Effect of fish oil supplementation in a rat model of multiple mild traumatic brain injuries.

PURPOSE: Repetitive mild traumatic brain injury (TBI) is a major military and sports health concern. The purpose of this study was to determine if a diet rich in omega-3 fatty acids would reduce cognitive deficits and neuronal cell death in a novel fluid percussion rat model of repetitive mild TBIs. METHODS: Thirty-two Sprague-Dawley rats were assigned to either an experimental rat chow enhanced with 6% fish oil (source of omega-3 fatty acids) or a control rat chow. Both rat chows contained equivalent quantities of calories, oil, and nutrients. After four weeks, both groups received mild repetitive bilateral fluid percussion TBIs on two sequential days. Pre-injury diets were resumed, and the animals were monitored for two weeks. On post-injury days 10-14, Morris Water Maze testing was performed to assess spatial learning and cognitive function. Animals were euthanized at 14 days post-injury to obtain specimens for neurohistopathology. RESULTS: There was no difference in pre-injury weight gain between groups. Post-injury, animals on the fish oil diet lost less weight and recovered their weight significantly faster. By 14 days, the fish oil diet group performed significantly better in the Morris Water Maze. Neurohistopathology identified a non-significant trend toward a higher density of hippocampal neurons in the fish oil diet group. CONCLUSIONS: Pre-injury dietary supplementation with fish oil improves recovery of body weight and provides a small improvement in cognitive performance in a rat model of multiple mild TBIs.

A pilot study of the use of kaolin-impregnated gauze (Combat Gauze) for packing high-grade hepatic injuries in a hypothermic coagulopathic swine model.

BACKGROUND: Severe hepatic injuries may be highly lethal, and perihepatic packing remains the mainstay of treatment. This is not always successful, particularly in the setting of hypothermia and coagulopathy. Kaolin-impregnated Combat Gauze (CG) is an effective hemostatic dressing used primarily to treat external wounds. The objective of this study was to determine the ability of CG to control severe hemorrhage in hypothermic, coagulopathic swine with a high-grade hepatic injury. METHODS: Anesthetized animals underwent splenectomy and were cooled to 32°C while undergoing a 60% exchange transfusion with Hextend. A grade V liver injury was created in the left middle hepatic lobe. Animals were allowed to freely bleed for 30 s and then randomized to treatment with CG or plain gauze laparotomy pads (PG) applied to the injury site. Animals were then resuscitated with warmed Hextend. RESULTS: There was no difference between groups in preinjury hemodynamic or laboratory values. Animals packed with CG had less blood loss when compared with standard packing (CG = 25 mL/kg versus PG = 58 mL/kg, P = 0.05). There was a trend towards lower hetastarch resuscitation requirements in the CG group (CG = 7 mL/kg versus PG = 44 mL/kg, P = 0.06) but no statistically significant difference in mortality (CG = 13% versus PG = 50%, P = 0.11). Histology of the injury sites revealed more adherent clot in the CG group, but no inflammation, tissue necrosis, or residual material. CONCLUSION: In pigs with severe hepatic injury, Combat Gauze reduced blood loss and resuscitation requirements when compared with plain laparotomy pads. Combat Gauze may be safe and effective for use on severe liver injuries.

Magnamosis III: delivery of a magnetic compression anastomosis device using minimally invasive endoscopic techniques.

PURPOSE: Magnamosis creates a secure sutureless anastomosis through magnetic compression. In this study, we further develop and test delivery devices capable of creating a secure duodeno-colonic anastomosis using available minimally invasive endoscopic techniques. METHODS: Eight pigs underwent general anesthesia. Colonoscopy was used to deliver 1 magnetic ring to the hepatic flexure. Simultaneously, upper endoscopy delivered the other magnetic ring into the duodenum using a variety of techniques. The 2 magnetic rings were brought into magnetic proximity under laparoscopic guidance. The pigs were recovered and examined daily followed by sacrificing at 1, 2, 4, and 6 weeks. RESULTS: The device designed to deliver and release each magnetic ring evolved from using a guide wire and balloon devices to redesigning the magnetic ring casing with a groove to accommodate an endoscopic snare. Laparoscopic visualization assured safe magnet mating of intestinal segments. The duodeno-colonic anastomoses created with the snare yielded widely patent anastomoses. In vitro testing revealed excellent burst pressure. Histology revealed complete healing as early as 1 week. CONCLUSION: We redesigned the magnamosis device to facilitate delivery by endoscopic techniques. The snare technique allows endoscopic positioning and controlled release of the magnetic rings for a secure side-to-side duodeno-colonic anastomosis.

Magnamosis II: Magnetic compression anastomosis for minimally invasive gastrojejunostomy and jejunojejunostomy.

BACKGROUND: Previously we demonstrated the safety and patency of a magnetic compression anastomosis (magnamosis). We present the further development of this technique, with specific focus on optimizing device design for minimally invasive magnamosis. STUDY DESIGN: The magnamosis device was designed to incorporate 3 features: 2 convex-concave radially symmetric halves that magnetically self-align, a central channel for immediate patency, and specially engineered radial topography of the mating surfaces to promote gradual remodeling. Each symmetrical half consists of a ring-shaped neodymium-iron-boron magnet encased in polycarbonate casing. Twenty-one young adult pigs underwent either magnetic gastrojejunostomy (n = 13) or jejunojejunostomy (n = 8). Animals were euthanized at 1, 2, 4, and 6 weeks after operation. Anastomoses were studied with contrast radiography, burst pressure, and histology. RESULTS: Gastrojejunostomy: In all animals with successful placement of magnets, anastomoses were patent by contrast fluoroscopy, well healed by histologic examination, and showed excellent burst strength. Jejunojejunostomy: All animals had uneventful clinical courses, indicating that the magnamosis with immediate patency functioned properly without device dislodgement. At sacrifice, all magnamoses were patent, well healed by histology, and had burst strengths that equaled or exceeded that of traditional stapled anastomoses. CONCLUSIONS: Minimally invasive placement of a custom magnetic device in the stomach and jejunum allows intraluminal self-alignment and subsequent compression anastomosis over 3 to 10 days. The magnamosis is immediately patent and develops strength equal to or greater than that of hand-sewn or stapled anastomoses. Magnamosis is effective in the pig model, and may be a safe, effective, and minimally invasive alternative to current anastomotic strategies in humans.

Preliminary study of the effects of smectite granules (WoundStat) on vascular repair and wound healing in a swine survival model.

BACKGROUND: WoundStat (WS) (TraumaCure, Bethesda, MD) is a topical hemostatic agent that effectively stops severe hemorrhage in animal models. To the best of our knowledge, no survival study has been conducted to ensure long-term product safety. We evaluated vascular patency and tissue responses to WS in a swine femoral artery injury model with survival up to 5 weeks. METHODS: Anesthetized swine received a standardized femoral artery injury with free hemorrhage for 45 seconds followed by WS application. One hour after application, the WS was removed, the wound copiously irrigated, and the artery repaired using a vein patch. Six groups of three animals received WS and were killed either immediately after surgery or at weekly intervals up to 5 weeks. Three control animals were treated with gauze packing and direct pressure followed by identical vascular repair and survival for 1 week. At the time of killing, angiograms were performed, and tissue was collected for histopathology. RESULTS: Hemostasis was complete in all WS animals. All animals survived the procedure, and there were no clinically evident postoperative complications. Vascular repairs were angiographically patent in 15 of 18 animals (83%) receiving WS. Histopathologic examination of WS animals revealed severe diffuse fibrogranulomatous inflammation, early endothelial degeneration with subsequent intimal hyperplasia, moderate myocyte necrosis, and fibrogranulomatous nerve entrapment with axonal degeneration. CONCLUSION: Although an effective hemostatic agent, WS use was associated with a substantial local inflammatory response and neurovascular changes up to 5 weeks postinjury.

In utero repair of gastroschisis in the sheep (Ovis aries) model.

OBJECTIVE: Gastroschisis is associated with inflammatory changes in the exposed bowel which leads to intestinal dysmotility after postnatal repair. The insult is a combined effect of amniotic fluid exposure and mechanical constriction. We hypothesized that in utero anatomic repair is possible in a sheep model, and that it may halt the inflammatory damage caused by both mechanisms. METHODS: Gastroschisis was surgically created in mid-gestation (day 75) in 8 sheep fetuses. On gestational day 100, 2 fetuses underwent open fetal gastroschisis repair, where the eviscerated bowel was returned to the peritoneal cavity, and the abdominal wall was primarily closed. All fetuses were harvested at 135 days of gestation. RESULTS: Six fetuses survived the initial operation, and both fetuses that underwent gastroschisis repair survived to term. At 100 and 135 days of gestation, the eviscerated bowel showed progressive signs of inflammation and peel development. The gross and microscopic inflammatory changes in the gastroschisis bowel at 100 days of gestation were completely resolved at term following in utero repair. CONCLUSION: In utero anatomic repair of gastroschisis is possible in mid-gestation in the fetal lamb model, and it appears to ameliorate the inflammatory process.

Magnamosis: magnetic compression anastomosis with comparison to suture and staple techniques.

PURPOSE: An ideal anastomosis between hollow viscera should be easily performed, strong, and operator independent. We hypothesized that transluminal attraction between magnets in the intestine could be harnessed to create an intestinal compression anastomosis (magnamosis) with these characteristics. We further hypothesized that variation of attraction force and geometry of compression would affect the quality of the intestinal anastomosis. METHODS: We designed a self-orienting device composed of 2 neodymium-iron-boron magnets affixed to polytetrafluoroethylene moldings. Two topologies were evaluated: one designed with 'uniform' compression and the other with 'gradient' compression. Sixteen young adult pigs (Sus scrofa) underwent laparotomy with creation of a magnetic side-to-side anastomosis: 8 with the uniform device and 8 with the gradient device. Each also had a stapled anastomosis, and 5 had an additional hand-sutured anastomosis. Animals were euthanized at 1, 2, and 3 weeks after operation, then anastomoses were compared on the basis of gross appearance, histology, functional radiography, and mechanical integrity. RESULTS: All magnetic devices formed patent anastomoses without leak. One stapled anastomosis resulted in a contained leak. Mechanical integrity of magnetic anastomoses was not statistically significantly different from staple or suture counterparts, and there was a trend toward greater strength with magnetic anastomoses. Comparison between device types revealed the gradient device trended toward greater strength and earlier patency (67% vs 33% at 1 week). There was no evidence of stenosis, and histologic examination demonstrated tissue remodeling with mucosal and serosal apposition across the magnamoses. CONCLUSIONS: The magnetic compression anastomosis (magnamosis) device is a safe and effective means of sutureless full-thickness intestinal anastomosis with serosal apposition in a pig model. Gradient compression is superior to uniform compression. This technique is compatible with endoscopic and natural orifice approaches.

The application of split-thickness skin graft as an autogenous arterial conduit in a goat (Capra hircus) model.

Adequate autogenous vein is often the limiting factor in achieving a successful infrainguinal bypass. Attempts have been made to find alternative conduits; however, these alternatives have demonstrated inferior patency rates. We attempt to show that a split-thickness skin graft conduit provides a feasible autogenous arterial conduit. Neoconduits were prepared with an autogenous split-thickness skin graft (STSG) tubularized for a length of 5-6 centimeters with an appropriate caliber match to native artery. The deep dermal side of the graft was randomized to form either the external surface or the luminal surface. The neoconduit was placed as an interposition graft in the left common carotid artery. Grafts were studied in vivo with duplex ultrasonography and ex vivo by histopathology and immunohistochemistry. Feasibility study involved 4 animals with grafts harvested for study at 24 hours (n = 2) and 7 days (n = 2). Two subsequent groups were studied to evaluate 3-month (n = 8) and 6-month (n = 5) patency. All grafts (n = 4) in the feasibility phase of the study were patent at the time of harvest without evidence of aneurysmal degeneration. In the subsequent 8 goats, grafts with the deep dermal side forming the extraluminal surface (n = 4) had a propensity to ulcerate and rupture or to become aneurysmal (75%). The patency rate of these grafts at 6 weeks was 25%. In contrast, grafts with the deep dermal side forming the intraluminal surface (n = 4) demonstrated 75% patency at 6 weeks. Because of these results the remaining goats underwent placement of neoconduits with the deep dermal side forming the luminal surface. These grafts maintained a patency rate of 80% at 6 months. Neoconduits implanted with a diameter greater than 1.5 times the native arterial diameter became aneurysmal. Histopathology demonstrated neointimal formation in all grafts patent for longer than 7 days. Immunohistochemical staining for Factor VIII/von Willebrand's factor (vWF) was reactive in the endoluminal cells of these grafts. Immunohistochemical staining for a-smooth muscle actin demonstrated reactivity in conduits patent for greater than 1 month. Split-thickness skin may provide a feasible source for autogenous conduit in arterial reconstructions and warrants further study. Technical factors affecting patency include orientation of the deep dermal surface of the STSG and the diameter of the neoconduit at the time of implantation.