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A Secchi

Publications and source records attributed to A Secchi.

At least 19 recordsLinked to original sources
PubMed2002

Secretory defects induced by immunosuppressive agents on human pancreatic beta-cells.

Despite the considerable interest for islet and pancreas transplantation, remarkably little is known about the direct effects of immunosuppressive drugs on human beta-cell function. We measured different insulin secretory parameters and insulin gene expression of human islets cultured for 5 days in the presence of mycophenolate mofetil (MMF), cyclosporin A (CsA), tacrolimus (FK506) or a mixture of 3 cytokines. Basal insulin release after exposure to cytokines and FK506 was significantly higher than in control islets. Responsiveness to an acute glucose stimulus did not differ significantly between control and treated islets. However, absolute incremental insulin responses (delta-AUCs) of islets exposed to cytokines or FK506 were significantly higher compared to islets exposed to CsA or MMF, mainly because of the higher basal release. Indeed, maximal over basal release (stimulation index, SI) tended to be lower in islets exposed to FK506 than in control islets. Insulin gene expression was significantly reduced only in islets exposed to CsA. FK506 was, among those tested, the immunosuppressive drug that most profoundly altered the normal insulin secretory pattern of human beta-cells, whereas CsA was the only inhibiting insulin gene expression. Although the abnormalities induced by the immunosoppressive drugs utilized in this study were modest, these in vitro data are consistent with the reported in vivo diabetogenicity of CsA and FK506 and point to MMF as the ideal immunosuppressive agent from a pancreatic beta-cell point of view.

Adult↗
PubMed2002

Successful [correction of Succesful] transplantation of human islets in recipients bearing a kidney graft.

AIMS/HYPOTHESIS: Islet transplantation is a minimally invasive approach to curing Type I (insulin-dependent) diabetes mellitus. Success has recently been reported in patients receiving solitary islet transplants but the outcome in patients receiving islets together with, or after, kidney transplants has been limited and unpredictable. METHODS: Here we report successful islet transplantation in a cohort of 15 patients with Type I diabetes who were followed for at least 1 year after islet transplantation, after having already received kidney allografts because of end-stage nephropathy. RESULTS: C-peptide after transplantation was higher than 0.17 nmol/l in all 15 recipients, reflecting the absence of primary non-function. Insulin requirement was reduced by over 50 % in all but one patient, and insulin independence was achieved in 10 (66 %) recipients, five of whom now have stable, prolonged insulin independence, well controlled fasting glycaemia, a substantial first-phase and normal second-phase response to glucose, normal insulin sensitivity (HOMA analyses) and HbA1 c of under 6.2 % (33, 26, 18, 13 and 12 months after transplantation respectively). Of importance for patient management, an assessment of fasting blood glucose and proinsulin values following overnight withdrawal of insulin administration one month after transplantation was a potent predictor of insulin independence, and could be used to decide patients who should have further islet preparations. CONCLUSION/INTERPRETATION: These findings support the use of islet transplantation as a cure for Type I diabetes in patients with severe complications.

Adult↗
PubMed2001

Anion allosteric effect in the recognition of tetramethylammonium salts by calix[4]arene cone conformers.

Rigid calix[4]arene cone conformers, which are efficient receptors for quaternary ammonium salts, are usually obtained through the functionalization of their lower rim with suitable groups. Using flexible cone conformer of calix[4]arene, bearing four 4-hydroxybenzyl groups as cooperative and rigidifying structural elements at the upper rim of the calix, which act as anion binding groups, a new heteroditopic cavitand, 7, was synthesized. Whereas the tetramethoxy derivative 8 does not show any complexing ability, its tetrahydroxy analogue 7 recognizes tetramethylammonium salts with high efficiency. The binding abilities of this new receptor toward a series of tetramethylammonium salts (tosylate, chloride, acetate, trifluoroacetate, and picrate) have been investigated in CDCl(3) solution and compared to the monotopic and rigidified, through the lower rim, cone biscrown-3-calix[4]arene 9. The results obtained confirmed that in CDCl(3) ion pairing strongly affects binding. In particular, the rigid monotopic receptor 9 experiences good efficiency toward tetramethylammonium salts having anions with low ion-pairing ability such as trifluoroacetate or picrate. On the contrary, for the new heteroditopic cavitand 7, a reverse order of efficiency was found. In the latter case a different complexation mode was hypothesized in which the tetramethylammonium cation is deeply entrapped into the host cavity and its counteranion participates to the recognition process by coordination via hydrogen bonding by the four OH groups. To further support the role of the anion in the recognition process, a "dual host" approach, employing 7 or 9 in the presence of a specific receptor for chloride anion (10), was utilized. Molecular modeling studies confirmed that in the complexes formed by 7 and TMA salts the counteranion is involved in hydrogen bonding with the host OH groups and that the guests are bound as ligand-separated ion pairs.

Allosteric Regulation↗
PubMed2001

Prediction of the long-term metabolic success of the pancreatic graft function.

BACKGROUND: Strategies to prevent the return to the diabetic state for graft loss or failure or any other cause after pancreas transplantation require the identification of the subjects at risk. This study evaluated whether daily glucose, insulin, and c-peptide profiles and studies of insulin sensitivity and secretion after transplantation predict pancreatic graft failure. METHODS: Fifty-three subjects with type 1 diabetes with end-stage renal failure who received a combined pancreas and kidney transplant underwent the following procedures 1 year after transplantation: 1-day metabolic profiles, sampling every 2 hours for plasma glucose, serum insulin, and c-peptide (n=51); an intravenous glucose tolerance test (IVGTT) to evaluate insulin secretion (n=48); and an euglycemic insulin clamp to evaluate insulin sensitivity (M value, n=14). The recipients were then followed up to 8 years (mean follow-up 4.8+/-0.3 years) to evaluate the return to the diabetic state. RESULTS: Survival analysis showed that plasma glucose in the profiles and insulin secretion in IVGTT were strongly related to the risk of returning to the diabetic state. A cutoff value of mean daily plasma glucose >127 mg/dL, corresponding to the top quartile of the mean plasma glucose distribution in the profiles, predicted the return to the diabetic state within 4 years from transplantation with a 93% specificity and a 100% sensitivity. A cutoff value of insulin delta peak <32 microU/ml in the IVGTT predicted the return to the diabetic state within 4 years from transplantation with a 75% specificity and a 75% sensitivity. In contrast, the M value in the clamp was devoid of predictive value. CONCLUSIONS: This study indicates that the mean 24-h plasma glucose 1 year after transplantation is the strongest predictor of the return to the diabetic state. The risk is related to defects in insulin secretion and not to insulin resistance. Metabolic profiles can be used to screen the subjects at risk to strictly monitor the graft function and to investigate early determinants of graft failure.

Adult↗
PubMed2001

Clinical evaluation of twice-daily emedastine 0.05% eye drops (Emadine eye drops) versus levocabastine 0.05% eye drops in patients with allergic conjunctivitis.

PURPOSE: The efficacy and safety of emedastine 0.05% eye drops (Emadine; Alcon Laboratories, Inc, Fort Worth, Texas), a new H(1) antagonist, were studied in comparison to levocabastine 0.05% eye drops (Livostin; Janssen-Cilag N V, Berchem, Belgium) during a twice-daily treatment schedule for 6 weeks in adult and pediatric patients with seasonal allergic conjunctivitis. METHODS: In a prospective, multicenter, randomized, double-masked, parallel group study, 222 patients with allergic conjunctivitis were randomized (221 received treatment) to either emedastine or levocabastine, instilled twice daily for 6 weeks. Patient diaries were completed four times daily (before the morning and evening instillations, at noon, and in the afternoon), and clinical examinations were conducted at regular intervals. Primary efficacy variables of ocular redness and itching and secondary efficacy variables of chemosis, eyelid swelling, patient diary data, and physician's global assessment were analyzed. RESULTS: Both emedastine and levocabastine produced a statistically significant (P =.0001) reduction in itching and redness within 5 minutes of the first instillation. All signs and symptoms improved progressively over the 6-week treatment period. After 7 days of use, and throughout the remainder of the study, emedastine was statistically superior to levocabastine (P <.006) in preventing and alleviating the signs and symptoms (itching, redness, chemosis, and eyelid swelling) of allergic conjunctivitis. CONCLUSIONS: Emedastine 0.05% eye drops administered twice daily are more efficacious than levocabastine 0.05% eye drops in the prevention and treatment of the signs and symptoms of allergic conjunctivitis in adults and children of 4 years and above. Both emedastine 0.05% eye drops and levocabastine 0.05% eye drops were well tolerated.

Adolescent↗
PubMed2001

Cardiovascular outcomes after kidney-pancreas and kidney-alone transplantation.

BACKGROUND: This study retrospectively assessed, with an intention-to-treat analysis, the effect of kidney-pancreas transplantation (KP) on survival and cardiovascular outcome in type 1 diabetic uremic patients. METHODS: A total of 351 uremic type 1 diabetic patients were enrolled on a waiting list for KP: 130 underwent KP transplantation, 25 underwent kidney transplantation alone (KA), whereas 196 patients remained on dialysis (WL). The three populations had similar cardiovascular conditions. Actuarial survival rates and causes of death were recorded over a period of seven years. Finally, 23 KP and 13 KA patients underwent left radionuclide ventriculography, during a follow-up of four years. RESULTS: In the entire group of 351 patients the seven-year survival rate was 77.4% for KP, 56.0% for KA and 39.6% for WL (KP vs. WL, P = 0.01). Cardiovascular death rate was 7.6% in KP, 20.0% in KA and 16.1% in WL (KP versus WL, P = 0.03; KP vs. KA, P = 0.16). In the subsample studied with radionuclide ventriculography, left ventricular ejection fraction improved in KP, but did not in KA, with significant differences between groups at two and four years. At four years only the KP patients presented normal values of diastolic parameters, including the peak filling rate, time-to-peak filling rate, and peak filling rate/peak ejection rate ratio. Glycated hemoglobin was negatively associated with the ejection fraction, peak filling rate and peak filling rate/peak ejection rate ratio, and positively associated with the time-to-peak filling rate. CONCLUSIONS: Normalization of blood glucose metabolism and improvement of blood pressure control obtained with KP transplant is associated with positive effects on survival, cardiovascular death rate, and left ventricular function.

Adult↗
PubMed2001

Effects of histamine-1 receptor antagonism on leukocyte-independent plasma extravasation during endotoxemia.

PURPOSE: The purpose of this study was to investigate the role of histamine in mediating leukocyte-independent microvascular permeability and mast cell activation during endotoxemia. Microvascular permeability and mast cell activity were determined after inhibition of the L-selectin mediated leukocyte-adherence by fucoidin and after inhibition of histamine effects by the histamine H1-receptor antagonist diphenhydramine. MATERIALS AND METHODS: In male Wistar rats, leukocyte rolling, leukocyte adherence, microvascular permeability, and mast cell activity were determined in mesenteric postcapillary venules using intravital microscopy. After pretreatment with the histamine H1-receptor antagonist diphenhydramine, animals in the ETX/H1-ANT group received a continuous infusion of endotoxin. Animals in the ETX group underwent the same procedure, but received saline 0.9% instead of diphenhydramine. In both groups, leukocyte adherence was prevented by administration of fucoidin. Animals in the control group received volume-equivalent saline 0.9%. RESULTS: In the endotoxin-challenged groups, fucoidin prevented leukocyte rolling and reduced leukocyte adherence to values comparable to control group. In the ETX group and the ETX/H1-ANT group both microvascular permeability and mast cell activity increased significantly, starting at 60 minutes. Differences in mast cell activity between the ETX group and the ETX/H1-ANT group were significant at 60 minutes and at 120 minutes. Differences in microvascular permeability between the ETX/H1-ANT group and the ETX group were not significant. CONCLUSIONS: The leukocyte-independent microvascular damage during early endotoxemia cannot be inhibited efficiently by the H1-receptor antagonist diphenhydramine, indicating that histamine seems to play only a minor role in that pathophysiology. Furthermore, mast cells do not seem to be involved in the development of leukocyte-independent plasma extravasation during endotoxemia.

Animals↗
PubMed2001

Effects of dobutamine and dopexamine on hepatic micro- and macrocirculation during experimental endotoxemia: an intravital microscopic study in the rat.

OBJECTIVE: To test the effects of dobutamine and dopexamine on hepatic portal and sinusoidal blood flow in a model of normodynamic endotoxemia. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats (250-350 g). INTERVENTIONS: A total of 40 male Wistar rats were randomized into four groups: a control group, which only received Ringer's solution; an endotoxin group, which received a continuous infusion of 2 mg/kg body weight (bw)/hr of endotoxin; a dobutamine group, which received endotoxin and a continuous infusion of dobutamine (3 microg/kg bw/min); and a dopexamine group, which received endotoxin and dopexamine (2 microg/kg bw/min). The experimental period was 120 min. MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) were detected. Portal blood flow was measured using an ultrasonic flow probe positioned around the portal vein, and sinusoidal blood flow was detected in the left liver lobe using intravital microscopy. All detected variables remained stable in the control group. In the endotoxin group, HR increased significantly and MAP decreased significantly from 111 +/- 10 mm Hg to 95 +/- 8 mm Hg at 120 mins, whereas CO remained unchanged. Both in the dobutamine and the dopexamine group HR increased and MAP decreased more than in the endotoxin group. CO increased in both groups significantly. Portal blood flow (23 +/- 4 mL/min to 16 +/- 3 mL/min) and sinusoidal blood flow (38.6 +/- 2.5 to 22.8 +/- 1.2 10(3) microm(3)/sec) decreased significantly in the endotoxin group. In the dobutamine and the dopexamine group portal and sinusoidal blood flow remained at baseline values. CONCLUSIONS: In our model of endotoxemia, dobutamine and dopexamine preserved systemic and hepatic blood flow. These preservations of hepatic blood flow during endotoxemia could portend beneficial effects but need to be studied further.

Adrenergic beta-Agonists↗
PubMed2001

Autoantibody response to islet transplantation in type 1 diabetes.

Islet allotransplantation into patients with autoimmune type 1 diabetes represents a reexposure to autoantigen. Here, measurement of antibodies to GAD and IA-2 autoantigens before and after islet transplantation in 36 patients (33 receiving islet plus kidney grafts with cyclosporin and steroid-based immunosuppression, and 3 receiving solitary islet transplants with mycophenolate but cyclosporin-free immunosuppression) demonstrated marked rises in GAD antibodies within 7 days posttransplantation in 5 patients (3 receiving islet after kidney transplants, and 2 receiving solitary islet transplants) and within 30 days in the third patient receiving solitary islet transplantation. GAD antibodies were of the IgG1 subclass, against major autoantigenic epitopes, and in cases of islet after kidney transplants, the responses were short-lived and not accompanied by HLA antibodies. Two of these patients had subsequent marked rises of IA-2 antibodies, and an additional patient had a marked rise in IgM-GAD antibodies 3 years after transplantation. Insulin independence was not achieved in patients with autoantibody elevations and was significantly less frequent in these patients. These data are consistent with a reactivation of autoimmunity that may be dependent on immunosuppression therapy and is associated with impaired graft function.

Adult↗
PubMed2001

Metabolic effects of restoring partial beta-cell function after islet allotransplantation in type 1 diabetic patients.

Successful intraportal islet transplantation normalizes glucose metabolism in diabetic humans. To date, full function is not routinely achieved after islet transplantation in humans, with most grafts being characterized by only partial function. Moreover, the duration of full function is variable and cannot be sufficiently predicted with available methods. In contrast, most grafts retain partial function for a long time. We hypothesized that partial function can restore normal protein and lipid metabolism in diabetic individuals. We studied 45 diabetic patients after islet transplantation. Labeled glucose and leucine were infused to assess whole-body glucose and protein turnover in 1) 6 type 1 diabetic patients with full function after intraportal islet transplantation (FF group; C-peptide > 0.6 nmol/l; daily insulin dosage 0.03 +/- 0.02 U x kg(-1) body wt x day(-1); fasting plasma glucose < 7.7 mmol/l; HbA1c < or = 6.5%), 2) 17 patients with partial function (PF group; C-peptide > 0.16 nmol/l; insulin dosage < 0.4 U x kg(-1) body wt x day(-1)), 3) 9 patients with no function (NF group; C-peptide < 0.16 nmol/l; insulin dosage > 0.4 U x kg(-1) body wt x day(-1)), and 4) 6 patients with chronic uveitis as control subjects (CU group). Hepatic albumin synthesis was assessed in an additional five PF and five healthy volunteers by means of a primed-continuous infusion of [3,3,3-2H3]leucine. The insulin requirement was 97% lower than pretransplant levels for the FF group and 57% lower than pretransplant levels for the PF group. In the basal state, the PF group had a plasma glucose concentration slightly higher than that of the FF (P = 0.249) and CU groups (P = 0.08), but was improved with respect to the NF group (P < 0.01). Plasma leucine (101.1 +/- 5.9 micromol/l) and branched-chain amino acids (337.6 +/- 16.6 micromol/l) were similar in the PF, FF, and CU groups, and significantly lower than in the NF group (P < 0.01). During insulin infusion, the metabolic clearance rate of glucose was defective in the NF group versus in the other groups (P < 0.01). Both the basal and insulin-stimulated proteolytic and proteosynthetic rates were comparable in the PF, FF, and CU groups, but significantly higher in the NF group (P = 0.05). In addition, the PF group had a normal hepatic albumin synthesis. Plasma free fatty acid concentrations in the PF and FF groups were similar to those of the CU group, but the NF group showed a reduced insulin-dependent suppression during the clamp. We concluded that the restoration of approximately 60% of endogenous insulin secretion is capable of normalizing the alterations of protein and lipid metabolism in type 1 diabetic kidney recipients, notwithstanding chronic immunosuppressive therapy. The results of the present study indicate that "success" of islet transplantation may be best defined by a number of metabolic criteria, not just glucose concentration/metabolism alone.

Adult↗
PubMed2001

Effects of kidney-pancreas transplantation on atherosclerotic risk factors and endothelial function in patients with uremia and type 1 diabetes.

Cardiovascular disease and the development of coronary artery disease play a pivotal role in increasing mortality in patients with type 1 diabetes. The aim of our study was to evaluate the effects of pancreas transplantation on atherosclerotic risk factors, endothelial-dependent dilation (EDD), and progression of intima media thickness (IMT) in patients with uremia and type 1 diabetes after kidney-alone (KA) or kidney-pancreas (KP) transplantation. A cross-sectional study comparing two groups of patients with type 1 diabetes was performed. Sixty patients underwent KP transplantation and 30 patients underwent KA transplantation. Age and cardiovascular risk profile were comparable in patients before transplantation. In all patients, atherosclerotic risks factors (lipid profile, fasting and post-methionine load plasma homocysteine, von Willebrand factor levels, D-dimer fragments, and fibrinogen) were assessed and Doppler echographic evaluation of IMT and endothelial function with flow-mediated and nitrate dilation of the brachial artery was performed. Twenty healthy subjects were chosen as controls (C) for EDD. Compared with patients undergoing KA transplantation, patients undergoing KP transplantation showed lower values for HbA1c (KP = 6.2 +/- 0.1% vs. KA = 8.4 +/- 0.5%; P < 0.01), fasting homocysteine (KP = 14.0 +/- 0.7 mcromol/l vs. KA = 19.0 +/- 2.0 micromol/l; P = 0.02), von Willebrand factor levels (KP = 157.9 +/- 8.6% vs. KA = 212.5 +/- 16.2%; P < 0.01), D-dimer fragments (KP = 0.29 +/- 0.02 microg/ml vs. KA = 0.73 +/- 0.11 microg/ml;P < 0.01), fibrinogen (KP = 363.0 +/- 11.1 mg/dl vs. KA = 397.6 +/- 19.4 mg/dl; NS), triglycerides (KP = 122.7 +/- 8.6 mg/dl vs. KA = 187.0 +/- 30.1 mg/dl; P = 0.01), and urinary albumin excretion rate (KP = 13.5 +/- 1.9 mg/24 h vs. KA = 57.3 +/- 26.3 mg/24 h; P < 0.01). Patients undergoing KP transplantation showed a normal EDD (KP = 6.21 +/- 2.42%, KA = 0.65 +/- 2.74%, C = 8.1 +/- 2.1%; P < 0.01), whereas no differences were observed in nitrate-dependent dilation. Moreover, IMT was lower in patients undergoing KP transplantation than in patients undergoing KA transplantation (KP = 0.74 +/- 0.03 mm vs. KA = 0.86 +/- 0.09 mm; P = 0.04). Our study showed that patients with type 1 diabetes have a lower atherosclerotic risk profile after KP transplantation than after KA transplantation. These differences are tightly correlated with metabolic control, fasting homocysteine levels, lower D-dimer fragments, and lower von Willebrand factor levels. Normal endothelial function and reduction of IMT was observed only in patients undergoing KP transplantation.

Adult↗
PubMed2000

Recognition of amides by new rigid Calix

The synthesis of new hosts specifically designed for the recognition of amides, characterized by two binding regions: a rigid calix[4]arene cavity and a sidearm, inserted at its rim, able to form strong hydrogen bonds, is described. The binding abilities of the new receptors toward amides of general structure R(1)CONR(2)R(3) have been investigated in CDCl(3) solution by (1)H NMR spectroscopy. When the additional binding site is the N-phenylureido group spaced by a methylene unit from the apolar cavity, binding constants up to 756 M(-)(1) were measured. Neither the two separate potential binding sites, nor the model host, where the calix[4]arene skeleton is flexible show detectable binding ability toward the series of guests examined. The rigidity of the calix[4]arene apolar cavity is the key control element in determining the efficiency of these molecular recognition processes. The presence of NH groups in the guest controls the efficiency and selectivity of binding.

Journal Article↗
PubMed2000

Calix

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

Persistence of anomalies in the growth hormone-releasing hormone-stimulated growth hormone response in diabetic-uremic patients after combined kidney-pancreas transplantation.

Increased circulating growth hormone (GH) levels and aberrant response to different stimuli characterize both type 1 diabetes mellitus and chronic uremia and are associated with severe retinal, kidney and heart complications. Combined kidney and pancreas transplantation is a therapy that restores the endogenous, closed-loop, insulin secretion in diabetes and cure uremia. To evaluate if combined transplantation can restore a normal secretion and response of GH to growth hormone releasing hormone (GH-RH), we studied four groups of subjects: (1) seven type 1 diabetic patients with end-stage renal failure who had received pancreas and kidney transplantation (KPTx); (2) six diabetic uremic subjects, candidates for combined transplantation (IDDUP); (3) nine patients with chronic uveitis on immunosuppressive therapy comparable to pancreas recipients, six of whom treated only with prednisone (UVEST), while three (4) were treated with both prednisone and cyclosporin (UVESTCY). All subjects underwent a GH-RH test (50 microg intravenously, i.v., at 13:00 h). Serum insulin levels were significantly higher in IDDUP compared to UVEST (P=0.05) both at baseline and post GH-RH stimulus, while were similar to KPTx (P=0.2) and UVESTCY (P=0.7). In contrast, plasma free fatty acids were similar in all groups. In IDDUP baseline plasma glycerol was higher than in KPTx (P=0.04) and UVEST (P=0.02) and similar to UVESTCY (P=0.36); glycerol concentration did not change after GH-RH (P=0.08). Before and after GH-RH, serum GH levels tended to be higher in IDDUP (P=0.5) and KPTx (P=0.2) compared to UVEST and UVESTCY. Our results indicate that: 1) kidney-pancreas transplantation does not normalize the GH response to GH-RH; 2) GH abnormalities are not due either to the chronic immunosuppressive therapy or to the insulin effect on GH release; 3) GH abnormalities are probably secondary to functional and/or organic complications of the hypothalamus and/or pituitary as a sequela of diabetes mellitus.

Adult↗
PubMed2000

Effect of endotoxemia on hepatic portal and sinusoidal blood flow in rats.

A decrease in liver blood flow leads to dysfunction of hepatocytes and Kupffer cells, with subsequent local and systemic liberation of proinflammatory mediators that may maintain systemic inflammatory response syndrome (SIRS) and may lead to multiple organ dysfunction syndrome (MODS). There is only limited knowledge on the hepatic micro- and macrocirculation during sepsis or endotoxemia. Therefore, the aim of our study was to investigate alterations in hepatic portal blood flow (PBF) and sinusoidal blood flow (SBF) during endotoxemia. In male Wistar rats endotoxemia was induced by continuous infusion of 2 mg/kg/h lipopolysaccharides from Escherichia coli 026:B6 immediately after baseline measurements (n = 8). The control group (n = 8) received an equivalent volume of Ringer's solution. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), PBF, and SBF were measured at baseline and 60 and 120 min after induction of endotoxemia. PBF was measured using an ultrasonic flow probe that was positioned around the portal vein. SBF was detected by in vivo videomicroscopy of the left liver lobe. In the LPS group MAP decreased, but CO remained at baseline values. During endotoxemia PBF decreased significantly from 23 +/- 3 to 15 +/- 4 mL/min (60 min) and 16 +/- 3 mL/min (120 min). SBF also significantly decreased to 68.5% (60 min) and 57.1% (120 min) of baseline value. Our results demonstrate that during early endotoxemia hepatic macro- and microcirculatory perfusion is significantly decreased despite unchanged CO. This early reduction of hepatic perfusion might be caused by an increased hepatic vessel resistance as a consequence of liberation of vasoconstrictive mediators or/and by a decrease in intestinal perfusion.

Animals↗
PubMed2000

Effects of hydrogen peroxide scavenger Catalase on villous microcirculation in the rat small intestine in a model of inflammatory bowel disease.

This study was conducted to quantify the effect of systemic Catalase, a hydrogen peroxide scavenger, on villous microcirculation in the inflamed small intestine of the rat. Intestinal inflammation was induced with s.c. application of Indomethacin. Intravital fluorescence microscopy and FITC-labeled erythrocytes were used to quantify erythrocyte velocity and arteriolar diameter in the main arteriole of the villi in the terminal ileum following i.v. application of Catalase in the inflamed intestine, and the blood flow was calculated. Control groups were formed for Ringer's lactate, Catalase and Indomethacin, respectively. We found that villous blood flow was significantly increased in the in the inflamed intestine. Application of Catalase led to a significant decrease in villous perfusion, but had no effect in the control group. The increase in villous blood flow was accompanied by changes in the diameter of the main arteriole. This effect on arteriolar diameter was reversed by i.v. Catalase. Our results provide evidence that systemic application of Indomethacin leads to vasodilatation of the main arteriole of the villus in the rat ileum and hyperemia in the mucosa. Hyperemia and the vascular diameter of the main arteriole were significantly reduced by H(2)O(2)-scavenger Catalase, suggesting that endogenous H(2)O(2) may be one of the mediators of hyperemia in the mucosa in this animal model of intestinal inflammation.

Animals↗