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Konrad Messmer

Publications and source records attributed to Konrad Messmer.

31 records · Page 2Linked to original sources
PubMed2003

Kinin-B1 receptors in ischaemia-induced pancreatitis: functional importance and cellular localisation.

In this study we compare the role of kinin-B1 and B2 receptors during ischaemia/reperfusion of rat pancreas. Our investigations were prompted by the observation that infusion of a kinin-B2 receptor antagonist produced significant improvement in acute experimental pancreatitis. In an acute model with two hours of ischaemia/two hours of reperfusion, application of the kinin-B1 receptor antagonist (CP-0298) alone, or in combination with kinin-B2 receptor antagonist (CP-0597), significantly reduced the number of adherent leukocytes in post-capillary venules. In a chronic model with five days of reperfusion, the continuous application of kinin-B1 receptor antagonist or a combination of kinin-B1 and B2 receptor antagonists markedly reduced the survival rate. In kinin-receptor binding studies kinin-B1 receptor showed a 22-fold increase in expression during the time of ischaemia/reperfusion. Carboxypeptidase M activity was up-regulated 10-fold following two hours of ischaemia and two hours of reperfusion, provided the appropriate specific ligand, des-Arg10-kallidin and/or des-Arg9-bradykinin, was used. The occurrence of kinin-B1 receptor binding sites on acinar cell membranes was demonstrated by micro-autoradiography. With a specific antibody, the localisation of kinin-B1 receptor protein was confirmed at the same sites. In conclusion, we have demonstrated the up-regulation of the pancreatic acinar cell kinin-B1 receptors during ischaemia/reperfusion. The novel functional finding was that antagonism of the kinin-B1 receptors decreased the survival rate in an experimental model of pancreatitis.

Animals↗
PubMed2002

Platelet adhesion mediated by fibrinogen-intercelllular adhesion molecule-1 binding induces tissue injury in the postischemic liver in vivo.

BACKGROUND: Platelets are thought to be involved in the induction of hepatic ischemia-reperfusion (I/R) injury. The mechanisms of platelet adhesion in the hepatic microvasculature and the role of platelets in the pathogenesis of I/R-induced liver damage in vivo remain unclear. METHODS: In C57BL/6 mice, platelet- and leukocyte-endothelial cell interactions were quantitatively analyzed using intravital fluorescence microscopy in sham-operated animals, after warm lobar hepatic I/R (90/20 min) in wild-type and intercellular adhesion molecule (ICAM)-1-deficient mice, and after I/R in wild-type mice treated with an antifibrinogen antibody. Fibrinogen deposition on the endothelium was detected by intravital microscopy and by immunostaining. Reperfusion injury was assessed by measurement of liver enzyme and caspase-3 activities and of lipid peroxidation. RESULTS: Hepatic I/R induced fibrinogen deposition on hepatic endothelium, followed by a dramatic increase in the number of firmly adherent platelets in the liver microvasculature. Simultaneously, the number of adherent leukocytes in postsinusoidal venules and the aspartate aminotransferase/alanine aminotransferase and caspase-3 activities were elevated. Although ICAM-1 deficiency attenuated postischemic adherence of both platelets and leukocytes, the application of an antifibrinogen antibody selectively reduced the number of adherent platelets but did not influence leukocyte adhesion. The selective blockade of platelet adherence significantly prevented the postischemic increase in liver enzyme and caspase-3 activities. Furthermore, sinusoidal perfusion failure and lipid peroxidation were attenuated in the treated group. CONCLUSIONS: These in vivo data show that platelet adhesion mediated through fibrinogen deposition on ICAM-1 expressed on the endothelium of postischemic hepatic microvessels induces microvascular injury and hepatocellular apoptosis after I/R of the liver during early reperfusion.

Animals↗
PubMed2002

Early inflammatory response to asbestos exposure in rat and hamster lungs: role of inducible nitric oxide synthase.

Recent studies have suggested that inducible nitric oxide synthase (iNOS) plays a role in the development of asbestos-related pulmonary disorders. The pulmonary reactions of rats and hamsters upon exposure to asbestos fibers are well known to be disparate. In addition, in vitro experiments have indicated that mononuclear phagocytes from hamsters, in contrast to those from rats, lack the iNOS pathway. Therefore, the purpose of this study was to investigate whether rats and hamsters differ in lung iNOS expression in vivo upon exposure to asbestos fibers and whether differences in iNOS induction are associated with differences in the acute pulmonary inflammatory reaction. Body weight, alveolar-arterial oxygen difference, differential cell count in bronchoalveolar lavage fluid, total protein leakage, lung myeloperoxidase activity and lipidperoxidation, wet/dry ratio, iNOS mRNA and protein expression, and nitrotyrosine staining of lung tissue were determined 1 and 7 days after intratracheal instillation of asbestos fibers in CD rats and Syrian golden hamsters. Exposure of rats to asbestos fibers resulted in enhanced pulmonary iNOS expression and nitrotyrosine staining together with an acute inflammation that was characterized by an influx of neutrophils, enhanced myeloperoxidase activity and lipid peroxidation, damage of the alveolar-capillary membrane, edema formation, and impairment of gas exchange. In comparison, instillation of asbestos fibers in hamsters resulted in a significantly milder inflammatory reaction of the lung with no induction of iNOS in pulmonary cells. The data obtained provide important information to understand the underlying mechanisms of species differences in the pulmonary response upon exposure to asbestos fibers.

Animals↗
PubMed2002

New method: the intravital videomicroscopic characteristics of the microcirculation of the urinary bladder in rats.

Intravital fluorescence microscopy (IVM) is a widely used method to study the microcirculation in several organs. Our aim was to develop a standard rat model to evaluate the microcirculatory characteristics of the urinary bladder under physiological pressure conditions using the most advanced fluorescence videomicroscopic techniques. Spraque-Dawley rats were used after filling their bladders with a constant volume of saline solution. The intravesical pressure was continuously monitored. The bladder was positioned on a specially designed stage and IVM measurements were made at the beginning, the 90th, 120th and 180th min. Arteriolar and venular diameters, functional capillary density, venular red blood cell velocity, arteriolar and venular macromolecular leakage and leukocyte-endothelial cell interactions (observation of rolling and firmly adherent leukocytes) were quantitatively assessed by a computer assisted analysis system. Neither microcirculatory parameters nor the intravesical pressure changed significantly during the observation period of 180 min using constant filling volume. We successfully established a new, well functioning and reproducible model to study the microcirculation of the rat bladder using intravital fluorescent microscopy.

Animals↗
PubMed2002

The role of endothelin-1 in ischemia-reperfusion induced acute inflammation of the bladder in rats.

PURPOSE: Endothelin (ET)-1 is causatively involved in ischemia-reperfusion induced acute inflammatory reactions and microcirculatory disturbances in many organs. We investigated the role of endothelin-1 in the microcirculatory consequences of ischemia-reperfusion of the bladder using intravital fluorescence videomicroscopy. MATERIALS AND METHODS: Male Sprague-Dawley rats were used in the experiments. The animals were randomly assigned to a sham operated group or to 1 of 2 ischemia-reperfusion groups that underwent 60 minutes of ischemia followed by 30 minutes of bladder reperfusion. In 1 ischemia-reperfusion group the animals were pretreated with BQ 610, a specific ET-A receptor blocker. The bladder was placed on an especially designed stage for intravital fluorescence videomicroscopy measurements. Venular red blood cell velocity, functional capillary density, venular and arteriolar diameter, venular and arteriolar macromolecular leakage, and leukocyte-endothelial cell interactions in postcapillary venules were determined using a computer assisted analyzing system. RESULTS: Functional capillary density, red blood cell velocity, venular and arteriolar diameter were significantly decreased and macromolecular leakage was significantly enhanced after bladder ischemia-reperfusion. The number of rolling and adherent leukocytes was significantly increased in postcapillary venules. Pretreatment with BQ 610 was effective for attenuating the effects of ischemia-reperfusion induced inflammation but could not completely prevent microcirculatory failure. CONCLUSIONS: Ischemia-reperfusion induced cystitis leads to significant impairment of the microcirculation and ET-1 is suggested to have an important role in this process. Pretreatment with an ET-A receptor antagonist reduces ischemia-reperfusion related microvascular disturbances in the bladder.

Acute Disease↗
PubMed2002

Microcirculation of the urinary bladder in a rat model of ischemia-reperfusion-induced cystitis.

OBJECTIVES: To determine the microcirculatory disturbances in a rat model of ischemia-reperfusion-induced cystitis using intravital fluorescence videomicroscopy. METHODS: Twenty male Sprague-Dawley rats were used for the experiments. In 10 animals, warm ischemia of the bladder was induced for 60 minutes. After 30 minutes of reperfusion, microvascular macromolecular leakage, leukocyte-endothelial cell interactions, venular red blood cell velocity, functional capillary density, and the arteriolar and venular diameters were determined by intravital videomicroscopy. In addition, the intravesical pressure and macrohemodynamic parameters were assessed during the experiments. Sham-operated animals served as the controls (n = 10). RESULTS: After ischemia-reperfusion, the numbers of rolling and firmly adherent leukocytes in the postcapillary venules were significantly increased. Venular red blood cell velocity and functional capillary density, as well as the arteriolar and venular diameters, were significantly decreased. The macromolecular leakage had increased in both arterioles and venules. CONCLUSIONS: After ischemia-reperfusion, inflammatory reactions and microcirculatory failure were observed in the urinary bladder. This study targeted the microcirculatory consequences of cystitis using intravital videomicroscopy. Because the parameters investigated are relevant not only for ischemia-reperfusion of the urinary bladder but also for cystitis caused by other stimuli, this model represents a novel tool in the field of inflammation research in urology.

Animals↗
PubMed2002

Perioperative hemodilution.

Acute normovolemic hemodilution (ANH) entails the removal of blood from a patient either immediately before or shortly after induction of anesthesia and the simultaneous replacement with cell-free fluid, preferably synthetic colloids with a predictable volume effect (6% dextran 60/70, 6% hydroxyethyl starch 200,000 and 130.000, respectively). Hemodilution is part of the concept for avoiding or limiting the use of allogeneic blood and should be considered for patients undergoing elective surgery free of contraindications and presenting with an initial hemoglobin concentration > or = 12 g/dl and an anticipated blood loss of > or = 1500 ml. The efficacy of ANH, judged by the necessity to transfuse homologous blood, depends on the preoperative (initial) hematocrit, the target hematocrit (to which hemodilution is performed), and the preset intra- and postoperative transfusion trigger. In the past data from clinical trials have shown that in healthy subjects a target hematocrit of 20-25% (7.0-8.0 g/dl hemoglobin concentration) is feasible and safe for the patient. The lower the target hemoglobin concentration, the more extensive monitoring is required: intraoperative target hemoglobin concentrations of 5.0 g/dl and less have been tolerated by young surgical patients without adverse effects. The safety as well as efficacy of acute normovolemic hemodilution in terms of reducing homologous blood transfusion requirements have been demonstrated in various clinical studies. ANH therefore is regarded an integral part of programs aimed at reducing the need for homologous blood, and can thus be successfully combined with preoperative autologous blood deposition, intraoperative blood salvage and carefully adjusted surgical techniques.

Contraindications↗
PubMed2002

Revascularization of transplanted adipose tissue: a study in the dorsal skinfold chamber of hamsters.

Adipose tissue seems to be an ideal material for use as a permanent soft-tissue substitute in reconstructive surgery. However, knowledge of the behavior of the graft--in particular, its revascularization--is scarce. Therefore, the aim of the current study was to establish a novel model that allows for long-term in vivo quantitative analysis of revascularization of adipose tissue after transplantation. Hamsters (n = 8) were fitted with transparent titanium dorsal skinfold chambers. Immediately after en bloc harvest of adipose tissue from the left inguinal area, the graft was placed gently into the chamber. At days 1, 3, 12, and 21, red blood cell-perfused vessels were assessed in surrounding host tissue, in the border of the graft, and in its center (n = 6 areas each) using intravital fluorescent microscopy. The model allowed for permanent observations of adipose tissue and quantitative analysis of functional vessel density (FVD). At the border zone of the graft, an FVD of 2 +/- 1 cm per cm(2) was measured at day 1. In this region FVD increased constantly and finally reached values (184 +/- 10 cm per cm(2); day 21) that were comparable with those of the surrounding host tissue. Revascularization in the center of the graft started at day 3 after transplantation (14 +/- 3 cm per cm(2)). Here, FVD increased constantly, but lower values compared with the grafts' border zone were measured (139 +/- 10 cm per cm(2); day 21). FVD data obtained from transplanted adipose tissue may contribute to understanding fundamental mechanisms of graft failure.

Adipose Tissue↗
PubMed2002

Tissue damage of non-heart-beating donor lungs after long-term preservation: evaluation of histologic alteration, bronchoalveolar lavage, and energy metabolism.

Several studies have shown that warm ischemia before short-term preservation of pulmonary grafts from non-heart-beating donors (NHBD) induced morphological changes, but still provided a good pulmonary graft function. The aim of this study was to investigate morphological and metabolic changes of NHBD lungs after long-term preservation. Left lung allotransplantation was performed on 12 native-bred pigs. In the NHBD group, lungs were subjected to 90 min of warm ischemia before harvesting, whereas lungs in the HBD group were harvested immediately after cardiac arrest. After a total ischemic period of 19 h, lungs were reperfused and pulmonary gas exchange was assessed. Bronchoalveolar lavage (BAL) and tissue specimen for wet-to-dry weight (W/D) ratio, histologic examination, and measurement of high-energy phosphates were taken 5 h after reperfusion. All parameters were compared with a sham-operated control group. Five hours after reperfusion, mean paO2 and paCO2 were 288 +/- 52 and 48 +/- 0.8 mmHg, respectively, during isolated ventilation of the pulmonary graft with 100% oxygen in the NHBD group. W/D ratio and high-energy phosphates of the pulmonary graft did not differ between our study groups. Histologic examination showed significant morphological changes in the HBD and NHBD group, but alterations were more pronounced in the NHBD group. The percentage of neutrophils, total protein content, and potassium concentration were significantly elevated in the BAL fluid of the NHBD group. Despite the observed aggravation of cellular injury after long-term preservation, NHBD lungs still performed a good pulmonary graft function.

Animals↗
PubMed2002

P-selectin mediates platelet-endothelial cell interactions and reperfusion injury in the mouse liver in vivo.

Platelets are suggested to participate in the pathogenesis of hepatic ischemia-reperfusion (I/R) injury. This study was designed to analyze platelet-endothelial cell interactions in the postischemic mouse liver in vivo and to define the role of endothelial versus platelet P-selectin for these interactions. Platelet-endothelial cell interactions were quantitatively analyzed using intravital fluorescence microscopy after lobar hepatic I/R in C57BL/6 wild-type and P-selectin-deficient mice after infusion of ex vivo rhodamine-6G-labeled wild-type and P-selectin-deficient platelets. Reperfusion injury and apoptosis were assessed by established methods. In wild-type animals, hepatic I/R caused significantly enhanced platelet-endothelial cell interactions in terminal arterioles and postsinusoidal venules as well as platelet stagnation in sinusoids. Concomitantly, transaminase and caspase-3 activities were elevated and sinusoidal perfusion was impaired. In contrast, platelet-endothelial cell interactions were nearly absent in arterioles and venules of mice lacking endothelial P-selectin, irrespective of the presence of P-selectin on infused platelets, but still significantly elevated in sinusoids. Simultaneously, sinusoidal perfusion failure was ameliorated, and transaminase- and caspase-3 activities were significantly reduced in P-selectin-deficient mice as compared with wild-type animals. The present intravital microscopic study provides, for the first time, quantitative analyses of platelet-endothelial cell interactions in the postischemic hepatic microcirculation. Our in vivo data show that endothelial P-selectin is critical for postischemic platelet-endothelial cell interactions within hepatic presinusoidal arterioles and postsinusoidal venules. P-selectin deficiency prevents microvascular injury and apoptosis after warm hepatic I/R.

Animals↗
PubMed2002

Orthogonal polarization spectral imaging (OPS): a novel method to measure the microcirculation in term and preterm infants transcutaneously.

Little is known about the microvascular perfusion of the skin postnatally. Skin microvascular parameters can be assessed noninvasively with orthogonal polarization spectral imaging (OPS), a technique where, through the use of special optics, a virtual light source is created at a depth of 1 mm within the tissue. The light is absorbed by the Hb, yielding an image of the illuminated Hb-carrying structures in negative contrast. In nine term (weight 2100-4470 g) and 28 preterm infants (weight 550-2070 g; gestational age 24-33 wk) red blood cell velocity and vessel diameter and density were determined off-line with the Cap-Image program in vessels video-recorded by OPS near the axilla on d 1 and 5 of life. Blood pressure, heart rate, hematocrit, and body and incubator temperature were noted. Vessel diameter ranged from 6 to 24 microm, vessel density from 219 to 340 cm/cm(2) with no change between d 1 or 5 and no difference between term and preterm infants. Red blood cell velocity increased in preterm infants from d 1 [median 528 microm/s, 95% confidence interval (CI) 486-564 microm/s] to d 5 (median 570 microm/s; 95% CI 548-662 microm/s; p = 0.001) and correlated with the decrease in median hematocrit from 44% (CI 40%-60%) to 39% (CI 37%-43%) with r(2) = -0.37 with a 95% CI -0.59 to -0.11, p = 0.006. Hematocrit correlates with red blood cell velocity in the microvessels of the skin. The new technology can be used to assess quantitative changes in the microvessels and thus allows noninvasive assessment of tissue perfusion in term and preterm infants.

Blood Flow Velocity↗
PubMedDate not supplied

Influence of platelet-derived growth factor on microcirculation during normal and impaired wound healing.

The aim of the current study was to evaluate the influence of platelet-derived growth factor (PDGF) on skin microcirculation during normal and impaired wound healing. Secondary healing wounds were created on the ears of hairless mice and treated once with 3 microg of PDGF-BB immediately after wound creation. Intravital fluorescence microscopy was used to quantify reepithelialization, revascularization, vessel diameters, vascular permeability, and leukocyte-endothelium interactions up to 24 days after wound creation. Microvascular perfusion was assessed by laser Doppler flowmetry. Wound healing was studied in normal (n = 15) and ischemic skin tissue (n = 15) as well as in mice (n = 17) rendered hyperglycemic by an intravenous injection of streptozotocin 7 days prior to wound creation. Treatment with PDGF accelerated reepithelialization and reduced the time for complete wound closure in ischemic skin from 14.9 +/- 2.5 (control) to 12.3 +/- 1.8 days (p < 0.03), and in hyperglycemic animals from 15.0 +/- 2.4 (control) to 12.0 +/- 3.0 days (p < 0.04). Revascularization of these wounds was also significantly enhanced after PDFG application. No other parameters were influenced by the treatment. Normal wound healing was not affected. This study confirms the positive influence of PDGF on wound healing under pathophysiological conditions. The effects in this model seem to be primarily due to the mitogenic potency of PDGF on keratinocytes and endothelial cells. A significant effect on leukocyte activation during the inflammatory process was not observed.

Animals↗