C. Töns

Intravascular volume depletion in a 24-hour porcine model of intra-abdominal hypertension

BACKGROUND The purpose of the study was to examine hemodynamic parameters and intravascular volume in a porcine model in the presence of intra-abdominal hypertension (IAH) lasting for 24 hours. METHODS Twelve pigs (52.5 +/- 4.9 kg) were studied over a period of 24 hours. In six animals, the intra-abdominal pressure was increased to 30 mm Hg via carbon dioxide-pneumoperitoneum. The others served as controls. Using the double-indicator dilution technique, intrathoracic blood volume (ITBV), total circulating blood volume, and cardiac output (CO) were measured. Standard parameters (e.g., central venous pressure [CVP]), were also recorded. RESULTS In the presence of IAH, ITBV and total circulating blood volume were significantly reduced to 55% and 67% of control values. CO decreased to 27% and CVP increased fourfold. CONCLUSION IAH leads to significant intravascular volume depletion that is not reflected by the CVP. Assessment of CO and ITBV in the presence of a critically increased intra-abdominal pressure is therefore recommended.

Induction of heat shock protein 70 by zinc-bis-(DL-hydrogenaspartate) reduces cytokine liberation, apoptosis, and mortality rate in a rat model of LD100 endotoxemia.

A prospective, randomized model of LD100/24 h endotoxemia was performed in male Wistar rats (n = 26; 250–300 g). The animals were divided into four groups: Group I (n = 5; saline treatment only), Group II (n = 5; Zn2+ treatment only), Group III (n = 8; saline pretreatment, lipdpolysaccharide (LPS) treatment), and Group IV (n = 8; Zn2+ pretreatment, LPS treatment). Zn2+ pretreatment was carried out by intraperitoneal injection of 50 mg/kg zinc-bis-(DL-hydrogenaspartate) (10 mg/kg Zn2+). LD100/24 h endotoxemia was induced by intraperitoneal administration of 20 mg/kg LPS of the Escherichia coli strain WO111:B4. Tumor necrosis factor α, interleukin-1β, and interleukin-6 were detected by enzyme-linked immunosorbent assay (ELISA). HSP70 expression in the lungs, the liver, and the kidneys was determined by immunohistochemistry, Western blotting, and an HSP70 ELISA. Apoptosis was also detected by an in situ apoptosis detection kit (TUNEL) and a cell death detection ELISA, respectively. This rat model of endotoxemia proves the close relationship between HSP70 expression, cytokine liberation, and development of apoptosis. The data demonstrate that: 1) Zn2+ is a potent inducer of HSP70 expression; 2) the application of Zn2+ leads to slightly increased cytokine plasma levels; and 3) the manipulation of the heat shock response by Zn2+ significantly increases the survival rate after LD100 endotoxemia. Enhanced survival rate in animals pretreated with Zn2+ may be explained by increased tissue levels of HSP70, a subsequent significantly decreased liberation of the proinflammatory cytokines after LPS challenge, and a significantly decreased rate of apoptosis.

Influence of heat shock protein 70 and metallothionein induction by Zinc-Bis-(DL-Hydrogenaspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. Recent in vitro studies with alveolar macrophages or monocytes show that induction of the stress response in these cells is followed by a decreased liberation of major cytokines [tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1)] after endotoxin challenge. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an altered pattern of inflammatory mediator release. Therefore, we measured the time course of thromboxane-B2 (TxB2), 6-keto-PGF1 alpha, platelet activating factor (PAF), TNF alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Klosterhalfen et al., Biochem Pharmacol 43: 2103-2109, 1992). Induction of the stress response was done by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenasparate = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 and metallothionein expression in the lungs, liver, and kidneys and increased plasma levels of TNF alpha, IL-1 beta, IL-6, and TxB2 as opposed to untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators as opposed to the untreated group. The time course of mediator release was identical with the decreasing and increasing three peak profiles described previously. Hemodynamic data presented significantly decreased peak pulmonary artery pressures and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of stress proteins by Zn2+ could be a practicable strategy to prevent sepsis.

Local and systemic inflammatory mediator release in patients with acute and chronic posttraumatic osteomyelitis

The local and systemic release of thromboxane A2, prostaglandin I2, leukotriene B4 (LTB4), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) were studied before and after operation in 29 patients with acute and 22 with chronic posttraumatic osteomyelitis. Twenty patients without osteomyelitis, who underwent operations for fractures of the lower extremities, served as controls. Blood and tissue samples from the osteomyelitic and control groups were collected under defined conditions and mediators were determined by radioimmunoassay (thromboxane B2, 6-keto-prostaglandin F1 alpha, LTB4) or by enzyme-linked immunosorbent assay (TNF-alpha, IL-1 beta, and IL-8). In addition, common parameters (leukocyte count, C-reactive protein, temperature) were measured. The best correlation with acute disease activity was given by TNF-alpha, IL-6, IL-8, and LTB4. Plasma levels of these mediators in acute osteomyelitis were significantly increased compared to chronic osteomyelitis and to controls, respectively. Tissue samples from osteomyelitic focus showed significantly increased levels for IL-8, IL-6, TNF-alpha, IL-1 beta, and LTB4 in acute osteomyelitis, whereas the values for TxB2 and 6-keto-prostaglandin F1 alpha were only slightly increased compared to the chronic osteomyelitis group. This study describes the local and systemic liberation of various mediators in acute and chronic posttraumatic osteomyelitis in detail for the first time and provides data for pre- and postoperative monitoring of disease activity and demonstrates new pathogenetic and therapeutic aspects of bone modulation in osteomyelitis.

The Influence Of Heat Shock Protein 70 Induction On Hemodynamic Variables In A Porcine Model Of Recurrent Endotoxemia

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an attenuation of hemodynamic alterations and an altered pattern of inflammatory mediator release. Therefore, we measured main hemodynamic variables such as systemic and pulmonary artery pressure, cardiac output, heart rate, central venous pressure, and pulmonary artery wedge pressure, as well as the time-course of thromboxane-B2, 6-keto-PGF1α, and interleukin 6 formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Circ Shock 35:237–244, 1991). Induction of the stress response was carried out by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenaspartate) = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 (HSP70) expression in the lungs, liver, and kidneys and significantly increased plasma levels of interleukin 6, 6-keto-PGF1α, and thromboxane-B2, compared with untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators compared with the untreated group. Hemodynamic data presented significantly decreased peak pulmonary artery pressure and pulmonary vascular resistance index values, significantly increased systemic artery pressure and systemic vascular resistance index values, and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of HSP70 by Zn2+ attenuates the liberation of inflammatory mediators, as well as the course of hemodynamic variables due to LPS.

Induction of heat shock protein 70 (HSP70) by zinc bis (DL-hydrogen aspartate) reduces ischemic small-bowel tissue damage in rats.

The aim of the study was to determine whether the induction of HSP70 by Zn2+ is able to protect the small bowel of rats against ischemia. Twenty-four male Wistar rats (weight 200–300 g) were divided into four groups: (1) saline treatment for 24 h (n=4); (2) Zn2+ treatment for 24 h (n=4); (3) Saline pretreatment for 24 h and ischemia (n=8); (4) Zn2+ pretreatment for 24h and ischemia (n=8). Pretreatment with Zn2+ was carried out by intraperitoneal administration of 50 mg/kg zinc bis (dl-hydrogen aspartate)=10 mg/kg Zn2+. Ischemia in a defined segment of the small bowel was produced by ligation of the mesenteric vein and artery and ligation of both ends of the segment. Tissue samples were collected before and 2, 4 and 6 h after ligation and investigated by histology, immunohistochemistry and Western blotting. Twenty-four h after i.p. Zn2+ injection, the small bowel expressed increased HSP70 tissue levels. Histology with subsequent grading of ischemic tissue injury showed significantly decreased tissue necrosis after Zn2+ pretreatment and HSP70 induction compared with saline pretreated controls. In conclusion, this study proves that Zn2+ is inducing HSP70 in the small bowel in vivo and hereby able to protect the small bowel against ischemia.ZusammenfassungZiel dieser Studie war es zu klären, ob die HSP70-Induktion durch Zn2+ den Dünndarm von Ratten gegen Ischämie schützen kann. Es wurden 24 männliche Wistar-Ratten (Gewicht 200–300 g) in 4 Gruppen aufgeteilt: I. NaCl-Behandlung über 24 h (n=4); II. Zn2+-Behandlung über 24 h (n=4); III. NaCl-Vorbehandlung über 24 h und Ischämie (n=8); IV. Zn2+-Vorbehandlung über 24 h und Ischämie (n=8). Die Zn2+-Vorbehandlung erfolgte durch intraperitoneale Gabe von 50 mg/kg Zink-di-dl-Hydrogenaspartat=10 mg/kg Zn2+. Die Ischämie in einem definierten Segment des Dünndarms wurde durch eine Ligatur der V. und A. mesenterica sowie der beiden Segmentenden erzeugt. Gewebeproben wurden jeweils vor und 2, 4 und 6 h nach der Ligatur histologisch, immunohistochemisch und durch «Western blotting» untersucht. 24 h nach intraperitonealer Zn2+-Injektion zeigten sich erhöhte HSP70-Dünndarmgewebespiegel. Histologische Untersuchungen mit nachfolgender Klassifizierung des Ischämieschadens ergaben geringere Gewebenekrotisierung nach Zn2+-Vorbehandlung sowie HSP70-Induktion im Vergleich zu den mit NaCl vorbehandelten Kontrolltieren.Schlußfolgerung: Diese Studie weist nach, daß Zn2+ im Dünndarm in vivo (bei Ratten) HSP70 induzieren kann und daß damit der Dünndarm gegen Ischämie geschützt werden kann.

Influence of suture material and suture technique on collagen fibril diameters in midline laparotomies

Background: Although laparotomy closure is associated with a cumulative 15% failure rate, the effect of different suture techniques and materials on the ultrastructural composition of the healing incision has not been investigated. Method: in 40 Wistar rats the collagen fibril diameters and the regenerative tissue were compared using electron microscopy 14 and 28 days after midline laparotomy. Wounds were closed with single and running sutures using either polypropylene or polyglactin 910. Results: Closure with polypropylene led to significantly larger mean fibril diameters than closure with polyglactin. Regardless of time and suture material, running closure resulted in significantly smaller mean collagen fibril diameters than single sutures. Four weeks after laparotomy, inflammatory reactions, disorganization of collagen and irregularities of the vascular architecture were found after closure with absorbable suture material but not after closure with nonabsorbable material. Conclusion: Suture material and suture method significantly influence the ultrastructural composition of the healing incision. Persisting mechanical irritation around the suture threads after single sutures and severe persisting inflammatory reactions after the use of absorbable suture material are important influencing factors.

Divertikelperforation der Appendix vermiformis

Summary. Diverticulitis of the vermiform appendix is an often disregarded disease. Diagnosis follows after appendectomy due to inflammatory complications in the form of diverticulitis and appendicitis. Diverticula can also be found as a reason for complaints in histologically unaltered appendix or as an incidental finding. Diverticula of the vermiform appendix are classified as false (acquired) or true (congenital). We report on the case of a 57-year-old man with a perforated appendix diverticulum as reason for peritonitis and a paralytic ileus of the colon and small intestine.Zusammenfassung. Die Divertikulose der Appendix vermiformis ist ein wenig beachtetes Krankheitsbild. Die Diagnose ergibt sich zumeist aus dem pathologischen Befund nach Appendektomie wegen entzündlicher Komplikationen in Form einer Diverticulitis oder Appendicitis. Man findet Divertikel jedoch auch als Beschwerdeursache bei histologisch nicht entzündlich veränderter Appendix oder als Zufallsbefund. Zu unterscheiden sind angeborene, echte Divertikel von erworbenen, falschen Divertikeln. Es wird über eine Divertikelperforation bei einem 57jährigen Patienten als Ursache für eine Peritonitis mit paralytischem Dick- und Dünndarmileus berichtet.

Leistenhernienreparation in Lokalanästhesie —eine vergleichende Analyse

Since February 1992 local anaesthesia has been routinely used for repair of inguinal hernias at the Surgical Department of the RWTU Aachen. All 607 patients undergoing Shouldice repair of primary inguinal hernia between January 1990 and March 1993 were retrospectively analysed with reference to need for analgesics, length of stay in hospital, and rate of complications. In addition, 50 patients treated with local anaesthesia and 50 patients treated under general anaesthesia underwent prospective pain analysis using a visual analogue scale and spirometric tests. Following local anaesthesia we found fewer need of analgesics, shorter stays in hospital, and less complications. The pain level was lower and ventilatory function was better. Repair of inguinal hernia with local anaesthesia is a safe method of lowering the risks involved in the operation and improving patient comfort without increasing complications.Since February 1992 local anaesthesia has been routinely used for repair of inguinal hernias at the Surgical Department of the RWTU Aachen. All 607 patients undergoing Shouldice repair of primary inguinal hernia between January 1990 and March 1993 were retrospectively analysed with reference to need for analgesics, length of stay in hospital, and rate of complications. In addition, 50 patients treated with local anaesthesia and 50 patients treated under general anaesthesia underwent prospective pain analysis using a visual analogue scale and spirometric tests. Following local anaesthesia we found fewer need of analgesics, shorter stays in hospital, and less complications. The pain level was lower and ventilatory function was better. Repair of inguinal hernia with local anaesthesia is a safe method of lowering the risks involved in the operation and improving patient comfort without increasing complications.ZusammenfassungSeit Februar 1992 wird die Lokalanästhesie als Routineverfahren zur Reparation der primären Leistenhernie in der Chirurgischen Klinik der RWTH Aachen eingesetzt. Retrospektiv wurden alle 607 Patienten, die sich zwischen Januar 1990 und März 1993 einer primären Leistenhernienreparation nach Shouldice in Lokalanästhesie oder Allgemeinnarkose unterzogen, bzgl. Analgetikabedarf, Dauer des stationären Aufenthalts und Komplikationsraten analysiert. Zusätzlich wurden an jeweils 50 Patienten aus jedem Kollektiv eine prospektive Schmerzanalyse mittels visueller Analogskala und Spirometrie durchgeführt. Nach Lokalanästhesie fanden wir einen geringeren Analgetikabedarf, eine kürzere Dauer des Krankenhausaufenthalts und weniger Komplikationen. Das subjektive Schmerzniveau und die schmerzbedingte Beeinträchtigung der Lungenfunktion waren ebenfalls niedriger. Die Anwendung der Lokalanästhesie zur Reparation der primären Leistenhernie ist ein Verfahren zur Senkung der Invasivität des Gesamteingriffs bei gleichzeitig gesteigertem Patientenkomfort, ohne damit die Komplikationsrate zu erhöhen.

Septischer Schock und multiples Organversagen in der chirurgischen Intensivmedizin

The study deals with an animal model for the problems of surgical intensive care patients. Following repeated applications of E. coli endotoxin W0111:134 under standard conditions, specific hemodynamic and biochemical (TNF, TXA2, PGI2, IL-6, PAF) and morphological (endothelium of the lung) alterations were detected. ARDS patterns induced by the sepsis were analyzed by high-frequency measurement of pressure and flow (385 measurements per breathing cycle). The role of the intestine in sepsis was investigated by ion-selective monitoring of surface potassium activity comparing mucosa and serosa. Every injection of endotoxin was followed by a selective increase of the potassium activity revealing relative ischemia induced by the endotoxin. The profile of the potassium levels on the surface correlates both with the cardiac output and with the prostacyclin levels. The continuous narrowing of the difference between mucosa and serosa, potassium during the period of investigation can be regarded as evidence for pathologic change in permeability fostering the septic course.ZusammenfassungBeschrieben wird ein tierexperimentelles Sepsismodell, das der Problematik chirurgischer Intensivpatienten entspricht. Nach rezidivierender Applikation von E.-coli-Endotoxin W0111:134 unter standardisierten Bedingungen konnten spezifische hämodynamische, biochemische (TNF, TXA2, PG I2, IL-6, PAF) und morphologische Veränderungen (pulmonales Endothel) nachgewiesen werden. Die sepsisinduzierten ARDS-Veränderungen werden mit einer Hochfrequenzdruck-und-flowmessung mit 385 Meßpunkten fiber einem Atemzyklus analysiert. Die Rolle des Darms in der Sepsis wurde mit ionenselektivem Kaliummonitoring vergleichend auf der Mukosa and Serosa untersucht. Jede Endotoxingabe wurde vom Dünndarm mit selektiven Anstiegen der Kaliumaktivität als Ausdruck einer Endotoxin-induzierten relativen Ischämie beantwortet. Das Profil der Oberflächenkaliumwerte korreliert sowohl mit dem „cardiaco output” als auch mit den Prostazyklinspiegeln. Die während der Versuchsdauer kontinuierlich abnehmende Mukosa-Serosa-Kaliumdifferenz kann als Nachweis einer die Sepsis katalysierenden intestinalen Permeabilitätsstörung interpretiert werden.The study deals with an animal model for the problems of surgical intensive care patients. Following repeated applications of E. coli endotoxin WO 111:B4 under standard conditions, specific hemodynamic and biochemical (TNF, TXA2, PGI2, IL-6, PAF) and morphological (endothelium of the lung) alterations were detected. ARDS patterns induced by the sepsis were analyzed by high-frequency measurement of pressure and flow (385 measurements per breathing cycle). The role of the intestine in sepsis was investigated by ion-selective monitoring of surface potassium activity comparing mucosa and serosa. Every injection of endotoxin was followed by a selective increase of the potassium activity revealing relative ischemia induced by the endotoxin. The profile of the potassium levels on the surface correlates both with the cardiac output and with the prostacyclin levels. The continuous narrowing of the difference between mucosa and serosa, potassium during the period of investigation can be regarded as evidence for pathologic change in permeability fostering the septic course.