appeared to migrate along random pathways with an average trajectory away from the venular wall. When histamine (1 microM) was applied topically in conjunction with fMLP, the overall migratory flux across the venular wall increased, although the cells migrated comparatively short distances into the interstitium. After pretreatment with phalloidin (25 micrograms/kg), an actin cross-linking agent, neutrophil adhesion and migration in response to fMLP stimulation was reduced. The mast cell stimulator 48/80 (25 mg/ml) resulted in rapid degranulation, which was accompanied by an insignificant increase in neutrophil diapedesis. After fMLP stimulation there was reduced neutrophil emigration in the presence of mast cell inhibitors, such as lodoxamide (1 microgram/kg) and ketotifin (microgram/kg).Our results demonstrate that both the endothelial cells and interstitial mast cells are involved in the rate of transvascular migration of leukocytes across postcapillary venules and into the interstitium.

1. We have compared the roles of adenosine in mediating dilator responses to acute hypoxia in mesenteric microcirculation of control, normoxic (N) rats and in chronically hypoxic (CH) rats kept in an hypoxic chamber at 10% O2 for 3-4 weeks. 2. In fifteen N rats, acute hypoxia (breathing 6% O2 for 3 min) induced mean increases in the diameter of arterial vessels of mesentery (whose internal diameter was 10-350 microns) of 8.0 +/- 1.9% (mean +/- S.E.M.) and of venous vessels (whose internal diameter was 12-360 microns) of 10.4 +/- 2.6%. These diameter changes were reduced by approximately 30% when the adenosine receptor antagonist 8-sulpho-phenyltheophylline (8-SPT, 10(-3) M) was applied topically to the mesentery. 3. In a further six N rats, topical application of graded concentrations of adenosine (10(-7)-10(-3) M) to the mesentery evoked graded increases in the diameter of all arterial and venous vessels, maximum increases with 10(-3) M being 12.5 +/- 3.3 and 8.4 +/- 4.3%, respectively; these responses were abolished by 8-SPT. 4. By contrast, in fourteen CH rats, the smaller change in inspirate from 10 to 8% O2 induced increases in diameter of arterial and venous vessels which had control diameters that were comparable to those of N rats, of 14.1 +/- 2.4 and 12.9 +/- 2.7%, respectively, and which were virtually equivalent to the responses induced by topical application of 10(-3) M adenosine (13.3 +/- 1.3 and 16.3 +/- 2.0% in arterial and venous vessels, respectively). The changes induced by acute hypoxia were abolished by 8-SPT, as were those induced by adenosine. 5. These results suggest that in the intestinal mesentery, where the blood vessels have negligible tissue parenchyma around them, locally released or synthesized adenosine makes a substantial contribution to the dilatation that is evoked in arteriolar vessels by acute hypoxia and to the active dilatation, or passive distension of the venous vessels. The results also suggest that this contribution is accentuated in chronic hypoxia either by greater release of adenosine or greater vascular sensitivity to it.

1. The effects of aminoguanidine on neutrophil adherence to venules and on the diameter of arterioles in the mesenteric vascular bed of the pentobarbitone-anaesthetized rat have been compared with those of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). 2. Administration of L-NAME (1-10 mg kg-1, i.v.) caused a dose-dependent increase in leukocyte adherence and a reduction in leukocyte rolling velocity in postcapillary venules of the rat mesentery over 1 h. 3. Likewise, aminoguanidine (10-100 mg kg-1, i.v.) dose-dependently increased leukocyte adherence and decreased leukocyte rolling velocity over 1 h. 4. Both L-NAME and aminoguanidine caused a dose-dependent reduction in mesenteric arteriolar diameter and an increase in systemic arterial blood pressure. 5. The effects of aminoguanidine (50 mg kg-1, i.v.) on leukocyte adherence, arteriolar diameter and on blood pressure were significantly reversed by pretreatment with L-arginine (300 mg kg-1, i.v.). 6. These findings indicate that, like L-NAME, aminoguanidine can acutely promote leukocyte adherence to the mesenteric venular wall and reduce arteriolar diameter. Moreover, these acute effects were reversed by L-arginine, suggesting they are mediated through inhibition of constitutive NO synthase.