Efficacy of the Novel Medical Adhesive, MAR-VIVO-107, in an Acute Porcine Liver Resection Model.

BACKGROUND: Despite modern surgical techniques, insufficient hemostasis after liver trauma is still a major cause of morbidity and mortality after injury. Therefore, efficient hemostatic agents are indicated. In this study, we evaluated the hemostatic efficacy of a novel synthetic wound adhesive (MAR-VIVO-107) based on polyurethane/polyurea, compared with a widely used fibrin adhesive (Tisseel). MATERIALS AND METHODS: Twelve German Landrace pigs were randomly assigned to 2 groups. The animals were operated under sterile conditions. A midline laparotomy was performed and the left liver lobe was isolated and resected, using a surgical scissor, in order to induce hepatic trauma. MAR-VIVO-107 or Tisseel was applied to the resected area. The animals were monitored for 60 minutes; thereafter, they were sacrificed under anesthesia. Blood and tissue samples were collected pre- and postresection for biochemical and hematological analyses. RESULTS: MAR-VIVO-107 versus Tisseel (mean ± SD, P value)-postsurgical survival rate was 100% in both groups. Bleeding time was significantly higher in Tisseel compared with MAR-VIVO-107 (10.3 ± 5.0 vs 3.7 ± 1.5 minutes, P = .0124). In trend, blood loss was less in the MAR-VIVO-107 group (54.3 ± 34.9 vs 105.5 ± 65.8 g, P = .222). Aspartate transaminase levels were significantly lower in the MAR-VIVO-107 group when compared with the Tisseel group (39.0 ± 10.0 vs 72.4 ± 23.4 U/L, P = .0459). CONCLUSION: The efficacy of MAR-VIVO-107 and comparable performance to the gold standard fibrin have been shown under pre-clinical conditions. MAR-VIVO-107 permits hemorrhage control within seconds, even in wet environment.

Impact of oxygen free radicals in rat partial liver transplantation.

BACKGROUND: Due to the shortage of suitable organs, the demand for partial liver transplantation from living donors has increased worldwide. N-acetylcysteine (NAC) has shown protective effects as a free radical scavenger during hypothermic preservation and warm ischemia-reperfusion liver injury; however, no study has reported the effects in partial liver transplantation. The aim of this study was to analyze the impact of NAC on liver graft microcirculation and graft function after partial liver transplantation in rats. METHODS: Orthotopic partial liver transplantations were performed in 40 rats following cold storage in histidine-tryptophan-ketoglutarate solution for 3 h with 20 mM NAC (NAC group, n = 20) or without (control group, n = 20). We assessed portal circulation, graft microcirculation, and biochemical analyses of plasma at 1, 3, 24, and 168 h after portal reperfusion. RESULTS: (Control versus NAC, median and range): Portal venous pressure was significantly lower with NAC (P = 0.03). Microcirculation measured by laser Doppler was significantly improved with NAC throughout the time course (P = 0.003). Alanine aminotransferase levels were significantly lower in the NAC group (P < 0.05). Total antioxidative capacity was significantly higher in the NAC group at 1 h after reperfusion (Trolox equivalents: median, 3 µM; range, 2.9-6.7 versus median, 16.45 µM; range, 10.4-18.8). Lipid peroxidation was significantly abrogated in the NAC group (median, 177.6 nmol/mL; range, 75.9-398.1 versus median, 71.5 nmol/mL; range, 58.5-79 at 3 h). CONCLUSIONS: This study showed that NAC treatment during cold storage resulted in improved microcirculation and preservation quality of partial liver graft likely because of enhanced antioxidant capacity and reduced lipid peroxidation.

L-α-glycerylphosphorylcholine reduces the microcirculatory dysfunction and nicotinamide adenine dinucleotide phosphate-oxidase type 4 induction after partial hepatic ischemia in rats.

BACKGROUND: We set out to investigate the microcirculatory consequences of hepatic ischemia-reperfusion (IR) injury and the effects of L-alpha-glycerylphosphorylcholine (GPC), a deacylated phospholipid derivative, on postischemic hepatocellular damage, with special emphasis on the expression of nicotinamide adenine dinucleotide phosphate oxidase type 4 (NOX4), which is predominantly expressed in hepatic microvessels. MATERIALS AND METHODS: Anesthetized male Sprague-Dawley rats were subjected to 60-min ischemia of the left liver lobes and 180-min reperfusion, with or without GPC treatment (50 mg/kg intravenously 5 min before reperfusion, n = 6 each). A third group (n = 6) served as saline-treated control. Noninvasive online examination of the hepatic microcirculation was performed hourly by means of modified spectrometry. Plasma tumor necrosis factor (TNF-α), high-mobility group box 1 protein (HMGB1), plasma aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels, tissue xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) activities, and expressions of NOX2 and NOX4 proteins were determined. RESULTS: Liver IR resulted in significant increases in NOX2 and NOX4 expressions and XOR and MPO activities, and approximately 2-fold increases in the levels of the inflammatory cytokines TNF-α and HMGB1. The microvascular blood flow and tissue oxygen saturation decreased by ∼20% from control values. GPC administration ameliorated the postischemic microcirculatory deterioration and reduced the liver necroenzyme levels significantly; the NOX4 expression, MPO activity, and HMGB1 level were also decreased, whereas the NOX2 expression, TNF-α level, and XOR activity were not influenced by GPC pretreatment. CONCLUSIONS: NOX4 activation is a decisive component in the IR-induced microcirculatory dysfunction. Exogenous GPC ameliorates the inflammatory activation, and preserves the postischemic microvascular perfusion and liver functions, these effects being associated with a reduced hepatic expression of NOX4.

Impact of venous systemic oxygen persufflation supplemented with nitric oxide gas on cold-stored, warm ischemia-damaged experimental liver grafts.

The increasing shortage of donor organs has led to the increasing use of organs from non-heart-beating donors. We aimed to assess the impact of venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the cold storage (CS) of warm ischemia (WI)-damaged experimental liver grafts. Rat livers (n = 5 per group) were retrieved after 30 minutes of WI induced by cardiac arrest (the WI group) and were thereafter preserved for 24 hours by CS in histidine tryptophan ketoglutarate solution. During CS, gaseous oxygen was insufflated via the caval vein with 40 ppm NO (the VSOP-NO group) or without NO (the VSOP group). Cold-stored livers without WI served as controls. Liver viability was assessed after the preservation period by normothermic isolated reperfusion for 45 minutes with oxygenated Krebs-Henseleit buffer. After 45 minutes of reperfusion, the VSOP-NO-treated livers showed significantly lower alanine aminotransferase values than the WI-damaged livers (10.2 ± 0.2 versus 78.2 ± 14.6 IU/L), whereas the control livers showed no differences from the VSOP-NO-treated livers. The mitochondrial enzyme release was lower in the VSOP-NO group (4.0 ± 0.7 IU/L) versus the WI group (18.2 ± 4.9 IU/L). An increased portal vein pressure was observed throughout reperfusion (45 minutes) in the WI group (21.7 ± 0.2 mm Hg) versus the VSOP-NO group (12.2 ± 0.8 mm Hg) and the control group (19.9 ± 0.4 mm Hg). Furthermore, the NO concentration in the perfusate after 5 minutes of reperfusion was highest in the VSOP-NO group. The release of malondialdehyde into the perfusate was significantly reduced in the VSOP-NO group (0.9 ± 0.1 nmol/mL) versus the WI group (31.3 ± 5.3 nmol/mL). In conclusion, the resuscitation of livers after 30 minutes of WI to a level comparable to that of nonischemically damaged livers is possible with VSOP supplemented with NO gas. Moreover, the application of VSOP with NO minimizes the extent of injuries caused by oxygen free radicals during preservation.

Novel synthetic adhesive as an effective alternative to Fibrin based adhesives.

AIM: To compare a novel, fully synthetic, polyurethane based glue (MAR-1) to fibrin sealant in a partial liver resection rat model. METHODS: After 50% resection of the lateral left liver lobe in male Wistar rats (n = 7/group/time point), MAR-1, Fibrin or NaCl was applied. After 14, 21 and 90 postoperative days, sealant degradation, intra-abdominal adhesions were scored, and histological examination of liver tissue was performed. RESULTS: (Mean ± SEM) (MAR-1 vs Fibrin vs NaCl). Bleeding mass was significantly higher in NaCl (3.36 ± 0.51 g) compared to MAR-1 (1.44 ± 0.40 g) and Fibrin (1.16 ± 0.32 g). At 14 and 90 d, bleeding time was significantly lower in MAR-1 (6.00 ± 0.9 s; 13.57 ± 3.22 s) and Fibrin (3.00 ± 0.44 s; 22.2 ± 9.75 s) compared to NaCl (158.16 ± 11.36 s; 127.5 ± 23.3 s). ALT levels were significantly higher in MAR-1 (27.66 ± 1 U/L) compared to Fibrin (24.16 ± 0.98 U/L) and NaCl (23.85 ± 0.80 U/L). Intrabdominal adhesions were significantly lower in MAR-1 (11.22% ± 5.5%) compared to NaCl (58.57% ± 11.83%). Degradation of the glue was observed and MAR-1 showed almost no traces of glue in the abdominal cavity as compared to the Fibrin (10% ± 5% 14 d; 7% ± 3% 21 d). Survival showed no significant differences between the groups. CONCLUSION: Compared to Fibrin, MAR-1 showed similar hemostatic properties, no adverse effects, and is biocompatible. Further studies on adhesion strength and biodegradability of synthetic sealants are warranted.

Gut-liver axis improves with meloxicam treatment after cirrhotic liver resection.

AIM: To investigate the effect of meloxicam on the gut-liver axis after cirrhotic liver resection. METHODS: Forty-four male Wistar rats were assigned to three groups: (1) control group (CG); (2) bile duct ligation with meloxicam treatment (BDL + M); and (3) bile duct ligation without meloxicam treatment (BDL). Secondary biliary liver cirrhosis was induced via ligature of the bile duct in the BDL + M and BDL groups. After 2 wk, the animals underwent a 50% hepatectomy. In the BDL + M group 15 min prior to the hepatectomy, one single dose of meloxicam was administered. Parameters measured included: microcirculation of the liver and small bowel; portal venous flow (PVF); gastrointestinal (GI) transit; alanine aminotransferase (ALT); malondialdehyde; interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-ß1) and hypoxia-inducible factor 1 alpha (HIF-1α) levels; mRNA expression of cyclooxigenase-2 (COX-2), IL-6 and TGF-ß1; liver and small bowel histology; immunohistochemical evaluation of hepatocyte and enterocyte proliferation with Ki-67 and COX-2 liver expression. RESULTS: Proliferative activity of hepatocytes after liver resection, liver flow and PVF were significantly higher in CG vs BDL + M and CG vs BDL group (P < 0.05), whereas one single dose of meloxicam ameliorated liver flow and proliferative activity of hepatocytes in BDL + M vs BDL group. COX-2 liver expression at 24 h observation time (OT), IL-6 concentration and mRNA IL-6 expression in the liver especially at 3 h OT, were significantly higher in BDL group when compared with the BDL + M and CG groups (P < 0.01, P < 0.001, P < 0.01, respectively). Liver and small bowel histology, according to a semi quantitative scoring system, showed better integrity in BDL + M and CG as compared to BDL group. ALT release and HIF-1α levels at 1 h OT were significantly higher in BDL + M compared to CG and BDL group (P < 0.001 and P < 0.01, respectively). Moreover, ALT release levels at 3 and 24 h OT were significantly higher in BDL group compared to CG, P < 0.01. GI transit, enterocyte proliferative activity and number of goblet cells were in favor of meloxicam treatment vs BDL group (P < 0.05, P < 0.001, P < 0.01, respectively). Additionally, villus length were higher in BDL + M as compared to BDL group. CONCLUSION: One single dose of meloxicam administered after cirrhotic liver resection was able to cause better function and integrity of the remaining liver and small bowel.

Recognition and management of abdominal compartment syndrome among German anesthetists and surgeons: a national survey.

BACKGROUND: Abdominal compartment syndrome (ACS) is a life threatening condition that may affect any critically ill patient. Little is known about the recognition and management of ACS in Germany. METHODS: A questionnaire was mailed to departments of surgery and anesthesia from German hospitals with more than 450 beds. RESULTS: Replies (113) were received from 222 eligible hospitals (51%). Most respondents (95%) indicated that ACS plays a role in their clinical practice. Intra-abdominal pressure (IAP) is not measured at all by 26%, while it is routinely done by 30%. IAP is mostly (94%) assessed via the intra-vesical route. Of the respondents, 41% only measure IAP in patients expected to develop ACS; 64% states that a simpler, more standardized application of IAP measurement would lead to increased use in daily clinical practice. CONCLUSIONS: German anesthesiologists and surgeons are familiar with ACS. However, approximately one fourth never measures IAP, and there is considerable uncertainty regarding which patients are at risk as well as how often IAP should be measured in them.

Influence of two different levels of intra-abdominal hypertension on bacterial translocation in a porcine model.

BACKGROUND: The purpose of the present study was to quantify bacterial translocation to mesenteric lymph nodes due to different levels of intra-abdominal hypertension (IAH; 15 vs. 30 mmHg) lasting for 24 h in a porcine model. METHODS: We examined 18 anesthetized and intubated pigs (52.3 ± 4.7 kg) which were randomly allocated to three experimental groups (each n = 6) and studied over a period of 24 h. After preparation and establishing a steady state, the intra-abdominal pressure (IAP) was increased stepwise to 30 mmHg in six animals using a carbon dioxide (CO2) insufflator (IAP-30 group). In the second group, IAP was increased to 15 mmHg (IAP-15 group), while IAP remained unchanged in another six pigs (control group). Using a pulse contour cardiac output (PiCCO®) monitoring system, hemodynamic parameters as well as blood gases were recorded periodically. Moreover, peripheral and portal vein blood samples were taken for microbiological examinations. Lymph nodes from the ileocecal junction were sampled during an intra-vital laparotomy at the end of the observational period. After sacrificing the animals, bowel tissue samples and corresponding mesenteric lymph nodes (MLN) were extracted for histopathological and microbiological analyses. RESULTS: Cardiac output decreased in all groups. In IAP-30 animals, volumetric preload indices significantly decreased, while those of IAP-15 pigs did not differ from those of controls. Under IAH, the mean arterial pressure (MAP) in the IAP-30 group declined, while MAP in the IAP-15 group was significantly elevated (controls unchanged). PO2 and PCO2 remained unchanged. The grade of ischemic damage of the intestines (histopathologically quantified using the Park score) increased significantly with different IAH levels. Accordingly, the amount of translocated bacteria in intestinal wall specimens as well as in MLN significantly increased with the level of IAH. Lymph node cultures confirmed the relation between bacterial translocation (BT) and IAP. The most often cultivated species were Escherichia coli, Staphylococcus, Clostridium, Pasteurella, and Streptococcus. Bacteremia was detected only occasionally in all three groups (not significantly different) showing gut-derived bacteria such as Proteus, Klebsiella, and E. coli spp. CONCLUSION: In this porcine model, a higher level of ischemic damage and more BT were observed in animals subjected to an IAP of 30 mmHg when compared to animals subjected to an IAP of 15 mmHg or controls.

Recognition and management of abdominal compartment syndrome among German pediatric intensivists: results of a national survey.

INTRODUCTION: Several decades ago, the beneficial effects of goal-directed therapy, which include decompressive laparotomy (DL) and open abdomen procedures in cases of intra-abdominal hypertension (IAH) in children, were proven in the context of closures of abdominal wall defects and large-for-size organ transplantations. Different neonatologic and pediatric disease patterns are also known to be capable of increasing intra-abdominal pressure (IAP). Nevertheless, a considerable knowledge transfer regarding such risk factors has hardly taken place. When left undetected and untreated, IAH threatens to evolve into abdominal compartment syndrome (ACS), which is accompanied by a mortality rate of up to 60% in children. Therefore, the present study looks at the recognition and knowledge of IAH/ACS among German pediatric intensivists. METHODS: In June 2010, a questionnaire was mailed to the heads of pediatric intensive care units of 205 German pediatric hospitals. RESULTS: The response rate was 62%. At least one case of IAH was reported by 36% of respondents; at least one case of ACS, by 25%. Compared with adolescents, younger critically ill children appeared to develop IAH/ACS more often. Routine measurements of IAP were said to be performed by 20% of respondents. Bladder pressure was used most frequently (96%) to assess IAP. Some respondents (17%) only measured IAP in cases of organ dysfunction and failure. In 2009, the year preceding this study, 21% of respondents claimed to have performed a DL. Surgical decompression was indicated if signs of organ dysfunction were present. This was also done in cases of at least grade III IAH (IAP > 15 mmHg) without organ impairment. CONCLUSIONS: Although awareness among pediatricians appears to have been increasing over the last decade, definitions and guidelines regarding the diagnosis and management of IAH/ACS are not applied uniformly. This variability could express an ever present lack of awareness and solid prospective data.