NEPHROPROTECTIVE EFFECT OF GAMMA-SECRETASE INHIBITOR ON SEPSIS- INDUCED RENAL INJURY IN MOUSE MODEL OF CLP.

OBJECTIVE: The aim: This study was set out to assess the potential protective impact of MK0752 (a gamma secretase inhibitor) on sepsis-induced renal injury through modulation of inflammatory and oxidative stress pathways. PATIENTS AND METHODS: Materials and methods: Twenty-four Swiss-albino mice aged between eight and twelve week and weighted twenty to thirty-seven grams were randomly allocated into four groups (n=6 in each group). Sham group (laparotomy without cecal ligation and puncture (CLP), sepsis group (laparotomy with CLP), vehicle-treated group (equivalent volume of DMSO before the CLP), MK0752 treated group (5 mg/kg) single daily dose for three days before the CLP. Blood samples were used to assess the serum levels of urea and creatinine. The kidneys were used to assess tissue levels of the TNF-α, IL-10, IL-6, TNFR1, VEGF, notch1, jagged1 and tissue damage by histopathological analysis. RESULTS: Results: The current study shows that pretreatment with MK0752 ameliorates the renal damage by significantly reducing the proinflammatory cytokines and notch1 signaling. CONCLUSION: Conclusions: Taken together, these results suggest that MK0752 could be protective against the renal injury induced by sepsis through its ameliorative impact on renal architecture and modulating cytokines and Notch1 singling pathway. Further studies regarding the role of Notch signaling pathways would be worthwhile.

SWIPT-Pairing Mechanism for Channel-Aware Cooperative H-NOMA in 6G Terahertz Communications.

The constraints of 5G communication systems compel further improvements to be compatible with 6G candidate technologies, especially to cope with the limited wavelengths of blockage-sensitive terahertz (THz) frequencies. In this paper integrating cooperative simultaneous wireless information and power transfer (SWIPT) and hybrid-non-orthogonal multiple access (H-NOMA) using THz frequency bands are suggested. We investigated and developed an optimal SWIPT-pairing mechanism for the multilateral proposed system that represents a considerable enhancement in energy/spectral efficiencies while improving the significant system specifications. Given the system performance investigation and the gains achieved, in this paper, wireless communication systems were optimized and upgraded, making use of promising technologies including H-NOMA and THz communications. This process aimed to alleviate the THz transmission challenges and improve wireless connectivity, resource availability, processing, robustness, capacity, user-fairness, and overall performance of communication networks. It thoroughly optimized the best H-NOMA pairing scheme for cell users. The conducted results showed how the proposed technique managed to improve energy and spectral efficiencies compared to the related work by more than 75%, in addition to the dynamism of the introduced mechanism. This system reduces the transceivers' hardware and computational complexity while improving reliability and transmission rates, without the need for complex technologies, e.g., multi-input multi-output or reflecting services.

Effectiveness of Epoxy Coating Modified with Yttrium Oxide Loaded with Imidazole on the Corrosion Protection of Steel.

The search for highly effective corrosion protection solutions to avoid degradation of the metallic parts is enabling the development of polymeric organic coatings. Of particular relevance, polymeric nanocomposite coatings, modified with corrosion inhibitors, have been developed to provide enhanced surface protection. In this work, yttrium oxide nanoparticles loaded with corrosion inhibitor (Imidazole), used as additives in the formulation of epoxy for coated on the steel substrate. The loading of Y2O3 with imidazole was confirmed by field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and Brunauer-Emmett-Teller analysis. UV-Vis analysis demonstrated the pH-sensitive behavior of the imidazole that helps in self-release when necessary. Electrochemical impedance spectroscopy (EIS) of the coated samples revealed that the coating modified with Y2O3/IMD provides better corrosion protection compared to coatings containing only Y2O3. XPS analysis validated the presence of an imidazole protective film on the steel substrate that enhanced the corrosion resistance of the coated samples.

Identification of a periodontal pathogen and bihormonal cells in pancreatic islets of humans and a mouse model of periodontitis.

Results from epidemiological and prospective studies indicate a close association between periodontitis and diabetes. However the mechanisms by which periodontal pathogens influence the development of prediabetes/diabetes are not clear. We previously reported that oral administration of a periodontal pathogen, Porphyromonas gingivalis (Pg) to WT mice results in insulin resistance, hyperinsulinemia, and glucose intolerance and that Pg translocates to the pancreas. In the current study, we determined the specific localization of Pg in relation to mouse and human pancreatic α- and ß-cells using 3-D confocal and immunofluorescence microscopy and orthogonal analyses. Pg/gingipain is intra- or peri-nuclearly localized primarily in ß-cells in experimental mice and also in human post-mortem pancreatic samples. We also identified bihormonal cells in experimental mice as well as human pancreatic samples. A low percentage of bihormonal cells has intracellular Pg in both humans and experimental mice. Our data show that the number of Pg translocated to the pancreas correlates with the number of bihormonal cells in both mice and humans. Our findings suggest that Pg/gingipain translocates to pancreas, particularly ß-cells in both humans and mice, and this is strongly associated with emergence of bihormonal cells.

Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice.

BACKGROUND: The results from cross sectional and longitudinal studies show that periodontitis is closely associated with cognitive impairment (CI) and Alzhemer's Disease (AD). Further, studies using animal model of periodontitis and human post-mortem brain tissues from subjects with AD strongly suggest that a gram-negative periodontal pathogen, Porphyromonas gingivalis (Pg) and/or its product gingipain is/are translocated to the brain. However, neuropathology resulting from Pg oral application is not known. In this work, we tested the hypothesis that repeated exposure of wild type C57BL/6 mice to orally administered Pg results in neuroinflammation, neurodegeneration, microgliosis, astrogliosis and formation of intra- and extracellular amyloid plaque and neurofibrillary tangles (NFTs) which are pathognomonic signs of AD. METHODS: Experimental chronic periodontitis was induced in ten wild type 8-week old C57BL/6 WT mice by repeated oral application (MWF/week) of Pg/gingipain for 22 weeks (experimental group). Another 10 wild type 8-week old C57BL/6 mice received vehicle alone (control group) MWF per week for 22 weeks. Brain tissues were collected and the presence of Pg/gingipain was determined by immunofluorescence (IF) microscopy, confocal microscopy, and quantitative PCR (qPCR). The hippocampi were examined for the signs of neuropathology related to AD: TNFα, IL1ß, and IL6 expression (neuroinflammation), NeuN and Fluoro Jade C staining (neurodegeneration) and amyloid beta1-42 (Aß42) production and phosphorylation of tau protein at Ser396 were assessed by IF and confocal microscopy. Further, gene expression of amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1), a disintegrin and metalloproteinase domain-containing protein10 (ADAM10) for α-secretase and presenilin1 (PSEN1) for É£-secretase, and NeuN (rbFox3) were determined by RT-qPCR. Microgliosis and astrogliosis were also determined by IF microscopy. RESULTS: Pg/gingipain was detected in the hippocampi of mice in the experimental group by immunohistochemistry, confocal microscopy, and qPCR confirming the translocation of orally applied Pg to the brain. Pg/gingipain was localized intra-nuclearly and peri-nuclearly in microglia (Iba1+), astrocytes (GFAP+), neurons (NeuN+) and was evident extracellularly. Significantly greater levels of expression of IL6, TNFα and IL1ß were evident in experimental as compared to control group (p<0.01, p<0.00001, p<0.00001 respectively). In addition, microgliosis and astrogliosis were evident in the experimental but not in control group (p <0.01, p<0.0001 respectively). Neurodegeneration was evident in the experimental group based on a fewer number of intact neuronal cells assessed by NeuN positivity and rbFOX3 gene expression, and there was a greater number of degenerating neurons in the hippocampi of experimental mice assessed by Fluoro Jade C positivity. APP and BACE1 gene expression were increased in experimental group compared with control group (p<0.05, p<0.001 respectively). PSEN1 gene expression was higher in experimental than control group but the difference was not statistically significant (p = 0.07). ADAM10 gene expression was significantly decreased in experimental group compared with control group (p<0.01). Extracellular Aß42 was detected in the parenchyma in the experimental but not in the control group (p< 0.00001). Finally, phospho-Tau (Ser396) protein was detected and NFTs were evident in experimental but not in the control group (p<0.00001). CONCLUSIONS: This study is the first to show neurodegeneration and the formation of extracellular Aß42 in young adult WT mice after repeated oral application of Pg. The neuropathological features observed in this study strongly suggest that low grade chronic periodontal pathogen infection can result in the development of neuropathology that is consistent with that of AD.

Hepatotoxic combination effects of three azole fungicides in a broad dose range.

Single active substances of pesticides are thoroughly examined for their toxicity before approval. In this context, the liver is frequently found to be the main target organ. Since consumers are generally exposed to multiple residues of different active substances via the diet, it is important to analyse combinations of active substances for potential mixture effects. For the (tri-)azoles, a group of agricultural fungicides and antifungal drugs, combination effects on the liver are likely because of a similar mode of action. Hepatotoxic effects of mixtures of two triazoles (cyproconazole and epoxiconazole) and an imidazole (prochloraz) were investigated in a 28-day feeding study in rats at three dose levels ranging from a typical toxicological reference value to a clear effect dose. Test parameters included organ weights, clinical chemistry, histopathology and morphometry. In addition, molecular parameters were investigated by means of pathway-focused gene expression arrays, quantitative real-time PCR and enzyme activity assays. Effects were compared to those caused by the individual substances as observed at the same dose levels in a previous study. Mixture effects were substantiated by increases in relative and absolute liver weights, histopathological findings and alterations in clinical chemistry parameters at the top dose level. On the molecular level also at lower dose levels, additive effects could be observed for the induction of several cytochrome P 450 enzymes (Cyp1a1, Cyp2b1, Cyp3a2), transporters (Abcb1a, Abcc3) and of genes encoding for enzymes involved in fatty acid or phospholipid metabolism (Ppargc1a, Sc4 mol). In most cases, treatment with mixtures caused a more pronounced effect as compared to the individual substances. However, the assumption of dose additivity was in general sufficiently conservative to cover mixture effects observed under the conditions of the present study.

Mixture effects of azole fungicides on the adrenal gland in a broad dose range.

Consumers are exposed to low concentrations of a variety of pesticide residues in or on food. Some of them might interfere with the endocrine system. While each individual active substance has been extensively tested for toxicity and safety, potential combination effects possibly resulting from combined exposure to different pesticides have seldomly been tested so far, especially in vivo. Since the adrenal gland is a key endocrine organ, we investigated if and how substances of a group of fungicides presumed to interfere with the biosynthesis of steroid hormones affect this organ when applied individually and in combination in a broad dose range. A 28-day feeding study was conducted in Wistar rats by using three (tri)azole fungicides considered to potentially affect the endocrine system (cyproconazole, epoxiconazole and prochloraz) individually at five dose levels, ranging from 0.9ppm to 2400ppm, and in combination at three dose levels. The parameters analysed included classical toxicology (pathology, histopathology, clinical chemistry) and molecular toxicology endpoints (gene expression arrays and quantitative real time PCR e.g. of Star, HSD3ß, Cyp11a1, Cyp11b1, Cyp11b2, Cyp 21, ApoE), as well as hormone analysis. A dose-dependent decrease in the adrenal gland weight of rats treated with epoxiconazole alone, which was accompanied by an atrophy of the adrenal gland as well as by an increase in the serum cholesterol level and which only became statistically significant at the top dose levels, was observed. These effects were attenuated in the combination experiments, although the same epoxiconazole concentration was used.

Combination effects of azole fungicides in male rats in a broad dose range.

Two 28-day feeding studies were performed in male rats to investigate combination effects of azole fungicides in a broad dose range. Following separate administration of cyproconazole, epoxiconazole, prochloraz, propiconazole, and tebuconazole at five dose levels, the first three compounds were selected to be administered in two different mixtures at three dose levels including very low doses. Here we present the data obtained by clinical observations, pathology, histopathology, clinical chemistry and haematology. The liver was the common main target organ of all compounds and their mixtures. In addition, epoxiconazole exhibited an effect on the adrenals. Furthermore, food consumption and efficiency and body weight (gain) were affected. Adverse effects of the combinations were observed at dose levels at which the individual substances caused similar effects. No evidence of adverse effects was found at dose levels below the previously established NOAELs. Our findings indicate that the concept of dose additivity appears sufficiently protective for risk assessment of the fungicides examined. Besides toxicological testing, tissue residues of the azole compounds in liver, testis and kidney were determined revealing remarkable differences following administration of the single substances and of the mixtures.

Sero-prevalence of Hepatitis B and C Virus from rural areas of northern Punjab (Sargodha District), Pakistan.

Pakistan is endemic for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections with 10 and 11 million infections, respectively. The epidemiological studies of these virus showed that the information is only from few cities of the country and is relevant to high risk groups. It is of great importance to have an idea about the prevalence of infectious agents in general population to help in identification of hot spot for infections. Identification of hot spots will help in disease management for future. As the there is no report form district Sargodha (Punjab Province) so this study was designed to analyze the prevalence of HBV and HCV in general population. Blood samples of 2373 randomly selected individuals from six different tehsils were collected and were analyzed for HBV and HCV sero-positivity. An overall prevalence of both HBV and HCV in district Sargodha was 28.10% (667/2373). HCV prevalence was (20.01%) and HBV seropositivity was (8.09%). Males were more infected than females, and a significant difference was found in positive cases between male (58.77%) and female (41.22%). The most common routes of transmission of hepatitis virus in present study were shaving assisted by barbers in male patients 143 (21.43%), non sterile or used needles and syringes 127 (19.04%), dental surgical procedures 88 (13.19%), and sharing razors in males 49 (7.34%). In female patients a significant factor is labor and child birth process. Most cases of hepatitis were seen in mesons, farmers and house wives. The prevalence of HBV and HCV in general population of district Sargodha is very high. The study will help for better management of disease to contain the disease spread. The study highlighted that District Sargodha is endemic for these viral infections and it is highly warranted to carry out more studies to get better idea about the infection spread. Community education campaigns are also highly warranted to general population as well as high risk population to control future disease spread.

Hepatotoxic effects of (tri)azole fungicides in a broad dose range.

The toxicological relevance of effects observed at molecular stage, which occur at dose levels well below classical no-observed adverse effect levels is currently subject to controversial scientific debate. While the importance of molecular effects for the identification of a mode of action or an adverse outcome pathway is undisputed, their impact for other regulatory purposes remains uncertain. Here, we report the results of a 28-day rat-feeding study including three widely used hepatotoxic (tri)azole fungicides (cyproconazole, epoxiconazole and prochloraz) administered individually at five dose levels, ranging from slightly above the reference values to a clear toxic effect dose. Parameters analysed included pathology, histopathology, clinical chemistry and particularly effects on the molecular level. Since azole fungicides are considered to cause liver toxicity by a mechanism involving the constitutive androstane receptor (CAR), a known CAR activator (phenobarbital, PB) was administered to investigate potential similarities between triazoles and PB-mediated liver toxicity by pathway-focused gene expression analysis. Our results show an increase in liver weights and additionally histopathological changes (hepatocellular hypertrophy) for all substances at the top dose levels. The effects on liver weight were most pronounced for cyproconazole by which also the animals receiving the next lower dose were affected. In addition, vacuolisation of hepatocytes was observed at the top dose level. No such findings were obtained with any substance at lower doses to which consumers and operators might be exposed to. In contrast, the expression of sensitive marker genes (like some cytochrome-P-450 isoforms) was significantly affected also at the lower dose levels. While some of these changes, like the induction of genes related to fatty acid and phospholipid metabolism (e.g. Fasn, Fat/Cd36, Ppargc1a) or xenobiotic metabolism (Cyp1a1, Cyp2b1, Cyp3a2), could be associated with high dose effects like hepatocellular vacuolisation or hypertrophy, a histopathological correlate was lacking for others.

The Austrian radon activities on the way to the national radon action plan.

Based on the new Euratom Basic Safety Standards (BSS), all EU member states will be obliged to design a strategy to address long-term risks from radon exposure, which is laid down in the 'national radon action plan'. In Austria, the National Radon Centre is responsible for the development of the action plan. This paper presents the current and planned radon protection activities on the way to establish the radon action plan--like the national radon database, the definition of radon risk areas by improving the existing radon map, as well as strategies and activities to increase the radon awareness of the public and decision-makers and to involve the building sector. The impact of and the need for actions caused by the BSS requirements on the Austrian radon legislation, strategy and programme are discussed.

Cytotoxicity of Metal Ions Released from Nitinol Alloys on Endothelial Cells.

Most implantable medical devices are expected to function in the body over an extended period of time. Therefore, immersion tests under simulated conditions can be useful for assessing the amount of metal ions released in situ. In this investigation, dissolved ions from as-received binary and ternary Nitinol alloys in cell culture media were periodically measured under static and dynamic conditions. Endothelial cells were grown in aliquots of culture media obtained and the effect of dissolved ions on cell proliferation and viability of endothelial cells (HUVEC) was studied by cytotoxicity assays. The concentration of metal ions in the media was measured by inductively coupled plasma mass spectrometry.

Effect of Manufacturing Process on the Biocompatibility and Mechanical Properties of Ti-30Ta Alloy.

Ti alloys have been widely used in the aerospace, chemical, and biomedical industries for their high strength/weight ratio and corrosion resistance. However, Nitinol's usage in the latter industry has been fraught with concerns of allergic and toxic effects of Ni released from implants. Recently, much attention has been placed on the development of Ni-free Ti-Ta alloys, which are considered prime candidates for applications such as metal-on-metal spinal disk replacements, orthopedic implants, cardiovascular stents, dental posts, and guide wires. In this research, the biocompatibility of Ti-30Ta alloys manufactured by powder metallurgy (PM) and arc melting (ARC) were investigated. The corrosion resistance of each alloy was determined in accordance with ASTM F 2129-08 in phosphate buffered saline (PBS) and PBS with amino acids at 37 °C. The concentration of metal ions released during corrosion was measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). Scanning Electron Microscopy (SEM) was used to assess the morphology of the alloys before and after corrosion. Vicker's hardness tests were performed to compare the hardness and tensile strength of the alloys. Human osteoblast cells were successfully grown on the surface of both alloys.

Cytotoxicity of Ni from Surface-Treated Porous Nitinol (PNT) on Osteoblast Cells.

The leaching of nickel from the surface of porous Nitinol (PNT) is mainly dependent on its surface characteristics, which can be controlled by appropriate surface treatments. In this investigation, PNT was subjected to two surface treatments, namely, water-boiling and dry-heating passivations. Phosphate buffer saline (PBS) solutions obtained from cyclic potentiodynamic polarization tests on PNT were employed to assess the cytotoxicity of Ni contained therein on osteoblast cells by Sulforhodamine B (SRB) assay. In addition, similar concentrations of Ni were added exogenously to cell culture media to determine cytotoxic effects on osteoblast cells. The morphologies of the untreated and the surface-treated PNTs were examined using SEM and AFM. Furthermore, growth of human osteoblast cells was observed on the PNT surfaces.

[Reaction of muscles to a stimulating environment--effects on the loin muscle (M. longissimus) of Landrace pigs]. / Reaktion der Muskulatur auf eine stimulierende Haltung--Befunde am Kotelettmuskel (M. longissimus) von Landrasse-Schweinen.

The effects of an enriched environment on growth, meat quality, and muscle biological traits were investigated using 64 castrated pigs (age range 7 to 20 weeks). Positive emotional appraisal was induced by a system that acoustically frequently called individuals out of a group (n=32) to a feeding station, where they were rewarded with small portions of feed. The results were compared with traditional fed pigs (Control; n = 32). There was no environmental effect on live weight and lean muscle percentage. However, the stimulating keeping regime reduced the intramuscular fat content of the M. longissimus by 0.2 % and increased the protein content by 0.5 %. Moreover, the drip loss of M. longissimus was 1.1 % lower in the treatment group. The analysis of muscle fibre traits (biopsy samples of M. longissimus) showed a 7 % higher proportion of oxidative muscle fibres in the pigs reared in the enriched environment. This fibre type showed a tendency to increased fibre areas. These findings indicate a higher oxidative capacity of the muscle. However, the activity of the inarker enzyme citrate synthase (CS) was not influenced and the activity of lactate dehydrogenase (LDH) was even increased compared to the control animals.

Effects of vinclozolin on spermatogenesis and reproductive success in the Japanese quail (Coturnix coturnix japonica).

In a one-generation reproduction study, the major agricultural fungicide vinclozolin was administered to adult Japanese quail for a period of 6 weeks at dietary levels of 125 and 500 ppm. Fertility and reproductive performance were not affected up to the highest concentration, although the examination of additional endpoints in the drakes (spermatid count, histology of the testis) provided some evidence of an inhibition of spermatogenesis at both dietary concentrations. Likewise, there were no indications of systemic toxicity in the adult birds. Plasma hormone concentrations (estradiol, testosterone, progesterone, T3, and T4) showed a large interindividual variance but treatment-related differences between the groups could not be established. There were no clear-cut indications of antiandrogenic effects in quail, although a limited transfer of the test substance into the eggs was proven.

Liver enzyme activity and histological changes in the liver of silver foxes (Vulpes vulpes fulva) experimentally infected with opisthorchiid liver flukes. A contribution to the pathogenesis of opisthorchiidosis.

Blood samples from silver foxes experimentally infected with Opisthorchis felineus and Metorchis bilis, respectively, were examined for the activity of liver enzymes. The average activities of aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), alkaline phosphatase and alanine aminotransferase in uninfected control animals were 20, 1.8, 57 and 44 units/l, respectively. The liver enzymes in infected foxes reacted differently, depending on dose, species of flukes and individual peculiarities. The highest individual deviation of infected from control animals was registered in the case of GLDH, reaching increases of up to 200-fold. In contrast, AST showed the lowest deviation from control values (less than 10-fold). By the end of the study period, enzyme activities had declined. The prepatent periods for M. bilis and O. felineus in foxes were 2 weeks and 4 weeks, respectively. High egg per gram values were established at the beginning of the patent period. At necropsy, chronic inflammatory reactions were found in the bile ducts and in the wall of the gall bladder. The number of flukes at the end of the study was low.

The effects of thoracic epidural analgesia with bupivacaine 0.25% on ventilatory mechanics in patients with severe chronic obstructive pulmonary disease.

UNLABELLED: Optimal analgesia is important after thoracotomy in pulmonary-limited patients to avoid pain-related pulmonary complications. Thoracic epidural anesthesia (TEA) can provide excellent pain relief. However, potential paralysis of respiratory muscles and changes in bronchial tone might be unfavorable in patients with end-stage chronic obstructive pulmonary disease (COPD). Therefore, we evaluated the effect of TEA on maximal inspiratory pressure, pattern of breathing, ventilatory mechanics, and gas exchange in 12 end-stage COPD patients. Pulmonary resistance, work of breathing, dynamic intrinsic positive end-expiratory pressure, and peak inspiratory and expiratory flow rates were evaluated by assessing esophageal pressure and airflow. An increase in minute ventilation (7.50 +/- 2.60 vs 8.70 +/- 2.10 L/min; P = 0.04) by means of increased tidal volume (0.46 +/- 0.16 vs 0.53 +/- 0.14 L/breath; P = 0.003) was detected after TEA. These changes were accompanied by an increase in peak inspiratory flow rate (0.48 +/- 0.17 vs 0.55 +/- 0.14 L/s; P = 0.02) and a decrease in pulmonary resistance (20.7 +/- 9.9 vs 16.6 +/- 8.1 cm H(2)O. L(-1). s(-1); P = 0.02). Peak expiratory flow rate, dynamic intrinsic positive end-expiratory pressure, work of breathing, PaO(2), and maximal inspiratory pressure were unchanged (all P > 0.50). We conclude that TEA with bupivacaine 0.25% can be used safely in end-stage COPD patients. IMPLICATIONS: Thoracic epidural anesthesia with bupivacaine 0.25% does not impair ventilatory mechanics and inspiratory respiratory muscle strength in severely limited chronic obstructive pulmonary disease patients. Thus, thoracic epidural anesthesia can be used safely in patients with end-stage chronic obstructive pulmonary disease.

[Glucose-insulin-potassium (GIK) in prevention and therapy of myocardial ischemia]. / Glukose-Insulin-Kalium (GIK) in der Prävention und Therapie bei myokardialer Ischämie.

Recent times are witnessing a resurge of metabolic interventions in order to preserve myocardial tissue and improve cardiac function after hypoxic or ischaemic events. The basic principle of this therapeutic approach which differs completely from surgical and radiological revascularisation techniques as well as from direct pharmacologic stimulation of contractility by catecholamines or phosphodiesterase inhibitors is illustrated by the effect of glucose-insulin-potassium (GIK) infusions. Physiology of myocardial metabolism and its pathophysiology in hypoxia and ischaemia are discussed in their relation to the administration of GIK with its main effect of switching from the preferential fat oxydation under normal conditions to a greater percentage of glucose utilisation. GIK can be used in therapeutic intention after an ischaemic insult (myocardial infarction, preoperatively) or as a preventive measure (pre-ischaemic) e.g. prior to a planned intervention (cardiac surgery). GIK improves myocardial energy supply, economizes oxygen utilisation, stabilizes hypoxic cells, diminishes the area of infarction, and increases myocardial contractility and coronary blood flow. Both in controlled trials and in meta-analyses, GIK administration resulted in reduced mortality from myocardial infarction. In conclusion, metabolic interventions present a promising alternative or adjunctive therapeutic tool for the restitution or maintenance of myocardial integrity and cardiac function impaired or threatened by ischaemic events.

Pulmonary artery thromboendarterectomy: a comparison of two different postoperative treatment strategies.

UNLABELLED: Pulmonary artery thromboendarterectomy (PTE) is a potentially curative surgical procedure for chronic thromboembolic pulmonary hypertension. It is, nevertheless, associated with considerable mortality caused by postoperative complications, such as reperfusion pulmonary edema (RPE) (i.e., pulmonary infiltrates in regions distal to vessels subjected to endarterectomy) and right heart failure (RHF). However, there are no reports about the influence of different postoperative treatment strategies on complications and mortality. Therefore, we compared two different treatment strategies. In Group I (n = 33), positive inotropic catecholamines and vasodilators were avoided during termination of cardiopulmonary bypass (CPB) and thereafter, and mechanical ventilation was performed with low tidal volumes < 8 mL/kg, duration of inspiration:duration of expiration = 3:1, and peak inspiratory pressures < 18 cm H(2)O. In Group II (n = 14), positive inotropic catecholamines and vasodilators were regularly used for termination of CPB and thereafter, and ventilation was performed with high tidal volumes (10-15 mL/kg) and peak inspiratory pressures up to 50 cm H(2)O. Hemodynamics, the incidence of RPE and RHF, duration of ventilation, morbidity, and mortality were recorded. Cardiac index was comparable before surgery (2.11 +/- 0.09 vs 2.08 +/- 0.09 L. min(-1). m(-2)) and 20 min after CPB (2.26 +/- 0.09 vs 2.60 +/- 0.20 L. min(-1). m(-2)). RPE occurred in 6.1% (Group I) versus 14.3% (Group II), and RHF was observed in 9.1% (Group I) versus 21.4% (Group II). Mortality was 9.1% (Group I) versus 21.4% (Group II). Thus, the avoidance of positive inotropic catecholamines and vasodilators in combination with nonaggressive mechanical ventilation after PTE was associated with a low incidence of RPE, RHF, duration of ventilation, and mortality after PTE. IMPLICATIONS: The avoidance of positive inotropic catecholamines and vasodilators in combination with nonaggressive mechanical ventilation was associated with a low incidence of reperfusion pulmonary edema and/or right heart failure after pulmonary artery thromboendarterectomy.