Biomedical subjects

Timothy Hancock

Publications and source records attributed to Timothy Hancock.

4 recordsLinked to original sources

PubMed2003

Ketone and pyruvate Ringer's solutions decrease pulmonary apoptosis in a rat model of severe hemorrhagic shock and resuscitation.

BACKGROUND: Resuscitation fluids containing beta-hydroxybutyrate (BHB) have been shown to decrease cellular injury after hemorrhagic shock and resuscitation through an unknown mechanism. We tested whether this effect was related to BHB-induced metabolic modulations. METHODS: Male Sprague Dawley rats (n=30) were subjected to volume-controlled hemorrhage (27 mL/kg during 10 minutes followed by 75 minutes of shock during which another 8 mL/kg of blood was withdrawn). Experimental groups included the following: (1) sham, (2) no resuscitation (NR), (3) racemic lactated Ringer's (DL-LR) solution, (4) LR containing L-isomer only (L-LR), (5) ketone Ringer's solution with lactate substituted by BHB (KR), and (6) pyruvate Ringer's solution with lactate substituted by pyruvate (PR). The resuscitation fluids were infused during 45 minutes simultaneously with additional hemorrhage of 8 mL/kg. Hemodynamic and physiologic parameters and the plasma levels of BHB were serially measured. The animals were killed 2 hours after resuscitation, and tissues were frozen instantaneously for cellular adenylate extraction and adenosine triphosphate (ATP) and adenosine diphosphate analysis. Pulmonary apoptosis was studied using Western blotting, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. Expression of enzymes involved in ketogenesis and ketolysis was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: NR and resuscitation with DL-LR increased the expression of apoptotic markers, whereas resuscitation with KR and PR significantly decreased the expression of apoptotic markers in rat lungs. Resuscitation with KR was followed by a profound increase in plasma BHB levels; however, the expression levels of ketolytic enzymes were essentially unaffected. KR infusion did not induce significant improvements in tissue ATP levels. CONCLUSIONS: Resuscitation with KR and PR protects against pulmonary apoptosis without improving tissue ATP content. Therefore, metabolic modulation is unlikely to be the major mechanism by which BHB exerts its protective effects during reperfusion.

3-Hydroxybutyric Acid↗

PubMed2003

Comparative analysis of hemostatic agents in a swine model of lethal groin injury.

BACKGROUND: Techniques for better hemorrhage control after injury could change outcome. A large-animal model of lethal, uncontrolled hemorrhage was developed to test whether the use of various hemostatic agents would decrease bleeding and improve early survival. METHODS: A complex groin injury was created in 30 Yorkshire swine (42-55 kg) to produce uncontrolled hemorrhage. This injury included semitransection of the proximal thigh and complete division of the femoral artery and vein. After 5 minutes, the animals were randomized to (n = 6 animals per group) no dressing (ND), standard dressing (SD), SD and Rapid Deployment Hemostat (RDH) bandage, SD and QuikClot hemostatic agent (QC), or SD and TraumaDEX (TDEX). Limited volume 0.9% saline (1,000 mL over 30 minutes) resuscitation was started 30 minutes after injury. We measured blood loss, early mortality (180 minutes), and physiologic markers of hemorrhagic shock (e.g., cardiac output, blood pressure, hemoglobin, metabolic acidosis). RESULTS: Application of wound dressing decreased mortality in all groups compared with the ND group (83% mortality). However, this difference was significant (p < 0.05) only for the QuikClot hemostatic agent (0% mortality). Before the application of dressing (first 5 minutes), there were no differences in blood loss between the groups. After application of dressings, the QC group had the lowest blood loss (4.4 +/- 1.4 mL/kg). CONCLUSION: Of the hemostatic agents tested, QuikClot improved survival and decreased bleeding in a swine model of lethal vascular and soft tissue injury.

Animals↗

PubMed2003

A portable handpump is effective in the evacuation of hemothorax in a swine model of penetrating chest injury.

BACKGROUND: Standard pleural evacuation devices are not practical for use on the battlefield. A small, portable, easy-to-use handpump (HP) that does not require continuous suction for treating hemopneumothorax would offer a major logistical advantage. In addition, using endotracheal tubes instead of regular pleural tubes would help minimize supplies carried on the battlefield. A swine model of penetrating chest injury was designed to test this concept. Our hypothesis was that an HP would be as effective as the standard of care for the evacuation of a large hemopneumothorax. METHODS: A 2-cm lung laceration was created in 18 Yorkshire swine (35-51 kg) under inhaled anesthesia and 1.4 L of blood was infused into the pleural space (200 mL every 15 minutes). Fluid resuscitation (2,000 mL of 0.9% saline) was started 15 minutes after injury, and animals were randomized into one of three groups: group 1, 36-Fr Argyle pleural tube and Pleur-Evac chest drainage unit with 20-cm H2O suction (control); group 2, 36-Fr pleural tube attached to the HP; and group 3, a No. 8 endotracheal tube in the pleural space attached to the HP. After 120 minutes, a thoracotomy was performed to determine the amount of residual blood in the pleural space. RESULTS: Effectiveness of the three methods as a percentage of total blood (evacuated and retained) removed was measured over 2 hours. The handpump (group 2) performed better than the standard of care (group 1) at numerous time points and evacuated significantly (p < 0.05) more blood at the end of the experiment. CONCLUSION: Using the handpump with a pleural tube was more effective than the standard of care in treating traumatic hemothorax. The use of an endotracheal instead of a conventional pleural tube had no adverse impact on efficacy of the pump in evacuating blood from the chest cavity.

Animals↗

PubMed2002

Learning and memory is preserved after induced asanguineous hyperkalemic hypothermic arrest in a swine model of traumatic exsanguination.

BACKGROUND: Induced asanguineous hypothermic metabolic arrest (suspended animation) could provide valuable time to repair major vascular injuries if safely induced in patients with trauma. We report a novel method of doing this in a swine model of uncontrolled lethal hemorrhage (ULH) that resulted in preservation of learning ability and memory. METHODS: Yorkshire swine (100 to 125 lb) underwent ULH before rapid intra-aortic infusion of a hypothermic (4 degrees C), hyperkalemic (70 mEq/L) organ preservation solution by a left thoracotomy. Cooling continued until core temperature reached 10 degrees C, and this was maintained for 60 minutes using low-flow cardiopulmonary bypass. Vascular injuries were repaired during this state of suspended animation, which was then reversed, and the animals were observed for 6 weeks. Cognitive functions were tested by training animals to retrieve food from color-coded boxes. Postoperatively, the ability to remember this task and a 75-point objective neurologic scale were used to test neurologic function. In experiment I, ULH was caused by lacerating thoracic aorta (n = 9). Five preoperatively untrained animals were trained to perform the task and compared with control animals (n = 15), and 4 preoperatively trained animals were tested for memory retention postoperatively. In experiment II, ULH was induced by creating an iliac artery and vein injury (n = 15). Animals were kept in shock for 15, 30, and 60 minutes before the induction of hypothermia. RESULTS: In experiment I, surviving animals (7/9) were neurologically intact, and their capacity to learn new skills was no different than for control animals. All pretrained animals demonstrated complete memory retention. In experiment II, survival with 15, 30, and 60 minutes of shock were 80%, 60%, and 80%, respectively. All animals (except 1) in the 60-minute group were neurologically intact and displayed normal learning capacity. CONCLUSIONS: Induction of hypothermic metabolic arrest (by thoracotomy) for repair of complex traumatic injuries is feasible with preservation of normal neurologic function, even after extended periods of shock from an intra-abdominal source of uncontrolled hemorrhage.

Animals↗