[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.

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.

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.

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.

Effects of ET(A) receptor antagonism on proinflammatory gene expression and microcirculation following hepatic ischemia/reperfusion.

BACKGROUND: The objective of this study was to investigate the effect of a specific endothelin(A) receptor antagonist (ET(A)-RA) on mRNA expression of genes encoding vasoactive mediators and proinflammatory cytokines and on the microhemodynamics (assessed by measurement of laser Doppler flow and tissue blood gases) following complete vascular exclusion of the porcine liver. STUDY DESIGN: Sixteen adult German landrace pigs were subjected to 120 min of warm hepatic ischemia by total vascular exclusion. To avoid portal congestion, a passive porto-femoro/jugular bypass was implanted. The animals were divided into 2 groups: the control group received saline solution and the therapy group was given the selective ET(A)-RA BSF 208075. Hepatic microcirculation was evaluated by p(O(2)) and p(CO(2)) measurement with the Paratrend sensor and by laser Doppler flow measurement. Liver tissue samples were collected 1 h after reperfusion and quantitative mRNA expression for prepro-ET-1, pro-IL-1beta, pro-IL-6, pro-TNF-alpha, eNOS was analyzed using the TaqMan system. Additionally, immunohistochemical analysis using a semiquantitative score for ET-1 was performed. Postischemic liver damage was monitored by measurement of liver enzymes and assessed by histological analysis using a semiquantitative scoring classification. RESULTS: Partial oxygen pressure in the hepatic tissue and laser Doppler flow were significantly improved in the therapy group. One hour after reperfusion, quantitative RT-PCR revealed significantly lower expression of prepro-ET-1, eNOS, pro-TNF-alpha, and pro-IL-6 in the therapy group compared to controls. Immunohistochemical analysis demonstrated significantly reduced ET-1 immunostaining after therapy. Furthermore, blockade of ET(A) receptors prevents tissue damage. CONCLUSIONS: Treatment with the selective ET(A)-RA BSF 208075 has protective effects on microcirculation after 120 min liver ischemia and reperfusion. The authors were able to show that ET(A)-RA not only affects the expression of vasoactive genes, but also decreases gene expression of proinflammatory cytokines such as TNF-alpha and IL-6.

Endothelin receptors in the detached retina of the pig.

Endothelin-1 (ET-1) is a potent vasoconstrictor that causes hypoperfusion of the neurosensory retina. We investigated immunohistochemically the expression of the receptors for ET-1, ET(A) and ET(B), in control and locally detached retinas of the pig. Immunoreactivity for ET(A) was expressed in the innermost retinal layers and in the outer plexiform layer in control retinas, and was additionally strongly expressed by retinal blood vessels at 7 days after detachment of the sensory retina from the pigment epithelium. Immunoreactivity for ET(B) was expressed by the innermost retinal layers, by ganglion cell somata, and by Müller glial cells in the control tissue, and was not altered in its expression after detachment. The vascular expression of ET(A) may suggest a hypoperfusion of the retina after detachment.

[The influence of normobaric hyperoxia on hepatic oxygenation--experience with an animal model]. / Der Einfluss von normobarer Hyperoxie auf die lebervenöse Oxygenierung--Erfahrungen mit einem Tiermodell.

We investigated the effect of a ventilation with an FiO2 of 1.0 on arterial and hepatic venous oxygenation in 23 Göttingen minipigs. Under balanced anaesthesia (isoflurane/fentanyl), a fibreoptic catheter was placed into a hepatic vein. The correct position of the tip of the catheter was controlled manually after laparotomy. After measurement of baseline values (arterial and hepatic blood gases, ShvO2), in 13 minipigs normoventilation with an FiO2 of 1.0 was performed for 15 minutes. Thereafter, ventilation was continued with an FiO2 of 0.4. In the control group (n = 10), the animals were oxygenated with an FiO2 of 0.4 permanently. The changes due to hyperoxia were measured in hepatic venous oxygen saturation (ShvbgaO2: from 81.2 +/- 1.43% to 87.5 +/- 1.77%, ShvoximO2: from 82.6 +/- 1.14% to 90.5 +/- 0.90%), arterial (from 217.5 +/- 5.0 mmHg to 467.2 +/- 22.0 mmHg) and hepatic venous (from 51.8 +/- 2.0 mmHg) oxygen partial pressure. We found a correlation between hepatic venous oxygen partial pressure und ShvbgaO2 in the blood (r = 0.84, p < 0.001) and between ShvO2 (ShvbgaO2/ShvoximO2), which was either measured directly in the blood or by a fibreoptic catheter (r = 0.6, p < 0.001). Whereas the increase in ShvO2 during hyperoxia may be a result of increased arterial supply, the decrease in ShvO2 after the end of hyperoxia below baseline values needs further investigations. The continuous fibreoptic measurement of ShvoximO2, also under hyperoxic conditions is a valuable parameter for the monitoring of hepatic venous oxygenation.

Assessment of hepatic ischemia-reperfusion injury by simultaneous measurement of tissue pO2, pCO2, and pH.

INTRODUCTION: The objective of this study was to determine whether the simultaneous measurement of tissue pH, pCO(2), and pO(2) with a multiple-parameter fiberoptic sensor (Paratrend 7) can be used for continuous monitoring of hepatic microperfusion in a pig model of hepatic ischemia given endothelin(A) receptor antagonist (ET(A)-RA) or isotonic saline. METHODS: Fourteen anesthetized swine were subjected to 2 h of hepatic vascular exclusion. The animals were randomized into two groups: control group (n = 7, saline solution iv) and therapy group (n = 7, ET(A)-RA). For evaluation of ischemia-reperfusion injury, the data of the multiple-parameter sensor (pO(2para), pCO(2para), and pH(para)) were compared with partial oxygen pressure in tissue (p(ti)O(2)), laser Doppler flow, and systemic hemodynamic, metabolic data, and time course of transaminases. RESULTS: In the control group 30 and 60 min after reperfusion, the following values were measured: p(ti)O(2): 34.0 +/- 8.6 / 36.3 +/- 7.0 mm Hg (P < 0.05 vs. preop.: 49.8 +/- 12.1 mm Hg), laser Doppler area: 133.3 +/- 23.2 / 156.4 +/- 15.4 (P < 0.05 vs. preop.: 215.9 +/- 14.8). Animals in the therapy group revealed significantly improved values (p(ti)O(2): 54.0 +/- 8.6 / 58.1 +/- 7.8 mm Hg, laser Doppler: 210.2 +/- 38.5 / 225.2 +/- 21.3; P < 0.05). Using the Paratrend, also an improvement in the therapy group was seen 30 and 60 min after reperfusion. The values showed a strong correlation with p(ti)O(2) (r = 0.895; P < 0.05) and laser Doppler flow (r = 0.807; P < 0.05). In the treatment group, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamate dehydrogenase (GLDH) were reduced 6 and 18 h after reperfusion, respectively, indicating hepatoprotection by the therapy (P < 0.05 vs. control). CONCLUSIONS: The Paratrend sensor offers the opportunity to study postischemic organ hemodynamics through the simultaneous measurement of interstitial pH, pCO(2), and pO(2) in a small tissue region. This method offers a prognostic tool for the study of the effects of experimental vasoactive therapy on liver microcirculation and perspectives for continuous monitoring of human liver microperfusion after liver surgery and trauma.

Changes of vasoregulatory gene expression following hepatic ischemia/reperfusion and treatment with endothelin-A receptor blockade.

The objective of this study was to investigate the effect of a specific endothelin-A receptor antagonist on mRNA expression of genes encoding vasoactive mediators and proinflammatory cytokines following complete vascular exclusion of the porcine liver. Fourteen adult German Landrace pigs were subjected to 120 minutes of warm hepatic ischemia by total vascular exclusion. The animals were divided into two groups: the control group received saline solution and the therapy group was given the selective endothelin-A receptor antagonist BSF 208075. Liver tissue samples were collected 1 hour after reperfusion and mRNA expression for preproendothelin-1, prointerleukin-1beta, prointerleukin- 6, pro-tumor necrosis factor-alpha and endothelial nitric oxide synthase was analyzed quantitatively using the TaqMan system. Additionally, immunohistochemical analysis using a semiquantitative score for endothelin-1 and endothelin-A receptor was performed. One hour after reperfusion, quantitative reverse transcriptase-polymerase chain reaction revealed significantly lower expression of preproendothelin-1, pro-tumor necrosis factor-alpha, and prointerleukin-6 in the therapy group compared to controls. Immunohistochemical analysis demonstrated significantly reduced endothelin-1 immunostaining after therapy. Treatment with the selective endothelin-A receptor antagonist exerts a protective effect on the microcirculation after liver ischemia and reperfusion. We were able to show that the endothelin-A receptor antagonist not only has effects on the expression of vasoactive genes, it also decreases gene expression of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6.