Search PubMed⌕ Search

Biomedical subjects

K Messmer

Publications and source records attributed to K Messmer.

At least 271 records · Page 15Linked to original sources
PubMed1993

Hyperbaric oxygen treatment enhances the recovery of blood flow and functional capillary density in postischemic striated muscle.

The effect of hyperbaric oxygen (HBO) at 2.5 atmospheres of absolute pressure (ATA) on postischemic reperfusion injury in striated muscle was studied using two different animal models. One used complete tourniquet ischemia (4 hr) in the rat hindlimb, measuring blood flow in the tibialis anterior muscle by the xenon washout method at 1-1.5 and 4.5-5 hr after the start of reperfusion. The other used 4 hr of pressure-induced ischemia in the fine striated skin muscle, contained within a dorsal skinfold chamber in hamsters. Vital fluorescence microscopy was employed to measure the functional capillary density using fluorescein isothiocyanate-dextran (mw 150,000) as a plasma marker. After 1-1.5 hr of reperfusion following 4 hr of total ischemia, postischemic blood flow was severely depressed, with no significant difference between the HBO-treated and the untreated rats. However, after 4.5-5 hr of reperfusion, blood flow rates in the postischemic muscle in the HBO-treated animals did not differ significantly from those in nonischemic muscle, compared to a persistent, significant depression in the untreated animals. No significant difference was seen in functional capillary density between HBO-treated and untreated hamsters following 1 hr of reperfusion. After 5 hr of reperfusion, capillary density was significantly improved in HBO-treated animals compared to untreated animals. These results suggest that HBO treatment enhances the recovery of blood flow and functional capillary density in postischemic muscle tissue, indicating attenuation of the microvascular dysfunction or damage in the postischemic period.

Animals↗
PubMed1993

Mechanisms of cytokine cascade activation in patients with sepsis: normal cytokine transcription despite reduced CD14 receptor expression.

BACKGROUND: Lipopolysaccharide causes activation of monocytes/macrophages with excessive secretion of cytokines resulting in hypotension and shock in patients with sepsis. Lipopolysaccharide may induce these responses by interacting with lipopolysaccharide-binding protein and then binding to the cell surface protein CD14 or by acting directly with CD11-CD18 on monocytes/macrophages. The role of CD14 and CD11-CD18 in the activation of macrophages with enhanced cytokine transcription in patients with septic shock remains to be determined. METHODS: To study this, heparinized blood was obtained from 16 patients with septic shock on days 0, 1, 3, 5, 7, and 10 and compared with 20 control patients. The expression of CD14 and CD11b on monocytes in whole blood was measured by direct immunofluorescence and flow cytometry. Moreover, whole blood was stimulated with lipopolysaccharide (1 microgram/ml) for 0, 1, 2, 4, 8, and 24 hours, and messenger RNA expression for tumor necrosis factor-alpha, interleukin-beta (IL-1 beta), and IL-6 was determined on isolated peripheral blood mononuclear cells with Northern blot analysis. RESULTS: Both CD14 expression and receptor density on monocytes from whole blood were markedly suppressed (-63% on day 3; p < 0.05) in the septic group compared with controls. Although CD11b expression was also decreased (-24% on day 1; p < 0.05), receptor density on monocytes was slightly increased in the septic group in comparison with the control group. Kinetics and intensity of messenger RNA expression for tumor necrosis factor-alpha, IL-1 beta, and IL-6 were similar in both groups. CONCLUSIONS: These data indicate that in patients with septic shock, lipopolysaccharide-mediated signaling and cytokine transcription are unchanged despite a significant reduction of CD14 expression and density on monocytes. Thus, lipopolysaccharide-induced activation of monocytes from patients with sepsis may occur through direct binding of lipopolysaccharide to the CD11-CD18 complex or other lipopolysaccharide receptors, whereas binding of the lipopolysaccharide-lipopolysaccharide-binding protein complex to the CD14 receptor may not play a pivotal role in sepsis.

Adult↗
PubMed1993

Dorsal skinfold chamber technique for intravital microscopy in nude mice.

For many years, observation chambers, implanted in various animal species and in man, have been used for intravital microscopy of the microcirculation in granulation tissue, preformed tissue, or of the microvascularization of tissue implants. We describe herein a skinfold chamber model for the intravital microscopic investigation of striated skin muscle in immunoincompetent, nude mice over a minimum period of 2 weeks. Using fluorescent markers for contrast enhancement of plasma (fluorescein isothiocyanate-dextran) and leukocytes (acridine orange), the presented model allows the quantitative analysis of 1) the microhemodynamic parameters microvessel diameter and red blood cell velocity in arterioles (16 to 50 mu diameter), capillaries (4 to 9 mu diameter), and post-capillary venules (19 to 60 mu diameter), 2) leukocyte/endothelium interaction in these vessel segments, 3) functional capillary density and intercapillary distance, and 4) endothelial cell integrity. These parameters can be assessed in the microcirculation of the striated muscle tissue under normal or pathological conditions, as well as in the microcirculation of transplanted xenogeneic (human) neoplastic and non-neoplastic tissue grafts.

Animals↗
PubMed1993

The impact of free radical-mediated reperfusion injury on acute and chronic rejection events following cadaveric renal transplantation.

In a prospective, randomized, double-blind, placebo-controlled trial, rhSOD was given to cadaveric renal allograft recipients intravenously in a dose of 200 mg during surgery, and its effect on both acute and chronic rejection was investigated. The results showed that rhSOD exerts a beneficial effect on acute rejection episodes as indicated by a statistically significant reduction of first acute rejection episodes to 18.5% compared with 33.3% in controls, and a reduction in early irreversible acute rejection to 3.7% compared with 12.5% in controls. With regard to longterm results, there was a statistically significant improvement in the actual 5-year graft survival rate for rhSOD-treated patients to 68% (with a corresponding 13-year half-life) compared with 50% in controls (with a corresponding 6-year half-life). The incidence of acute rejection episodes did not prove to be a risk factor for long-term graft outcome. Rather only the combination of acute rejection episodes and the presence of uninfluenced reperfusion injury appeared to have a detrimental effect on long-term prognosis. The beneficial effect of rhSOD observed in this trial is not well understood, although one can assume that the effect is brought about by interference of rhSOD with ischemia or reperfusion injury to the allograft by oxygen-free radicals. In this sense, rhSOD may mitigate increased MHC expression and presentation, cytokine-adhesion molecule expression, and APC activation induced by reperfusion injury. In addition, in accordance with the "response-to-injury" hypothesis to explain the pathogenesis of arteriosclerosis, rhSOD may mitigate acceleration of chronic obliterative rejection or arterio-/arteriolosclerosis induced by reperfusion injury. In this sense, rhSOD may act indirectly by reducing acute rejection-mediated endothelial injury, or directly, by ablation of reperfusion-mediated acute endothelial injury.

Acute Disease↗
PubMed1993

Stimulation of leukocyte/endothelium interaction by oxidized low-density lipoprotein in hairless mice. Involvement of CD11b/CD18 adhesion receptor complex.

BACKGROUND: The adhesion of leukocytes to the vascular endothelium has been identified as a constant, early feature of atherogenesis. Using a skinfold chamber model in hamsters for intravital microscopy, we have recently demonstrated the chemotactic and adhesion-promoting action of oxidatively modified low density lipoprotein (oxLDL) in vivo. EXPERIMENTAL DESIGN: In order to rule out a species specificity of the experimental approach, and to investigate the involvement of leukocyte adhesion receptors in oxLDL-induced leukocyte/endothelium interaction, we have adapted the skinfold chamber model to hairless mice. Using intravital fluorescence microscopy, leukocyte/endothelium interaction in a fine striated skin muscle was assessed during the time course after intravenous injection of native human LDL (4 mg/kg body weight) and oxLDL (oxidized in vitro by 7.5 microM Cu2+, 6 hours, 37 degrees C) into control mice and into mice pretreated with either the selective inhibitor of leukotriene biosynthesis MK-886 (20 mumol/kg body weight, intravenously, 10 minutes before oxLDL) or with a monoclonal antibody directed towards the CD11b subunit of the CD11b/CD18 adhesion receptor complex on leukocytes (monoclonal antibody anti-Mac1, 0.5 mg/kg, iv, 10 minutes before oxLDL). RESULTS: We demonstrate in this study that injection of oxLDL (4 mg LDL-cholesterol/kg, intravenously, oxidized by 7.5 microM Cu2+, 6 hours, 37 degrees C), but not of native LDL or LDL-free Cu(2+)-solution, elicits the adhesion of fluorescently stained leukocytes to the endothelium of postcapillary venules (173 +/- 75 cells/mm2 at 20 minutes after oxLDL, mean +/- SD) and arterioles (119 +/- 74 cells/mm2 at 20 minutes after oxLDL, mean +/- SD) in the mice. OxLDL-induced leukocyte adhesion was entirely prevented by pretreatment of the animals with the inhibitor of leukotriene biosynthesis or with monoclonal antibody anti-Mac-1. CONCLUSIONS: These results demonstrate the involvement of leukotrienes and of the CD11b/CD18 adhesion receptor complex in oxLDL-induced leukocyte adhesion in vivo and rule out a species specificity of this pathophysiologic event.

Animals↗
PubMed1993

Heterogeneity of left ventricular perfusion during pulmonary edema and microembolism treated with positive end-expiratory pressure and norepinephrine.

Regional left ventricular myocardial blood flow was studied in an experimental model of pulmonary edema and microembolization (PEM) ventilated with positive end-expiratory pressure (PEEP). The analysis was based on a 3-dimensional extension of the autocorrelation function used to assess the spatial correlation (rspat) of myocardial perfusion. Experiments were performed on 8 premedicated, anesthetized and mechanically ventilated dogs. PEM was induced with oleic acid (0.01 mg/kg) and glass beads. Successive PEEP values of 10, 15 and 20 cm H2O (P20) were applied and norepinephrine (NE, 0.2-1.0 microgram min-1 kg-1) was administered after P20. Regional perfusion was measured with radioactive microspheres. The left ventricle (LV) was dissected into 256 samples. rspat was computed as the correlation of regional perfusions of samples p units apart in the apex-to-base, endo-epicardial and angular directions. Analysis was performed after anesthesia and instrumentation (control, C), P20 and NE. Control values of rspat were around 50% in the apex-to-base and angular directions and the sign was inverted in the endo-epicardial direction. A reduction of rspat to values close to zero was observed in all directions for P20 and NE. This is the typical pattern of independent distribution. Thus, the results indicate that, under the experimental conditions used, there is some degree of neighborhood dependence of regional LV myocardial blood flow. This dependence is not observed under PEM, mechanical ventilation with PEEP and NE.

Animals↗
PubMed1993

Role of leukocytes in the initial hepatic microvascular response to endotoxemia.

INTRODUCTION: Accumulation and adherence of leukocytes within the hepatic microvasculature have been emphasized to play a major role in the pathogenesis of endotoxin/lipopolysaccharide (LPS)-induced liver injury. However, there is no information on their interrelation with hepatic microvascular perfusion failure, hepatocellular damage and liver dysfunction following LPS exposure. AIM AND METHODS: Therefore, we quantitatively assessed the initial LPS-induced hepatic microvascular response, including leukocyte-endothelium interaction and their interrelation with sinusoidal perfusion, hepatocellular integrity (serum AST/ALT activity) and excretory function (bile flow). After infusion of LPS (E. coli 0128:B12; 10 mg.kg-1 i.v.) intravital fluorescence microscopy was applied to livers of Sprague-Dawley rats. RESULTS: 1 h after LPS exposure deterioration of hepatic microcirculation was hallmarked by significant accumulation of leukocytes, stagnant within sinusoids and adherent to the endothelial lining of postsinusoidal venules. This was accompanied by a progressive increase of the number of non-perfused sinusoids (20 +/- 4%). During the 1 h period after LPS exposure, bile flow was found significantly (p < 0.05) reduced, while serum AST/ALT activities remained unchanged. Leukocytes appear to contribute to sinusoidal perfusion failure, since the number of non-perfused sinusoids significantly (p < 0.01) correlated with the number of leukocytes stagnant within the sinusoids. In addition, the inverse correlation (p < 0.01) of bile flow with the number of both, leukocytes stagnant within the sinusoids and non-perfused sinusoids indicates that microvascular injury initiates hepatic dysfunction. CONCLUSION: Inasmuch as LPS exposure initially induces only microcirculatory disturbances without substantial loss of hepatocellular integrity, we propose that therapeutic strategies during early endotoxemia should focus on attenuation of microvascular injury to prevent manifestation of hepatocellular damage.

Animals↗
PubMed1993

[Blood replacement in elective surgery: results of the Sanguis Study].

The aim of the Sanguis study, a project sponsored by the European Community, is to assess the use of blood and blood components including the use of programs for autologous blood transfusion in 43 hospitals in 10 European countries. The study was inaugurated by Prof. G. Sirchia, Milan, who formed a study group of experts from 10 countries. The study group defined the study design, identified the centers, and followed the progress of the project. From October 1990 until September 1991 data were collected in the 43 hospitals from patients undergoing one of six elective surgical procedures. The results obtained from interim analysis (70% of expected data) of patients with total hip replacement revealed differences in the frequency of homologous blood transfusion between hospitals and also regional differences between different countries. There was great variation in the use of alternative programs for reduction or even avoidance of homologous blood transfusion between hospitals. For total hip replacement, the calculated probability to receive homologous blood varied between 0 and 100% in different hospitals. This observational study will provide a data base concerning the transfusion practice in 6 elective surgical procedures in 10 European countries. According to the findings of this study, recommendations for improving the transfusion practice shall be elaborated and indications for alternative programs identified. In a subsequent study (Sanguis 2), these recommendations are to be validated.

Aged↗
PubMed1993

[Microcirculation of skeletal muscle after ischemia and reperfusion].

The postischemic reperfusion-damage in the microcirculation of skeletal muscle is characterized by 1) heterogenous capillary perfusion with capillary perfusion deficiency ("no reflow"), 2) microvascular accumulation of leukocytes, which adhere to the endothelium of postcapillary venules, and 3) increase of vessel permeability with swelling of endothelial cells and with interstitial edema. Two models of pathomechanism may be differentiated: The capillary perfusion-deficiency of the no-reflow phenomenon prolongs the duration of ischemia extending the period of postischemic reperfusion and induces the tissue-damage by further decrease of tissue-pH, by loss of energy rich phosphates and by a deficit of oxygen supply to tissue. On the other hand, reperfusion with consecutive reentry of molecular oxygen into the microvasculature provokes the formation of oxygen-radicals and the accumulation of leukocytes adhering to the endothelium of postcapillary venules ("reflow-paradox"). The activated white blood cells release additional oxygen-radicals and deliver aggressive mediators, such as proteases, cytokines and eicosanoids, which have chemotactic influence on leukocytes. This results in a vicious circle in which oxygen-radicals and mediators are responsible for the augmentation of postischemic tissue-damage. Prophylactic isovolemic hemodilution to a hematocrit of 30% with dextran 60 reduces the postischemic capillary perfusion deficiency (no reflow); therapy with "oxygen radical scavengers" and xanthinoxydase-inhibitors reduces accumulation/adherence of leukocytes as well as the damage to the endothelial lining with increased microvascular permeability (reflow-paradox). Intermittent reperfusion/reoxygenation influences both components of postischemic microcirculation damage and is therefore a simple clinical approach for reducing the ischemia/reperfusion-syndrome in elective surgery.

Animals↗
PubMed1993

Improvement of impaired pancreatic microcirculation by isovolemic hemodilution protects pancreatic morphology in acute biliary pancreatitis.

Impairment of the pancreatic microcirculation is a characteristic finding in experimental biliary pancreatitis. Isovolemic hemodilution with dextran 60 has been proven to maintain pancreatic capillary perfusion. To evaluate the significance of this therapeutic approach with respect to histologic changes, intravital microscopic assessment of the microcirculation was combined with a morphometric analysis of the pancreas by means of light microscopy in rabbits (n = 18). Pancreatic capillary perfusion was maintained in the rabbits subjected to hemodilution 30 minutes after the induction of pancreatitis with 54 percent of the capillaries still being perfused at 12 hours, compared with only 16 percent in the control group. The improved capillary perfusion resulted in a significant reduction of those changes considered potentially reversible (cell vacuolization and interstitial edema) that surround zones of necrosis. However, because of the early establishment of necrosis in this model, hemodilution was unsuccessful in preventing all cell death. Hemodilution can limit the progressive extension of pancreatic injury in this model of biliary pancreatitis.

Acute Disease↗
PubMed1993

Impact of leukocyte adhesion on myocardial ischemia/reperfusion injury: conceivable mechanisms and proven facts.

Leukocyte activation, adhesion, and emigration serve a protective role during a well-contained inflammatory response. However, under certain pathologic conditions such as endotoxemia, inflammatory bowel disease, and ischemia-reperfusion injury, leukocytes may turn against the host and aggravate--rather than prevent--tissue damage. Numerous experimental studies have been performed during the last decade to investigate the pathophysiologic role of leukocyte accumulation and adhesion during ischemia/reperfusion injury of various organs, in particular of the myocardium. Most of the latter studies investigated whether the consequences of experimental myocardial infarction could be attenuated by interventions aimed at the inhibition of chemotactic leukocyte infiltration or adhesion (or both) to microvascular endothelial cells. Although many promising results were reported, the consequent step towards an introduction of these strategies into experimental or even routine clinical management of patients with myocardial infarction has so far not been undertaken. In this manuscript, the authors try to give an overview on the state of the art of "antileukocyte" strategies in myocardial ischemia-reperfusion injury and to offer explanations for incongruent data obtained with diverse experimental approaches (animal species, treatment modalities, surgical and anesthesiologic artifacts, techniques for morphologic and functional evaluation of tissue damage). The authors conclude that long-term preclinical studies on suitable animal models, thoroughly investigating the positive and negative effects of antileukocyte interventions on the functional consequences of myocardial ischemia-reperfusion injury, are mandatory before the first clinical trial can be advocated.

Animals↗
PubMed1993

[Microcirculation of the liver in hemorrhagic shock in the rat and its significance for energy metabolism and function].

INTRODUCTION: Shock induced microcirculatory failure is proposed to be causative for the impairment of hepatic function, which contributes to the development of multiple organ failure. In order to quantify the interrelation between hepatic microcirculatory disturbances and organ dysfunction, we have analyzed hepatic microcirculation (in vivo microscopy), energy metabolism (ketone body ratio) and liver excretory function (bile flow) during hemorrhagic shock in rats. METHODS: Under chloralose anesthesia and mechanical ventilation Sprague-Dawley rats (n = 6) were laparotomized and the left liver lobe was exteriorized for in vivo fluorescence microscopy. Sinusoidal perfusion was assessed after i.v. injection of Na-fluorescein (2 mumol.kg-1), in vivo staining of white blood cells by Rhodamin-6G (0.1 mumol.kg-1 i.v.) enabled for analysis of leukocyte-endothelium interaction. Erythrocyte flux was measured by means of laser Doppler flowmetry. Hepatic function was estimated by measurement of bile flow via cannulation of the common bile duct. Ketone body ratio (acetoacetate/beta-hydroxybutyrate, Ac-Ac/beta-OHB) was measured spectrophotometrically from arterial blood and served as indicator of hepatic energy metabolism (n = 12). After baseline recordings hemorrhagic shock (MAP: 40 mmHG) was induced by blood withdrawal and maintained for a total of 2 h. Measurements were performed during baseline as well as 1 h and 2 h after induction of hemorrhage. RESULTS: After 1 h and 2 h of hemorrhagic shock sinusoidal perfusion was found markedly impaired (p < 0.05) from 100% (baseline) to 78.3 +/- 2.4% and 60.9 +/- 13.4%, accompanied by a significant fall of erythrocyte flux to 52 +/- 2% and 46 +/- 4% (p < 0.05). Leukocyte velocity was significantly (p < 0.05) reduced both in sinusoids and in postsinusoidal venules, while leukocyte adherence to the endothelial lining cells was found increased (sinusoids: 183.2 +/- 55.6% and 178.8 +/- 39.0% (p < 0.05); postsinusoidal venules: 232.4 +/- 43.1% and 297.6 +/- 65.8% (p < 0.05)). In addition, 2 h of hemorrhagic shock caused an increase of beta-OHB, while Ac-Ac levels remained unchanged. This resulted in a significant reduction of ketone body ratio. Concomitantly, bile production was significantly decreased from 20.8 +/- 2.9 microliters.min-1 during control to 6.1 +/- 1.0 microliter.min-1 after 2 h of shock (p < 0.05). The alteration of energy metabolism and the impairment of bile flow correlated significantly (p < 0.01) with the extent of microcirculatory disturbances. CONCLUSION: Liver microcirculation in hemorrhagic shock is characterized by sinusoidal perfusion failure with a reduction of erythrocyte flux, leukocyte velocity and enhancement of leukocyte adherence to the microvascular endothelial lining. Correlation of the impairment of energy metabolism and liver dysfunction with these microcirculatory disturbances may indicate their crucial role in the development of shock-induced organ failure.

Animals↗
PubMed1992

Angiogenesis, microvascular architecture, microhemodynamics, and interstitial fluid pressure during early growth of human adenocarcinoma LS174T in SCID mice.

To date, most quantitative information on tumor angiogenesis, microcirculation, and transport has been derived from rodent tumors grown in transparent chamber preparations. In this paper we present a chamber technique adapted to immunodeficient mice for the study of human tumor xenografts. Microcirculatory parameters in severe combined immunodeficient mice bearing a dorsal skin fold chamber preparation were quantified using intravital microscopy and image analysis. The take rate of the human colon adenocarcinoma LS174T in the chamber preparation was 100%, and the tumor area doubling time was 6.5 days. Three days following implantation of 2 x 10(5) tumor cells onto the striated skin muscle, capillary sprouts were noted in the tumor cell mass. Microvasculature in the tumors was established after 10 days. Capillary density, vessel diameter, red blood cell velocity, and blood flow rates in individual microvessels measured on days 10, 14, 18, and 22 showed no statistical difference in the striated muscle (capillaries) and subcutaneous tissue (arterioles and venules) of the skin of tumor-free animals (N = 6), whereas these parameters increased slightly, but not significantly, in the LS174T tumors (N = 7). Mean interstitial fluid pressure (+/- SD) in these small tumors was 4.6 +/- 1.7 mmHg (N = 4) on day 10 and 5.1 +/- 0.9 mmHg (N = 4) on day 22 and significantly elevated compared to that in the subcutaneous and skin tissue (-0.9 +/- 0.8 mmHg) (N = 4) (P < 0.001). To our knowledge, this is the first model enabling intravital microscopic studies of human tumor xenografts in a transparent chamber preparation in severe combined immunodeficient mice. Studies on angiogenesis, microcirculation, and transport using such a preparation should provide new insights into microcirculation-mediated mechanisms for cancer treatment.

Adenocarcinoma↗
PubMed1992

Interstitial hypertension in head and neck tumors in patients: correlation with tumor size.

Elevated interstitial fluid pressure (IFP) is associated with poor blood supply and inadequate delivery of drugs to solid tumors. IFP was measured in squamous cell carcinomas of the head and neck region in humans using the wick-in-needle technique. In all lesions (n = 19), the IFP was elevated (4-33 mm Hg). Furthermore, the IFP increased with tumor size. The highest IFP was 33 mm Hg in a 24-ml tumor. In one tumor, the IFP was found to be negative (-2.6 mm Hg), which is comparable to that in human skin or subcutaneous tissue. The histopathology of this tumor was benign. If this pressure difference between malignant and benign lesions can be confirmed in a large number of tumors, then the IFP could be used to aid tumor detection during needle biopsy. The value of IFP as a predictor of response to radiotherapy, photodynamic therapy, hyperthermia, and chemotherapy should be assessed prospectively.

Aged↗