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Biomedical subjects

M Nagelschmidt

Publications and source records attributed to M Nagelschmidt.

At least 37 records · Page 2Linked to original sources

[Effect of pneumoperitoneum on hemodynamics and intestinal integrity in endotoxinemia: CO2 versus helium].

In a study in pigs pathophysiological effects of a pneumoperitoneum (PP) established during endotoxemia (2 micrograms/kg b.w./hr) were investigated. In this situation a PP with carbon dioxide (CO2) or helium induces a deterioration of systemic hemodynamics or acid-base-stability. Some of these effects threaten vital stability. PP with either gas causes a mucosal acidosis of the small bowel within the meaning of an impairment of intestinal oxygen supply. A CO2-PP adversely affects the intestinal energy metabolism and leads to significantly increased endotoxin levels in contrast to helium after desufflation of the abdominal cavity. Data of this study at least demand for a careful monitoring, if laparoscopy is performed in septic and critically ill patients.

Acid-Base Equilibrium↗

[Revitalizing donor livers after cardiovascular arrest with venous oxygen persufflation].

The experimental study investigates the resuscitation of livers procured from non heart beating donors by venous systemic oxygen persufflation in a pig transplantation model. In group 1 livers were harvested from donor animals after 60 min of potassium induced cardiac arrest. Livers were then flushed and preserved in 4 degrees C cold University of Wisconsin solution for 4 hrs. Then liver transplantation was performed in recipient animals. Animals of group 2 received the same treatment, but during hypothermic storage we applied venous systemic oxygen gas persufflation (VSOP) via the supra-hepatic vena cava. Livers of group 3 were harvested without warm ischemia and without oxygen treatment during cold ischemic storage and were then transplanted. All recipient animals of group 2 and 3 survived the five day follow-up time. All recipient animals of group 1 died a few hours after liver reperfusion due to circulatory shock or liver failure. The liver quality of group 2 recipient animals was similar to group 3 livers, because serum transaminase levels and blood coagulation test showed no significantly different values between those groups. Our data suggest that livers procured from non heart beating donors after 1 hr of cardiac arrest can be resuscitated and successfully transplanted by therapeutic treatment with VSOP.

Animals↗

Reduction of proteolysis by venous-systemic oxygen persufflation during rat liver preservation and improved functional outcome after transplantation.

An increase of cytosolic proteolytic activity during ischemic preservation and consecutive tissue degradation have recently been recognized as a major pathogenetic factor for liver injury during ischemia/reperfusion. In the present study, we propose a method for preventing proteolytic tissue disintegration, which results in improved recovery of the liver after transplantation. Livers were harvested from rats and stored for 24 hr at 4 degrees C in University of Wisconsin solution (group A). Others were additionally persufflated with gaseous oxygen via the inferior caval vein during this time (group B). At the end of ischemic preservation, proteolysis was confirmed in group A, with significantly elevated tissue levels of free alanine and free amino groups, whereas proteolysis was prevented in group B. After transplantation, the integrity of the graft was significantly improved in group B, in which there was a 50% reduction of plasma activities of alanine amino-transferase and a twofold increase in hepatic bile production after the onset of reperfusion, as compared with group A. Moreover, venous-systemic oxygen persufflation during cold preservation significantly attenuated the rise in plasma levels of malondialdehyde (MDA) after liver transplantation. In conclusion, venous-systemic oxygen persufflation during ischemic storage prevents tissue proteolysis and reduces parenchymal injury after transplantation in vivo; this technique may, thus, represent a useful adjunct in long-term liver preservation with University of Wisconsin solution.

Animals↗

Influence of polyethylene glycol 4000 and dextran 70 on adhesion formation in rats.

Studies on the prevention of peritoneal adhesions often address the impairment of adhesion formation by a special drug without any attempts to elucidate the working principles. In the present study PEG 4000 was compared with dextran 70 with respect to the influence on adhesion formation, inflammatory reaction, and collagen deposition. Adhesions were created in 30 rats by standardized crushing of the cecum. The animals were randomly allocated to 3 experimental groups receiving an intraabdominal instillation of 5 ml 20% PEG, dextran 70, or 0.9% NaCl. On Day 7 the adhesions were scored; additionally, the amount of leukocytes in the peritoneal cavity and the incorporation of collagen into the adhesion strands were determined. Administration of PEG resulted in a significant reduction of the adhesion score from 10.3 (NaCl) to 2.3, whereas dextran had no effect (score 11.0). This finding correlated with the leukocyte number which was reduced by 44% after PEG but was not affected by dextran. The collagen content of the adhesion strands was significantly decreased by PEG as well as by dextran when compared to the NaCl controls. In our model PEG was highly effective in the impairment of adhesion formation. The positive effect was mediated by a reduction of the inflammatory reaction which resulted in a decreased deposition of collagen into the adhesion strands.

Animals↗

[Analysis of the publication spectrum of 4 German-language medical specialty periodicals "Der Chirurg", "Der Unfallchirurg", "Langenbecks Archiv für Chirurgie" and "Medizinische Klinik"].

All 1994 publications of four leading journals in surgery, orthopedics and internal medicine in Germany (Der Chirurg, Der Unfallchirurg, Langenbecks Archiv für Chirurgie, Medizinische Klinik) were reviewed by means of a structured analysis. The type of article, authorship, number of references, geographical location, quality, and main conclusion (positive; neutral; negative) of each article were documented. The journals focused on clinical studies (32.2-59.6%), case reports (11.0-26.1%) and reviews (6.4-40.9%). Articles about surgical techniques were mainly found in Der Chirurg (16.9%), experimental studies in Der Unfallchirurg (14.7%) and Langenbecks Archiv für Chirurgie (25.7%). Most articles were written by university clinic personnel (62.6-81.4%). In 11.0-22.6% of all articles, the head of a clinic was the first author and the co-author in 36.5-58.7%. Women were found to be first author in 4% in surgery, and in 10.4% in internal medicine. Of a total of 495 publications, 53.9% were written in Northrhine-Westphalia, Bavaria or Baden-Württemberg and only 1.6% in the five new federal states. Of all articles 16.4% were by foreign authors, with 10.5% originating from German-speaking countries. The portion of controlled randomized trials ranged between 4.9% (Der Unfallchirurg) and 11.3% (Der Chirurg) of all published studies. Studies and case reports with negative results were found to be more evident in Der Chirurg and Langenbecks Archiv für Chirurgie (ca. 20%) as compared to Der Unfallchirurg and Medizinische Klinik (ca. 6%). All journals provided good general information about the actual developments in a variety of topics to the reader. However, some improvement concerning international contributions, participation of the new federal states, and the quality of studies is recommended.

Authorship↗

H1-antagonism improves intestinal mucosal pH and heart function in porcine hypodynamic endotoxic shock.

Porcine hypodynamic shock was induced by continuous infusion of 5 micrograms lipopolysaccharide/kg per hour. This resulted in a decrease of cardiac output from baseline values of 3.5 +/- .9 L/min to 1.5 +/- .8 L/min and a reduced left ventricular stroke work index in the endotoxin-group (n = 6 animals). Pretreatment with the H1-antagonist dimethindene (2 mg/kg) in a second group (n = 6) significantly prevented these effects. Furthermore animals pretreated with the H1-antagonist showed a stable mean arterial blood pressure, whereas the control endotoxin-treated group revealed a drastic reduction in mean arterial blood pressure (99 +/- 4.7 mmHg versus 65.8 +/- 10 mmHg after 240 min, respectively). Pulmonary function and systemic vascular resistance were not ameliorated by the H1-antagonist in hypodynamic shock. Gastrointestinal mucosal pH (pHi), which indicates oxygenation of the mucosa, was decreased by endotoxin-infusion (7.45 +/- .32 baseline value to 6.92 +/- .24 after 120 min). This parameter as well as base excess values and lactate levels were significantly improved by dimethindene-pretreatment (p < .05). These results may indicate a beneficial effect of H1-antagonist-pretreatment on endotoxin-induced deterioration of the microcirculation. Furthermore our results clearly demonstrated that only pretreatment before endotoxemia with H1-antagonism is effective, since infusion of H1-antagonist in hypodynamic shock 45 min after addition of endotoxin (n = 6 animals) did not improve the cardiovascular system or the microcirculation.

Animals↗

Effect of H1-antagonism on cardiovascular, pulmonary, and immunological dysfunction in porcine endotoxic shock.

The definite role of histamine in early hyperdynamic septic shock is not yet clear. Therefore a randomized, controlled, blind trial was performed to investigate the effect of the H1-antagonist dimethindene in hyperdynamic porcine shock. Lipopolysaccharide (LPS) infusion (5 micrograms/kg/h) in anesthetized pigs (n = 6) in the control-group induced a hyperdynamic shock state with a decrease in mean arterial blood pressure, and systemic vascular resistance (SVR), and an increase in mean arterial pulmonary pressure and pulmonary vascular resistance (PVR). In the verum group (n = 6) dimethindene (2 mg/kg) administered 15 min before LPS application prevented the decrease in SVR significantly (p < .05) and ameliorated the increase in MPAP and PVR. The impairment in pulmonary function, as measured by the oxygenation ratio (PaO2/FiO2) in LPS-treated animals, was reduced by the H1-antagonist (p = .01). Tissue oxygenation was ameliorated by the H1-antagonist treatment, as demonstrated by plasma lactate levels and base excess values (p < .05, control group versus dimethindene group). The increase in tumor necrosis factor alpha by LPS infusion was not influenced by H1-antagonist pretreatment. The early decrease in SVR did not correlate with an enhanced nitric oxide formation, as measured by nitrate/nitrite plasma levels.

Animals↗

Meniscal healing: a biomechanical study.

Insight into the functional role of menisci has stimulated investigators to repair meniscal tears even in regions of poor vascularity. Data on scar strength resulting from different forms of therapy can be obtained applying biomechanical methods to animal models. With our new tear load propagation test, tissue strength in the scar as well as in the scar periphery was determined in rabbit medial menisci. Standardized longitudinal lesions localized in the microvascular zone II near the posterior horn were left untreated, fixed by suture, or sealed with fibrin glue. In two consecutive trials healing was determined after 6 weeks and after 12 weeks. After 6 weeks the mean scar strength was 19% (no therapy), 26% (suture), and 42.5% (fibrin glue) of the value measured in the equivalent region of the intact contralateral controls. In the peri-scar tissue in the line of the scar a section of secondary tissue weakness was discovered, which was shorter after treatment with fibrin glue. Although the scar strength was the same at Week 12, the area of tissue weakness was reduced. These biomechanical data point to the necessity of long-term studies to evaluate ultimate scar strength. They may explain the development of a bucket handle tear by extension of an initial lesion across an adjoining zone of secondary tissue weakness. The good results obtained with fibrin glue should encourage clinicians to use this therapy in clinical studies on meniscus repair in the inner zones of low healing capacity.

Animals↗

Beneficial effect of H2-agonism and H1-antagonism in rat endotoxic shock.

Although histamine release is generally considered harmful in endotoxic shock, several data exist to doubt this view. Own previous studies in rats let us assume a possible beneficial effect only with H1-antagonists, however a detrimental effect on survival with H2-antagonists. Consequently H1- and H2-agonists and antagonists were studied to prove the hypothesis of a beneficial H2-agonistic and H1-antagonistic effect. Two randomized studies were performed in a standardized rat endotoxic shock model (45 mg of Escherichia coli endotoxin/kg body weight (b.w.)). In both, methylprednisolone (50 mg/kg b.w.) and saline were used as positive and negative controls, respectively. Study I compared the effects of H1- and H2-agonists (betahistine, .1 mg/kg/h, and impromidine, 100 micrograms/kg/h) with H1- and H2-antagonists (astemizole and famotidine both 1 mg/kg b.w.; 20 rats/dose). Study II was performed to estimate the dose-response relationship of a new, highly potent H2-agonist with additional H1-antagonistic features (BU-E 75: .01, .1, 1.0, 10, and 100 micrograms/kg/h; 20 rats/dose). Animals receiving impromidine or BU-E 75 all received omeprazole (1 mumol/kg b.w.) to suppress gastric acid secretion. In study I impromidine significantly increased the survival-time and -course compared to famotidine treated animals (p = .01 and p < .05). Study II showed a positive dose-response relationship of BU-E 75 with an increase in survival rates from 30% (.01 microgram/kg/h) to 70% (100 micrograms/kg/h). These data strongly support the hypothesis of a beneficial effect of H2-agonism and H1-antagonism on survival parameters in rat endotoxic shock.

Animals↗

Meniscal healing: a histological study in rabbits.

Repair of meniscal tears occurs best in the region of the capsular attachment. The further the tear from the site of capsular attachment, the less the vascularity, and healing becomes dubious. For an evaluation of healing in the poorly vascularised zone of the meniscus a histological study was performed in rabbits with standard longitudinal incisions in the posterior horn of the left medial menisci. In addition a biomechanical investigation of scar strength was performed. Three groups of animals were studied: group 1 were allowed to heal spontaneously, group 2 were sutured and group 3 were treated with fibrin glue. After 6 weeks, macroscopically, 4 out of the 10 menisci in groups 1 and 3 exhibited incomplete scar formation, whereas all menisci in group 2 looked well. This result fell short of statistical significance because 2 menisci in group 2 had to be excluded due to faulty localisation of the standard injury. In all groups the scars contained fundamental elements of healing, such as fibroblasts, blood vessels and fibrous material. Repair seemed to be significantly influenced by the proliferating synovial membrane. Histologically there was no difference between group 1 and 3. In both groups the lesions were filled with a broad strip of reparative tissue mostly consisting of plexiform collagenous fibres. Although the appearance of the menisci in group 2 was similar, the scar tissue was distinctly thinner due to the close adaptation of the wound margins, and the vascularity seemed better. In all specimens the tissue located towards the free rim of the meniscus showed signs of degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reversal of gelatin-impaired wound healing in rats by exogenous fibronectin.

Animal experiments have shown that administration of gelatin results in a deprivation of plasma fibronectin (FN) and impaired wound healing. For further elucidation of these findings a therapy study with purified human FN was performed in rats. Fifty animals received a standard burn injury of 1% body surface and were divided into five experimental groups. Positive controls given no further treatment or treated with solvent only served for estimation of normal healing. For a negative control, 10 animals received three intraperitoneal injections of gelatin (58 mg/kg body wt) on Days 0, 1, and 2 after injury. They exhibited a striking lack of plasma FN (Day 1) and a significant delay of wound contraction (Days 7 and 14). In the therapy groups each administration of gelatin was followed by an intraperitoneal or intracardiac injection of FN (58 mg/kg body wt) 1 hr later. In these animals the negative effect of gelatin upon plasma FN and wound contraction was prevented. According to this study wound healing is menaced by FN deficiency and can be optimized by substitution of exogenous FN.

Animals↗

[Effect of different fibrin sealants on fibroblast activity in skin wounds. Experimental studies in rats].

The effects of two different fibrin sealants on synthetic activity of fibroblasts in incisional skin wounds of rats were studied by tracer experiments with 14C-proline. Additionally the wounds and the subcutaneous rests of the fibrin sealants were examined histologically. When the sealants were applied immediately after wounding there was no difference to untreated controls. However, administration on day 3 after injury resulted in a significant increase of 14C-incorporation by both preparations. This stimulation of synthetic activity after retarded treatment must be caused by the direct contact between the sealants with their soluble components and the fibroblasts, which are more frequent in the wounds on day 3. Differences between the two preparations could only be observed in the histological examination of the subcutaneous fibrin clots. Preparation 2 induced stronger encapsulation, cell invasion, and fibrinolysis of the clots than preparation 1.

Animals↗

[Action and biocompatibility of two collagen-based hemostatics in animal experiments].

Efficacy and biocompatibility of two collagen hemostatic wound dressings (usual agent: Collastypt, fluid-stabilised agent: Lyostypt) were compared. In a prospective randomized study the local hemostatic effect (bleeding time and blood loss) of the two agents were investigated after liver trauma of 45 rats. Liver wounds which remained untreated served as controls. Both preparations significantly reduced bleeding. The fluid-stabilised agent was significantly superior to the second collagen agent of different manufacturing.

Animals↗

[Biocompatibility and mechanical strength of various dura mater preparations after intraperitoneal implantation in rats].

Biocompatibility and mechanical strength of 3 different dura mater preparations were studied during 1, 2 and 4 weeks in a rat model. Two preparations produced by conventional methods did not markedly differ, whereas the third one, which had been freeze-dried after addition of glycerol, exhibited some special properties, showing higher mechanical strength throughout the whole period of implantation, and lower tendency to form adhesions, and inducing weaker leucocytic reaction. For certain surgical problems this soft, strong and compatible dura preparation could be an appropriate alternative.

Animals↗

[The effect of subtherapeutic quantities of native gelatin and Haemaccel 35 (polygeline) on the fibronectin level and wound healing. An experimental animal study in rats with burn wounds].

Posttraumatically, opsonic plasma fibronectin is consumed by collagen-like degradation products that enter the vascular system. Additional administration of gelatin (= denatured collagen) results in an essential lack of fibronectin with subsequent retardation of wound healing even when subtherapeutic amounts are given. Therefore, in an experiment with rats we studied the question of whether similar effects are evoked by equal amounts of Haemaccel 35 (cross-linked polypeptides from degraded gelatin). The animals received standardized third degree burn injuries of about 1% of body surface. Immediately after wounding and on the following 2 days native gelatin or Haemaccel was applied intraperitoneally in 2 different dosages (61 mg/kg and 122 mg/kg). The burn injury by itself did not cause a significant decrease of plasma fibronectin. After injection of gelatin a dramatic deprivation of plasma fibronectin occurred and, in consequence, a delay of the healing process. After administration of equal amounts of Haemaccel 35, however, there was neither a depletion of plasma fibronectin nor any significant effect on wound healing.

Animals↗

Polarimetric assay for the determination of the native collagen content of soluble collagen.

Two standardized assays for determining the amount of native collagen in a collagen solution are described which are based on polarimetric measurements. Native collagen content is calculated from the loss of optical rotation during transition from the original to the denatured conformation using constants which were obtained from standard collagen of highest available native collagen content. While Method I gives information on the content of helical collagen, Method II estimates collagen which is resistant to peptic degradation. Both methods are simple to perform and suitable for routine quality control.

Animals↗

The effect of fibronectin therapy and fibronectin deficiency on healing of rat burns and excision wounds.

Rats with standardized burns and skin excision wounds were treated i.p. with human fibronectin or swine skin gelatin. Controls received bovine albumin, solvent, or no treatment. Wound healing was assessed by planimetry, additionally plasma fibronectin was determined. Solvent or albumin did not influence the healing process, neither did fibronectin. However, when opsonizing fibronectin was additionally consumed by application of gelatin, a significant retardation of wound healing was observed. The results support the opinion that fibronectin is of essential importance for posttraumatic opsonization of gelatin-like material originating from the damaged tissue.

Animals↗