Biomedical subjects

Thea Koch

Publications and source records attributed to Thea Koch.

5 recordsLinked to original sources

PubMed2003

Modulation of host defense by hydrocortisone in stress doses during endotoxemia.

OBJECTIVE: To investigate the effects of low-dose hydrocortisone (HC) on neutrophil respiratory burst, phagocytosis, and elimination of E. coli from blood and tissue under endotoxemic and non-endotoxemic conditions. DESIGN. Randomized, controlled trial. SETTING: Experimental laboratory, university hospital. SUBJECTS: Forty-eight female chinchilla rabbits ( n=8 in six groups A-F). INTERVENTIONS: In order to quantify the bacterial clearance process, defined numbers [10(8) colony forming units (CFU)] of Escherichia coli were injected intravenously into all anesthetized rabbits. Group A did not receive further intervention. Group B received bolus administration of HC 1.4 mg/kg and group C 14 mg/kg. Endotoxin (LPS, 40 microg/kg/h) was given to groups D, E, and F. Group E received additional bolus administration of HC 1.4 mg/kg and group F 14 mg/kg. All HC groups (B, C, E, and F) were continuously infused with HC 0.18 mg/kg/h. MEASUREMENTS: Monitored parameters were neutrophil respiratory burst and phagocytosis activity, rates of bacterial elimination from the blood, arterial blood pressure, serum lactate and LPS concentrations, as well as nitrite and nitrate levels. Tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts. MAIN RESULTS: In controls HC significantly delayed elimination of injected E. coli from the blood (P<0.01). LPS also prolonged bacterial elimination but additional HC did not further delay removal of E. coli from the blood. Under endotoxemia HC depressed respiratory burst, whereas phagocytosis functions remained unaltered. Moreover, bacterial colonization of organs was reduced after HC in the LPS groups. Significance, however, was reached only in the liver (P<0.05). Due to HC, clearance from LPS (P<0.01) and lactate (P<0.05) were improved. Levels of nitrite and nitrate did not differ among the groups. CONCLUSION: HC demonstrated immunomodulatory effects even in stress doses. In endotoxemic states use of low-dose HC seems to be favorable, although not in non-septic conditions.

Animals↗

PubMed2003

One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure is injurious in the isolated rabbit lung model.

UNLABELLED: We tested the hypothesis that one-lung ventilation (OLV) with high tidal volumes (VT) and zero positive end-expiratory pressure (PEEP) may lead to ventilator-induced lung injury. In an isolated, perfused rabbit lung model, VT and PEEP were set to avoid lung collapse and overdistension in both lungs, resulting in a straight pressure-time (P-vs-t) curve during constant flow. Animals were randomized to (a) nonprotective OLV (left lung) (n = 6), with VT values as high as before randomization and zero PEEP; (b) protective OLV (left lung) (n = 6), with 50% reduction of VT and maintenance of PEEP as before randomization; and (c) control group (n = 6), with ventilation of two lungs as before randomization. The nonprotective OLV was associated with significantly smaller degrees of collapse and overdistension in the ventilated lung (P < 0.001). Peak inspiratory pressure values were higher in the nonprotective OLV group (P < 0.001) and increased progressively throughout the observation period (P < 0.01). The mean pulmonary artery pressure and lung weight gain values, as well as the concentration of thromboxane B(2), were comparatively higher in the nonprotective OLV group (P < 0.05). A ventilatory strategy with VT values as high as those used in the clinical setting and zero PEEP leads to ventilator-induced lung injury in this model of OLV, but this can be minimized with VT and PEEP values set to avoid lung overdistension and collapse. IMPLICATIONS: One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure (PEEP) is injurious in the isolated rabbit lung model. A ventilatory strategy with tidal volumes and PEEP set to avoid lung overdistension and collapse minimizes lung injury during one-lung ventilation in this model.

Airway Resistance↗

PubMed2003

Clusterin protects the lung from leukocyte-induced injury.

Clusterin (CLU) is a multifunctional 75- to 80-kDa glycoprotein that is upregulated during cellular stress and might represent a defense mechanism during local cellular damage. Mechanisms discussed are antiapoptotic, antioxidative, and anticomplement properties as well as chaperone-like features protecting stressed proteins. The aim of this study was to investigate potential protective effects of CLU on pulmonary vasculature after in situ PMN activation in isolated rabbit lungs. The experiments were performed on 24 isolated and ventilated rabbit lungs that were perfused with 200 mL of Krebs-Henseleit-10% blood buffer with a constant flow of 150 mL/min in a recirculating system. It was tested whether pretreatment with CLU (2.5 microg/ml; n = 8) or catalase (CAT, 5000 U/ml; n = 8) before N-formyl-Met-Leu-Phe (fMLP; 10(-8) M) injection influenced pulmonary artery pressure (PAP) peak airway pressures (PAW) and edema formation as compared with controls (n = 8). Baseline values of PAP were 9-11 mmHg and PAW 11-13 cm H2O. Application of fMLP resulted in an acute significant (P < 0.01) increase of PAP (48 +/- 29 mmHg) within 2 min in the control group and PAW increased to 35 +/- 7 cm H2O within 30 min. Pretreatment with CLU completely suppressed the PAP and PAW response as a result of the fMLP challenge (P < 0.001), whereas a transient PAW increase up to 27 +/- 15 mmHg was observed after CAT. Complement factor C3a release was suppressed by CAT, whereas CLU blocked the complement cascade at the level of C5b-9 formation. Moreover, generation of thromboxane A(2) was reduced after CLU and CAT. Lung edema occurred in the fMLP group but was absent (P < 0.001) after CLU and CAT treatment. Both CLU and CAT prevented fMLP-induced lung injury. Stabilizing effects of CLU, point towards complement regulating features at the level of the terminal complement sequence. Elevated levels of CLU during inflammation could reflect a compensatory organ protective mechanism. Further studies are required to elucidate the clinical impact of the observed organ-protective properties of CLU.

Acute-Phase Reaction↗

PubMed2003

Fish or chips?

Cell membranes are not simply barriers separating intracellular from extracellular space. Rather, they represent a dynamic high-turnover system that adapts to current demands. During inflammation, prostaglandins and leukotrienes are formed from membrane-derived phospholipids. Encouraging improvements in critically ill patients were observed after nutritional replacement of long-chain omega-6 fatty acids with long-chain omega-3-fatty acids, contained in fish oil.

Animals↗

PubMed2002

Cellular localization of the endothelin receptor subtypes ET(A) and ET(B) in the rat heart and their differential expression in coronary arteries, veins, and capillaries.

In the heart, the endothelin (ET)/endothelin-receptor system is markedly involved in pathophysiological mechanisms underlying various cardiac diseases. Based upon pharmacological studies both ET-receptor subtypes take part in the regulation of coronary vascular tone, however, their detailed cellular distribution in the coronary vascular bed based upon direct mRNA and protein detection is unknown. This issue was addressed in the rat heart by means of non-radioactive in situ hybridization, RT-PCR, and immunohistochemistry. Expression of vascular ET(A)-receptors was detected in arterial smooth muscle and capillary endothelium while ET(B)-receptors were present in arterial, venous, and capillary endothelium, and in arterial and venous smooth muscle cells. This differential distribution of the ET-receptor subtypes supports the concept that ET(A)- as well as ET(B)-receptors mediate arterial vasoconstriction, while postcapillary vascular resistance is exclusively regulated by ET(B)-receptors. The observed capillary endothelial expression of the ET(A)-receptor correlates with the known ability of ET(A)-receptor antagonists to attenuate increases in cardiac microvascular permeability during endotoxin shock and ischemia/reperfusion injury.

Animals↗