Biomedical subjects

J Schmeck

Publications and source records attributed to J Schmeck.

23 records · Page 2Linked to original sources

PubMed1998

Endothelin-1 and thromboxane A2 increase pulmonary vascular resistance in granulocyte-mediated lung injury.

OBJECTIVE: To examine the pathophysiologic role of vasoactive eicosanoids and endothelin-1 in granulocyte-mediated effects in the pulmonary vasculature. DESIGN: Prospective experimental study in rabbits. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Thirty adult rabbits. INTERVENTIONS: The experiments were performed on 30 isolated and ventilated rabbit lungs that were perfused with a cell- and plasma-free buffer solution. MEASUREMENTS AND MAIN RESULTS: The pulmonary arterial pressure and the lung weight gain were continuously registered. Intermittently perfused samples were taken to determine endothelin-1 and thromboxane A2 concentrations. Six experiments without intervention served as the sham group. The granulocytes in the pulmonary circulation were stimulated with N-formyl-L-leucin-methionyl-L-phenylalanine (FMLP; 10(-6) M; control, n = 6). To investigate whether activated granulocytes influence the pulmonary vasculature via endothelin-1, the endothelin-A receptor antagonist LU135252 (10(-6) M) was added to the perfusate before FMLP injection (n = 6). The potential involvement of thromboxane A2 in granulocyte-endothelial interaction was investigated by pretreatment with the cyclooxygenase inhibitor diclofenac (10 microg/mL; n = 6). Activation of granulocytes resulted in an acute increase in pulmonary arterial pressure (>9 mm Hg), which was followed by a second delayed pressure increase after 60 mins (>14 mm Hg) and was paralleled by a massive generation of thromboxane A2 (>250 pg/ mL). Fifteen minutes after FMLP-injection, endothelin-1 was detectable in the perfusate. Pretreatment with the selective endothelin-A antagonist LU135252 significantly (p< .01) reduced the initial pressure response after FMLP stimulation, while diclofenac significantly reduced (p < .05) the delayed pressure increase. Using diclofenac (10 microg/mL) in conjunction with LU135252 (10(-6) M; n = 6) before FMLP injection significantly reduced the early and the delayed pressure increase. CONCLUSIONS: Activated granulocytes seem to enhance pulmonary vascular resistance via endothelin-1 and thromboxane A2. The endothelin-1 effects are probably mediated via endothelin-A receptors since the endothelin-A receptor antagonist LU135252 was able to suppress the early pressure reaction after FMLP injection, whereas the cyclooxygenase inhibitor diclofenac was able to reduce the second pressure increase.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

Role of NO and endothelin in hemoglobin-induced pulmonary vasoconstriction.

UNLABELLED: The underlying mechanisms of hemoglobin (Hb)-induced vasoconstriction are not yet well understood. The aim of this study was to elucidate the influence of nitric oxide (NO) and endothelin (ET) on Hb-induced pulmonary vasoconstriction. Therefore, an autologous Hb preparation was administered into isolated rabbit lungs, in which pulmonary artery pressure (PAP) and weight gain was monitored. Either glyceroltrinitrate (GTN; 10(-5) M; n=6), L-arginine (10(-2) M; n=6), L-NAME (10(-4)M; n=6), ET(A)- or ET(B)-receptor antagonists (BQ,23, 10 6M, n=6) or (BQ788, 10(-6) M, n=6) were added to the perfusion fluid and NOx and thromboxane A2 levels were measured. RESULTS: In the control group the Hb-stimulation resulted in a pressure response up to 25.1+/-2.1 mmHg (p < .05), which was 136+/-6% of the reference value. The PAP increase was significantly (p < .05) blunted after GTN (71+/-5%), L-arginine (93+/-6%) and BQ788 (88+/-7%). Pretreatment with L-NAME (139+/-13%) or BQ123 (115+/-9%) did not show significant changes in PAP. CONCLUSION: The reduction of the Hb-induced pulmonary hypertension by NO-donors points toward the inactivation of NO by free hemoglobin. Likewise, ET(B)-receptor mediated vasoconstrictive effects without changes in NOx concentrations seem to play a pathogenetic role in the Hb-induced pulmonary vasoconstriction.

Animals↗

PubMed1998

Lipid mediators in inflammatory disorders.

During the past few decades, intensive collaborative research in the fields of chronic and acute inflammatory disorders has resulted in a better understanding of the pathophysiology and diagnosis of these diseases. Modern therapeutic approaches are still not satisfactory and shock, sepsis and multiple organ failure remain the great challenge in intensive care medicine. However, the treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis or psoriasis also represents an unresolved problem. Many factors contribute to the complex course of inflammatory reactions. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of interleukins and lipid-mediators are released and play a crucial role in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the mother substance of the pro-inflammatory eicosanoids, is released from membrane phospholipids in the course of inflammatory activation and is metabolised to prostaglandins and leukotrienes. Various strategies have been evaluated to control the excessive production of lipid mediators on different levels of biochemical pathways, such as inhibition of phospholipase A2, the trigger enzyme for release of AA, blockade of cyclooxygenase and lipoxygenase pathways and the development of receptor antagonists against platelet activating factor and leukotrienes. Some of these agents exert protective effects in different inflammatory disorders such as septic organ failure, rheumatoid arthritis or asthma, whereas others fail to do so. Encouraging results have been obtained by dietary supplementation with long chain omega-3 fatty acids like eicosapentaenoic acid (EPA). In states of inflammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.

Animals↗

PubMed1997

[The significance of endothelin for physiologic and pathophysiologic processes of the lung].

The endothelins (ETs) are a family of three vasoactive peptides (ET-1, ET-2, ET-3) that were first described in 1988. ETs have a wide range of action including vasoconstriction, vasodilatation, bronchoconstriction, and mitogenesis. Two types of ET receptors, classified as ETA and ETB receptors, have been identified in gene technology. Endothelins are produced by endothelial cells, smooth muscle cells, and bronchial epithelial cells. Their vasoactive effects contribute not only to homoeostasis but ETs seem also to be involved in several pulmonary diseases. Elevated ET plasma levels have been found in patients suffering from asthma, pulmonary fibrosis, pulmonary hypertension, and acute lung injury. This review gives a short summary of the actual facts in endothelin research, focussing on the effects of ET-1 in pulmonary circulation.

Animals↗

PubMedDate not supplied

Generating a learning curve for pediatric caudal epidural blocks: an empirical evaluation of technical skills in novice and experienced anesthetists.

BACKGROUND AND OBJECTIVES: Learning curves for anesthesia procedures in adult patients have been determined, but no data are available on procedures in pediatric anesthesia. The aim of this study was to assess the number of caudal blocks needed to guarantee a high success rate in performing caudal epidural analgesia in children. METHODS: At a teaching hospital, the technical skills of 7 residents in anesthesiology who performed caudal blocks were evaluated during 4 months using a standardized self-evaluation questionnaire. At the start of the study period, the residents had no prior experience in pediatric anesthesia or in performing caudal epidural blocks. All residents entered the pediatric rotation after a minimum of 1 year of training in adult general and regional anesthesia. The blocks were rated using a binary score. For comparison, the success rates of 8 experienced staff anesthesiologists were collected during the same period using the same self-evaluation questionnaire. Statistical analyses were performed by generating individual and institutional learning curves using the pooled data. The learning curves were calculated with the aid of a least-square fit model and 95% confidence intervals were estimated by a Monte Carlo procedure with a bootstrap technique. RESULTS: The success rate of residents was 80% after 32 procedures (95% confidence interval of 0.59 to 1.00). The pooled success rate of the staff anesthesiologists was 0.73 (mean) with a standard deviation of 0.45, which was not statistically different from the success rate of the residents. CONCLUSION: High success rates in performing caudal anesthesia in pediatric patients can be acquired after a limited number of cases. Success rates of residents learning this procedure are comparable to the results of staff anesthesiologists.

Anesthesia, Caudal↗