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Biomedical subjects

K Messmer

Publications and source records attributed to K Messmer.

At least 145 records · Page 8Linked to original sources
PubMed1998

Impact of dextran on microvascular disturbances and tissue injury following ischemia/reperfusion in striated muscle.

The aim of this study was to evaluate the effect of dextran (Dx) 1 versus Dx 60 (molecular weights 1,000 and 60,000) on microvascular disturbances and tissue injury in striated muscle after ischemia/reperfusion (I/R). Experiments were performed using a 4 h pressure-induced ischemia model in the hamster dorsal skinfold chamber. Three groups (n=6) of animals received a continuous infusion (45 min, 3 microL/min) of either Dx 1 or Dx 60 (total dose 5 mg/kg) or saline solution beginning 15 min before reperfusion. Intravital fluorescence microscopy allowed for quantification of functional capillary density, leukocyte adherence, extravasation of fluorescein isothiocyanate-Dx, and nonviable (propidium-positive) cell count before ischemia and .5, 2, and 24 h after reperfusion. Experiments were terminated with tissue preservation for electron microscopy. Postischemic functional capillary density was significantly improved by Dx 60 (at 24 h, 88% vs. 51% in controls). In animals receiving postischemic Dx 1 or Dx 60, leukocyte adherence was significantly reduced (at .5 h, 44% and 58%, respectively) as compared with controls, whereas macromolecular extravasation was unchanged. Nonviable cell count was significantly decreased by both Dx fractions (at 24 h, Dx 1, 75%; Dx 60, 87%), indicating a reduction of tissue injury, which was also confirmed by electron microscopy. These results provide evidence that Dx 60 at 5 mg/kg attenuates I/R injury more effectively than Dx 1. Leukocytes play a major role in the development of I/R injury, but macromolecular extravasation does not always correlate with the leukocyte-endothelium interaction and the manifestation of I/R injury.

Animals↗
PubMed1998

Striated muscle microvascular response to zymosan-induced generalized inflammation in awake hamsters.

The effect of zymosan-induced generalized inflammation on the microcirculation of distant striated skin muscle was studied for a 12 day period in awake Syrian golden hamsters (n = 18) using the dorsal skinfold chamber model and intravital fluorescence microscopy. Intraperitoneal zymosan exposure (125 mg/100 g body weight) induced significant nutritive perfusion failure in the distant striated muscle tissue at Day 1 without complete recovery over the 12 day observation period, as indicated by the marked reduction of functional capillary density when compared with both baseline values and values of sham-treated control animals. Moreover, intraperitoneal zymosan exposure induced endothelial disintegration, as demonstrated by the continuous increase of macromolecular leakage throughout the 12 days of observation. Strikingly, zymosan did not induce significant leukocyte adherence to the endothelial lining of postcapillary and collecting venules of the striated muscle tissue. Thus, we conclude that in this model of generalized inflammation nutritive perfusion failure and loss of endothelial integrity in distant striated muscle is not mediated by activated leukocytes, but must rather be attributed to direct toxic effects of mediators, elicited by the local (intraperitoneal) zymosan challenge and systemically released.

Animals↗
PubMed1998

Buflomedil hydrochloride reduces systemic activation of polymorphonuclear leukocytes during hyperdynamic endotoxemia.

The purpose of the study was to examine the effects of buflomedil hydrochloride (BFL) on the expression of adhesion molecules (beta2-integrins) and oxygen radical production of circulating and emigrated intra-abdominal polymorphonuclear leukocytes (PMNL) in a standardized porcine model of hyperdynamic endotoxemia. A total of 20 anesthetized pigs were randomly assigned to one of the following groups: endotoxin group (endotoxin 5 microg / kg x h, intravenously (i.v.), n = 7), BFL group (BFL (3 mg/kg initial i.v. bolus followed by a continuous infusion (.1 mg / kg x h) and endotoxin 5 microg / kg x h, i.v., n = 7), and control group (NaCl .9%; n = 6). Experiments were terminated at 330 min. Infusion of endotoxin alone resulted in the activation of circulating and emigrated PMNL as evidenced by neutropenia, functional and numerical up-regulation of beta2-integrins, and enhanced oxygen radical production. BFL was able to attenuate functional and numerical up-regulation of beta2-integrins as well as oxygen radical production of circulating and emigrated PMNL. An unexpected decrease in the plasma concentration of BFL during the experiments was associated with an increase in the oxygen radical production of PMNL at the end of the experiments. In addition, BFL attenuated the fall in the intramucosal pH and the increase in plasma concentration of lactate observed in the late phase of endotoxemia. These findings suggest that BFL is able to decrease systemic activation of PMNL and to improve local tissue oxygenation during endotoxemia.

Animals↗
PubMed1998

PEEP only partly restores disturbed distribution of regional pulmonary blood flow in lung injury.

The effects of lung injury, positive end-expiratory pressure (PEEP), and norepinephrine on heterogeneity of regional pulmonary blood flow (rPBF, radioactive microspheres) were investigated. We hypothesized that lung injury increases heterogeneity of rPBF and that PEEP ventilation reduces these effects. Heterogeneity of rPBF is scale dependent and was therefore assessed in detail. Local correlation (p), relative dispersion (RD), fractal dimension (D), perfusion gradients, and histograms of rPBF each measures a different aspect of heterogeneity. In eight anesthetized dogs, lung injury was induced with oleic acid and glass bead injection. Afterward, PEEP of 10-20 cmH2O was instituted. Norepinephrine was infused at 20 cmH2O PEEP. Heterogeneity increased upon lung injury (p, 0.44 +/- 0.09 vs. 0.24 +/- 0.09; RD, 0.36 +/- 0.06 vs. 0.64 +/- 0.12; both P < or = 0.05), but fractal dimension remained constant. PEEP did not change p, RD, or D. Perfusion gradients were reversed after lung injury (right, -27 +/- 18 vs. 196 +/- 115%; -24 +/- 18 vs. 282 +/- 184%; P < or = 0.05). PEEP (10 cmH2O) reduced gradients (116 +/- 73 and 143 +/- 62%, respectively; P < or = 0.05). Norepinephrine, in part, further reduced gradients (right, 50 +/- 58%; P < or = 0.05; left, 102 +/- 94%; P = NS). We conclude that oleic acid- and glass bead-induced lung injury produces abnormal distribution of rPBF. Of these changes, application of PEEP only reverses perfusion gradients.

Animals↗
PubMed1998

Hemodilution and hyperoxia locally change distribution of regional pulmonary perfusion in dogs.

In seven anesthetized dogs, the effects of acute normovolemic hemodilution (ANH) to a hematocrit of 20 and 8% and the effects of hyperoxic ventilation (100% oxygen) on distribution of regional pulmonary blood flow (rPBF; radioactive microspheres) were investigated. Normovolemia was monitored with blood volume measurements (indocyanine green dilution kinetics). Before ANH, fractal dimension (D) of rPBF in the whole lung was 1.19 +/- 0.09 (mean +/- SD). Spatial correlation (rho) of rPBF in the whole lung was 0.6 +/- 0.08. D is a resolution-independent measure for global rPBF distribution, and rho is the averaged flow relationship of directly neighboring lung samples. With regard to the entire lung, neither ANH nor hyperoxia changed D or rho. With regard to horizontal, isogravitational planes, ANH induced opposite changes of rPBF heterogeneity depending on the vertical location of the plane and the parameter used. In ventral planes, a change in relative dispersion (SD/mean) indicated decreased homogeneity. However, rho suggested more homogeneous perfusion. Hyperoxia restored baseline rPBF distribution. Our data suggest that ANH causes different alterations of heterogeneity of rPBF depending on location within the lung.

Animals↗
PubMed1998

Attenuation of postischemic reperfusion injury in striated skin muscle by diaspirin-cross-linked Hb.

Hemoglobin-based oxygen carriers have been suggested to enhance the formation of oxygen free radicals, especially under conditions of ischemia-reperfusion (I/R), in which activation and adhesion of leukocytes play a pivotal role for propagation of reperfusion injury. This study investigates the effects of the hemoglobin-based oxygen carrier diaspirin-cross-linked hemoglobin (DCLHb) in an I/R model of hamster striated skin muscle. The dorsal skinfold chamber model in the awake Syrian golden hamster was used for analysis of the microcirculation and local tissue PO2 in striated skin muscle utilizing the technique of intravital fluorescence microscopy and a multiwire platinum surface (Clark type) electrode. Measurements were made before 4 h of pressure-induced ischemia and at 0.5, 2, and 24 h of reperfusion. Animals were treated with 5 ml/kg body wt of either 10% DCLHb (n = 8), 6% Dextran 60 (Dx-60; 60 kDa, n = 8), or 0.9% NaCl (n = 7), which was given intravenously 15 min before reperfusion. In animals treated with DCLHb or Dx-60, a significant decrease of leukocytes rolling along and sticking in postcapillary venules, associated with a recovery of functional capillary density and red blood cell velocity, was observed compared with saline-treated controls. In the early reperfusion period (0.5 h), DCLHb and Dx-60 efficiently restored local tissue PO2, whereas tissue PO2 decreased from 18.3 +/- 1.9 to 15.3 +/- 5.3 mmHg in 0.9% NaCl-treated animals. Electron microscopic analysis of the postischemic tissue at 24 h of reperfusion revealed markedly reduced tissue damage in animals treated with DCLHb compared with Dx-60 or isotonic saline. These results indicate that DCLHb attenuates postischemic reperfusion injury of striated skin muscle, presumably through alterations of leukocyte-endothelial cell interactions.

Animals↗
PubMed1998

Application of a novel method for subsequent evaluation of sinusoids and postsinusoidal venules after ischemia-reperfusion injury of rat liver.

Although several intravital fluorescence microscopic studies demonstrated that microcirculatory derangement is induced during liver ischemia-reperfusion, these data were obtained from randomly selected microvascular areas and microvessels. Repeated observation of the identical microvessels has not been performed yet. Using a specially designed cover glass, it is now possible to relocate desired sites of observation repeatedly over the whole reperfusion time. The aim of this study was to determine the impact of reperfusion time on hepatic microvascular perfusion state. Twenty minutes of ischemia induced a significant decrease in sinusoidal perfusion rate (29.1 +/- 10.2%) as compared with baseline values (98.0 +/- 0.3%). At 30, 60, and 120 min of reperfusion, the percentage of perfused sinusoids recovered to 62.8 +/- 6.6, 67.5 +/- 5.7, and 77.2 +/- 5.4%. The number of stagnant leukocytes in the same sinusoids was 6.2 +/- 1.9/lobule at baseline and increased to 22.3 3.6/lobule at 120 min of reperfusion. The number of leukocytes adhering within postsinusoidal venules was 53.5 12.5/mm2 before ischemia and increased to 414.2 62.5/mm2 at 120 min of reperfusion. We have demonstrated that during 120 min of reperfusion, there was a steady increase in both sinusoidal and venular leukocyte adhesion along with an attenuation of the initially severely depressed sinusoidal perfusion. A no-reflow phenomenon at an early phase of reperfusion and subsequent reflow were proven.

Animals↗
PubMed1998

[Effect of hypothermic preservation on ICAM-1 mRNA induction, leukocyte-endothelium interaction and microvascular perfusion after pancreas transplantation in the rat].

A prolonged period of 18 h hypothermic preservation in pancreas grafts led to a significant induction of ICAM-1 mRNA, enhanced leukocyte-adherence/-extravasation and compromised microvascular perfusion upon 2 h of reperfusion when compared to a 2 h preservation period. Therefore, during the period of prolonged cold ischemia changes within the graft must take place causing a reinforced ICAM-1 mRNA-induction already early after the onset of reperfusion. These results underline the relevance of the ischemia/reperfusion injury for the development of complications arising in the early course following pancreas transplantation.

Animals↗
PubMed1998

[Effect of adenosine on intravascular accumulation of leukocytes and tissue damage in striated muscle in endotoxemia].

Under the experimental conditions of endotoxinemia, the therapeutic use of an intravenous infusion of adenosine (110 micrograms x kg-1 x min-1) has been investigated in the microcirculation model of the BALB/c mouse. Injection of S. abortus-equi endotoxin (2 mg x kg-1 body wt. i.v.) elicited a significant increase of sticking leukocytes in postcapillary venules of striated skin muscle, which was associated with a swelling of microvascular endothelium and striated skin muscle. Infusion of adenosine effectively attenuated the endotoxin induced enhancement of leukocyte sticking and preserved microvascular endothelial and striated muscle integrity. These results imply the use of adenosine as therapeutic concept during endotoxinemia.

Adenosine↗
PubMed1998

[Influence of selective versus nonselective inhibitors of nitric oxide synthases on synovial microcirculation of the knee joint of the mouse in vivo].

Nitric oxide production by the inducible NO-synthase in the synovium and chondrocytes is known to be enhanced during chronic joint inflammation and aseptic loosening of joint prostheses. Due to the distinct side effects of non-selective NO-inhibitors on the macro- and microhemodynamics, we investigated the in vivo changes after selective (N-iminoethyl-L-lysine (NIL)) versus non-selective NO-synthase inhibition (NG-nitro-L-arginine methyl ester (L-NAME)) in the synovium of the mouse knee joint. Our results show a significant decrease in the functional capillary density and an increase in the leukocyte accumulation after L-NAME injection. In contrast, NIL did not alter the microhemodynamics or the leukocyte-endothelial cell interaction in the synovium, indicating its potential use for therapeutic selective inhibition of iNOS in joint inflammation.

Animals↗
PubMed1998

[Effect of Daflon 500 mg on reperfusion damage following ischemia and reperfusion of striated muscle].

The results of the current study indicate that Daflon 500 mg effectively reduces permeability for macromolecules induced by ischemia-reperfusion, thus reducing postischemic edema formation in the early reperfusion period. The inhibitory effect of Daflon 500 mg on leukocyte emigration may account for the reduction of edema formation in the postischemic tissue and favor the therapeutic use Daflon 500 mg of reperfusion-injury.

Animals↗
PubMed1998

[Selective bradykinin B1 receptor block in ischemia/reperfusion of the rat pancreas].

The selective bradykinin B1-receptor-antagonist CP-0298 reduces ischemia/reperfusion induced enhanced leukocyte adherence in postcapillary venules of the pancreas, but has no influence on the microvascular perfusion failure. The postischemic enzyme release will effectively attenuated by the antagonist. Wether the activation of the B1-receptor under pathophysiological conditions exerts protective effects to maintain the integrity of the pancreas, has to be evaluated in further experiments.

Acute Disease↗
PubMed1998

[Oxaceprol reduced leukocyte adhesion and extravasation and preserves perfusion of tissue after ischemia/reperfusion].

The present data indicate that treatment with Oxaceprol results in a significant protection of the microvasculature against I/R injury. The infusion of Oxaceprol during reperfusion leads to a significant reduction in the post-ischemic leukocyte adherence and extravasation as well as an improvement of the nutritive perfusion of the skin muscle. Thus, Oxaceprol treatment would appear to be a promising therapy for the reduction of I/R injury.

Animals↗