Wound healing and the immune response in swine treated with a hemostatic bandage composed of salmon thrombin and fibrinogen.

We investigated the inflammatory response in pigs exposed to salmon fibrinogen/thrombin dressings. Animals were exposed to the material in 3 ways: (a) thrombin and fibrinogen were injected intravenously, (b) dual full-thickness skin lesions were surgically created on the dorsal aspect of the swine and treated with the fibrinogen/thrombin bandage and a commercial bandage or (c) a fibrinogen/thrombin bandage was inserted through an abdominal incision into the peritoneal cavity. Blood was collected twice weekly and animals were sacrificed at 7, 10 or 28 days. Animals in the 28-day dermal lesion group were given an injection of salmon fibrinogen/thrombin at the 10 day point to simulate a second bandage application. The immune response manifested itself as induction of germinal centers in mesenteric lymph nodes and in the white pulp of the spleen. Examination of the histology of the skin and organs showed a cellular inflammatory response with granulation tissue and signs of edema that resolved by the 28-day stage. Antibodies reactive to salmon and human thrombin and fibrinogen were detected, but fibrinogen levels and coagulation processes were not affected. In conclusion, animals treated with salmon fibrinogen/thrombin bandages demonstrated a smooth recovery course in terms of both tissue healing and the immune response without adverse effects from the exposure to the fish proteins.

A salmon thrombin-fibrin bandage controls arterial bleeding in a swine aortotomy model.

BACKGROUND: Recently, a wide variety of bandages have been formulated to attempt to improve the effectiveness of emergency intervention in situations of uncontrolled bleeding. The best of these dressings contain a mixture of human thrombin and fibrinogen. The presence of human components in these bandages, although effective, increases the cost of the dressing and raises questions of availability of raw materials and transmission of pathogens. The purpose of this study was to investigate the efficacy of dressings composed of salmon thrombin and fibrinogen in a swine aortotomy model. METHODS: A 4.4-mm aortotomy was produced in the abdominal aorta of 19 anesthetized, splenectomized swine. The United States Army standard field gauze was applied to 8 animals, and the salmon thrombin-fibrin dressing (SFD) was applied to 11 animals. Survival, blood loss, and other parameters were measured over a 60-minute period. RESULTS: All 11 animals that received the SFD survived the aortotomy injury, and bleeding stopped within 7.5 +/- 1.5 min. Seven of 8 animals in the control group were killed when bleeding continued and blood pressures decreased to the cutoff values as outlined in the animal protocol. Bleeding was significantly less in the SFD group compared with the gauze group (241 +/- 65.3 vs. 932.7 +/- 142.4 mL). CONCLUSION: Fibrin dressing using salmon-derived thrombin and fibrinogen is effective in controlling severe, uncontrolled bleeding. This dressing may offer an alternative to dressings composed of human coagulation proteins.

Effects of bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine.

HBOC-201, a bovine polymerized hemoglobin, has been proposed as a novel oxygen-carrying resuscitative fluid for patients with hemorrhagic shock (HS). Herein, we evaluated the hemostatic effects of HBOC-201 in an animal model of HS. A 40% blood loss-controlled hemorrhage and soft tissue injury were performed in 24 invasively monitored Yucatan mini-pigs. Pigs were resuscitated with HBOC-201 (HBOC) or hydroxyethyl starch (HEX), or were not resuscitated (NON) based on cardiac parameters during a 4-h prehospital phase. Afterward, animals received simulated hospital care for 3 days with blood or saline transfusions. Hemostasis measurements included in vivo bleeding time (BT), thromboelastography (TEG), in vitro bleeding time (platelet function; PFA-CT), prothrombin time (PT), and partial thromboplastin time (PTT). Serum lactate was measured and lung sections were evaluated for microthrombi by electron microscopy. During the prehospital phase, BT remained unchanged in the HBOC group. TEG reaction time increased in HBOC pigs during the late prehospital phase and was greater than in NON or HEX pigs at 24 h (P = 0.03). TEG maximum amplitude was similar for the two fluid-resuscitated groups. PFA-CT increased in both resuscitated groups but less with HBOC (P = 0.02) in the prehospital phase; this effect was reversed by 24 h (P = 0.02). In the hospital phase, PT decreased (P < 0.02), whereas PTT increased above baseline (P < 0.01). Lactic acidosis in HBOC and HEX groups was similar. Aspartate aminotransferase was relatively elevated in the HBOC group at 24 h. Electron microscopy showed no evidence of platelet/fibrin clots or microthrombi in any of the animals. Twenty-four-hour group differences mainly reflected the fact that all HEX animals (8/8) received blood transfusions compared with only one HBOC animal (1/8). In swine with HS, HBOC resuscitation induced less thrombopathy than HEX during the prehospital phase. Mild delayed effects on platelet and clot formation during the hospital phase are transient and likely related to fewer blood transfusions. In swine with HS, HBOC resuscitation induced less thrombopathy than HEX during the prehospital phase but more thrombopathy in the hospital phase. The delayed effects on platelet and clot formation during the hospital phase are transient and may be related to the need for fewer blood transfusions.