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K Messmer

Publications and source records attributed to K Messmer.

At least 325 records · Page 18Linked to original sources
PubMed1991

Dietary fish oil reduces leukocyte/endothelium interaction following systemic administration of oxidatively modified low density lipoprotein.

BACKGROUND: In vitro and in vivo experiments have demonstrated the role of oxidatively modified low density lipoprotein (oxLDL) in eliciting leukocyte/endothelium interaction during early atherogenesis. METHODS AND RESULTS: In the present study we investigated the effect of dietary fish oil on oxLDL-induced leukocyte/endothelium interaction using intravital fluorescence microscopy in the dorsal skinfold chamber model in awake Syrian golden hamsters. Hamsters were fed for 4 weeks prior to the experiments with either standard laboratory chow or a diet supplemented with 5% of a fish oil concentrate (18% eicosapentaenoate, 12% docosahexaenoate). The efficacy of the fish oil diet was demonstrated by the incorporation of fish oil-derived omega-3 fatty acids into plasma, leukocyte, and erythrocyte lipids. In control hamsters (n = 7) and fish oil-fed hamsters (n = 7), leukocyte/endothelium interaction was assessed in the time course after intravenous injection of human LDL (4 mg/kg), oxidized by 7.5 microM Cu2+ (6 hours, 37 degrees C). In control hamsters, injection of oxLDL elicited the rolling and sticking of leukocytes to the endothelium of arterioles and postcapillary venules with a maximum 15 minutes after injection (arterioles: from 3 +/- 1 to 91 +/- 25 cells/mm2 at 15 minutes; venules: from 13 +/- 6 to 150 +/- 46 cells/mm2 at 15 minutes; mean +/- SD). This phenomenon was significantly reduced in fish oil-fed hamsters, where 15 minutes after injection of oxLDL leukocyte sticking reached a maximum of only 15 +/- 7 and 20 +/- 5 cells/mm2 in arterioles and postcapillary venules, respectively (p less than 0.01 versus control animals). CONCLUSIONS: The results of the present study suggest that inhibition of leukocyte/endothelium interaction may be one of the mechanisms by which dietary fish oil exerts its protective effects on experimental and clinical atherogenesis.

Animals↗
PubMed1991

Leukotrienes as mediators in ischemia-reperfusion injury in a microcirculation model in the hamster.

Leukotriene (LT)B4 promotes leukocyte chemotaxis and adhesion to the endothelium of postcapillary venules. The cysteinyl leukotrienes, LTC4, LTD4, and LTE4, elicit macromolecular leakage from this vessel segment. Both leukocyte adhesion to the endothelium and macromolecular leakage from postcapillary venules hallmark the microcirculatory failure after ischemia-reperfusion, suggesting a role of leukotrienes as mediators of ischemia-reperfusion injury. Using the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle in awake hamsters and sequential RP-HPLC and RIA for leukotrienes, we demonstrate in this study that (a) the leukotrienes (LT)B4 and LTD4 elicit leukocyte/endothelium interaction and macromolecular leakage from postcapillary venules, respectively, that (b) leukotrienes accumulate in the tissue after ischemia and reperfusion, and that (c) selective inhibition of leukotriene biosynthesis (by MK-886) prevents both postischemic leukotriene accumulation and the microcirculatory changes after ischemia-reperfusion, while blocking of LTD4/E4 receptors (by MK-571) inhibits postischemic macromolecular leakage. These results demonstrate a key role of leukotrienes in ischemia-reperfusion injury in striated muscle in vivo.

Animals↗
PubMed1991

Role of leukotrienes in leukocyte adhesion following systemic administration of oxidatively modified human low density lipoprotein in hamsters.

In vitro studies indicate that oxidatively modified low density lipoprotein (oxLDL) promotes leukocyte adhesion to the vascular endothelium, a constant feature of early atherogenesis. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in awake Syrian golden hamsters, we studied whether (a) oxLDL elicits leukocyte/endothelium interaction in vivo, and whether (b) leukotrienes play a mediator role in this event. Leukocyte/endothelium interaction was assessed in the time course after intravenous injection of native human LDL (4 mg/kg body wt) and of oxLDL (7.5 microM Cu++, 6 h, 37 degrees C) into control hamsters and into hamsters, pretreated with the selective leukotriene biosynthesis inhibitor MK-886 (20 mumol/kg, i.v.). While no effect was seen after injection of native LDL, oxLDL elicited an immediate induction of leukocyte adhesion to the endothelium of arterioles and postcapillary venules. Total and differential leukocyte counts suggest that all leukocyte subsets were likewise affected by oxLDL with no specific preference for monocytes. Stimulation of leukocyte adhesion was entirely prevented in inhibitor-treated animals, suggesting the important mediator role of leukotrienes in oxLDL-induced leukocyte/endothelium interaction.

Adult↗
PubMed1991

[Organ blood supply and oxygenation during limited isovolemic hemodilution with 6% HES 200/0.62 and 6% Dextran 70].

Oxygen delivery (systemic oxygen transport) is directly dependent upon cardiac output and oxygen content of the blood. The rheology of blood, however, represents a co-determinant of oxygen delivery. It has recently been argued that the increase in plasma viscosity occurring under hemodilution with dextran could be detrimental to blood flow and, hence, tissue oxygenation. METHODS. Twelve splenectomized beagles (12.5 +/- 1.7 kg) were anesthetized and randomly assigned to hemodilution to 20 vol% hematocrit (hct) with 6% hydroxyethyl starch (HES 200/0.62) or 6% dextran-70 (DX-70). The effects of hemodilution (HD) upon macrohemodynamics, plasma and blood volumes (131I dog albumin distribution), organ blood flow (radioactive-labelled microspheres, phi 15 microns), and local tissue oxygenation (pO2 multiwire surface electrode) were evaluated with special reference to any actual plasma viscosity. RESULTS. Moderate HD with either solution resulted in equivalent changes in macrohemodynamics and plasma and blood volumes. Tissue oxygen extraction increased (p less than 0.05) due to a small rise (maximally 28%) in cardiac output. HD with either solution resulted in an increase in plasma viscosity that was more pronounced in the DX-70 group (1.45 +/- 0.07 mPa.s) as compared to HES-diluted animals (1.16 +/- 0.04 mPa.s). Blood flow increased (p less than 0.01) in all organs after HD independently of the diluent. Both higher pO2 values on the surface of liver and skeletal muscle (p less than 0.01) as well as a shift of the pO2 histograms to the right indicated a more homogeneous tissue perfusion during HD. CONCLUSIONS. In normotensive animals without peripheral arterial occlusive disease undergoing moderate hemodilution, organ blood flow was independent of plasma viscosity. Systemic oxygen transport was not affected by plasma viscosity changes, but is primarily determined by systemic hct. Local surface tissue oxygenation on skeletal muscle and liver was not impaired, but rather improved during hemodilution despite raised plasma viscosity. Of the rheological factors influencing oxygen delivery, hct thus plays the predominant role while plasma viscosity is of minor importance.

Animals↗
PubMed1991

Optimizing autologous blood donation by recombinant human erythropoietin (rhu-EPO) and interleukin 3 (IL-3).

The transfusion of autologous blood protects surgical patients from both the transfusion transmitted diseases (AIDS, posttransfusion hepatitis) and the immunosuppressive effects of homologous blood. Nevertheless, the use of autologous blood is still unsatisfactory, mainly because of the elaborated logistics, organization and technique required and the often insufficient amounts of autologous blood gained. Today, the major growth-factors of erythropoiesis are available as recombinant analogues. In the studies reviewed here, we investigated the effects of rhu-EPO and IL-3 on perioperative erythropoiesis in two canine models of acute isovolemic hemodilution. Different therapeutic concepts are compared with respect to preoperative changes in hematocrit, the volume of autologous blood gained and the duration of postdilutional anemia.

Animals↗
PubMed1991

[Use of hypertonic saline solutions in intensive care and emergency medicine--developments and perspectives].

The primary factor rendering patients at risk of developing multiple system organ failure after shock and trauma is the persistence of impaired microcirculation along with its sequelae for cellular and organ function. Bolus infusion (2-5 min) of 4 ml/kg hypertonic/hyperoncotic saline solution through a peripheral vein is a new concept for primary resuscitation from severe hypovolemia associated with trauma and hemorrhage and is termed "small-volume resuscitation". The experimental data obtained by various research groups have demonstrated the efficacy of 7.2%-7.5% saline solution in restoring central hemodynamics and organ blood flow. The simultaneous application of a hyperoncotic colloid (6%-10% dextran 60/70; 6%-10% hydroxyethylstarch 200,000) aims at prolonging the circulatory effect of saline. Of particular importance are the data obtained in experiments on traumatic-hemorrhagic hypovolemia in beagles, which proved that the infusion of 10% dextran 60 in 7.2% saline (hypertonic-hyperoncotic solution) restores nutritional blood flow within less than 5 min, thereby enhancing the circulatory effect of hypertonic saline alone. In the pre-clinical setting, small-volume resuscitation by means of hypertonic saline/dextran solution is aimed at the rapid normalization of the compromised microcirculation and, thus, at the prevention of late complications such as sepsis and multiple system organ failure. The novelty of hypertonic saline/dextran resuscitation lies in its operational mechanism at the microcirculatory level, which also renders this concept attractive for volume support in endotoxemia and septic shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Volume↗
PubMed1991

Increase in skin-flap survival by the vasoactive drug buflomedil.

The effect of buflomedil to protect skin tissue from ischemia and necrosis was studied in random cutaneous flaps. Measurements were performed by intravital microscopy on the microcirculatory level of capillary perfusion in a flap model in the hairless mouse. In 30 hairless mice, single-pedicle flaps measuring 6 x 16 mm were raised perpendicular to the spine of the animal. This flap develops a reliable amount of necrosis at its distal edge over a period of 7 days. A group of 10 mice received intravenous injections of buflomedil in doses of 3 mg/kg per day diluted in 0.1 ml normal saline beginning 4 hours before flap elevation and for 6 consecutive days postoperatively. In addition, 10 further animals received the same treatment except that it was started 5 minutes after flap elevation. In 10 mice serving as controls, normal saline in equal volumes as in the experimental groups was applied. By means of intravital microscopy, functional vessel density (FVD) was determined in 2.5-mm increments from the flap's base to its distal edge at 1, 6, and 24 hours after elevation. Skin-flap survival was quantified by measuring the necrotic area on day 7 by means of digital planimetry. Functional vessel density was preserved in the distal flap of animals pretreated with buflomedil, revealing a higher functional vessel density at 10.0 mm (p less than 0.01), 12.5 mm (p less than 0.05), and 15.0 mm (p less than 0.001) from the flap's base as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A local area network for medical research; planning, realization and experience.

This report focuses on the planning and realization of an interdisciplinary local area network (LAN) for medical research at the University of Heidelberg. After a detailed requirements analysis, several networks were evaluated by means of a test installation, and a cost-performance analysis was carried out. At present, the LAN connects 45 (IBM-compatible) PCs, several heterogeneous mainframes (IBM, DEC and Siemens) and provides access to the public X.25 network and to wide-area networks for research (EARN, BITNET). The network supports application software that is frequently needed in medical research (word processing, statistics, graphics, literature databases and services, etc.). Compliance with existing "official" (e.g., IEEE 802.3) and "de facto" standards (e.g., PostScript) was considered to be extremely important for the selection of both hardware and software. Customized programs were developed to improve access control, user interface and on-line help. Wide acceptance of the LAN was achieved through extensive education and maintenance facilities, e.g., teaching courses, customized manuals and a hotline service. Since requirements of clinical routine differ substantially from medical research needs, two separate networks (with a gateway in between) are proposed as a solution to optimally satisfy the users' demands.

Costs and Cost Analysis↗
PubMed1990

Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy.

Much clinical and experimental evidence suggests that pancreatic ischaemia in the early phase of acute pancreatitis is important in the development of pancreatic necrosis. While depletion of intravascular volume has often been assumed to be the main circulatory defect, an additional disturbance of pancreatic microcirculation has been demonstrated experimentally. Possible contributory mechanisms include chemical-induced vasoconstriction, direct injury of vessel wall, intravascular coagulation and increased endothelial permeability resulting in pancreatic oedema, haemoconcentration and impaired venous drainage. Pancreatic ischaemia as a consequence of these local effects seems to be responsible for the transition of mild pancreatitis to parenchymal necrosis. In experimental models the beneficial effect of various drugs and of sympathetic blockade has been ascribed to an improvement in pancreatic perfusion. Although effective volume therapy is generally accepted as the mainstay of conservative treatment in acute pancreatitis, the efficacy of different fluid preparations is still controversial, and simple fluid resuscitation has not been shown to prevent the development of parenchymal necrosis. The specific impairment of pancreatic microcirculation cannot be prevented merely by replenishment of intravascular volume with crystalloids, albumin or plasma despite normalization of macrohaemodynamics. In contrast, partial replacement of blood by dextran preparations has been shown to increase pancreatic perfusion by improving blood fluidity. Isovolaemic haemodilution in conjunction with conventional fluid therapy may provide a new and effective means of protecting the pancreas from secondary injury due to the early ischaemic phase of acute pancreatitis.

Acute Disease↗
PubMed1990

Effects of normovolemic hemodilution on blood flow in the rabbit ear.

The effect of isovolemic hemodilution using dextran-60 on arterial blood flow in the rabbit ear was investigated. The animals were anesthetized and an electromagnetic flow probe was applied around the central artery of the ear. Isovolemic hemodilution was performed during a 15 min exchange period. Two degrees of hemodilution were investigated [8.5 and 17 ml dextran-60/kg body weight (b.w.)] and compared with a nontreated control group. The two levels of hemodilution induced reductions in hematocrit to 29 and 21%, respectively, from the control level of about 40%. In all groups, blood pressure maintained constant levels throughout each experiment, which lasted 240 min. In the controls, ear artery blood flow was unchanged or decreased slightly during the experiment. The lower level of hemodilution caused a slight increase of blood flow after 4 h. In the group treated with 17 ml/kg b.w. dextran, blood flow gradually increased after 90 min following hemodilution. After 240 min, flow rates had increased to two- or threefold the initial rate in this group. Although other possibilities exist, the increased blood flow following hemodilution may be interpreted as reflecting a decreased resistance to flow in the tissue due to the decreased viscosity of the blood.

Animals↗
PubMed1990

Microvascular ultrastructure in non-freezing cold injuries.

The effects of repeated local exposure to cold on the integrity of the subcutaneous microcirculation were studied in a model using a transparent tissue chamber implanted into a dorsal skin fold of Syrian hamsters. A detailed study of the vascular ultrastructure within the chamber revealed the following features: Endothelial damage was prominent in true capillaries and venous vessels, while arterioles remained unaffected. The endothelial lining appeared extremely attenuated around the entire vascular perimeter causing the development of "gaps", some of which contained leukocytes or platelets. Smaller vessels were often completely filled with blood cells with leukocytes integrated into the endothelial wall. Fibrin was never observed within these occluded vessels. Finally, only veil-like remnants of the endothelium persisted, and compressed erythrocytes were still mimicking the original vascular outline. It is concluded that the ultrastructural changes observed after a repeated non-freezing cold injury closely resemble those observed during ischemia/reperfusion injury.

Animals↗
PubMed1990

The evaluation of radioactive microsphere data: remarks on the use of the BMDP and SAS statistical software packages.

We investigated the suitability of BMDP and SAS as an integrated tool for the evaluation of regional blood flow data obtained from the radioactive microsphere technique. Both packages were applied to a recent study on muscle blood flow with a 3-factorial design. The organization of data and files, the strategy of data reduction, and the evaluation by means of statistical and graphical techniques are shown. The method may be applied to any microsphere study design. A considerable amount of time can be saved and data integrity may be improved. The statistical quality of the results may benefit from the broad spectrum of statistical tests available.

Algorithms↗
PubMed1990

Instantaneous restoration of regional organ blood flow after severe hemorrhage: effect of small-volume resuscitation with hypertonic-hyperoncotic solutions.

The acute effects of small-volume infusion of hypertonic-hyperoncotic solutions on central hemodynamics, regional organ blood flow (RBF; 15-microns-diameter radiolabeled microspheres), and respiratory function following severe hemorrhage (MAP = 40 mm Hg for 45 min, approx 50% blood loss) were analyzed in anesthetized beagles. Treatment regimens used were: 10% Dextran 60 in 7.2% NaCl (HHS); 10% Dextran 60 in 0.9% NaCl (HDS); or 7.2% NaCl (HSS) alone, administered over 2 min in a volume equivalent to 10% of the blood loss (4 ml/kg iv). Within 5 min, cardiac output reached (HSS, HDS) or even exceeded prehemorrhage values (HHS), and MAP increased to 56% (HDS)-74% (HHS) of baseline. At the same time, RBF in kidneys (all groups), pancreas (HHS, HSS) and gastric mucosa (HHS) was completely restored, while flow in myocardium, brain, skeletal muscle, adrenal glands (all groups), and small intestine and colon (HHS) rose even above baseline values (P less than 0.05). Fractional blood flow (percentage of cardiac output) favored heart and brain in all three groups. These effects tended to persist for at least 30 min. Respiratory function was not affected by either of the three solutions, and no adverse effects were noted. Small-volume resuscitation with 7.2% saline/10% Dextran 60 provides instantaneous restitution of regional organ blood flow; it appears to result in a more uniform circulatory response than 7.2% saline or 10% Dextran 60 alone and might ensure improved organ perfusion during evacuation of patients from the accident site.

Animals↗
PubMed1990

MIC-III--an integrated software package to support experiments using the radioactive microsphere technique.

MIC-III is a versatile program system to support gamma spectrometry data management and data collection for experiments using the radioactive microsphere technique. It is mainly written in PASCAL and running on a minicomputer. Hierarchical organ dissection schemes are used for unique classification and identification of samples. For each series of experiments, up to 12 different nuclides and up to 20 different organ dissection schemes can be handled simultaneously. Sample weights are collected on-line and sample radioactivities are measured automatically by gamma spectrometry under process control. The spectra with a resolution of 1022 channels are analyzed using a modified linear regression technique and a strategy to compensate for global spectrum shifts. The spectrum deconvolution algorithm was evaluated by calculating the recovery indices for known nuclide mixtures and compared to the stripping method, matrix method and a linear regression technique using window counts. Recovery values produced by MIC-III are better balanced than those of the other methods. MIC-III showed the smallest dispersion of the recovery index and exhibited least error accumulation in case of spectrum shift. MIC-III computes regional blood flow and arterio-venous shunt, and provides interfaces to customized programs or statistical software packages for further analysis. It has successfully been employed in more than 140 experiments.

Animals↗