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Biomedical subjects

H Neuhof

Publications and source records attributed to H Neuhof.

At least 37 records · Page 2Linked to original sources
PubMed1993

Influence of a pentoxifylline-analogue on the granulocyte-mediated pulmonary mediator release and vascular reaction.

The influence of a novel pentoxifylline-analogue, HWA 138, on the polymorphonuclear neutrophil leukocyte (PMN)-mediated changes in pulmonary resistance and mediator release was investigated in the isolated perfused and ventilated rabbit lung model. Isolated, washed human granulocytes were injected into the pulmonary artery and stimulated by either 10(-6) mol/L N-formyl-L-leucin-methionyl-L-phenylalanine (FMP) or 3 x 10(-8) mol/L phorbol 12-myristate 13-acetate (PMA) in the presence or absence (controls) of HWA 138 (10(-4) mol/L). Shortly after granulocyte activation, there was a massive generation and release of thromboxane (> 110 pg/ml) and histamine (150-400 nmol/L), with an acute increase of pulmonary artery pressure (> 8 mmHg) in the control groups. Application of HWA 138 almost completely suppressed mediator formation and release as well as pulmonary vascular reaction in the FMP stimulated group. In contrast to this, HWA 138 was unable to influence either mediator release, the pulmonary pressure reaction or interstitial edema formation following PMA stimulation. In the present model, HWA 138 is supposed to be effective via granulocytes by decreasing mediator release, obviously due to burst reaction.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Experimental studies of the influence of priming solutions on the systemic activation of complement during cardiopulmonary bypass: comparison between the use of albumin, hydroxyethyl starch and HWA-138.

Cardiopulmonary bypass surgery may be complicated by a systemic inflammatory reaction, which has been ascribed to activation of complement. For such activation, the choice of priming solution for the heart-lung machine may be of importance. The peripheral blood of three groups of eight donors was exposed to albumin, hydroxyethyl starch (HES) or to HWA-138 (pentoxifylline analogue) in addition to the priming solutions. The study confirmed that activation of complement is a consistent phenomenon during cardiopulmonary bypass surgery. The concentration of the C3 activation product C3a in the plasma was significantly increased after simulated extracorporeal circulation. However there were no differences within the increase of C3a concentrations between the various priming solutions.

Albumins↗
PubMed1992

Influence of 4 different membrane oxygenators on inflammation-like processes during extracorporeal circulation with pulsatile and non-pulsatile flow.

The influence of four different membrane oxygenators (HF 4000, BOS-CM 50, CML 2, Maxima) on leucocyte count, concentrations of PMN-elastase, clotting factor XII, AT-III, C1-INH, alpha 2-antiplasmin and C3a was registered before, during and after CPB with pulsatile and nonpulsatile flow in 80 male patients aged between 36 and 67 years. With all systems tested, there was a drop in the concentrations of clotting factor XII, AT-III, C1-INH and alpha 2-antiplasmin in the early extracorporeal circulation (ECC) phase, exceeding the average hematocrit reduction accounted for by dilution. This drop was the least distinct with CML 2 systems, both with pulsatile and nonpulsatile perfusion, indicating system-inherent influences. Leucocyte cound and PMN-elastase concentration rose significantly during ECC irrespective of oxygenator tested of flow type applied. The rise in leucocyte count even continued for about 4 h after ECC. During the first 40 min of ECC, these changes were paralleled by a significant rise in C3a concentration, suggesting complement activation as a main cause for PMN activation. However, there is reason to suppose involvement of further mechanisms operating in PMN activation, since the elevated C3a-concentrations began to fall off while leucocyte count and PMN-elastase concentrations were still increasing.

Acute-Phase Proteins↗
PubMed1992

Effects of pulsatile and nonpulsatile perfusion mode during extracorporeal circulation--a comparative clinical study.

In a prospective randomized study with 80 male patients scheduled for aorto-coronary bypass grafting we investigated the influence of pulsatile and nonpulsatile perfusion mode on cell count (leukocytes, platelets, hematocrit), concentrations of thromboxane (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), plasma hemoglobin, PMN-elastase, complement C3a, clotting factor XII, lactate, plasmatic inhibitors (C1-INH, AT-III, alpha 2-antiplasmin), arterio-venous oxygen difference (AVDO2) and hemodynamic parameters. Changes in hematocrit were similar in both groups, whereas plasma hemoglobin concentration was significantly higher with pulsatile perfusion. Platelet count paralleled changes in hematocrit and was not influenced by the perfusion mode. Leukocyte count as well as concentrations of PMN-elastase and C3a showed a strong increase during cardiopulmonary bypass, but there were no significant differences between the two groups. Similar changes of the concentrations of TXB2 and 6-keto-PGF1 alpha were noted irrespective of the perfusion mode applied. The observed alterations in the concentrations of clotting factor XII, alpha 2-antiplasmin, AT-III and C1-INH largely paralleled hematocrit changes in either flow mode. Significant differences between the two groups were found with lactate: with nonpulsatile perfusion there was a slight but continuous increase, while with pulsatile flow lactate levels remained unchanged. There was no evidence for a better oxygen uptake (AVDO2) with pulsatile perfusion. Pulsatile perfusion seems to be advantageous to tissue perfusion, however, at the cost of a higher rate of hemolysis. We cannot confirm further salutary effects of the pulsatile perfusion mode with the 1-pump-system on cellular and humoral blood constituents.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Alterations of filtration coefficients in pulmonary edema of different pathogenesis.

Different pathomechanisms in the development of pulmonary edema are being discussed. We investigated the effect of pathogenetically varying forms of edema on lung vascular barrier function in isolated cell-free perfused rabbit lungs. As an index of permeability, capillary filtration coefficients (Kfc) were determined from the slope of lung weight change over periods of stepwise venous pressure elevation (5, 7.5, and 10 mmHg) before (controls) and 60 min after edema induction. Edema was induced by venous congestion (n = 6), by application of arachidonic acid in the presence of diclofenac sodium (n = 6), and by elastase application (n = 6). Control values ranged from 0.28 to 0.51 ml.min-1 x mmHg-1 x 100 g-1. Kfc was significantly enhanced after edema induction up to 243% of control value in the hydrostatic edema, 357% in the arachidonic acid edema, and 594% in the elastase edema. When the alterations in capillary filtration due to the different types of edema were compared, Kfc was significantly higher in the proteinase edema, indicating an irreversibly damaged barrier function. These data exemplify different pathophysiological characteristics due to the pathogenesis of interstitial edema formation.

Airway Resistance↗
PubMed1991

Glutathione redox cycle is an important defense system of endothelial cells against chronic hyperoxia.

Exposure of cultured pulmonary artery endothelial cells to 95% O2 resulted in the following sequence of events: decrease in [3H]thymidine incorporation after 24 h; increase of intracellular glutathione (GSH) and loss of cellular protein after 48 h; increase of spontaneous and decrease of provoked prostacyclin formation as well as increased release of cellular LDH after 72 h. This oxygen toxicity model was used to study the following 2 questions. (1) What is the relative importance of the GSH redox cycle compared to catalase as antioxidative defense against hyperoxia? Endothelial cells were grown in selenium-depleted medium to inhibit glutathione peroxidase activity. Endothelial GSH biosynthesis was inhibited by buthionine sulfoximine. Catalase activity was reduced by aminotriazole. Endothelial cells with an impaired GSH redox cycle were easily killed by hyperoxia within 24 h, while inhibition of catalase did not enhance the susceptibility of endothelial cells to hyperoxia. (2) Can endothelial GSH content be increased by exogenous sulfhydryl reagents and does this result in an increase of endothelial cells' resistance to hyperoxia? Exogenous GSH, N-acetylcysteine, cysteine, and L-2-oxothiazolidine-4-carboxylate (L-2-oxo) increased intracellular GSH. All sulfhydryl reagents (with the exception of L-2-oxo) protected endothelial cells from hyperoxia. Concentrations of exogenous GSH and N-acetylcysteine that did not increase intracellular GSH reduced hyperoxia-induced endothelial cell injury. Thus the capacity of the GSH redox cycle rather than intracellular GSH levels or catalase determines endothelial cells' resistance to hyperoxia.

Animals↗
PubMed1991

Actions and interactions of mediator systems and mediators in the pathogenesis of ARDS and multiorgan failure.

A great variety of mediators and mediator systems are involved in the disturbance of the microcirculation and vascular permeability following polytrauma and sepsis. The locally accentuated, organ related activation and the cooperation of several of these mediators and mediator systems over a longer period of time seem to be responsible for the development of an acute organ failure in terms of ARDS and MOF. Cytokines from macrophages seem to be the determining factors converting a primarily functional and reversible systemic vascular reaction into organ related morphological lesions. This pathogenetic complexity has to be considered in future concepts for therapy and prophylaxis with regard to the hierarchical rank of the mediators involved.

Arachidonic Acid↗
PubMed1991

Bradykinin-induced oedema formation proceeds from B2 receptor stimulation and is potentiated by concomitantly released prostaglandins.

Bradykinin, a stimulator of B1 and B2 receptors, significantly increased PGI2 synthesis and fluid extravasation, as assessed by the increase of organ weight when injected intraarterially into the artificially perfused rabbit hindquarters preparation. Diclofenac pretreatment prevented PGI2 synthesis and significantly reduced fluid extravasation. Oedema formation and PGI2 synthesis were also significantly reduced by a simultaneous infusion of papaverine. Selective stimulation of B1-type receptors with des-Arg9-bradykinin was not accompanied by edema formation nor PGI2 synthesis but by a significant rise in vascular resistance. The combined application of bradykinin and the selective B1 receptor antagonist des-Arg9-[Leu8]-bradykinin also resulted in oedema formation and PGI2 synthesis, the extent, however, being significantly reduced in comparison to the application of bradykinin only. The data suggest that bradykinin-induced oedema proceeds from B2 receptor stimulation and is potentiated by simultaneous stimulation of B1 receptors. The kinin-induced fluid extravasation seems to be augmented by concomitantly generated prostaglandins.

Animals↗
PubMed1989

Surfactant abnormalities in patients with respiratory failure after multiple trauma.

We present a prospective study, designed to evaluate surfactant abnormalities in severely injured patients during the course of post-traumatic pulmonary dysfunction. Serially obtained bronchoalveolar lavage fluids from noncontused lung areas (in total, 132 samples from 17 patients) were analyzed for alveolar phospholipid composition and surfactant function in vitro during the first 14 days after trauma. The data were compared with those of 29 lavage samples obtained from 10 healthy control subjects and correlated to severity of respiratory failure. In the traumatized patients, the total lavage phospholipid content was unchanged, but there was a progressive decrease in the relative amounts of phosphatidylcholine (%PC) and phosphatidylglycerol and an increase in phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin. These alterations were paralleled by a marked decrease in the hysteresis area of the surface tension isotherm. The decrease in %PC and reduction of hysteresis area were significantly correlated. The alterations in alveolar phospholipid composition and in vitro surfactant function were more pronounced in patients with severe respiratory failure. There was a significant inverse correlation between severity of respiratory dysfunction and %PC or hysteresis area for all traumatized patients. Protein leakage into the alveolar space was significantly higher in patients with severe respiratory failure and appeared to precede surfactant abnormalities in such patients. The neutrophil content in the alveolar space was markedly increased in all patients with multiple injuries however, no significant correlation with the noted alterations in alveolar phospholipid composition or surfactant function was found. We concluded that surfactant abnormalities occur during the course of post-traumatic pulmonary dysfunction and are correlated with the severity of respiratory failure.

Adolescent↗
PubMed1988

Pulmonary vasoconstrictor response to soluble fibrin in isolated lungs: possible role of thromboxane generation.

The blood coagulation system is activated regularly in severe forms of shock, polytrauma, and sepsis. Arising thrombin cleaves the fibrinopeptides A and B from fibrinogen, and it generates monomers of fibrin, which are initially kept in solution by the remaining excess fibrinogen. The effects of soluble fibrin (fibrin monomer/oligomer-fibrinogen complexes) and fibrinopeptides A and B were investigated in blood-free perfused, isolated rabbit lungs. Urea Tris buffer-dissolved fibrin monomers were injected into the pulmonary artery in the presence of circulating excess fibrinogen. In doses above 5 mg, the monomers consistently provoked a sharp rise in pulmonary artery pressure, which was followed by an elevated pressure plateau. Changing to fresh perfusate devoid of soluble fibrin did not restore the pressure to baseline, and a second administration of the soluble fibrin caused a pressor response larger than the first. Only a modest increase in lung weight (less than 2 g) was observed, and lung inflation pressure was not altered. The pressor responses were accompanied by a rapid release of thromboxane A2 and a more delayed release of prostaglandin I2 into the perfusion fluid. A significant correlation between the height of the fibrin-induced pressure rise and the amount of thromboxane release was noted. Inhibition of cyclooxygenase (indomethacin) suppressed the generation of both prostanoids, whereas inhibition of thromboxane synthetase (OKY-046 and imidazole) selectively blocked the liberation of thromboxane. All three inhibitors caused an immediate decline in pulmonary artery pressure, which had been previously elevated due to administration of soluble fibrin, and markedly reduced the pressor response evoked by a subsequent fibrin application in the same lung.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

A highly sensitive gas chromatographic method does not detect exhalation of volatile hydrocarbons from isolated ventilated lungs under massive peroxidative stress.

Lung lipid peroxidation is thought to be a basic pathophysiological phenomenon responsible for pulmonary damage in different types of oxidant attack. Measurement of volatile hydrocarbons, especially ethane and pentane, produced during peroxidative degradation of polyunsaturated fatty acids and exhaled into an animal housing chamber, has attracted increasing interest for the monitoring of in vivo lipid peroxidation. However, this approach cannot distinguish between pulmonary exhalation of hydrocarbons generated in different organs or even the intestinum and pulmonary generation of these lipid peroxidation markers. In the present study we developed a respiration and hydrocarbon trapping system for isolated, ventilated, and perfused lungs that avoided rebreathing and allowed complete sampling and gas chromatographic separation and quantification of exhaled alkanes and alkenes (C1-C5) in the absence of background levels. Using an "artificial lung," the recoveries of exogenously administered hydrocarbons ranged between 80 and 95% with good reproducibility (SD between 1.7 and 9.6%). The detection limit of the system was approximately 3 fmol of each alkane or alkene/g wet lung weight.min. However, neither under basal conditions nor during massive peroxidative stress by the application of high doses of H2O2, FeCl3/ascorbate, paraquat, or ozone was any material with a retention time similar to that of hydrocarbons exhaled from isolated rabbit lungs. We conclude that under the experimental conditions employed, there is only insignificant generation of hydrocarbons in intact lungs.

Animals↗
PubMed1987

[Causes and therapy of organ failure: mediators, their role and therapeutic implications as exemplified by the infected patient].

Mediators from the coagulation system, the complement system, the kallikrein-kinin system and the arachidonic acid metabolism are made responsible for the pathogenesis of organ failure (ARDS) following sepsis. Products from these systems influence, directly or indirectly, vascular tone and permeability, especially in the pulmonary circulation. Besides these mediators, toxic oxygen species and proteases released from activated granulocytes and macrophages injure endothelial cells and provoke vascular leakage.

Arachidonic Acid↗