Bilateral vagotomy inhibits apnea and attenuates other physiological responses after blunt chest trauma.

BACKGROUND: Behind armor blunt trauma (BABT) is defined as the nonpenetrating injury resulting from a ballistic impact on body armor. Some of the kinetic energy is transferred to the body, causing internal injuries and, occasionally, death. The aim of this study was to investigate if apnea and other pathophysiological effects after BABT is a vagally mediated reflex. METHODS: Sixteen anesthetized pigs wearing body armor, of which five were vagotomized, were shot with a standard 7.62 mm assault rifle. These animals were compared with control animals (n = 8), shot with blank ammunition. We performed bilateral vagotomy before the shot and assessed the outcome on the apnea period, respiration, circulation, and brain function. Animals were monitored during a 2-hour period after the shot. RESULTS: Nonvagotomized animals had a mean apnea period of 22 (6-44) seconds. This group also showed a significant decrease in oxygen saturation compared with control animals. Furthermore, electroencephalogram-changes were more pronounced in nonvagotomized animals. In contrast, vagotomized animals were protected from apnea and showed only a minor decrease in oxygen saturation. All exposed animals showed impaired circulation, and postmortem examination revealed a pulmonary contusion. CONCLUSION: This study shows that apnea after BABT is a vagally mediated reflex that can be inhibited by bilateral vagotomy. Our results indicate that the initial apnea period is an important factor for hypoxia after BABT. Supported ventilation should begin immediately if the affected person is unconscious and suffers from apnea. It should continue until the neurologic paralysis disappears and sufficient spontaneous breathing begins.

Electroencephalogram, circulation, and lung function after high-velocity behind armor blunt trauma.

BACKGROUND: Behind armor blunt trauma (BABT) is defined as the nonpenetrating injury resulting from a ballistic impact on personal body armor. The protective vest may impede the projectile, but some of the kinetic energy is transferred to the body, causing internal injuries and occasionally death. The aim in this study was to investigate changes in electroencephalogram (EEG) and physiologic parameters after high-velocity BABT. METHODS: Eight anesthetized pigs, wearing body armor (including a ceramic plate) on the right side of their thorax, were shot with a 7.62-mm assault rifle (velocity approximately 800 m/s). The shots did not penetrate the armor and these animals were compared with control animals (n = 4), shot with blank ammunition. EEG and several physiologic parameters were thereafter monitored during a 2-hour period after the shot. RESULTS: All animals survived during the experimental period. Five of the exposed animals showed a temporary effect on EEG. Furthermore, exposed animals displayed decreased cardiac capacity and an impaired oxygenation of the blood. Postmortem examination revealed subcutaneous hematomas and crush injuries to the right lung. CONCLUSION: The results in our animal model indicate that high-velocity BABT induce circulatory and respiratory dysfunction, and in some cases even transient cerebral functional disturbances.

Effect of maleimide-polyethylene glycol hemoglobin (MP4) on hemodynamics and acid-base status after uncontrolled hemorrhage in anesthetized swine: comparison with crystalloid and blood.

BACKGROUND: Maleimide-polyethylene glycol hemoglobin, 4.3 g/dL (MP4), is a hemoglobin-based oxygen carrier consisting of native human hemoglobin modified with maleimide polyethylene glycol. This study evaluated resuscitation with MP4 after uncontrolled hemorrhage in anesthetized swine, and compared the effects of MP4 alone with those of standard-of-care crystalloid or crystalloid + blood. METHODS: Pigs were anesthetized with isoflurane and hemorrhaged 250 mL by controlled withdrawal, which was followed by a 5-mm tear in the abdominal aorta. Three groups of pigs (n = 7 each) were randomized after aortic tear to receive 500 mL of MP4, unlimited Ringer's acetate (RA), or 2 L of RA + 250 mL of autologous blood. Measurements included arterial and pulmonary artery pressures, central venous and pulmonary capillary wedge pressures, cardiac output, renal blood flow, urine output, arterial and venous blood gases, lactate concentration, and hemoglobin. Animals were monitored for 150 minutes after hemorrhage. RESULTS: Average body weight (22-24 kg) and hemorrhage volume (28-34 mL/kg) were similar in the three groups. The nadir of mean arterial pressure (23-25 mm Hg) and base excess (-3 to -4 mEq/L) after hemorrhage were similar in all groups, indicating equivalent shock in the three groups. Two hours after administration of MP4, arterial pressure and base excess were significantly improved compared with those of animals administered RA or RA + blood, despite a significantly lower volume of infused fluids (MP4 = 36 +/- 2 mL/kg; RA = 224 +/- 28 mL/kg; RA + blood = 110 +/- 10 mL/kg), and a significantly lower total hemoglobin than achieved with RA + blood. Arterial pressure did not rise above baseline values, cardiac output was not diminished, and systemic vascular resistance was unchanged after administration of MP4, indicating the lack of cardiac effects or peripheral vasoconstriction. CONCLUSIONS: These data demonstrate that resuscitation with a small volume of MP4 induces recovery from hemorrhage without vasoconstriction. Overall, the effects of MP4 alone on hemodynamic and acid-base indices appear to be of greater benefit than those observed with a large volume of RA alone or RA + blood.

Proinflammatory reaction and cytoskeletal alterations in endothelial cells after shock wave exposure.

BACKGROUND: Although the effects on human organs by shock waves (SWs) induced by medical treatments or high-energy trauma are well recognized, little is known about the effects on the cellular level. Since blood vessel injury is a common finding after SW exposure, we assessed the in vitro effects of SWs on human umbilical vein endothelial cells (HUVECs). METHODS: An in vitro trauma model was used to expose HUVEC monolayers to focused SWs or to shock waves plus cavitation (SWC), a subsequent phenomenon that is often considered the main cause of SW vascular injury. RESULTS: SWs alone did not cause any changes in the studied variables. In contrast, HUVEC monolayers exposed to SWC exhibited discrete central lesions with extensive cell death. Cells peripheral to the main lesion area displayed disassembly of dense peripheral bands and formation of actin stress fibers, indicating increased intercellular gaps. Expression of P-selectin was enhanced 11-fold compared with controls, whereas expression of E-selectin and intercellular adhesion molecule 1 was enhanced 8-fold (p < .05) and 1.5-fold (p < .01), respectively. The latter responses were preceded by nuclear translocation of nuclear factor kappaB subunit p65 by 16% (p < .01). When compared with mechanically produced lesions used as controls, SWC lesions exhibited an impaired regeneration rate of the endothelial cell layer (p < .001). Redistribution of centrosomes toward the lesion borders was less effective in the SWC samples compared with the mechanically produced lesions (p < .01). CONCLUSIONS: SWC lesions were associated with a switch to an endothelial proinflammatory phenotype, with an impaired regeneration rate and changes in cytoskeletal functions.

Ballistic variables and tissue devitalisation in penetrating injury--establishing relationship through meta-analysis of a number of pig tests.

BACKGROUND: Assessment of the injury potential is central to ascertaining that a law enforcement bullet does not cause unjustified and excessive injuries. There seems to prevail an understanding that tissue devitalisation correlates with kinetic energy dissipated into the tissue. Other views exist too. The purpose of the study was to find out whether such a correlation can be found and at what level of confidence. METHODS: A number of reported tests done with live pigs with sufficient primary data have first been brought to the same temporally comparable level and then analysed. The tests comprise of 140 shots. To maintain consistency tests with other animals were excluded. RESULTS: The best correlation was obtained between excised muscle tissue and dissipated kinetic energy per millimetre of wound channel. An equation describing the relationship between dissipated energy E(d) and devitalised tissue m(deb) is presented as a regression function m(deb)=44.575xE(d)+10.319 with R2=0.293. An experimental method for estimating the energy used for bullet deformation of controlled deformation bullets is also presented. CONCLUSIONS: A method for using the regression function for obtaining tissue destruction figures for any point of wound channel formed in tissue simulant is presented. The figures are intended for meaningful comparison of the injury potential of various bullets and not for forecasting actual tissue injuries. The documentation of the ballistic properties in animal tests also seems somewhat lacking. Some changes in documenting firearms injuries are proposed in order to validate the methods and further enhance the fidelity of simulant testing.

Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4).

Cell-free Hb increases systemic and pulmonary pressure and resistance and reduces cardiac output and heart rate in animals and humans, effects that have limited their clinical development as "blood substitutes." The primary aim of this study was to evaluate the hemodynamic response to infusion of several formulations of a new polyethylene glycol (PEG)-modified human Hb [maleimide PEG Hb (MalPEGHb)] in swine, an animal known to be sensitive to Hb-induced vasoconstriction. Anesthetized animals underwent controlled hemorrhage (50% of blood volume), followed by resuscitation (70% of shed volume) with 10% pentastarch (PS), 4% MalPEG-Hb in lactated Ringer (MP4), 4% MalPEG-Hb in pentastarch (HS4), 2% MalPEG-Hb in pentastarch (HS2), or 4% stroma-free Hb in lactated Ringer solution (SFH). Compared with baseline, restoration of blood volume after resuscitation was similar and not significantly different for the PS (103%), HS2 (99%), HS4 (106%), and MP4 (87%) animals but significantly less for the SFH animals (66%) (P < 0.05). All solutions that contained MalPEG-Hb restored mean arterial and pulmonary pressure and cardiac output. Systemic vascular resistance was unchanged, and pulmonary arterial pressure and resistance were increased slightly. Both systemic and pulmonary vascular resistance increased significantly in animals that received SFH, despite less adequate blood volume restoration. Oxygen consumption was maintained in all animals that received MalPEG-Hb, but not PS. Base excess improved only with MalPEG-Hb and PS, but not SFH. Red blood cell O2 extraction was significantly increased in animals that received Hb, regardless of formulation. These data demonstrate resuscitation with MalPEG-human Hb without increasing systemic vascular resistance and support our previous observations in animals suggesting that the efficacy of low concentrations of PEG-Hb in the plasma results from reduced vasoconstriction.

Effects of induced hypothermia after soft-tissue injury.

BACKGROUND: Hypothermia is occasionally employed to reduce the metabolic rate and to protect the brain in patients undergoing surgery, but it is controversial whether hypothermia (HT) is beneficial or harmful in trauma victims with soft-tissue injuries. For this purpose, we studied the acute effects of hypothermia induced after infliction of a standardized soft-tissue injury. METHODS: After a standardized high-energy gunshot wound to the right hind leg of 14 anesthetized piglets, the animals were randomized to normothermia or HT (30 degrees C) induced with a HT bed. The cardiovascular and hematological status was monitored for 6 h after the injury. RESULTS: The heart rate, mean arterial pressure, neutrophil count, and plasma adrenaline level were significantly lower in the HT pigs than in the controls (p<0.05). The arterial oxygen tension was significantly elevated in the HT group. Cardiac index and oxygen delivery decreased slightly in both groups, but no difference developed between the groups in these parameters. Serum potassium increased significantly in the controls (p<0.001). CONCLUSION: HT down to 30 degrees C following high-energy penetrating soft-tissue injury had a modest effect on the hemodynamics and oxygen delivery. However, evidence of 'stress' was reduced, and the pigs developed a progressive increase in their serum potassium concentration.

Induced hypothermia and rewarming after hemorrhagic shock.

BACKGROUND: Recent patient and animal studies have shown protective effects of hypothermia (HT) in traumatic brain injury and hemorrhagic shock. We have demonstrated a reduced stress level and a lack of additive hemodynamic effects of HT. The present work was undertaken to evaluate whether these effects persist during and after rewarming. METHODS: Pigs were quickly exsanguinated of 40% of their individually calculated blood volume and randomized to HT (32.5 degrees C) or normothermia (controls). After 30 min of HT, rewarming to baseline temperature was initiated. All animals were followed for 7 h. Thrombolelastography was used to evaluate blood coagulation. RESULTS: HT did not aggravate the hemodynamic signs of hemorrhagic shock. HT decreased the oxygen uptake, however, which reduced the oxygen extraction ratio to the prehemorrhage level (P < 0.05). Serum levels of potassium were transiently stabilized by cooling. Coagulation was slower, but blood clot strength was normal. HT also delayed fibrinolysis (P < 0.05). Rewarming reversed all physiological changes induced by HT including those involving the coagulation system. CONCLUSIONS: HT produced few hemodynamic effects in the presence of hemorrhagic shock, but created a surplus of oxygen in the core circulation. Blood clotting was delayed by HT.

Mechanisms of shock wave induced endothelial cell injury.

BACKGROUND AND OBJECTIVES: Medical procedures, for example, laser angioplasty and extracorporeal lithotripsy as well as high-energy trauma expose human tissues to shock waves (SWs) that may cause tissue injury. The mechanisms for this injury, often affecting blood vessel walls, are poorly understood. Here we sought to assess the role of two suggested factors, viz., cavitation or reactive oxygen species (ROS). STUDY DESIGN/MATERIALS AND METHODS: A laser driven flyer-plate model was used to expose human umbilical cord vein endothelial cell (HUVEC) monolayers to SWs or to SWs plus cavitation (SWC). Cell injury was quantified with morphometry, trypan blue staining, and release of (51)Cr from labeled HUVECs. RESULTS: HUVECs, exposed to SWs only, could not be distinguished from controls in morphological appearance or ability to exclude trypan blue. Yet, release of (51)Cr, indicated a significant cell injury (P < 0.05). HUVEC cultures exposed to SWC, exhibited cell detachment and cell membrane damage detectable with trypan blue. Release of (51)Cr was fourfold compared to SW samples (P < 0.01). Signs of cell injury were evident at 15 minutes and did not change over the next 4 hours. No protective effects of ROS scavengers were demonstrated. CONCLUSIONS: Independent of ROS, SWC generated an immediate cell injury, which can explain, for example, vessel wall perturbation described in relation to SW treatments and trauma.

Induced hypothermia after high-energy soft-tissue injury and subsequent hemorrhagic shock.

Many cases of hypothermia (HT) occur in trauma victims subjected to soft tissue injury and hemorrhage. The aim of the present study was to study the effects of HT on the combination of these insults. A standardized gunshot wound was inflicted on the right hind leg of 14 anesthetized piglets. They were then exsanguinated of 50% of their blood volume and randomized to normothermia or HT (30 degrees C). The animals were observed for 4 h after the injury with measurements of hemodynamics, oxygen consumption, and of plasma catecholamines and electrolytes. The insults reduced cardiac output and the arterial pressure by approximately 50%, but no further reduction occurred when HT was induced. The oxygen extraction ratio increased from approximately 35% to 75% in both groups. The gradual reduction of oxygen consumption in HT animals (P < 0.05) decreased the oxygen extraction ratio to around 50%. Heart rate, the serum potassium and creatinine concentrations, and the leukocyte counts were all maintained closer to baseline in the presence of HT. Hypothermia tended to decrease oxygen extraction and was associated with less evidence of tissue injury. These effects are potentially beneficial in soft-tissue trauma combined with hypovolemia.