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D Nolte

Publications and source records attributed to D Nolte.

At least 19 recordsLinked to original sources
PubMed1992

Reduction of postischemic leukocyte-endothelium interaction by adenosine via A2 receptor.

The adhesion of leukocytes to the endothelium of postcapillary venules hallmarks a key event in ischemia-reperfusion injury. Adenosine has been shown to protect from postischemic reperfusion injury, presumably through inhibition of postischemic leukocyte-endothelial interaction. This study was performed to investigate in vivo by which receptors the effect of adenosine on postischemic leukocyte-endothelium interaction is mediated. The hamster dorsal skinfold model and fluorescence microscopy were used for intravital investigation of red cell velocity, vessel diameter, and leukocyte-endothelium interaction in postcapillary venules of a thin striated skin muscle. Leukocytes were stained in vivo with acridine orange (0.5 mg kg-1 min-1 i.v.). Parameters were assessed prior to induction of 4 h ischemia to the muscle tissue and 0.5 h, 2 h, and 24 h after reperfusion. Adenosine, the adenosine A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA), the A2-selective agonist CGS 21,680, the non-selective adenosine receptor antagonist xanthine amine congener (XAC), and the adenosine uptake blocker S-(p-nitrobenzyl)-6-thioinosine (NBTI) were infused via jugular vein starting 15 min prior to release of ischemia until 0.5 h after reperfusion. Adenosine and CGS 21,680 significantly reduced postischemic leukocyte-endothelium interaction 0.5 h after reperfusion (p less than 0.01), while no inhibitory effect was observed with CCPA. Coadministration of XAC blocked the inhibitory effects of adenosine. Infusion of NBTI alone effectively decreased postischemic leukocyte-endothelium interaction. These findings indicate that adenosine reduces post-ischemic leukocyte-endothelium interaction via A2 receptor and suggest a protective role of endogenous adenosine during ischemia-reperfusion.

Adenosine↗
PubMed1992

Attenuation of postischemic microvascular disturbances in striated muscle by hyperosmolar saline dextran.

The underlying mechanisms of the beneficial therapeutic effects of small-volume resuscitation with hyperosmolar solutions for treatment of hypovolemic shock are still poorly understood. Using the dorsal skinfold chamber model and intravital fluorescence microscopy, we investigated the effects of hyperosmolar saline dextran on ischemia-reperfusion injury in striated skin muscle of awake normovolemic golden hamsters. Test solutions (4 ml/kg body wt i.v.) were administered 2 min before reperfusion after 4 h of pressure-induced ischemia. In animals receiving 0.9% saline (control), we observed a drastic enhancement of leukocyte rolling along and sticking to the endothelium of postcapillary venules 0.5 h after reperfusion. Postischemic leukocyte rolling and sticking were significantly reduced when animals were treated with 7.2% saline alone (HSS), 10% Dextran 60 in 0.9% saline (HDS), or 10% Dextran 60 in 7.2% saline (HHS). In control animals, capillary perfusion was reduced to approximately 60% of preischemic values 0.5 h after reperfusion. Concomitantly, leakage of the macromolecule fluorescein isothiocyanate-dextran (5 mg in 0.1 ml saline i.v., M(r) 150,000) into the perivascular space increased from 0% before ischemia to approximately 12% at 0.5 h reperfusion. In contrast, when animals were treated with HSS, HDS, or HHS before reperfusion, capillary perfusion decreased to a significantly minor extent of approximately 15%, and macromolecular leakage was slightly increased to approximately 5%. Our results suggest that hyperosmolar saline dextran effectively attenuates postischemic microvascular disturbances elicited by ischemia-reperfusion, presumably through reduction of postischemic leukocyte-endothelium interaction and capillary swelling.

Animals↗
PubMed1991

Dietary fish oil blocks the microcirculatory manifestations of ischemia-reperfusion injury in striated muscle in hamsters.

Epidemiologic observations and experimental studies have demonstrated a protective effect of dietary fish oil on the clinical manifestations of ischemia-reperfusion injury. To investigate the underlying mechanisms, we used the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle of awake hamsters. In control hamsters (n = 7), reperfusion after a 4-hr pressure-induced ischemia to the muscle tissue elicited the adhesion of fluorescently stained leukocytes to the endothelium of postcapillary venules, capillary obstruction, and the break-down of endothelial integrity. These microvascular manifestations of ischemia-reperfusion injury were significantly attenuated in animals (n = 7) when fed with a fish oil-enriched diet for 4 weeks prior to the experiments. In leukocyte total lipids, the fish oil diet resulted in a substantial displacement of arachidonic acid, the precursor of the potent adhesion-promoting leukotriene (LT) B4, by fish oil-derived eicosapentaenoic acid, the precursor of biologically less potent LTB5, emphasizing the mediator role of LTB4 in ischemia-reperfusion injury. These results suggest that the preservation of microvascular perfusion by dietary fish oil contributes to its protective effects on the clinical manifestations of ischemia-reperfusion injury.

Animals↗
PubMed1991

Oxidatively modified human low-density lipoprotein stimulates leukocyte adherence to the microvascular endothelium in vivo.

In vitro studies indicate that oxidatively modified low-density lipoprotein (oxLDL) promotes leukocyte sticking to the vascular endothelium, a constant feature of early atherogenesis. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in hamsters, we investigated whether systemic administration of human LDL, oxidized by Cu2+, elicited leukocyte/endothelium interaction in vivo. While no effect was seen after injection of native LDL, oxLDL administration resulted in an immediate induction of leukocyte rolling along the microvascular endothelium and subsequent firm sticking to the wall of postcapillary venules as well as arterioles. The presented model may provide an alternative experimental approach to long-term feeding studies with atherogenic diets for the in vivo investigation of leukocyte/endothelium interaction in early atherogenesis.

Adult↗
PubMed1991

A Plasmodium falciparum blood stage antigen highly homologous to the glycophorin binding protein GBP.

We have isolated a gene coding for a protein highly homologous to an antigen known as the glycophorin binding protein (GBP) which was therefore called GBPH. The gene consists of 2 exons interrupted by an intron located at a position corresponding to that of the GBP gene. The deduced amino acid sequence of GBPH comprises 427 residues and is characterized by a signal sequence and by an extended repeat region consisting of 8 units of 40 amino acid residues. The comparison of the amino acid sequences of GBPH and GBP reveals an identity of 69%. Antisera raised against a GBPH fragment that carries part of the repetitive region cross-react with GBP (105 kDa) and additionally detect some bands between 40 and 70 kDa, one of which may correspond to GBPH. The genes coding for GBP and GBPH are located on chromosomes 10 and 14, respectively. The GBP gene is transcribed as a highly abundant 6.5 kb mRNA in the blood-stage form, whereas Northern blot analysis using a GBPH specific probe detects 2 less abundant mRNAs of 2.3 kb and 2.7 kb. Southern blot analysis of P. falciparum DNA identifies a third member of the GBP gene family.

Amino Acid Sequence↗
PubMed1991

Adenosine inhibits postischemic leukocyte-endothelium interaction in postcapillary venules of the hamster.

The reduction of postischemic reperfusion injury by exogenous adenosine has been ascribed to reduced oxygen radical generation and adhesion of leukocytes to the vascular endothelium. To provide in vivo evidence for this concept we investigated the effects of adenosine (110 micrograms.kg-1.min-1 iv) on postischemic leukocyte-endothelium interaction in the dorsal skinfold chamber model in awake hamsters by intravital fluorescence microscopy. Leukocytes were stained in vivo with acridine orange and classified according to their interaction with the endothelium as nonadherent, rolling, or sticking leukocytes. In control animals, reperfusion after a 4-h pressure-induced ischemia to the striated muscle in the dorsal skinfold chamber elicited a marked increase in leukocyte rolling and sticking. This phenomenon was significantly attenuated in adenosine-treated animals 30 min after reperfusion. Postischemic changes in vessel diameters and red cell velocities were not affected by adenosine. The data suggest that systemic adenosine administration reduces reperfusion injury by the inhibition of postischemic leukocyte adherence to the microvascular endothelium.

Adenosine↗
PubMed1991

Reduction of postischemic reperfusion injury by the vasoactive drug buflomedil.

The effect of buflomedil on postischemic reperfusion injury was studied in the dorsal skin fold chamber preparation of awake hamsters. Microvascular events were investigated in the striated skin muscle by means of intravital fluorescence microscopy prior to 4 h of pressure-induced ischemia and 30 min, 2 and 24 h after reperfusion. In untreated control animals, ischemia and reperfusion provoked marked leukocyte sticking and macromolecular leakage while functional capillary density was reduced. Treatment with buflomedil (3 mg/kg b.w. in 0.3 ml saline, administered as bolus of 0.1 ml 10 min prior to release of ischemia followed by i.v. infusion of 0.2 ml during the first 20 min of reperfusion) significantly reduced leukocyte sticking and macromolecular leakage, while functional capillary density was effectively preserved. No differences in macro- and microhemodynamic parameters were observed between buflomedil-treated and untreated animals. These findings support the concept that activated leukocytes are involved in the microvascular manifestation of reperfusion injury and indicate that leukocyte sticking and its sequelae can be efficiently prevented by treatment with buflomedil.

Animals↗
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

[Value of non-plethysmographic methods in determining airway resistance].

To examine whether the complicated method of body plethysmography can be replaced by non-plethysmographic methods, such as oscilloresistometry (Ros), the closing pressure method (Run) or the forced expiration volume method (FEV1), the authors studied the results obtained with 247 hospitalised patients between 18 and 81 years of age suffering from, or free from, airway obstruction. Although satisfactory correlations were obtained by linear and curvilinear regression analysis, considerable differences were seen in individual patients suffering from obstructions to a higher degree. Oscilloresistometry showed at the standard value limit of the airway resistance applicable in body plethysmography (0.30 kPa/l/s) a sensitivity of 89%, whereas the specificity was only 62%. Almost identical values of sensitivity (92%) and specificity (61%) were attained by the closing pressure method only if the standard value limit was set a little higher, namely, at 0.35 kPa/l/s. FEV1, which is easiest to measure, was able to objectivate an airway obstruction in a manner comparable to that of Ros and Run; there was in fact even a closer statistical correlation between the body plethysmographic resistance mographic methods are suitable for screening examinations on account of their sensitivity. However, if the results on the examination are not in keeping with the overall clinical findings, further diagnostic clarification must be sought by performing a body plethysmographic measurement.

Adolescent↗