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K Messmer

Publications and source records attributed to K Messmer.

At least 217 records · Page 12Linked to original sources
PubMed1996

Expression of adhesion molecules on circulating PMN during hyperdynamic endotoxemia.

In a porcine model of hyperdynamic endotoxemia, we studied the numerical expression of L-selectin and beta 2-integrins on circulating polymorphonuclear leukocytes (PMN). Functional changes of beta 2-integrins were determined by the adhesion of PMN to C3-coated zymosan particles. Anesthesized pigs received a continuous infusion of Salmonella abortus-equi endotoxin (5 micrograms.kg body wt-1.h-1) for 270 min (endotoxin group; n = 7). A control group received 0.9% NaCl (n = 6). L-selectin had decreased 30 min after the induction of endotoxemia [59.1 +/- 11.9 vs. 91.6 +/- 15.5 relative fluorescence units (RFU) at baseline; P < 0.05], reaching minimal values after 150 min (23.9 +/- 3.9 RFU in endotoxin group vs. 95.2 +/- 30.4 RFU in control group; P < 0.05). PMN adhesion to C3-coated zymosan increased at 30 min (41.3 +/- 9.9% in endotoxin group vs. 2.4 +/- 1.1% in control group; P < 0.05) and remained significantly elevated thereafter. In contrast to the rapid shedding of L-selectin and functional upregulation of beta 2-integrins, the numerical expression of beta 2-integrins remained unchanged until 60 min (44.8 +/- 2.8 vs. 32.2 +/- 1.7 RFU at baseline; P < 0.05); compared with the control group, significantly elevated values were observed 150 min after the start of endotoxin (48.9 +/- 2.4 RFU in endotoxin group vs. 36.5 +/- 2.7 RFU in control group; P < 0.05). We conclude that numerical and functional expressions of beta 2-integrins are dissociated during endotoxemia. Although upregulation of beta 2-integrins might render PMN more adhesive to the vascular endothelium, the presence of activated PMN in the circulation suggests that low expression of L-selectin might impede adhesion.

Animals↗
PubMed1996

Determination of regional pulmonary blood flow with systemically injected nonentrapped microspheres.

Radioactive microspheres (MS) injected into the systemic circulation shunt to the venous side of the circulation and are trapped in the lung vasculature. We hypothesized that regional pulmonary perfusion could be determined by using systemically injected shunted MS. In seven anesthetized mechanically ventilated foxhounds, regional pulmonary perfusion was measured at baseline and during experimental acute respiratory distress syndrome with MS injected into both the right and left atrium (protocol 1). Methodological error of the MS technique was assessed by simultaneous injection of two different batches of MS into the right atrium (protocol 2). Measurement of perfusion during baseline and during experimental acute respiratory distress syndrome with shunted MS had a mean bias of 0.8 and 5.6% and mean precision of 19.2 and 34.7% (r = 0.94 and r = 0.95), respectively, compared with data from nonshunted MS. Simultaneous perfusion measurements displayed bias of -2.7 and 6% and precision of 8.2 and 5.3% (r = 0.98 and r = 0.99), respectively. Systemic shunt should be high for this method to prevent bronchial circulation from imposing significant error. We conclude that systemically injected MS can be used for simultaneous measurement of regional systemic and regional pulmonary perfusion, provided that MS that shunted in the first pass are measured in lung tissue.

Animals↗
PubMed1996

Roundtable of Experts in Surgery Blood Management--consensus statement.

UNLABELLED: A Roundtable of Experts in Surgery Blood Management was held 7 to 9 April 1995, in Vienna, where all the available published and unpublished epoetin alfa clinical data was thoroughly discussed and where the following CONSENSUS STATEMENT was developed to give the clinician some practical guidelines for the administration of epoetin alfa in elective surgery patients. CONSENSUS STATEMENT: For elective surgery patients it is important to facilitate, via blood conservation methods, the elimination or reduction of exposure to allogeneic blood transfusion and its associated risks. Adjunctive use of epoetin alpha therapy in specific patients is one method to accomplish this goal. Patients with small body size, predicted low blood volume (< or = 51), and/or a hematocrit too low to be enrolled in or to complete their prescribed ABD (autologous blood donation) program especially benefit from epoetin alfa therapy. Generally, epoetin alfa therapy is well tolerated, with an acceptable risk-to-benefit ratio.

Blood Loss, Surgical↗
PubMed1996

[The role of reperfusion damage].

Following reperfusion of preserved organ grafts, various pathomechanisms are activated that may impair graft function and viability beyond ischemic damage. This so-called reperfusion injury includes generation of oxygen radicals, recruitment and activation of circulating inflammatory cells, and liberation of numerous mediators acting both locally and systemically. Alterations in microvascular perfusion are of central importance where further graft damage is concerned. The present review covers the current knowledge about the underlying mechanisms, the organ-specific application in the clinical setting, and the possible immunological consequences of reperfusion injury.

Animals↗
PubMed1996

[Bradykinin antagonism in ischemia and reperfusion of the pancreas].

INTRODUCTION: Acute pancreatitis is characterized by two different courses of the disease, edematous and hemorrhagic-necrotizing pancreatitis. The pathogenesis and causes for the progression of pancreatitis are unknown. Ischemia/reperfusion with formation of oxygen free radicals, activation of leukocytes and consecutive failure of the microcirculation has gained attention as a causative factor. Furthermore, the degree of microcirculatory injury correlates with the severity of pancreatitis. The aim of the study was to investigate the influence of long term reperfusion after ischemia of the pancreas for 2 hours on morphological changes and enzyme release of the pancreas in rats. Since the characteristic features of postischemic pancreatic reperfusion injury are kinin-mediated we employed the bradykinin B2-receptor antagonist HOE 140 to inhibit the progression of postischemic changes of the pancreas. METHODS: Under ether anesthesia Sprague-Dawley rats (n = 28) were laparotomized, the 4 supplying arteries of the pancreas were isolated (gastroduodenal artery, left gastric artery, splenic artery and caudal pancreaticoduodenal artery) and occluded with microvascular clips for 2 hours. At the end of ischemia the abdomen was closed and the animals were allowed to awake. 15 minutes before end of ischemia an osmotic minipump filled with NaCl (ischemia group NaCl), phosphate buffer (ischemia group phosphate buffer) or HOE 140 dissolved in phosphate buffer (ischemia group HOE 140) was placed intraperitoneally. Control animals underwent sham operation without vessel occlusion; the osmotic minipump was filled with 0.9 % NaCl. Five days after ischemia the animals were sacrificed for histology. Amylase concentration and peripheral leukocyte count were determined at baseline and daily after operation. RESULTS: After ischemia of 2 hours during reperfusion of 5 days all 14 animals developed histopathological changes as seen in hemorrhagic-necrotizing pancreatitis with a mortality rate of 50 %. These morphological changes were associated with a significant increase (p < 0.05) of pancreas amylase concentration from 1850 +/- 149 U/L before ischemia to a maximum of 3934 +/- 435 U/L at 1st postoperative day and decreased to 1518 +/- 399 U/L at 4th postoperative day. Leukocyte count increased significantly (p < 0.05) from 10 x 10(12)/L to 31 x 10(12)/L. In control animals as well as in animals receiving HOE 140, morphological and enzyme changes typical for acute pancreatitis were absent, leukocyte count increased only slightly. CONCLUSION: Ischemia of the pancreas of 2 hours with ensuing reperfusion of 5 days induces morphological and biochemical changes as observed in hemorrhagic-necrotizing pancreatitis. Organ dysfunction after ischemia/ reperfusion can be effectively inhibited by administration of the bradykinin-antagonist HOE 140.

Amylases↗
PubMed1996

Bradykinin antagonists HOE-140 and CP-0597 diminish microcirculatory injury after ischaemia-reperfusion of the pancreas in rats.

Ischaemia-reperfusion of the pancreas was performed in 35 anaesthetized Sprague-Dawley rats. The effects of two bradykinin antagonists, HOE-140 (13 micrograms kg-1 intravenous bolus injection, n = 7) and CP-0597 (18 micrograms kg-1 h-1 intravenous infusion, n = 7) on pancreatic microvascular perfusion and leucocyte-endothelium interaction were quantitatively analysed by intravital fluorescence microscopy. Three further groups underwent sham operation (n = 7), ischaemia of 2 h without treatment (n = 7), and ischaemia of 2 h with infusion of phosphate buffer (n = 7). Functional capillary density was significantly greater in animals treated with HOE-140 or CP-0597 than in sham-treated animals, and was decreased to only 60 per cent. Adherence of leucocytes to the endothelium of postcapillary venules was significantly reduced when compared with ischaemia without antagonist. These results demonstrate a positive effect of the two bradykinin antagonists HOE-140 and CP-0597 on microvascular perfusion failure after ischaemia-reperfusion of the pancreas.

Animals↗
PubMed1995

Inhaled sodium nitroprusside. Non-selective reduction of thromboxane analogue-induced pulmonary vasoconstriction in healthy sheep.

Both inhaled nitric oxide (NO) and inhaled prostacyclin have been shown to selectively decrease pulmonary hypertension of various origin. The aim of the present study was to assess the potential of the NO donor sodium nitroprusside (SNP) to elicit selective pulmonary vasodilation. SNP spontaneously liberates nitric oxide in the presence of reducing substances like cysteine or glutathione, ubiquitous in many different tissues. Inhaled as an aerosol in 3 healthy lambs presenting pulmonary hypertension induced by infusion of a thromboxane analogue, low concentrations of SNP (0.02-0.6 mg/ml) revealed no effect at all. In contrast, high concentrations of SNP (1.0-20.0 mg/ml) lowered pulmonary artery pressure in conjunction with systemic arterial hypotension, suggesting systemic resorption of SNP with subsequent release of its nitroso-group. Selective pulmonary vasodilation was never observed. In conclusion, the present results do not support a selective effect of inhaled SNP in the pulmonary circulation.

Administration, Inhalation↗
PubMed1995

Investigating the origin of cyclic changes in limb volume using mercury-in-silastic strain gauge plethysmography in man.

1. Vasomotion, a phenomen frequently observed in skeletal muscle microcirculation, has been observed under physiological conditions and found enhanced during critical reduction of tissue perfusion due to hypoxic hypoxia, haemorrhage and local hypotension. We used a computer assisted non-invasive plethysmographic method to investigate periodic changes of limb volume (volumotion), which we previously found in critically ill patients. The current study was designed to investigate the origin of volumotion. 2. Simultaneous recordings of limb circumference of both calves were obtained. In patients with peripheral vascular disease and patients with minor surgery the cross-correlation with spontaneous breathing was investigated. In patients who had undergone major abdominal or vascular surgery we analysed for cross-correlations between MSG plethysmography signals of both legs and changes in central venous, arterial and ventilation pressures. In this group the effects of positive-pressure ventilation and positive end-expiratory pressure (PEEP) were also studied. 3. No ventilation-related volumotion was observed during spontaneous breathing. During positive-pressure ventilation a ventilation-related peak was found in the Fourier transform in agreement with the ventilation frequency applied. The amplitude of ventilation-related volumotion decreased significantly after a pressure cuff applied to the thigh was inflated above central venous pressure. We observed a significant increase in the amplitude of ventilation-related volumotion when PEEP was applied. 4. Ventilation-related volumotion showed significant cross-correlation between both legs. Slow wave volumotion (0.5-7 cycles min-1) was frequently observed, but always appeared unilaterally. Whilst we looked for correlations between slow wave volumotion and changes in central venous pressure and arterial blood pressure, respectively, significant cross-correlation with the MSG plethysmography recordings was only observed at the frequency of the positive-pressure ventilation. 5. The fact that periodic changes of limb circumference matching the frequency of the positive-pressure ventilation were detectable with the MSG plethysmography system demonstrates that small volume changes (less than 0.02 ml (100 ml tissue)-1) can be assessed using this system. As slow wave volumotion was observed unilaterally and revealed no correlation either with breathing, ventilation or arterial and central venous pressure, we suggest that slow wave volumotion is a local event most likely reflecting arteriolar vasomotion.

Aged↗
PubMed1995

Angiogenesis and vascularization of murine pancreatic islet isografts.

Although the microvascular endothelium has been identified as the primary target site for the initiation of pancreatic islet graft rejection, little is known of the microvascular and cellular mechanisms involved, partly due to the lack of adequate models. Herein, we present a model for the in vivo assessment of the microcirculation of pancreatic islet grafts in mice. Isolated islets of Langerhans from immunocompetent hairless mice and immunoincompetent athymic nude mice were transplanted syngeneically into a specially designed dorsal skinfold chamber mounted on nondiabetic recipients. The islets' microcirculation was visualized by means of intravital fluorescence microscopy, and microcirculatory parameters were quantitatively analysed over a period of 14 days in the awake animal. Between day 2 and 4 after transplantation 84% (31/37; hairless mice) and 69% (36/52; nude mice) of the islet grafts revealed capillary sprouts and formation of new microvessels. On day 6, these sprouts were found interconnected, and red blood cell movement within the newly formed microvascular network was observed. The process of angiogenesis and revascularization was completed within 10 days after transplantation yielding a glomerulus-like network of capillaries as known for pancreatic islets in situ. Functional capillary density of the islet grafts ranged between 650 and 700 cm-1 in both hairless and nude mice. Within the islets' microvessels neither accumulation of leukocytes nor leukocyte-endothelial cell interaction was observed, indicating the lack of rejection and inflammation in these syngeneic islet grafts. We propose that this model provides a wide spectrum of promising experimental approaches for the study of microcirculatory and cellular mechanisms in free pancreatic islet transplantation.

Animals↗
PubMed1995

Ischemia reperfusion of the pancreas: a new in vivo model for acute pancreatitis in rats.

Based on the concept that ischemia is an important factor in the pathogenesis of acute pancreatitis, we developed a new model of complete ischemia/reperfusion of the pancreas in the rat. The aim of this study was to investigate the microcirculation of the pancreas after complete and reversible ischemia at different times after reperfusion by using intravital fluorescence microscopy. In addition, the effect of ischemia/reperfusion on the pancreas was assessed by means of light and electron microscopy and measurement of serum pancreas amylase concentration. In 35 adult Sprague-Dawley rats ischemia of the pancreas was induced by temporary occlusion of the four supplying arteries. Sham-operated animals served as controls (group A). After periods of 30 min (group B), 60 min (group C) or 120 min (group D) of ischemia the organ was reperfused. To exclude the influence of hypovolemia on microcirculation in group E (120 min ischemia) hydroxyethylstarch (HES) was given i.v. to maintain central venous pressure at baseline values. For intravital fluorescence microscopy the pancreas was exteriorized on a stage and quantitative analysis of microcirculation, including functional capillary density and leukocyte-endothelium interaction, was performed after 30 min, 1 h and 2 h of reperfusion. Serum pancreas-amylase was measured at control (prior ischemia) and at 2 h after reperfusion. Tissue samples for light and electron microscopy were taken 2 h after reperfusion. In sham-operated animals, functional capillary density (FCD) remained within baseline values (FCD 407.7 +/- 9 cm-1) during reperfusion. Dependent on the time of ischemia and time of reperfusion a gradual reduction in functional capillary density was observed; after 2 h of ischemia only 35% of capillaries were perfused (FCD 140.9 +/- 28.3 cm-1). Reduced functional capillary density was associated with an increase of perfusion heterogeneity to a maximum of 0.65 +/- 0.12, as against 0.13 +/- 0.02 in control animals. With a 2 h ischemia leukocyte-endothelium interaction was enhanced after 0.5 h of reperfusion (8-fold increase of adherent leukocytes in comparison to control) followed by a further significant increase until 2 h after the beginning of reperfusion. Amylase concentration after ischemia of 2 h (2967 +/- 289 U/l) was significantly higher as compared to controls (1857 +/- 99 U/l). Differences between group E and D were not observed. Pancreatic tissue injury was ascertained by histopathological studies. These results indicate that complete ischemia/reperfusion of the pancreas induces pancreatic microvascular failure. The severity of changes depends on duration of ischemia and duration of reperfusion. The morphological and biochemical changes suggest that ischemia/reperfusion causes an inflammatory reaction as observed in acute pancreatitis.

Animals↗
PubMed1995

Impact of vitamin E supplement in standard laboratory animal diet on microvascular manifestation of ischemia/reperfusion injury.

Aimed at improving animal fertility and health, diets for farm and laboratory animals have over the last few years been supplemented with increasing amounts of the antioxidant vitamin E. We now demonstrate by intravital microscopy that feeding hamsters with a vitamin E-supplemented "standard" rodent diet (60 ppm vitamin E) significantly reduces the microvascular manifestations of ischemia/reperfusion injury when compared to animals fed a nonsupplemented diet. Postischemic leukocyte adhesion to venular endothelium was reduced from 770 +/- 204 cells/mm2 at 24 h after reperfusion in control animals on the nonsupplemented diet to 403 +/- 105 cells/mm2 in animals on the "standard" rodent diet (means +/- SD, n = 7 animals per group, p < 0.01). Animals on the nonsupplemented diet showed a dramatic loss of capillary perfusion density until 7 days after reperfusion (to 21 +/- 13% of preischemic baseline values), whereas this loss was significantly attenuated (to 71 +/- 12% of preischemic values, p < 0.01) in animals on the "standard" rodent diet. No difference in the extent of reperfusion injury was seen between animals on the "standard" rodent diet and animals on diets with substantially higher vitamin E supplements (300 ppm-30,000 ppm). Besides underscoring the benefit of vitamin E in reducing the extent of ischemia/reperfusion injury, this study raises the concern that vitamin E supplements in "standard" laboratory animal diets may have a far-reaching impact on biomedical research by jeopardizing established animal models of disease.

Animals↗
PubMed1995

Leukocytes contribute to hepatic ischemia/reperfusion injury via intercellular adhesion molecule-1-mediated venular adherence.

BACKGROUND: Leukocytes are suggested to modulate ischemia/reperfusion injury via membrane receptor-controlled interaction with the microvascular endothelium. METHODS: With the use of intravital fluorescence microscopy we investigated the role of the intercellular adhesion molecule-1 (ICAM-1) in a rat model of hepatic reperfusion injury with a neutralizing monoclonal antibody (anti-ICAM-1). RESULTS: Sixty minutes of left lobar ischemia and reperfusion (isotype-matched immunoglobulin G1 control antibody) caused leukostasis in sinusoids (240 +/- 15 cells per liver lobule), leukocyte adherence in postsinusoidal venules (679 +/- 76 cells per mm2 endothelial surface of postsinusoidal venules), nutritive perfusion failure (15% +/- 2% nonperfused sinusoids), excretory dysfunction (bile flow, 1.2 +/- 0.3 microliters.min-1.gm-1), and loss of hepatocellular integrity (serum aspartate aminotransferase, 1353 +/- 317 units.L-1; serum alanine aminotransferase, 1055 +/- 265 units.L-1). Anti-ICAM-1 did not affect sinusoidal leukostasis; however, it effectively inhibited postischemic leukocyte adherence to the venular endothelial lining (217 +/- 38 cells/mm2, p < 0.01). Concomitantly, hepatic reperfusion injury, including sinusoidal perfusion (6% +/- 1% nonperfused sinusoids, p < 0.01), excretory function (bile flow, 1.8 +/- 0.1 microliters.min-1.gm-1, p < 0.05), and hepatocellular integrity (aspartate aminotransferase, 480 +/- 108 units.L-1; alanine aminotransferase, 447 +/- 80 units.L-1, p < 0.05), was significantly ameliorated by anti-ICAM-1. CONCLUSIONS: These findings prove in vivo the pivotal role of ICAM-1 in leukocyte-dependent manifestation of postischemic liver damage.

Animals↗
PubMed1995

Effects of inhaled prostacyclin as compared with inhaled nitric oxide in a canine model of pulmonary microembolism and oleic acid edema.

OBJECTIVE: Recently, it has been shown that the inhalation of nitric oxide (NO) and of prostacyclin (PGI2) elicits selective pulmonary vasodilation in a canine model of pulmonary hypertension induced by hypoxic pulmonary vasoconstriction. The present study was designed to investigate whether inhaled NO or PGI2-aerosol, respectively, is also effective in decreasing pulmonary artery pressure in a canine model of acute pulmonary microembolism and oleic acid edema. DESIGN: Prospective, randomized, cross-over design. SETTING: University animal research laboratory. PARTICIPANTS: Eight anesthetized, mechanically ventilated dogs (28 +/- 1 kg). INTERVENTIONS: Acute pulmonary microembolization (PME) was induced using glass microbeads (mean diameter: 100 microns) and 0.01 mL/kg of oleic acid. Subsequently, inhaled PGI2 (concentration: 10 micrograms/mL) or NO (50 ppm), respectively, was randomly administered for 15 minutes each and then withdrawn. MEASUREMENTS AND MAIN RESULTS: Central hemodynamics (heart rate [HR], cardiac output [CO], stroke volume [SV], mean arterial pressure [MAP], systemic vascular resistance [SVR], mean pulmonary artery pressure [PAP], pulmonary vascular resistance [PVR]) and gas exchange (PaO2/FIO2 ratio, intrapulmonary shunt [Qs/Qt], alveolar-arterial oxygen difference, [AaDO2]) were assessed. Measurements were performed at control, after PME, and during administration of PGI2 and NO, respectively. PME induced a significant increase (p < 0.001) of MAP (+9%), PAP (+68%), and PVR (+163%), whereas HR, CO, and SV remained unchanged and lung function deteriorated. Inhalation of NO slightly decreased PAP (-10%; p < 0.05) and PVR (-26%; p < 0.01) and improved AaDO2 and PaO2/FIO2. In contrast, inhalation of PGI2 had no consistent effect on pulmonary vascular tone or gas exchange. CONCLUSION: The data demonstrate that inhaled NO may elicit selective pulmonary vasodilation and improve gas exchange in a canine model of pulmonary microembolism and respiratory insufficiency. However, the degree of these effects was relatively small. The aerosolization of PGI2 under conditions of positive-pressure ventilation did not exert a significant vasodilatory effect on pulmonary vessels and did not improve pulmonary gas exchange in this model.

Administration, Inhalation↗