[Thoracic Surgery during Pregnancy and Breastfeeding - an Interdisciplinary Consensus Paper]. / Operieren in der Schwangerschaft und Stillzeit (OpidS) in der Thoraxchirurgie ­ ein interdisziplinäres Konsensuspapier.

If thoracic surgery is to remain an attractive career path for young physicians, it is essential to provide opportunities to balance work, residency, and family time. With an increasing proportion of women in thoracic surgery, it has become increasingly important to create a work environment that allows safe employment during pregnancy and breast feeding becomes an important concern.Based on the legal requirements of the German Maternity Protection Act (Mutterschutzgesetz), this interdisciplinary consensus paper was developed by representatives of thoracic surgery, anaesthesiology, and occupational medicine.The vast majority of thoracic operations can be performed by pregnant or breast-feeding surgeons. We established a risk-stratified list of operations with potentially acceptable risk, and a list of operations that pregnant or breast-feeding surgeons should not perform. A checklist aims to aid the individual implementation of thoracic surgery during pregnancy and breast feeding.Thoracic surgery can be performed by pregnant or breast-feeding surgeons when certain protective measures are observed. The prerequisite is the voluntary and independent decision of the surgeon, and the implementation of safety precautions by the employer.

The Influence of Positive End-Expiratory Pressure on Leakage and Oxygenation Using a Laryngeal Mask Airway: A Randomized Trial.

BACKGROUND: The value of positive end-expiratory pressure (PEEP) in maintaining oxygenation during ventilation with a laryngeal mask airway (LMA) mask is unclear. To clarify the potential benefit or harm to PEEP application during positive pressure ventilation with a ProSeal LMA® mask, we compared the effect of PEEP versus zero end-expiratory pressure (ZEEP) on gas leakage and oxygenation. We hypothesized that a PEEP of 8 mbar (8.2 cm H 2 O) would be associated with an increased incidence of gas leakage compared to ZEEP. METHODS: We designed a prospective, controlled, randomized, single-blinded, multicenter clinical trial. Patients >18 years of age with an American Society of Anesthesiologists (ASA) physical status I/II without increased risk of aspiration were enrolled if they were scheduled for elective surgery under general anesthesia with an LMA mask. Patients were randomized to a control group managed with ZEEP or an intervention group managed with a PEEP of 8 mbar. Both groups received positive pressure ventilation. The primary end point was the occurrence of gas leakage. The Student t test and χ 2 test were used for statistical analysis. RESULTS: A total of 174 patients were enrolled in the ZEEP group, and 208 were enrolled in the PEEP group. The incidence of gas leakage did not differ between the 2 groups (ZEEP: 23/174, 13.2%; PEEP: 42/208, 20.2%; P = .071; odds ratio [OR], 1.611; 95% confidence interval [CI], 0.954-2.891). However, more patients required reseating of the LMA mask in the PEEP group (ZEEP: 5/174, 2.9%; PEEP: 18/208, 8.7%; P = .018; OR, 3.202; 95% CI, 1.164-8.812). The need for endotracheal intubation did not differ between groups (ZEEP: 2/174, 1.1%; PEEP: 7/208, 3.4%; P = .190; OR, 2.995; 95% CI, 0.614-14.608). After positive pressure ventilation for 25 minutes, the mean peripheral oxygen saturation (Sp o2 ) was higher in the PEEP than in the ZEEP group (98.5 [1.9]% vs 98.0 [1.4]%; P = .01). Peak inspiratory pressure (PIP; 16 [2] vs 12 [4] mbar; P < .001) and dynamic compliance (57 [14] vs 49 [14] mL/mbar; P < .001) were both higher in the PEEP group than in the ZEEP group. CONCLUSIONS: Use of PEEP did not affect the overall incidence of gas leakage. However, PEEP did result in a higher incidence of attempts to reseat the LMA mask compared to ZEEP, whereas the incidence of rescue intubation did not differ between groups. We concluded that a PEEP of 8 mbar did not increase overall gas leakage during positive pressure ventilation with an LMA mask, but it did slightly improve gas exchange and compliance. Overall, our study does not provide strong arguments for using PEEP during ventilation with an LMA mask in elective surgery.

Recipient obesity as a risk factor in kidney transplantation.

BACKGROUND: The aim of the study was to investigate the effect of recipient obesity on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). PATIENTS AND METHODS: A total of 578 patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into normal weight (BMI 18.5-24.9 kg/m2; N = 304), overweight (BMI 25-29.9 kg/m2; N = 205) and obese (BMI ≥ 30 kg/m2; N = 69) groups. Their clinicopathological characteristics, outcomes, and survival rates were analyzed retrospectively. RESULTS: Obesity was associated with an increased rate of surgical complications such as wound infection (P < 0.001), fascial dehiscence (P = 0.023), and lymphoceles (P = 0.010). Furthermore, the hospital stay duration was significantly longer in the groups with obese patients compared to normal weight and overweight patients (normal weight: 22 days, overweight: 25 days, and obese: 33 days, respectively; P < 0.001). Multivariate analysis showed that recipient obesity (BMI ≥ 30) was an independent prognostic factor for delayed graft function (DGF) (OR 2.400; 95% CI, 1.365-4.219; P = 0.002) and postoperative surgical complications (OR 2.514; 95% CI, 1.230-5.136; P = 0.011). The mean death-censored graft survival was significantly lower in obese patients (normal weight: 16.3 ± 0.6 years, overweight: 16.3 ± 0.8 years, obese 10.8 ± 1.5 years, respectively; P = 0.001). However, when using the Cox proportional hazards model, the association between recipient obesity and death-censored renal graft failure disappeared, after adjustment for important covariates, whereas the principal independent predictors of graft loss were recipient diabetes mellitus and hypertension and kidneys from donors with expanded donor criteria. CONCLUSION: In conclusion, obesity increases the risk of DGF and post-operative surgical complications after primary KT. Appropriate risk-adapted information concerning this must be provided to such patients before KT. Furthermore, obesity-typical concomitant diseases seem to negatively influence graft survival and need to be considered after the transplantation of obese patients.

Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-ß.

Post-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). Previously, we demonstrated in the pig model that transplantation of mesenchymal stromal cells (MSC) improved circulatory maintenance and supported multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. Here we performed 70% liver resection in pigs with and without MSC treatment, and animals were monitored for 24 h post surgery. Gene expression profiles were determined in the lung and liver. Bioinformatics analysis predicted organ-independent MSC targets, importantly a role for thrombospondin-1 linked to transforming growth factor-ß (TGF-ß) and downstream signaling towards providing epithelial plasticity and epithelial-mesenchymal transition (EMT). This prediction was supported histologically and mechanistically, the latter with primary hepatocyte cell cultures. MSC attenuated the surgery-induced increase of tissue damage, of thrombospondin-1 and TGF-ß, as well as of epithelial plasticity in both the liver and lung. This suggests that MSC ameliorated surgery-induced hepatocellular stress and EMT, thus supporting epithelial integrity and facilitating regeneration. MSC-derived soluble factor(s) did not directly interfere with intracellular TGF-ß signaling, but inhibited thrombospondin-1 secretion from thrombocytes and non-parenchymal liver cells, therewith obviously reducing the availability of active TGF-ß.

Procedural times in early non-intubated VATS program - a propensity score analysis.

BACKGROUND: Non-intubated video-assisted thoracic surgery (NiVATS) has been introduced to surgical medicine in order to reduce the invasiveness of anesthetic procedures and avoid adverse effects of intubation and one-lung ventilation (OLV). The aim of this study is to determine the time effectiveness of a NiVATS program compared to conventional OLV. METHODS: This retrospective analysis included all patients in Leipzig University Hospital that needed minor VATS surgery between November 2016 and October 2019 constituting a NiVATS (n = 67) and an OLV (n = 36) group. Perioperative data was matched via propensity score analysis, identifying two comparable groups with 23 patients. Matched pairs were compared via t-Test. RESULTS: Patients in NiVATS and OLV group show no significant differences other than the type of surgical procedure performed. Wedge resection was performed significantly more often under NiVATS conditions than with OLV (p = 0,043). Recovery time was significantly reduced by 7 min (p = 0,000) in the NiVATS group. There was no significant difference in the time for induction of anesthesia, duration of surgical procedure or overall procedural time. CONCLUSIONS: Recovery time was significantly shorter in NiVATS, but this effect disappeared when extrapolated to total procedural time. Even during the implementation phase of NiVATS programs, no extension of procedural times occurs.

Thoracotomy for emergency repair of iatrogenic tracheal rupture: single center analysis of perioperative management and outcomes.

BACKGROUND: Iatrogenic tracheal ruptures are rare but life-threatening airway complications that often require surgical repair. Data on perioperative vital functions and anesthetic regimes are scarce. The goal of this study was to explore comorbidity, perioperative management, complications and outcomes of patients undergoing thoracotomy for surgical repair. METHODS: We retrospectively evaluated adult patients who required right thoracotomy for emergency surgical repair of iatrogenic posterior tracheal ruptures and were admitted to a university hospital over a 15-year period (2004-2018). The analyses included demographic, diagnostic, management and outcome data on preinjury morbidity and perioperative complications. RESULTS: Thirty-five patients who met the inclusion criteria were analyzed. All but two patients (96%) presented with critical underlying diseases and/or emergency tracheal intubations. The median time (interquartile range) from diagnosis to surgery was 0.3 (0.2-1.0) days. The durations of anesthesia, surgery and one-lung ventilation (OLV) were 172 (128-261) min, 100 (68-162) min, and 52 (40-99) min, respectively. The primary airway management approach to OLV was successful in only 12 patients (34%). Major complications during surgery were observed in 10 patients (29%). Four patients (11%) required cardiopulmonary resuscitation, one of whom received extracorporeal membrane oxygenation, and another one of these patients died during surgery. Major complications were associated with significantly higher all-cause 30-day mortality (p = 0.002) and adjusted mortality (p = 0.001) compared to patients with minor or no complications. CONCLUSIONS: Surgical repair of iatrogenic tracheal ruptures requires advanced perioperative care in a specialized center due to high morbidity and potential complications. Airway management should include early anticipation of alternative OLV approaches to provide acceptable conditions for surgery.

Mesenchymal stem cells correct haemodynamic dysfunction associated with liver injury after extended resection in a pig model.

In patients, acute kidney injury (AKI) is often due to haemodynamic impairment associated with hepatic decompensation following extended liver surgery. Mesenchymal stem cells (MSCs) supported tissue protection in a variety of acute and chronic diseases, and might hence ameliorate AKI induced by extended liver resection. Here, 70% liver resection was performed in male pigs. MSCs were infused through a central venous catheter and haemodynamic parameters as well as markers of acute kidney damage were monitored under intensive care conditions for 24 h post-surgery. Cytokine profiles were established to anticipate the MSCs' potential mode of action. After extended liver resection, hyperdynamic circulation, associated with hyponatraemia, hyperkalaemia, an increase in serum aldosterone and low urine production developed. These signs of hepatorenal dysfunction and haemodynamic impairment were corrected by MSC treatment. MSCs elevated PDGF levels in the serum, possibly contributing to circulatory homeostasis. Another 14 cytokines were increased in the kidney, most of which are known to support tissue regeneration. In conclusion, MSCs supported kidney and liver function after extended liver resection. They probably acted through paracrine mechanisms improving haemodynamics and tissue homeostasis. They might thus provide a promising strategy to prevent acute kidney injury in the context of post-surgery acute liver failure.

Cerebrospinal fluid melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) in Alzheimer's disease.

Ancillary to decline in cognitive abilities, patients with Alzheimer's disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62) = 8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r = 0.47; p<0.01) and P-tau (r = 0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = -0.362, p<0.05) and was increased in more severely affected patients (MMSE≤20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31) = 4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.

Is perioperative low molecular weight hydroxyethyl starch infusion a risk factor for delayed graft function in renal transplant recipients?

BACKGROUND: Crystalloid or colloid fluids may be utilized during kidney transplantation. Histopathological and clinical data indicate that hydroxyethyl starch (HES) may have nephrotoxic potential. METHODS: This retrospective single-centre cohort study screened 192 and included 113 patients who underwent renal transplantation between 2003 and 2007 at University of Leipzig Medical Faculty, Germany. The primary outcome parameter was delayed graft function (DGF). Patients were divided into two groups. Patients in group CRYS (N = 73) received crystalloid solution (acetated Ringer's or normal saline) only. Patients in the group HES (N = 40) received a minimum of 500 mL 6% HES 130/0.4 and additional crystalloid solution by discretion of the transplant team. RESULTS: Patients in both groups did not differ with respect to demographic data and American Society of Anesthesiologists Physical Status Classification System scores, except for the donor age, which was significantly lower in the group HES. The rate of DGF was not found to be different in group CRYS (31.5%) when compared to group HES (32.5%) (P = 1.00, n.s.). CONCLUSION: In this single-centre retrospective cohort study, infusion of low molecular weight 6% HES 130/0.4 during and after renal transplantation was found to have no significant negative effect upon the rate of DGF.

Effects of propofol and isoflurane anesthesia on the intraocular pressure and hemodynamics of pigs.

To determine the conditions under which anesthetized pigs can be used in acute noninvasive investigations of ocular hydro- and hemodynamics, the intraocular pressure (IOP) of adult pigs was recorded under the following conditions: (1) after intravenous injection of propofol plus ketamine; (2) during inhalation of isoflurane, and (3) 2 h after topical administration of bimatoprost or (4) timolol. Propofol/ketamine and isoflurane induced significant decreases in the IOP. The pulsation of the ophthalmic artery appeared at a significantly higher IOP in animals anesthetized with isoflurane than in those anesthetized with propofol/ketamine. Bimatoprost and timolol did not significantly decrease the IOP within 2 h after topical administration. It is concluded that different techniques for the acute noninvasive investigation of ocular hydro- and hemodynamics are applicable in anesthetized pigs. To test the effects of antiglaucoma agents, investigation periods longer than 2 h are required. We recommend the use of intravenous propofol/ketamine anesthesia rather than isoflurane anesthesia in future experiments using pigs.

Blood lactate and pyruvate levels in the perioperative period of liver resection with Pringle maneuver.

INTRODUCTION: Bleeding during liver surgery is often routinely controlled by the Pringle maneuver consisting in the temporary clamping of hepatic artery, portal vein, and bile duct. This study aimed at investigating a possible influence of the Pringle maneuver on tissue hypoxia during liver resection. METHODS: Twenty-five consecutive patients undergoing elective liver resection were prospectively randomized either to be treated with the Pringle maneuver (Pringle group, n = 14) or without clamping (Controls, n = 11). Blood lactate levels, pyruvate levels, and hepatic vein oxygen saturation were monitored perioperatively. RESULTS: Patients were comparable with respect to resection time, intraoperative blood loss, and duration of surgery. The Pringle maneuver induced a significant increase in arterial lactate levels during liver resection when compared to Controls (2.6 +/- 0.3 vs 1.8 +/- 0.2 mmol/l; p < 0.05). Further, the Pringle maneuver significantly increased hepatic venous lactate (3.3 +/- 0.3 vs 1.6 +/- 0.3 mmol/l; p < 0.05) and lactate/pyruvate ratio in hepatic venous blood (43 +/- 8 vs 21 +/- 5; p < 0.05) during surgery. This was paralleled by a temporal decrease in hepatic venous oxygen saturation in the Pringle group (61 +/- 4 vs 73 +/- 4%; p < 0.05). CONCLUSION: Our findings demonstrate that liver metabolism and tissue oxygenation were markedly affected by occlusion of the liver hilus. Restricting the use of the Pringle maneuver to cases with severe bleeding might therefore be beneficial in patients undergoing liver resection.

A new vagal anchor electrode for real-time monitoring of the recurrent laryngeal nerve.

BACKGROUND: Despite conventional neuromonitoring, the recurrent laryngeal nerve (RLN) is still at risk for damage during thyroid surgery. The feasibility of continuous RLN monitoring by vagal nerve (VN) stimulation with a new anchor electrode should be shown, and electromyographic signal alterations of stressed RLN were analyzed to be alerted to imminent nerve failure whereby the nerve damage becomes reversible. METHODS: VN stimulation was achieved in 23 pigs. Sensed signals were analyzed and stored as real-time audio/video feedback EMG system. RLN was stressed by mechanical and thermal injury; signal alterations were evaluated. RESULTS: VNs were successfully real-time stimulated by using the anchor electrode. No complications or side effects during stimulation were detected. RLN injury led to an alteration of signal amplitude and latency period but signal restitution after injury. CONCLUSIONS: Real-time monitoring of the RLN is technically feasible to perceive imminent nerve failure. The anchor electrode was safely and easy to handle. Its implementation is being tested in an ongoing clinical trial.

Percutaneous intragastric catheter (PIC) for administration of an unpalatable substance to large animals.

We studied an easy and reliable technique for administration of an unpalatable substance to large animals. There were three groups of pigs: group I (n = 6) received 1 g ethanol/kg body weight per day orally with water for 24 days, group II (n = 6) received 2 g ethanol/kg orally with water for 24 days and 4 g ethanol/kg via percutaneous intragastric catheter (PIC) for the next 24 days, group III (n = 6) received 6 g ethanol/kg via PIC for 72 days. The catheter was placed after insufflation of the stomach using an orogastric tube. PIC was successfully placed in each pig. No complications occurred during placement. The total amount of the administrated dose was assimilated each time. PIC is a safe, effective, well tolerated, and precise method of administering ethanol that is inexpensive and easy to perform. Ethanol administration via PIC is a convenient and effective mean of exposing animals to high levels of alcohol on a long-term basis.

[Anesthesia and bodybuilding]. / Anästhesie und Bodybuilding - Risiken des Medikamentenmissbrauchs.

A strong tendency toward body enhancement and body forming in western industrial societies makes it more likely for each anesthesiologist to get involved in the care of bodybuilders. These patients quite frequently consume androgenic anabolic steroids, human growth hormone and other drugs or substances which are believed to accelerate muscle gain. Cardiovascular, hepatic, psychiatric, hormonal and infectious side effects or complications are common and rarely monitored by health care professionals. The anesthesia risk is not exactly known but seems to be determined mainly by cardiovascular events like myocardial ischemia and dysrhythmias.

Gastric dysmotility in patients with major depression.

BACKGROUND: Depressed patients frequently complain about vegetative symptoms. The aim of the present study was to evaluate gastric electrical activity in patients suffering from major depression in relation to their symptoms. METHODS: Electrogastrography (EGG) was performed before and after a test meal ingestion in 21 patients suffering from major depression and control subjects. A structured interview was used to assess the severity of clinical as well as abdominal symptoms. RESULTS: Patients presented with significantly elevated proportions of tachygastria. Significant differences were found for the parameter arrhythmia, the coefficient of dominant frequency and slow wave after the test meal ingestion. A positive correlation was found between tachygastria and ANS score as well as tachygastria and the item "sweating". LIMITATIONS: Further studies are warranted to include more patients and to investigate interaction with specific antidepressive drugs. DISCUSSION: This is the first study demonstrating an increased amount of tachygastria in patients suffering from major depression which might be caused by increased sympathetic modulation. The correlation of tachygastria with the amount of gastric symptoms underlines the clinical significance of this finding.

Regenerative capacity differs between micro- and macrovesicular hepatic steatosis.

INTRODUCTION: Independent of etiology, the hepatic microvesicular steatosis has a worse prognosis compared with macrovesicular steatosis. Proliferation compensates for apoptosis and reflects regenerative mechanisms following liver injury. It is unknown whether these two types of fatty liver have differences in regenerative capacity and apoptosis, which could have an impact on their prognosis. METHODS: Two groups of pigs were studied for 72 days under a protein-deficient diet. One group received only protein-deficient diet (n=6), the other was treated in addition to the diet with 6g ethanol/kg/day by means of a percutaneous intragastric catheter (n=6). The rate of proliferating and apoptotic hepatocytes was determined, respectively, by proliferation cell nuclear antigen (PCNA) and ISEL/TUNEL staining for apoptosis in liver biopsies with similar steatosis grade in pigs with micro- or macrovesicular fatty liver. RESULTS: The ethanol-treated group developed microvesicular steatosis, the other group developed macrovesicular steatosis. Proliferation index was significantly increased in macrovesicular in comparison with microvesicular steatosis (p<0.05). Apoptosis rate was similar in both groups. CONCLUSIONS: Regeneration, but not apoptosis rate differs between micro- and macrovesicular steatosis. The reduced regenerative capacity in microvesicular steatosis may contribute to the worse prognosis of this subtype of fatty liver disease.

Changes in membrane conductance play a pathogenic role in osmotic glial cell swelling in detached retinas.

Detachment of the neural retina from the pigment epithelium may be associated with tissue edema; however, the mechanisms of fluid accumulation are not understood. Because retinal detachment is usually not accompanied by vascular leakage, we investigated whether the osmotic swelling characteristics of retinal glial (Müller) cells are changed after experimental detachment of the porcine retina. Osmotic stress, induced by application of a hypotonic bath solution to retinal slices, caused swelling of Müller cell bodies in 7-day-detached retinas, but no swelling was inducible in slices of control retinas. Müller cell somata in slices of retinal areas that surround local detachment in situ also showed osmotic swelling, albeit at a smaller amplitude. The amplitude of osmotic Müller cell swelling correlated with the decrease in the K+ conductance, suggesting a causal relationship between both gliotic alterations. Further factors implicated in Müller cell swelling were inflammatory mediators and oxidative stress. We propose that a dysregulation of the ion and water transport through Müller cells may impair the fluid absorption from the retinal tissue, resulting in chronic fluid accumulation after detachment. This knowledge may lead to a better understanding of the mechanisms involved in retinal degeneration after detachment.

Glial cell reactivity in a porcine model of retinal detachment.

PURPOSE: Detachment of the neural retina from the pigment epithelium causes, in addition to photoreceptor deconstruction and neuronal cell remodeling, an activation of glial cells. It has been suggested that gliosis contributes to the impaired recovery of vision after reattachment surgery that may involve both formerly detached and nondetached retinal areas. Müller and microglial cell reactivity was monitored in a porcine model of rhegmatogenous retinal detachment, to determine whether gliosis is present in detached and nondetached retinal areas. METHODS: Local detachment was created in the eyes of adult pigs by subretinal application of hyaluronate. Retinal slices were immunostained against glial intermediate filaments and K+ and water channel proteins (aquaporin-4, Kir4.1, Kir2.1), and P2Y receptor proteins. In retinal wholemounts, adenosine 5'-triphosphate (ATP)-induced intracellular Ca2+ responses of Müller cells were recorded, and microglial and immune cells were labeled with Griffonia simplicifolia agglutinin isolectin I-B4. K+ currents were recorded from isolated Müller cells. RESULTS: At 3 and 7 days after surgery, Müller cells in detached retinas showed a pronounced gliosis, as revealed by the increased expression of the intermediate filaments glial fibrillary acidic protein and vimentin, by the decrease of Kir4.1 immunoreactivity and of the whole-cell K+ currents, and by the increased incidence of cells that showed Ca2+ responses on stimulation of purinergic (P)2 receptors by ATP. By contrast, the immunohistochemical expression of Kir2.1 and aquaporin-4 were not altered after detachment. The increase in the expression of intermediate filaments, the decrease of the whole-cell K+ currents and of the Kir4.1 immunolabeling, and the increase in the Ca2+ responsiveness of Müller cells were also observed in attached retinal areas surrounding the focal detachment. The density of microglial-immune cells at the inner surface of the retinas increased in both detached and nondetached retinal areas. The immunoreactivities for P2Y1 and P2Y2 receptor proteins apparently increased only in detached areas. CONCLUSIONS: Reactive responses of Müller and microglial cells are not restricted to detached retinal areas but are also observed in nondetached regions of the porcine retina. The gliosis in the nondetached retina may reflect, or may contribute to, neuronal degeneration that may explain the impaired recovery of vision observed in human subjects after retinal reattachment surgery.

Attenuation of proinflammatory gene expression and microcirculatory disturbances by endothelin A receptor blockade after orthotopic liver transplantation in pigs.

BACKGROUND: Endothelin-1 (ET-1), a very potent mediator of vasoconstriction, leads to microcirculatory disturbances and release of proinflammatory cytokines under pathophysiologic conditions. Our aim was to evaluate the effect of a selective ET(A)-receptor antagonist (ET(A)-RA) on cold ischemia/reperfusion (I/R) injury in a pig model. METHODS: Twenty pigs revealed orthotopic liver transplantation. The animals were randomized into 2 groups: control pigs received isotonic saline; the treated group received the selective ET(A)-RA BSF 208075 at the beginning of reperfusion. On postoperative days 4 and 7, animals were re-laparotomized to obtain tissue specimens. Liver tissue samples were collected and quantitative mRNA expression for prepro-ET-1, ET(A) receptor, pro-IL-1beta, pro-IL-6, pro-TNF-alpha, and endothelial nitric oxide synthase was analyzed using the TaqMan system. Additionally, immunohistochemical analysis for ET-1 was performed. Hepatic microcirculation was evaluated by laser Doppler flow measurement and partial pressure of oxygen and carbon dioxide measurements with the Paratrend sensor. Postischemic liver damage was monitored by measurement of liver enzymes and by histologic analysis using a semiquantitative scoring classification. RESULTS: Treatment with the ET(A)-RA significantly reduced the severity of I/R injury evidenced by lower serum AST, ALT and GLDH. Analysis of partial pressure of oxygen and blood flow revealed a significant improvement of capillary perfusion and blood flow in the treated group and was associated with a relevant reduction of tissue injury. One hour after reperfusion, quantitative RT-PCR revealed significantly lower expression of prepro-ET-1, ET(A) receptor, endothelial nitric oxide synthase, pro-TNF-alpha, pro-IL-1beta and pro-IL-6 in the therapy group. Immunohistochemical analysis demonstrated significantly reduced ET-1 immunostaining after therapy. Histologic investigation suggested less tissue damage in treated animals. CONCLUSIONS: Treatment with the selective ET(A)-RA BSF 208075 has protective effects on microcirculation after liver transplantation. ET(A)-RA not only affects the expression of vasoactive genes, but also decreases gene expression of proinflammatory cytokines such as TNF-alpha, IL-1beta and IL-6.