Use of autologous dermal flap as mesh coverage in the treatment of large abdominal-wall defect in patients following massive weight loss: presentation of a novel surgical technique.

PURPOSE: Reconstruction of large abdominal-wall defects (AWD) in patients after massive weight loss (MWL) can be challenging. Patients are left with a sizeable amount of excess skin and subcutaneous tissue which can serve as a natural and readily available source of mesh coverage. In this article, we present our experience in the reconstruction of large AWD in patients after MWL, using autogenous dermal flaps combined with a synthetic mesh. METHOD: All patients with large AWD and MWL, diagnosed between January 2012 and December 2016, were considered to be candidates for the procedure. During the operation, an attempt was made to attain full closure of the defect above the mesh. In those patients for whom such closure was not possible, a dermal flap technique was used. Patients were closely monitored for at least 1 year. Outcome measures included early and late postoperative complications. Data are presented as mean ± standard deviation (SD). RESULTS: Over the study period, a total of 14 patients underwent a surgery involving combined mesh and dermal flap technique. Early post-operative complications included three patients who suffered from minor wound disruption and were treated with local dressings. One patient had an abdominal-wall hematoma that required an evacuation. Two patients suffered from an epidermal cyst and chronic sinuses that required surgical debridement. None of the patients experienced intra-abdominal complication, respiratory failure, or required ICU treatment. No mesh contamination or hernia recurrence was observed during the follow-up period of 22.25 ± 6.4 months. CONCLUSION: Autologous dermal flap combined with mesh technique may serve as an effective surgical alternative in patients after MWL with large AWD for whom full muscular coverage of the underlying prosthesis is not possible.

Fenofibrate reduces intestinal damage and improves intestinal recovery following intestinal ischemia-reperfusion injury in a rat.

PURPOSE: Fenofibrate (FEN) is known as a nuclear receptor activator which regulates many pathophysiological processes, such as oxidative stress, inflammation, and leukocyte endothelium interactions. Recent studies have demonstrated an anti-oxidant, anti-inflammatory, and anti-ischemic role of FEN in the attenuation of ischemia-reperfusion (IR) injury in the kidney, liver, brain, and heart. The purpose of the present study was to examine the effect of FEN on intestinal recovery and enterocyte turnover after intestinal IR injury in rats. METHODS: Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy, (2) sham-FEN rats underwent laparotomy and were treated with intraperitoneal (IP) FEN (20 mg/kg); (3) IR rats underwent occlusion of both the superior mesenteric artery and the portal vein for 30 min followed by 24 h of reperfusion, and (4) IR-FEN rats underwent IR and were treated with IP FEN immediately before abdominal closure. Intestinal structural changes, Park's injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real-time PCR, Western blot, and immunohistochemistry. RESULTS: Treatment with FEN resulted in a significant decrease in Park's injury score in jejunum (32 %) and ileum (33 %) compared to IR animals. IR-FEN rats also demonstrated a significant increase in mucosal weight in jejunum (23 %) and ileum (22 %), mucosal DNA (38 %) and protein (65 %) in jejunum, villus height in jejunum (17 %) and ileum (21 %), and crypt depth in ileum (14 %) compared to IR animals. IR-FEN rats also experienced significant proliferation rates as well as lower apoptotic indices in jejunum and ileum which was accompanied with higher Bcl-2 levels compared to IR animals. CONCLUSIONS: Treatment with fenofibrate prevents intestinal mucosal damage and stimulates intestinal epithelial cell turnover following intestinal IR in a rat model.

Effect of taurine on intestinal recovery following intestinal ischemia-reperfusion injury in a rat.

PURPOSE: Taurine (TAU) is a sulfur-containing amino acid that is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation. Several studies have established that treatment with TAU significantly protects cerebral, cardiac and testicular injury from ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of TAU on intestinal recovery and enterocyte turnover after intestinal IR injury in rats. METHODS: Male Sprague-Dawley rats were divided into four experimental groups: (1) Sham rats that underwent laparotomy, (2) Sham-TAU rats that underwent laparotomy and were treated with intraperitoneal (IP) TAU (250 mg/kg); (3) IR-rats that underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 48 h of reperfusion, and (4) IR-TAU rats that underwent IR and were treated with IP TAU (250 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park's injury score, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. The expression of Bax, Bcl-2, p-ERK and caspase-3 in the intestinal mucosa was determined using Western blot and immunohistochemistry. RESULTS: Treatment with TAU resulted in a significant decrease in Park's injury score compared to IR animals. IR-TAU rats also demonstrated a significant increase in mucosal weight in jejunum and ileum, villus height in jejunum and ileum and crypt depth in ileum compared to IR animals. IR-TAU rats also experienced significantly lower apoptotic indices in jejunum and ileum which was accompanied by a higher Bcl-2/Bax ratio compared to IR animals. CONCLUSIONS: Treatment with taurine prevents gut mucosal damage and inhibits intestinal epithelial cell apoptosis following intestinal IR in a rat.

From a radial operating theatre to a self-contained operating table.

Equipment congestion and a disarray of wires, tubes and lines (the spaghetti syndrome) is a common scenario in operating theatres. The radial arrangement of input and output signals and their interconnecting lines has been identified as the main source of clutter and congestion in this environment. Our aim was to present a comprehensive design concept for reducing electrical and physical clutter in the operating theatre. Data were collected from different operating theatres, including identification and sorting of equipment, cables, tubes and lines according to the direction and the features of the transmitted information and materials. We suggest a concept of a self-contained, 'built-in' operating table as a design solution for avoiding the clutter and congestion caused by the radial configuration. The operating table will function as a central integrated unit for management of the entire process of patient flow and control of supply systems and environmental conditions.

Development of laser-induced retinal damage in the rabbit.

BACKGROUND: Laser lesions may induce retinal damage that is larger than expected from the size of the coagulated area. This study was designed to follow the development of laser-induced reduction in retinal function and to correlate it with structural changes. METHODS: Pigmented rabbits were treated in one eye with 225 argon laser lesions. The ERG responses were recorded at different times after treatment. The effect of the laser treatment upon the functional integrity of the retina was assessed from the ERG responses. Structural damage was examined by light microscopy. RESULTS: Shortly (1-2 h) after laser treatment, the ERG responses were reduced by about 50%. ERG deficit continued to develop and reached a maximal level about 24 h after treatment. Thereafter, slow recovery was observed but permanent deficit, relative to the initial laser effect, was seen even 30 days after treatment. Histological observations indicated extensive serous retinal detachment between laser lesions that developed within 24 h after treatment. At 30 days post-treatment, lesioned areas were completely destroyed and heavily pigmented. The retina between lesions was attached to the pigment epithelium but exhibited different degrees of structural damage. CONCLUSIONS: The immediate laser damage is confined to the coagulated areas while secondary functional damage develops within 24 h and probably reflects serous retinal detachment between lesions. The serous retinal detachment completely resolves with time but may induce permanent structural abnormalities in non-coagulated retinal areas that is reflected in a functional deficit larger than the initial laser effect.

L-arginine-NO pathway and CNS oxygen toxicity.

The involvement of the L-arginine-nitric oxide (NO) pathway in the pathogenesis of hyperoxia-induced seizures was studied by using agents controlling NO levels. We selected two inhibitors of nitric oxide synthase, the systemic inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) and the novel cerebral-specific inhibitor 7-nitroindazole, and two generators of NO, the NO donor S-nitroso-N-acetylpenicillamine and the physiological precursor L-arginine. Rats with chronic cortical electrodes were injected intraperitoneally with different doses of one of the agents or their vehicles before exposure to 0.5 MPa O2 and O2 with 5% CO2 at an absolute pressure of 0.5 MPa. The duration of the latent period until the onset of electrical discharges in the electroencephalogram was used as an index of central nervous system O2 toxicity. The two nitric oxide synthase inhibitors L-NAME and 7-nitroindazole significantly prolonged the latent period to the onset of seizures on exposure to both hyperbaric O2 and to the hypercapnic-hyperoxic mixture. Pretreatment with the NO donor S-nitroso-N-acetylpenicillamine significantly shortened the latent period, whereas L-arginine, the physiological precursor of NO, significantly prolonged the latent period to onset of seizures. Our results suggest that the L-arginine-NO pathway is involved in the pathophysiology of hyperoxia-induced seizures via various regulating mechanisms.

Starvation and dehydration attenuate CNS oxygen toxicity in rats.

We tested the effect of moderate food or water deprivation and a combination of the two on sensitivity to hyperoxia-induced seizures in rats. Seventy rats with chronic cortical electrodes were exposed to seven experimental protocols: starvation, dehydration or a combination of both for 24 or 36 h, prior to exposure to 0.5 Mp(a)O2. Blood glucose and hematocrit were measured before and after exposure to hyperbaric oxygen (HBO). Starvation and dehydration significantly prolonged the latent period to the onset of hyperoxia-induced seizures (P < 0.05 in the Tukey test), in a dose-related manner. Our results suggest that deprivation of food or water, prior to exposure to HBO, may postpone the development of hyperoxia-induced seizures.

Effects of oxygen on regional hemodynamics in hemorrhagic shock.

This study investigated mechanisms of the hemodynamic effects of oxygen in hemorrhagic shock induced by bleeding 30% of the total blood volume in anesthetized rats. An ultrasonic flowmeter was used to monitor regional blood flow. Changes in tissue perfusion were assessed by the laser-Doppler technique. The inhalation of 100% oxygen induced a significant increase in mean arterial blood pressure (MABP) and vascular resistance in the hindquarters, with a concomitant decrease in blood flow in the distal aorta and biceps femoris muscle. In contrast, oxygen did not change vascular resistance in the superior mesenteric artery (SMA) and renal beds and induced a significant increase in blood flow to the renal artery, SMA, and small bowel in hemorrhaged rats. L-Arginine (100 mg/kg iv) but not D-arginine or the vehicle (0.9% NaCl) completely abolished the effects of oxygen on blood pressure and reversed its effects on blood flow and resistance in the hindquarters and biceps femoris muscle. Administration of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (50 mg/kg iv) significantly increased MABP and the resistance in the three vascular beds. Pretreatment of hemorrhaged rats with a superoxide dismutase mimic, the NO-stable radical 2,2,6,6-tetramethylpiperidine-N-oxyl (5 mg/kg iv), resulted in significantly diminished effects of oxygen on hindquarter hemodynamics. These results demonstrate a differential effect of oxygen, which increases vascular resistance in the hindquarters without a significant effect in the splanchnic and renal beds, thus favoring an increase in splanchnic and renal perfusion. It is suggested that inactivation of NO by reactive oxygen species may underlie the effects of oxygen on hindquarter vascular tone during shock.

Exposure to hyperbaric oxygen induces tumour necrosis factor-alpha (TNF-alpha) secretion from rat macrophages.

We investigated the secretion of TNF-alpha by monocytes and macrophages derived from the peripheral blood, spleen, and lungs after a single exposure to a therapeutic profile of hyperbaric oxygen (HBO). Rats were exposed for 90 min to either 100% oxygen at 0.28 MPa (2.8 atmospheres absolute) or air. Immediately after exposure, mononuclear cells were isolated from blood, spleen, and lungs and cultured for 18 h. The secretion of TNF-alpha from the cultured monocytes/macrophages was determined with and without stimulation with lipopolysaccharide (LPS). Exposure to hyperbaric oxygen induced a significant increase in the spontaneous ex vivo secretion of TNF-alpha (without LPS) by mononuclear cells from the blood, spleen, and lung (P < 0.05 from air controls). Stimulation with LPS after exposure to HBO induced a significant increase in TNF-alpha secretion by lung and spleen macrophages compared with air controls (P < 0.05). However, absolute TNF-alpha levels were not significantly higher than those achieved 'spontaneously' in macrophages exposed to HBO without LPS. Stimulation with LPS induced a marked increase in secretion of TNF-alpha from blood monocytes after exposure to air, but not after exposure to HBO. These results provide evidence in support of a role played by TNF-alpha in mediating HBO effects on different tissues and their immune responses.

Caffeine attenuates CNS oxygen toxicity in rats.

We tested the effect of caffeine, on hyperoxia-induced seizures. Thirty-seven rats with chronic cortical electrodes were injected i.p. with caffeine (1.25, 2.5, and 10 mg/kg) or vehicle before exposure to 0.5 MPa oxygen and 17 rats to oxygen with 5% CO2 at 0.5 MPa. EEG monitoring and spectral analysis of EEG activity were carried out. Caffeine significantly prolonged the latent period to the onset of seizures (P < 0.05 in ANOVA), in a dose-related manner. Our results suggest that caffeine may be used in low doses for protection against hyperoxia-induced seizures.

The effect of flumazenil on CNS oxygen toxicity in the rat.

The toxicity of hyperbaric oxygen in the central nervous system is expressed by generalized tonic-clonic seizures. In the search for drugs effective against these seizures, we tested flumazenil, a benzodiazepine antagonist known to have antiepileptic properties. Forty rats with chronic cortical electrodes were injected i.p. with one of three doses of flumazenil (0.2, 2, and 20 mg/kg) or their vehicle, before exposure to 0.5 MPa oxygen. EEG and the spectral analysis of background EEG activity were monitored. The duration of the latent period until the appearance of electrical discharges in the EEG was used as an index of oxygen toxicity. Significant prolongation of the latent period preceding oxygen seizures was noted in the group of rats treated with 0.2 mg/kg flumazenil (p < 0.05 in Tukey test). However, when the dose of flumazenil was increased, the duration of the latent period returned to control values. These diverse effects of flumazenil on the benzodiazepine receptor may account for its complex effects on hyperoxic-induced seizures.

Salutary consequences of oxygen therapy on the long-term outcome of hemorrhagic shock in awake, unrestrained rats.

Decreased oxygen delivery and cellular hypoxia are major factors in the pathophysiology of shock. We studied the effects of 100% O2 at 0.1 and 0.3 MPa (1 and 3 atm abs) in severe hemorrhagic shock in awake, unrestrained rats. Shock was induced by withdrawing 50% of the total blood volume within 120 min. Blood pressure, heart rate, and the electroencephalogram (EEG) were recorded during the first 6 h of the protocol. The animals were observed for 7 days. The shock protocol resulted in 60 and 90% mortality after 1 day and at the end of 7 days, respectively. A single 90-min exposure to O2 at 0.1 and 0.3 MPa, which was started 30 min after bleeding, maintained mean arterial blood pressure at significantly higher values compared to untreated controls throughout the exposure period (P < 0.05). Oxygen therapy at both doses also improved the long-term survival rate and survival time significantly (P < 0.01). No clinical or EEG sign of CNS O2 toxicity was detected in O2-treated animals. Our results indicate that O2 given alone after severe bleeding exerts a beneficial effect on the long-term outcome of hemorrhagic shock in awake, unrestrained rats.

Effect of hyperbaric oxygen on tissue distribution of mononuclear cell subsets in the rat.

In a previous study we found a significant temporary decrease in the ratio of CD4/CD8 (helper, inducer/suppressor, cytotoxic) T lymphocytes in the peripheral blood of healthy human volunteers after exposure to a single commonly used profile of hyperbaric oxygen (HBO). The transient nature of the changes suggested redistribution of T-cell subsets. The purpose of the present study was to verify such a redistribution and to locate possible target organs in an animal model. A single exposure of rats to HBO (0.28 MPa) induced a highly significant rapid decrease in the CD4/CD8 ratio in peripheral blood count (P < 0.0001), confirming our previous findings in humans. HBO also induced a significant increase in the CD4/CD8 ratio in the lungs and lymph nodes (P < 0.001) and a significant decrease in the ratio in the spleen (P < 0.01). Furthermore, exposure to HBO induced a significant increase in T cells bearing surface interleukin-2 receptors in the blood, spleen, lungs, and lymph glands (P < 0.001) and a significant decrease in T cells expressing alpha beta-receptors in the lungs (P < 0.001) and lymph glands (P < 0.05). Our findings suggest rapid T-cell activation after a brief exposure to HBO, with shifts of CD4 and CD8 subsets and variations in T-cell receptor type. These rapid changes in the parameters of cell-mediated immunity may represent the activation of protective mechanisms against the toxic effect of oxygen or the early stages of pulmonary oxygen toxicity.

Beta-carotene and CNS oxygen toxicity in rats.

Beta-carotenes are reported to be potent free radical quenchers, singlet oxygen scavengers, and lipid antioxidants. Oxygen free radicals that are produced in excess during exposure to oxygen at high pressures and overwhelm the body's normal antioxidant defense systems seem to mediate the hyperoxic insult. We decided to test the possible protective effect against central nervous system oxygen toxicity of a natural beta-carotene composed of equal amounts of the all-trans and 9-cis isomers obtained from the unicellular halotolerant alga Dunaliella bardawil. Rats implanted with chronic cortical electrodes for continuous electroencephalogram monitoring were fed on ground commercial food enriched with natural beta-carotene (1 g/kg diet). On completion of 1 wk of the diet, the rats were exposed to 0.5 MPa oxygen and then their livers were removed for beta-carotene and vitamin A analysis. A significant increase was noted in the latent period preceding oxygen seizures in the group of rats in which the diet was supplemented by natural beta-carotene compared with rats given a normal diet (38.5 +/- 3.4 vs. 16.8 +/- 1.8 min; P < 0.05). Further experiments are required to evaluate the potential benefit of supplementing the diet of divers and patients exposed to high pressures of oxygen with the beta-carotene-rich D. bardawil.

Effect of a single exposure to hyperbaric oxygen on blood mononuclear cells in human subjects.

We studied the effect of a single exposure to a therapeutic profile of hyperbaric oxygen on blood mononuclear cell subset. Twenty healthy volunteers were exposed to 0.28 MPa for 90 min. Thirteen breathed pure oxygen and seven were control subjects exposed to compressed air at the same pressure. Venous blood samples were drawn before HBO exposure, immediately on exit from the chamber, and 24 h later. Immediately after the exposure, a significant increase was observed in the percentage and absolute number of CD8 (suppressor/cytotoxic) T cells, with a concomitant decrease in the CD4 (helper/inducer) T cells. These changes resulted in a decreased CD4:CD8 ratio. A rise was also observed in the number of HLA-DR antigen-bearing cells, with a transient increase in monocytes. There was no change in the total count and percentage of T cells (CD3), B cells, and NK cells. Twenty-four hours after HBO exposure there was a partial reversal of the decrease in the mean CD4:CD8 ratio, but it was still significantly lower than preexposure values. The fast reversibility of the change in the CD4:CD8 ratio suggests specific HBO-induced shifts and sequestration of T-cell subpopulations.

The effect of flunarizine on central nervous system oxygen toxicity in rats.

The toxicity of hyperbaric oxygen in the central nervous system is expressed by generalized tonic-clonic seizures. In the search for drugs effective against these seizures, we tested flunarizine, a calcium antagonist known to have antiepileptic properties and only minimal cardiovascular side effects. 49 rats with chronic cortical electrodes were injected i.p. with six different doses of flunarizine (10-300 mg/kg) or vehicle, before exposure to 0.5 MPa oxygen. Two doses of flunarizine and vehicle were given to rats exposed to oxygen with 5% CO2 at an absolute pressure of 0.5 MPa. EEG and spectral analysis of background EEG activity were monitored. The duration of the latent period before the appearance of electrical discharges in the EEG was used as an index of oxygen toxicity. There was no statistical difference between the duration of the latent periods for the seven groups treated by flunarizine or by vehicle on exposure to 0.5 MPa pure oxygen (P = 0.9 in ANOVA), but on exposure to oxygen with CO2, there was significant prolongation of the latent periods in comparison with vehicle (P < 0.001). Our results suggest that on exposure to hyperbaric oxygen, the antiepileptic effect of flunarizine might be masked, probably by its cerebral antivasoconstrictive effect.

The effect of vigabatrin on central nervous system oxygen toxicity in rats.

The toxicity of hyperbaric oxygen in the central nervous system is expressed by clinical and electroencephalographic (EEG) manifestations resembling those of generalized tonic-clonic seizures. In the search for drugs effective against these seizures, we tested vigabatrin, an irreversible inhibitor of GABA (gamma-aminobutyric acid) transaminase. Five different doses of vigabatrin (ranging from 50 to 500 mg/kg) or vehicle were injected i.p. in rats implanted with cortical electrodes, 4 h prior to exposure to 5 ATA (0.5 MPa) oxygen. EEG and spectral analysis of the background EEG activity were monitored for the different dosages of the drug. The duration of the latent period before the appearance of electrical discharges in the EEG was used as an index of oxygen toxicity. The protective effect of vigabatrin was dose-related, and complete protection against hyperoxic-induced discharges was at 180 mg/kg. The protective effect lasted 24 h and decreased gradually disappearing completely on the third day. An increase in the low frequency bands of the EEG and a decrease in the faster activity were correlated with the vigabatrin dosage injected. Our results suggest that vigabatrin has the potential of being a useful drug in the treatment and prevention of oxygen-induced seizures during hyperbaric oxygen therapy.

Hyperbaric oxygen and scopolamine.

Scopolamine (Hyoscine), an anticholinergic compound is widely used for the prophylaxis and treatment of motion sickness and might be used with oxygen diving and hyperbaric oxygen therapy. We therefore decided to test the interaction of scopolamine with oxygen at high pressure. Thirty-six rats implanted with cortical EEG electrodes were injected subcutaneously with two doses of scopolamine (0.02 or 0.2 mg.kg-1), or the vehicle (saline), 30 min before exposure to 5 atm abs (0.5 MPa) oxygen. Electroencephalogram and heart rate were monitored continuously. Spectral analysis of the EEG was carried out, and the duration of the latent period before convulsions was determined. No significant difference was found in the duration of the latent period between the control rats receiving vehicle (saline) and rats injected with scopolamine (n = 12 for each group). Changes in background EEG activity and maximal dilation of the pupil were detected at both scopolamine doses. Heart rate significantly decreased at 0.02 mg.kg-1 and increased at the dose of 0.2 mg.kg-1 scopolamine. Our findings indicate that the duration of the latent period preceding hyperoxic seizures is not altered by scopolamine in rats; however, other side effects of the drug regarding visual and cardiovascular symptoms should be considered when scopolamine is used in combination with hyperbaric oxygen.

The effect of carbamazepine and ethosuximide on hyperoxic seizures.

The main manifestations of CNS oxygen toxicity are generalized tonic-clonic seizures. We tested the protective effect of 2 antiepileptic drugs, carbamazepine and ethosuximide, which are commonly used for the treatment of generalized seizures, on hyperbaric oxygen-induced convulsions. Rats implanted with chronic cortical electrodes for continuous EEG monitoring were injected i.p. with either carbamazepine (5 doses in the range of 1.5-50 mg/kg), ethosuximide (400 mg/kg), or their vehicles (40% propylene glycol and saline, respectively). The rats were exposed to 5 ATA (0.5 MPa) oxygen. The duration of the latency until the appearance of electrical discharges in the EEG was used as an index of toxicity. Ethosuximide did not protect against hyperoxic seizures. In contrast, rats pretreated (30 min) with carbamazepine exhibited a dose-related protective effect against hyperoxically induced seizures. The results of our study suggest that carbamazepine should be considered for prevention of oxygen-induced seizures during hyperbaric oxygen therapy.