Animal Models for Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS): Achievements and Future Perspectives.

BACKGROUND: Since 2012, Associated Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been standing in the limelight of modern liver surgery and numerous questions have been raised regarding this novel approach. On the one hand, ALPPS has proved to be a valuable method in the treatment of hepatic tumors, while on the other hand, there are many controversies, such as high mortality and morbidity rates. Further surgical research is essential for a better understanding of underlying mechanisms and for enhancing patient safety. SUMMARY: Until recently, only 8 animal models have been created with the purpose to mimic ALPPS-induced liver regeneration. From these 7 are rodent (6 rat and 1 mouse) models, while only 1 is a large animal model, which uses pigs. In case of rodent models, portal flow deprivation of 75-90% is achieved via portal vein ligation leaving only the right (20-25%) or left median (10-15%) lobes portally perfused, while liver splitting in general is carried out positioned according to the falciform ligament. As for the swine model, the left lateral and medial lobes (70-75% of total liver volume) are portally ligated, and the right lateral lobe (accounting for 20-24% of the parenchyma) is partially resected in order to reach critical liver volume. Each model is capable of reproducing the accelerated liver regeneration seen in human cases. However, all species have significantly different liver anatomy compared with the human anatomic situation, making clinical translation somewhat difficult. Key Messages: Unfortunately, there are no perfect animal models available for ALPPS research. Small animal models are inexpensive and well suited for basic research, but may only provide limited translational potential to humans. Clinically large animal models may provide more relevant data, but currently no suitable one exists.

[Laparoscopic resection of giant hepatocellular carcinoma and the Barcelona staging]. / Nagyméretû hepatocelluláris karcinóma laparoszkópos reszekciója és a barcelonai kritériumok.

Liver resection is the most effective treatment for hepatocellular carcinoma, however, decision for surgery remained confusing. In Europe the most accepted Barcelona staging system sets minimal value on surgical interventions. Long lasting diagnostic steps and uncertainty for indication of resection are possible consequences of this approach. The reported case is an example for the fact that exceptionally large tumor having been grown during time-consuming diagnostic attempts might be removed by laparoscopic surgery. The case hopefully could lead to widespread acceptance of up-to-date surgical treatment of hepatocellular carcinoma.

[The importance of postoperative circulatory alterations in hepatic surgery]. / A posztoperatív keringésváltozások jelentosége a májsebészetben.

There are two afferent (hepatic artery, portal vein) and one efferent (hepatic veins) systems responsible for the unique circulation of the liver. Given this special form of vasculature, acute, isolated (i.e. involving selectively one particular vessel) vascular occlusions may lead to different, however still life threatening conditions. Hence, it is essential to recognize these anomalies in order to preserve the healthy state of both the liver and the patient's lives. Acute circulatory failures are dominantly associated with liver surgery. Adequate therapy can only be provided promptly, if the clinician is well aware of the peculiarities of these conditions. The aim of this study is to overview the etiology and symptoms of these clinical conditions; furthermore to offer technical proposals for the required diagnostic and therapeutical steps via case reports. Furthermore, hepatic injury, caused by ischemia-reperfusion secondary to total vascular occlusion (Pringle maneuver) used in hepatic surgery is outlined.

Postconditioning of the small intestine: which is the most effective algorithm in a rat model?

BACKGROUND: Mesenteric ischemia is a serious clinical condition requiring immediate surgical intervention. The unavoidable ischemic-reperfusion (IR) injury may be ameliorated using the appropriate postconditioning protocol. The aim of the present study was to investigate the optimal postconditioning algorithm in a rat model of intestinal ischemic-reperfusion injury. MATERIALS AND METHODS: Male Wistar rats were randomized into five groups (n = 10), one sham-operated, one IR, and three postconditioned groups, each with different protocols. The animals were subjected to 60 min of mesenteric ischemia, followed by 60 min of reperfusion. Postconditioning was applied at the onset of reperfusion using three different algorithms. Arterial pressure and mucosal microcirculation were monitored throughout the experiment. Mesenteric pH was determined at the early phase of reperfusion. Blood and tissue samples were taken at the end of reperfusion for histologic evaluation, serum lactate dehydrogenase, serum creatine kinase, serum tumor necrosis factor-α, serum interleukin-6, detailed mucosal antioxidant, and scavenger capacity assays. RESULTS: The shorter and intermediate length cycles of postconditioning enhanced mucosal microcirculation and redox state and significantly delayed the normalization of mesenteric pH. Furthermore, milder histopathologic lesions and lower concentrations of serum necroenzymes and proinflammatory cytokines were detected compared with the IR group. The protective effect of postconditioning using longer cycles could only be seen in a tendentious manner. CONCLUSIONS: In a rat model of intestinal ischemia-reperfusion, the shorter and intermediate length cycles of postconditioning proved to be more effective than the use of longer cycles.

[Bacterial translocation: gap in the shield]. / Bakteriális transzlokáció: rés a pajzson.

The gastrointestinal tract is not only regarded as a system where nutrient absorption takes place, but also as a vital barrier against intraluminal pathogens entering the circulation and the maintenance of immune homeostasis. Bacterial translocation is defined as the penetration of viable bacteria or bacterial compounds from the gastrointestinal tract to extraintestinal sites. This disorder has been described in several clinical conditions. The main promoting factors for bacterial translocation have been proposed to be changes in the intestinal microflora, mucosal barrier failure and defects in host immunity. The presence of bacterial translocation has been associated with higher complications and mortality rates; therefore it should be taken into account in the therapeutic strategies of patients with predisposing factors.

Remote ischemic perconditioning protects the liver from ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion (IR)-induced injury is a frequent sequel of major liver resections. IR injury after prolonged surgical interventions could be the source of increased risk of postoperative morbidity and mortality. Hepatoprotective effects of this new feasible method called remote ischemic perconditioning (RIPER) were investigated in our rat model of IR injury. MATERIALS AND METHODS: Male Wistar rats underwent ischemia for 60 min on two-thirds of their livers, followed by 1, 6, and 24 h of reperfusion (n = 72, 8 per group). During liver ischemia, but before reperfusion, rats in the treated groups received four cycles of brief infrarenal aortic clamping as perconditioning. Liver microcirculation was monitored by laser Doppler flowmeter parallel with mean arterial pressure measurements. Liver tissue injury and redox homeostasis were investigated. Furthermore, serum tumor necrosis factor alpha (TNF-α) levels were measured. RESULTS: In the RIPER group, compared with the IR group, serum transaminase levels were significantly lower after each reperfusion period (alanine aminotransferase: 1 h, P < 0.001; 6 h, P < 0.05; 24 h, P < 0.01 and aspartate aminotransferase: 1 h, P < 0.001; 6 h, P < 0.05; 24 h, P < 0.05). Reperfusion microcirculatory parameters significantly improved in the perconditioned group compared with those in the IR group (reperfusion area: P = 0.005; maximal plateau: P = 0.0002). Regarding TNF-α levels, significant differences were detected between the two IR injured groups (RIPER versus IR: 1 h, 34.3 ± 12.8 pg/mL versus 205.7 ± 60.9 pg/mL, P < 0.001; 6 h, 60.6 ± 11.7 pg/mL versus 110.4 ± 21.6 pg/mL, P < 0.05). Results of the histologic assessment and redox state measurements also showed favorable changes. CONCLUSIONS: Our team firstly reported the protective effects of RIPER on liver morphology, redox homeostasis, and microcirculation and proposed the changes of TNF-α expression.

Therapeutic option for managing lung injury induced by infrarenal aortic cross-clamping.

BACKGROUND: Operations on the infrarenal aorta can cause ischemic-reperfusion (IR) injury in local tissues, which could result in remote organ (e.g., lung) damage. Treatment of such injuries remains an unresolved problem. OBJECTIVES: Our aim was to reduce remote lung damage after lower limb IR by means of postconditioning. MATERIALS AND METHODS: Male Wistar rats were divided into three groups: Sham-operated, IR, and Postconditioned (PostC). In the latter two groups rats underwent 180 min of exclusion of the infrarenal aorta. The reperfusion time was 4 h. Serum-free radical levels, tumor necrosis factor-α and interleukin-6 concentrations, histologic changes in the lung, wet/dry-ratio, myeloperoxidase activity, heat shock protein 72 level and blood gas changes were investigated. RESULTS: Postconditioning reduced histological damage in the lung (P < 0.05). Free radical levels and tumor necrosis factor-α concentrations were significantly lower in the PostC group than in the IR group (P < 0.05 and P < 0.01, respectively). Interleukin-6 concentrations did not significantly differ in the PostC group. Compared with the IR group, lung myeloperoxidase activity was lower in the PostC group. Decreased pulmonary heat shock protein 72 level was observed in the PostC group compared with the IR group and the wet/dry-ratio was also significantly lower in the PostC group (P < 0.05). A noticeably higher arterial pO2 level was manifest in the PostC group after 2 and 4 h of reperfusion (P < 0.05). CONCLUSIONS: Postconditioning reduced lung damage under experimental conditions, in the early period of reperfusion after lower limb IR injury.

[Postconditioning can reduce long-term lung injury after lower limb ischemia-reperfusion]. / Alsó végtagi ischaemiás-reperfusiós károsodás hosszú távú tüdoszövodményeinek megelozése posztkondicionálással.

INTRODUCTION: Operation on the infrarenal aorta could cause ischemic-reperfusion (IR) injury in local tissues and remote organs (e.g. the lung). OBJECTIVES: Our aim was to reduce long-term lung damage, after lower limb IR with postconditioning. MATERIALS AND METHODS: Male Wistar rats underwent 180 minutes of bilateral lower limb ischemia. Animals were divided into three groups: Sham-operated, IR, Postconditioned (PostC) and further to two subgroups according to reperfusion time: 24 h and 72 h. Serum free radical and IL-6 levels, histological changes, Wet/Dry (W/D) ratio, tissue myeloperoxidase (MPO) activity and Hsp72 levels were investigated. RESULTS: Postconditioning can reduce histological changes in the lung. Free radical levels are significantly lower in PostC groups than in IR groups (42.9 ± 8.0 vs. 6.4 ± 3.4; 27.3 ± 4.4 vs. 8.3 ± 4.0 RLU%; p < 0.05). IL-6 level (238.4 ± 31.1 vs. 209.1 ± 18.8; 190.0 ± 8.8 vs. 187.0 ± 14.9 pg/ml) and Hsp72 expression did not show any significant difference. Compared to the IR group, lung MPO activity did not change in the PostC groups. W/D ratio in PostC groups is significantly lower at all measured time-points (68% vs. 65%; 72% vs. 68%; p < 0.05). CONCLUSION: Postconditioning may reduce long-term damages of the lung after lower limb ischemic-reperfusion injury.

A clinical trial of efficacy and safety of inhalation sedation with a 50% nitrous oxide/oxygen premix (Kalinox™) in general practice.

The current study aimed to verify if the safety and effectiveness of inhalation sedation with 50% nitrous oxide in oxygen (N(2)O/O(2)) is maintained when the premix is administrated by trained general practitioners in their dental surgeries compared to its use in the hospital. Success (completion of planned treatment), cooperation (modified Venham scale), and adverse events were recorded. The acceptability of the technique to the patients, the level of patient cooperation, the ease of use, and the satisfaction of the dentist were also evaluated. Thirty-three general practitioners included 549 patients and recorded 638 sessions of N(2)O/O(2) sedation for dental treatment. Of the sessions, 93.7% were successful in terms of both sedation and treatment. Patient cooperation was seen to improve under N(2)O/O(2) sedation, and for 91% of the sessions, the patients declared that they would like future treatment to be undertaken in the same way. No serious adverse events were recorded. Minor adverse events were noted for 10% of the sessions (behavioural, vagal, and digestive disorders). These results were similar to those found for sessions undertaken in hospital practice. The main difference was in the type of patient treated-more patients received N(2)O/O(2) sedation in general practice for a one-off indication or for dental phobia, and more patients with intellectual disability and more pre-cooperative children were treated in hospital practice. This study gives strong supporting evidence for the safety and effectiveness of inhalation sedation using 50% N(2)O/O(2) in general dental practice for healthy patients.

[Postconditioning -- effective method against distant organ dysfunction?]. / Posztkondicionálás - A távoli szervi dysfunctiók ellenszere?

INTRODUCTION: The ischemia-reperfusion injury of the small intestine is a condition of high mortality, which occurs following superior mesenteric artery (SMA) embolization or circulatory redistribution. The aim of the study was to evaluate the local and systemic effects of postconditioning in a rat model of small intestine ischemia-reperfusion. METHODS: Male Wistar rats underwent 60 min ischemia by the clamping of the SMA, followed by 6 hrs of reperfusion. The animals (n = 30) were randomized into three groups: sham-operated, control-, and postconditioned. Postconditioning was performed at the very onset of reperfusion by 6 alternating cycles of 10-10 seconds reperfusion/reocclusion, for a total of 2 min. At the end of the reperfusion blood and tissue (small intestine, lungs, kidney, liver) samples were taken for histological examination. The antioxidant status of small intestine was measured from intestinal homogenates. RESULTS: Histologic results revealed increased damage in control-group lungs, kidney, liver and small intestine in comparison with the postconditioned group. The injury was supported by significantly higher wet/dry weight ratio (p = 0.026), and serum levels of creatinine (p = 0.013), ASAT (p = 0.038), LDH (p = 0.028) and CK (p = 0.038) in the control group. The postconditioned group showed lower serum IL-6 levels (420 pg/ml vs. 188 pg/ml), as well as significantly higher mucosal antioxidant concentration. CONCLUSIONS: Postconditioning was able to decrease not only local, but the systemic damage intensity also, after a small intestinal ischemic-reperfusion episode.

The application of pudendal nerve blockade in the treatment of pudendal neuralgia related chronic pelvic pain / Nervus pudendus idegblokád alkalmazása krónikus kismedencei fájdalmat okozó pudendusneuralgia kezelésében

Pudendal neuralgia is a rare and ­ in the absence of somatic, radiological and laboratory abnormalities ­ often unrec-ognizable problem, posing a serious challenge to therapeutic management. Our case study presents the complete diagnostic and therapeutic algorithm of a female patient with chronic pudendal pain. In addition, our paper draws attention to the role of pelvic pain workgroups ­ such as the Pelvic Pain Task Force of the Semmelweis University ­ where cases of chronic pelvic pain with no clear medical reason can be assessed and treated with higher efficiency.

Postconditioning of the lower limb--protection against the reperfusion syndrome.

BACKGROUND: Postconditioning-alternating brief cycles of reperfusion/reocclusion applied at the beginning of revascularization-is a potent therapeutic technique, attenuating ischemia-reperfusion injury. Vascular surgery on the lower limb with ischemia-reperfusion injury may give rise to serious systemic complications [organ dysfunction syndrome (MODS), systemic inflammatory response syndrome (SIRS)], a phenomenon called reperfusion-syndrome. MATERIAL AND METHODS: We studied the effects of postconditioning on reperfusion-syndrome in a rodent experimental model. Wistar rats underwent 180 min of bilateral lower limb ischemia using an infrarenal crossclamping of the abdominal aorta. Postconditioning consisted of six cycles of 10-s aortic occlusion/10-s declamping at the beginning of reperfusion. Microcirculation of the lower limb was detected with laser Doppler flowmeter. After 4 h of reperfusion, plasma, urine, and histologic samples were collected. RESULTS: One hundred eighty-minute ischemia resulted in significant hemodynamic changes after reperfusion. Postconditioning affected the character of the microcirculatory flow, the limb circulation stabilized with hyperemia during reperfusion. Postconditioning caused a significant reduction in systemic inflammatory response (TNF-α, oxygen-derived free radicals). The laboratory and histologic samples implied a significant decrease in distant organ (lung and renal) dysfunctions after postconditioning. CONCLUSION: Postconditioning proves to be capable of conferring protection against different organ injuries caused by longer circulatory occlusions during elective major vascular operations.

Reduction of liver ischemia-reperfusion injury via glutamine pretreatment.

BACKGROUND: Surgical methods that reduce bleeding during major hepatic resections lead to warm ischemia-reperfusion (I-R) injury of the liver. This is well known to have a considerable impact on the postoperative outcome. Much research work has been done to develop possible protective techniques. We aimed to investigate the effectivity of L-alanyl-L-glutamine dipeptide pretreatment in an animal model of hepatic I-R injury. MATERIALS AND METHODS: Male Wistar rats underwent normothermic, 60 min segmental liver ischemia followed by 24 h of reperfusion. The animals (n=30) were divided into three experimental groups: sham operated, I-R, and glutamine (Gln) pretreated. Twenty-four h prior to I-R injury, rats in the Gln group received 500 mg/kg Dipeptiven infusion as glutamine pretreatment. Hepatic microcirculation during the first hour of reperfusion was monitored by noninvasive laser Doppler flowmeter. After a 24-h reperfusion period, liver tissue was analyzed by histologic and immunohistochemical assessments. Serum necroenzyme and antioxidant levels were measured. RESULTS: In the Gln group, the integral of the reperfusion curve (RA) and the plateau maximum (PM(10)) of the flow graph showed improving tendency (RA: P=0.096; PM(10): P=0.084). Severity of histologic damage was reduced. Serum necroenzymes (ALT: P=0.042, AST: P=0.044) were significantly lower. Chemiluminescent intensity of liver and plasma was significantly decreased (P=0.0003 and P=0.0496). Further spectrophotometric analysis of liver homogenate samples also showed significant improvement of the redox homeostasis. CONCLUSIONS: Our results suggest that L-alanyl-L-glutamine dipeptide pretreatment given 24 h prior to I-R injury could be an effective method to reduce liver damage caused by hepatic inflow occlusion.

[Investigation of postconditioning in intestinal ischemia-reperfusion experimental models]. / Posztkondicionálás kísérletes vizsgálata vékonybél ischaemiás-reperfusiós modelljében.

INTRODUCTION: The ischemic-reperfusion injury of the intestine, which occurs as a consequence of circulatory redistribution or occlusion of the superior mesenteric artery, is associated with high mortality rates. Postconditioning may reduce ischemic-reperfusion damage in such cases. Effects of this new surgical method were investigated in rats. METHODS: Male Wistar rats underwent 60 minutes of superior mesenteric artery occlusion in four groups: sham-operated, control and two postconditioned groups with different algorithms. Postconditioning was performed immediately at the beginning of reperfusion, by repetitive cycles of reperfusion and reocclusion. 3 cycles of 1 minute and 6 cycles of 10 seconds were applied according to groups. Intestinal microcirculation was followed by laser Doppler flowmetry. Blood and tissue samples were taken after 60 minutes of reperfusion. Histological analayses of the small intestine, measurement of serum necroenzyme levels and IL-6, mesenterial venous blood gas analyses were preformed and antioxidant state of the mucosa was investigated. RESULTS: The microcirculation during the reperfusion showed significant improvement in both postconditioned groups. Histological damage, necroenzyme and IL-6 levels were significantly reduced, while antioxidant state was improved in the postconditioned groups. CONCLUSION: Postconditioning was capable of increasing the guts chance to survive ischemic-reperfusion injury caused by superior mesenteric artery occlusion.

[Effect of postconditioning in major vascular operations on rats]. / Posztkondicionálás kísérletes alkalmazása aortakirekesztés kapcsán.

BACKGROUND: Postconditioning - using alternating brief cycles of reperfusion/reocclusion applied just at the very beginning of reperfusion - has recently been described as a potent therapeutic technique, attenuating ischaemia-reperfusion injury. In vascular surgery, certain elective interventions involve cross-clamping of major arteries, resulting in temporary ischaemia in large peripheral organs, which thus suffer ischaemia-reperfusion injury. Patients undergoing these operations may develop also serious systemic complications such as multiple distant organ dysfunctions, SIRS, detrimental redistribution of the circulation or even shock, a phenomenon called reperfusion-syndrome. We studied the effects of postconditioning on reperfusion-syndrome in a rodent experimental model. MATERIAL AND METHODS: Anaesthetized male Wistar rats underwent 180 minutes of bilateral lower limb ischaemia and 4 hours of reperfusion using an infrarenal cross-clamping of the abdominal aorta. Control animals underwent no additional intervention. Postconditioning consisted of 6 cycles of 10-second aortic occlusion/10-second declamping starting at the beginning of reperfusion. Haemodynamic parameters were observed with invasive arterial manometer, microcirculation of the lower limb was detected with laser-Doppler-flowmeter. After 4 hours of reperfusion serum, urine, and histological samples were collected. RESULTS: 180-minute ischaemia resulted in significant haemodynamic changes after reperfusion. Postconditioning affected the character of the microcirculatory flow curves, the limb circulation stabilized with hyperaemia after reperfusion. Postconditioning caused a significant reduction in systemic inflammatory response (TNF-alpha, oxygen-derived free radicals). The laboratory and histological samples implied a significant decrease in remote organ (lung and renal) dysfunctions after postconditioning. CONCLUSION: Postconditioning proves to be capable in conferring protection against different organ injuries caused by longer circulatory occlusions during elective major vascular surgeries.

Evaluation of safe and effective administration of nitrous oxide after a postgraduate training course.

BACKGROUND: Conscious sedation is used in dentistry to improve access and quality of care in patients who have difficulty coping with treatment. The aim of this prospective study was to describe a postgraduate training course in conscious sedation for dentists, with specific evaluation of the safe and effective administration of a 50% nitrous oxide in oxygen premix. METHODS: 45 practitioners were trained between 2002 and 2004. They carried out 826 sessions of inhalation sedation in 662 patients. The clinical competency of this group was compared with an expert group. RESULTS: There was no difference between trainees and experts in ability to complete the planned dental treatment under sedation (89.6% vs 93.2%). Trainees were less successful than experts for patients with intellectual disability (87.4% vs 94.2%, p < 0.01). For both groups, the degree of cooperation improved between initial induction and each perioperative step (Wilcoxon test, p < 0.01). However, for trainees, Venham behaviour scores varied with the type of patient (Kruskal Wallis test, p < 0.001). No major adverse effects were recorded. Trainees reported more minor adverse effects than experts (13% vs. 5.3% respectively, Fisher exact test, p < 0.001) CONCLUSION: The trainee practitioners provided effective and safe inhalation sedation. This challenges the current French restriction of the 50% nitrous oxide in oxygen premix to the hospital setting. Further emphasis is required on the teaching of behaviour management skills for patients with intellectual disability.

Tolerability of an equimolar mix of nitrous oxide and oxygen during painful procedures in very elderly patients.

BACKGROUND AND OBJECTIVE: Although an equimolar mix of nitrous oxide-oxygen (N(2)O/O(2)) [Kalinox] is widely used as an analgesic, there have been few specific studies of this product in the elderly. In this article, we investigate the tolerability of this equimolar mix in very elderly patients undergoing painful procedures. METHODS: This was a prospective, observational study of patients hospitalised in the geriatric short-stay unit of a teaching hospital between July 2001 and September 2003. All patients aged >/=80 years who were scheduled for invasive care procedures were eligible for inclusion. Sixty-two patients were recruited and underwent a total of 68 procedures. The procedures were divided into four classes based on the degree of pain they were expected to cause and their duration. Patients received the equimolar N(2)O/O(2) mix (Kalinox) for 5 minutes before the beginning of the procedure and throughout its duration. The inhaled treatment was administered via a high-concentration mask. Assessments were carried out during the inhalation and over the 15 minute period following inhalation. The primary endpoint of the study was tolerability of the equimolar N(2)O/O(2) mix, and all adverse events were recorded. Secondary endpoints were the efficacy of the product (assessed on a verbal rating scale and/or the Doloplus scale), its ease of use and its acceptability to patients and staff. RESULTS: Fourteen patients (22.6%) each reported at least one adverse event: impaired hearing (n = 1), altered perception of the environment (n = 8), anxiety (n = 1), headache (n = 3) and drowsiness at the end of the procedure (n = 2). All these disorders subsided rapidly after treatment was completed. CONCLUSION: This study shows the favourable tolerability of the equimolar N(2)O/O(2) mix in very elderly subjects, which makes this product a valuable tool for the management of acute pain in this age group.

Postconditioning: "Toll-erating" mesenteric ischemia-reperfusion injury?

BACKGROUND: Postconditioning may prove to be a suitable method to decrease ischemia-reperfusion injury of intestine after mesenteric arterial occlusion. Toll-like-receptor-4 is involved in the pathophysiology of organ damage after ischemia-reperfusion; therefore, the aim of our study was to investigate the effect of postconditioning on the mucosal expression of toll-like-receptor-4. METHODS: Male Wistar rats (n = 10/group) underwent 60 minutes of superior mesenteric artery occlusion followed by 6 hours of reperfusion in 3 groups: sham-operated, ischemia-reperfusion, and a postconditioned group. Postconditioning was performed by 6 alternating cycles of 10 seconds of reperfusion/reocclusion. Blood and tissue samples were collected at the end of reperfusion. Intestinal histopathologic changes and immunohistochemical expression of mucosal caspase-3, antioxidant status, and protein levels of high-mobility group box-1 and toll-like-receptor-4 were assessed. Immunofluorescent labeling and confocal microscopic analysis of toll-like-receptor-4 were performed. Mucosal and serum levels of interleukin-6 and tumor necrosis factor-α protein were measured. RESULTS: Histologic alterations in the postconditioned group were associated with decreased caspase-3 positivity, less toll-like-receptor-4 mRNA, and less protein expression of high-mobility group box-1 and toll-like-receptor-4 in the intestinal villi compared with the ischemia-reperfusion group. Furthermore, a significantly improved antioxidant state of the intestinal mucosa and less mucosal and serum protein levels of interleukin-6 and tumor necrosis factor-α were detected in the postconditioned group. CONCLUSION: Small intestinal ischemia-reperfusion injury in male Wistar rats caused by the occlusion of the superior mesenteric artery was ameliorated by the use of postconditioning, showing a more favorable inflammatory response, which may be attributed to the decreased mucosal expression of toll-like-receptor-4.

Safety of inhalation of a 50% nitrous oxide/oxygen premix: a prospective survey of 35 828 administrations.

BACKGROUND: A 50% nitrous oxide/oxygen (N(2)O/O(2)) premix is widely used to alleviate pain or anxiety during brief care procedures in various medical domains. In some countries, recent changes in regulation status for medical gases state that they should be considered as drugs. Consequently, more valuable data gained from exhaustive clinical surveys are needed. This prospective study, conducted in the same conditions imposed for testing a drug, aims to analyse the factors that affect tolerance of the 50% N(2)O/O(2) premix in a wide range of clinical indications. METHODS: In a 4-year prospective survey, 35 942 data sheets were received from 191 French hospital paediatric (82%) and adult units (18%). Of these, 35 828 sheets were sufficiently complete to be included in the study. The number and the type of adverse events declared to the manufacturer were analysed. RESULTS: A total of 1581 (4.4%) adverse events were reported on 1384 data sheets, which were mostly gastrointestinal and neuropsychiatric disorders (86%). The main factors associated with adverse events were age, concomitant drug administration and longer duration of inhalation. Among the 27 (0.08%) reported serious adverse events, only 9 (0.03%) were possibly attributed to the N(2)O/O(2) premix. Among the serious adverse events that were not attributed to the gas, a concomitant drug association and insufficient patient surveillance occurred in 12 and 2 cases, respectively. CONCLUSION: This survey confirms the pharmacological safety of the 50% N(2)O/O(2) premix in a wide variety of clinical indications and emphasises the need for rational training of medical personnel in its administration.

Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection.

AIMS AND OBJECTIVES: Acute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia-reperfusion injury and the corollary renal dysfunction. METHODS: Male Wistar rats underwent 180 min bilateral lower limb ischemia followed by 4 or 24 hours of reperfusion. Intravenous Levosimendan was administered continuously (0.2µg/bwkg/min) throughout the whole course of ischemia and the first 3h of reperfusion. Results were compared with sham-operated and ischemia-reperfusion groups. Hemodynamic monitoring was performed by invasive arterial blood pressure measurement. Kidney and lower limb muscle microcirculation was registered by a laser Doppler flowmeter. After 4h and 24h of reperfusion, serum, urine and histological samples were collected. RESULTS: Systemic hemodynamic parameters and microcirculation of kidney and the lower limb significantly improved in the Levosimendan treated group. Muscle viability was significantly preserved 4 and 24 hours after reperfusion. At the same time, renal functional laboratory tests and kidney histology demonstrated significantly less expressive kidney injury in Levosimendan groups. TNF-α levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion. CONCLUSION: The results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications.