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Samuel A. Tisherman - One of the best experts on this subject based on the ideXlab platform.
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Suspended Animation can allow survival without brain damage after traumatic exsanguination cardiac arrest of 60 minutes in dogs
Journal of Trauma-injury Infection and Critical Care, 2004Co-Authors: Ala Nozari, Patrick M. Kochanek, Peter Safar, Ann Radovsky, William Stezoski, Jeremy Henchir, Miroslav Klain, Samuel A. TishermanAbstract:BACKGROUND We have previously shown in dogs that exsanguination cardiac arrest of up to 120 minutes without trauma under profound hypothermia induced by aortic flush (Suspended Animation) can be survived without neurologic deficit. In the present study, the effects of major trauma (laparotomy, thoracotomy) are explored. This study is designed to better mimic the clinical scenario of an exsanguinating trauma victim, for whom Suspended Animation may buy time for resuscitative surgery and delayed resuscitation. METHODS Fourteen dogs were exsanguinated over 5 minutes to cardiac arrest. Flush of saline at 2 degrees C into the femoral artery was initiated at 2 minutes of cardiac arrest and continued until a tympanic temperature of 10 degrees C was achieved. The dogs were then randomized into a control group without trauma (n = 6) or a trauma group (n = 8) that underwent a laparotomy and isolation of the spleen before hemorrhage and then, at the start of cardiac arrest, spleen transection and left thoracotomy. During cardiac arrest, splenectomy was performed. After 60 minutes of no-flow cardiac arrest, reperfusion with cardiopulmonary bypass was followed by intensive care to 72 hours. RESULTS All 14 dogs survived to 72 hours with histologically normal brains. All control dogs were functionally neurologically intact. Four of eight trauma dogs were also functionally normal. Four had neurologic deficits, although three required prolonged mechanical ventilation because of airway edema and evidence of multiple organ failure. Blood loss from the chest and abdomen was variable and was associated with poor functional outcomes. CONCLUSION Rapid induction of profound hypothermic Suspended Animation (tympanic temperature, 10 degrees C) can enable survival without brain damage after exsanguination cardiac arrest of 60 minutes even in the presence of trauma, although prolonged intensive care may be required. This technique may allow survival of exsanguinated trauma victims, who now have almost no chance of survival.
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Novel Potentials for Emergency Hypothermia: Suspended Animation with Delayed Resuscitation from Exsanguination Cardiac Arrest
Hypothermia for Acute Brain Damage, 2004Co-Authors: Patrick M. Kochanek, Samuel A. Tisherman, S. William Stezoski, Ala Nozari, Peter SafarAbstract:Most combat fatalities result from rapid exsanguination in the field and resuscitation via fluid administration is generally unsuccessful. In a series of experiments over the past 5 years, we have developed a novel approach targeting the use of rapid induction of profound hypothermia by aortic flush to produce a state of Suspended Animation for delayed resuscitation after experimental exsanguination cardiac arrest in dogs. In over 200 experiments in dogs, exsanguination cardiac arrest was induced by rapid hemorrhage over ~5 min. After the 5-min hemorrhage and an additional 2 min of cardiac arrest, hypothermia (8°–34°C, tympanic temperature) was induced by aortic or femoral flush of ice-cold saline via a balloon catheter. Cardiac arrest was then continued for durations ranging between 15 and 120 min. The specific duration and temperature selected depended on the goals of the specific study. Delayed resuscitation after the predefined Suspended Animation interval was achieved using cardiopulmonary bypass (for 1–2h), mild hypothermia (34°C to 12h), and 72–90 h of continuous intensive care. In some studies, the insult also included laparotomy, splenectomy, and thoracotomy, to simulate trauma. In other studies, pharmacological agents were combined with hypothermia to test for therapeutic synergy. Final neurologic outcome was assessed at 72–96 h by overall performance category and neurological deficit scores. Brain histopathology was also evaluated. Normal neurologic outcome with minimal histopathologic damage was routinely achieved after a cardiac arrest of 90 min using this Suspended Animation approach. In some dogs, good neurologic outcome was achieved even after a cardiac arrest of 120 min. A delay of 5–8 min in the induction of Suspended Animation attenuated its preservative effect. Of 14 drugs tested, only the antioxidant tempol produced a synergistic effect with hypothermia. The addition of trauma worsened organ function without affecting brain histopathology. Suspended Animation with delayed resuscitation represents a revolutionary approach to resuscitation of the trauma victim with otherwise lethal exsanguination cardiac arrest. Our studies suggest additional benefit from the combination of antioxidants with hypothermia, and challenge the previously posed limits of hypothermic protection and preservation of the brain. In ongoing studies we are testing Suspended Animation after prolonged shock, evaluating the mechanisms of hypothermic protection using proteomics, and probing beyond the 2-h theoretical limit for cardiac arrest duration with intact survival.
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Hypothermia and injury.
Current opinion in critical care, 2004Co-Authors: Samuel A. TishermanAbstract:PURPOSE OF REVIEW Recent studies demonstrating that mild therapeutic hypothermia can improve the outcome from several ischemic and traumatic insults have led to increased interest in the potential benefits of hypothermia after injury. Previous clinical studies, however, have suggested that hypothermia is detrimental to trauma patients. This most likely is a result of differences in the physiologic effects between uncontrolled exposure hypothermia and controlled therapeutic hypothermia. The laboratory and clinical data regarding traumatic hemorrhagic shock and hypothermia are presented, as well as a novel approach to the patient with exsanguinating trauma: Suspended Animation. Therapeutic hypothermia for traumatic brain injury is discussed. RECENT FINDINGS Laboratory studies of hemorrhagic shock demonstrate improved survival with mild hypothermia. For the first time, this was shown in a study in a large animal outcome model of hemorrhagic shock with trauma and intensive care. Because clinical studies continue to suggest an association between the development of hypothermia and worse outcomes in trauma patients, clinicians are continuing efforts to prevent and treat hypothermia. For exsanguination cardiac arrest, laboratory studies have demonstrated the feasibility of inducing hypothermic preservation via a rapid aortic flush (Suspended Animation). For traumatic brain injury, the most recent clinical trial did not show an overall benefit, but it seems that patients who arrive mildly hypothermic have better outcomes if hypothermia is maintained. SUMMARY The dichotomy between laboratory findings that show a benefit of hypothermia and clinical findings that suggest detrimental effects remains difficult to explain. For now, preventing hypothermia remains prudent. Suspended Animation seems promising for patients with exsanguinating trauma. Clinical trials of mild hypothermia during hemorrhagic shock and Suspended Animation for exsanguination are indicated. Clinical trials of hypothermia for traumatic brain injury are in progress.
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Suspended Animation for resuscitation from exsanguinating hemorrhage.
Critical care medicine, 2004Co-Authors: Samuel A. TishermanAbstract:In dogs, isotonic saline at 0-4 degrees C, flushed into the aorta at a rate of 1-2 L/min, with drainage of the vena cava, can achieve deep to profound hypothermia of vital organs at a cooling rate of up to 3 degrees C per minute. This achieves preservation of viability of the organism during predictable durations of no flow: cardiac arrest of 15-20 mins at Tty of 30-35 degrees C, cardiac arrest of 30 mins at Tty of 25 degrees C, cardiac arrest of 60 mins at Tty of 15 degrees C, and cardiac arrest of 90 mins at Tty of 10 degrees C. So far, pharmacologic approaches have not resulted in any breakthrough effect on outcome above that achieved with hypothermia, except perhaps the antioxidant tempol. Additional studies of novel drugs and, perhaps, combination therapies remain warranted. The optimal fluids to have in the circulation during circulatory arrest and reperfusions need to be determined. As laboratory studies to optimize Suspended Animation proceed, clinical trials should be initiated. In addition, devices should be developed to facilitate induction of Suspended Animation, eventually in the field.
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Suspended Animation can allow survival without brain damage after traumatic exsanguination cardiac arrest of 60 minutes in dogs.
The Journal of trauma, 2004Co-Authors: Ala Nozari, Patrick M. Kochanek, Peter Safar, Ann Radovsky, William Stezoski, Jeremy Henchir, Miroslav Klain, Samuel A. TishermanAbstract:We have previously shown in dogs that exsanguination cardiac arrest of up to 120 minutes without trauma under profound hypothermia induced by aortic flush (Suspended Animation) can be survived without neurologic deficit. In the present study, the effects of major trauma (laparotomy, thoracotomy) are explored. This study is designed to better mimic the clinical scenario of an exsanguinating trauma victim, for whom Suspended Animation may buy time for resuscitative surgery and delayed resuscitation. Fourteen dogs were exsanguinated over 5 minutes to cardiac arrest. Flush of saline at 2 degrees C into the femoral artery was initiated at 2 minutes of cardiac arrest and continued until a tympanic temperature of 10 degrees C was achieved. The dogs were then randomized into a control group without trauma (n = 6) or a trauma group (n = 8) that underwent a laparotomy and isolation of the spleen before hemorrhage and then, at the start of cardiac arrest, spleen transection and left thoracotomy. During cardiac arrest, splenectomy was performed. After 60 minutes of no-flow cardiac arrest, reperfusion with cardiopulmonary bypass was followed by intensive care to 72 hours. All 14 dogs survived to 72 hours with histologically normal brains. All control dogs were functionally neurologically intact. Four of eight trauma dogs were also functionally normal. Four had neurologic deficits, although three required prolonged mechanical ventilation because of airway edema and evidence of multiple organ failure. Blood loss from the chest and abdomen was variable and was associated with poor functional outcomes. Rapid induction of profound hypothermic Suspended Animation (tympanic temperature, 10 degrees C) can enable survival without brain damage after exsanguination cardiac arrest of 60 minutes even in the presence of trauma, although prolonged intensive care may be required. This technique may allow survival of exsanguinated trauma victims, who now have almost no chance of survival.
Mark B. Roth - One of the best experts on this subject based on the ideXlab platform.
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H2S induces a Suspended Animation-like state in mice
Science, 2015Co-Authors: Eric Blackstone, Mike Morrison, Mark B. RothAbstract:Many organisms respond to changes in en-vironmental conditions by entering into a Suspended Animation–like state in which a decrease in metabolic rate (MR) is follow-ed by a reduction in core body temperature (CBT) (1). Regulated induction of a hypo-metabolic state is hypothesized to have great medical benefit for a variety of conditions, including ischemia and reperfusion injury, pyrexia, and other trauma (2). Suspended Animation–like states may also be useful for creating beneficial hypothermia in surgical situations and for improving organ preser-vation (1). Inhibiting oxidative phosphorylation re-versibly induces states of profound hypome-tabolism in several model organisms (3–5). Because hydrogen sulfide (H 2 S) is a specific, potent, and reversible inhibitor of complex IV (cytochrome c oxidase), the terminal en-zyme complex in the electron transport chain (6), we hypothesized that it could reduce MR and CBT in mammals. When mice were exposed to 80 ppm o
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Suspended Animation extends survival limits of Caenorhabditis elegans and Saccharomyces cerevisiae at low temperature.
Molecular biology of the cell, 2010Co-Authors: Kin Chan, Jesse P. Goldmark, Mark B. RothAbstract:The orderly progression through the cell division cycle is of paramount importance to all organisms, as improper progression through the cycle could result in defects with grave consequences. Previously, our lab has shown that model eukaryotes such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Danio rerio all retain high viability after prolonged arrest in a state of anoxia-induced Suspended Animation, implying that in such a state, progression through the cell division cycle is reversibly arrested in an orderly manner. Here, we show that S. cerevisiae (both wild-type and several cold-sensitive strains) and C. elegans embryos exhibit a dramatic decrease in viability that is associated with dysregulation of the cell cycle when exposed to low temperatures. Further, we find that when the yeast or worms are first transitioned into a state of anoxia-induced Suspended Animation before cold exposure, the associated cold-induced viability defects are largely abrogated. We present evidence that by imposing an anoxia-induced reversible arrest of the cell cycle, the cells are prevented from engaging in aberrant cell cycle events in the cold, thus allowing the organisms to avoid the lethality that would have occurred in a cold, oxygenated environment.
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Anoxia-induced Suspended Animation in budding yeast as an experimental paradigm for studying oxygen-regulated gene expression.
Eukaryotic cell, 2008Co-Authors: Kin Chan, Mark B. RothAbstract:A lack of oxygen can force many organisms to enter into recoverable hypometabolic states. To better understand how organisms cope with oxygen deprivation, our laboratory previously had shown that when challenged with anoxia, both the nematode Caenorhabditis elegans and embryos of the zebrafish Danio rerio enter into Suspended Animation, in which all life processes that can be observed by light microscopy reversibly halt pending the restoration of oxygen (P. A. Padilla and M. B. Roth, Proc. Natl. Acad. Sci. USA 98:7331-7335, 2001, and P. A. Padilla, T. G. Nystul, R. A. Zager, A. C. Johnson, and M. B. Roth, Mol. Biol. Cell 13:1473-1483, 2002). Here, we show that both sporulating and vegetative cells of the budding yeast Saccharomyces cerevisiae also enter into a similar state of Suspended Animation when made anoxic on a nonfermentable carbon source. Transcriptional profiling using cDNA microarrays and follow-on quantitative real-time PCR analysis revealed a relative derepression of aerobic metabolism genes in carbon monoxide (CO)-induced anoxia when compared to nitrogen (N(2)) gas-induced anoxia, which is consistent with the known oxygen-mimetic effects of CO. We also found that mutants deleted for components of the mitochondrial retrograde signaling pathway can tolerate prolonged exposure to CO but not to N(2). We conclude that the cellular response to anoxia is dependent on whether the anoxic gas is an oxygen mimetic and that the mitochondrial retrograde signaling pathway is functionally important for mediating this response.
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Suspended Animation-like state protects mice from lethal hypoxia
Shock, 2007Co-Authors: Eric Blackstone, Mark B. RothAbstract:Joseph Priestley observed the high burn rate of candles in pure oxygen and wondered if people would "live out too fast" if we were in the same environment. We hypothesize that sulfide, a natural reducer of oxygen that is made in many cell types, acts as a buffer to prevent unrestricted oxygen consumption. To test this, we administered sulfide in the form of hydrogen sulfide (H2S) to mice (Mus musculus). As we have previously shown, H2S decreases the metabolic rate of mice by approximately 90% and induces a Suspended Animation-like state. Mice cannot survive for longer than 20 min when exposed to 5% oxygen. However, if mice are first put into a Suspended Animation-like state by a 20-min pretreatment with H2S and then are exposed to low oxygen, they can survive for more than 6.5 h in 5% oxygen with no apparent detrimental effects. In addition, if mice are exposed to a 20-min pretreatment with H2S followed by 1 h at 5% oxygen, they can then survive for several hours at oxygen tensions as low as 3%. We hypothesize that prior exposure to H2S reduces oxygen demand, therefore making it possible for the mice to survive with low oxygen supply. These results suggest that H2S may be useful to prevent damage associated with hypoxia.
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H2S induces a Suspended Animation-like state in mice.
Science (New York N.Y.), 2005Co-Authors: Eric Blackstone, Mike Morrison, Mark B. RothAbstract:Mammals normally maintain their core body temperature (CBT) despite changes in environmental temperature. Exceptions to this norm include Suspended Animation-like states such as hibernation, torpor, and estivation. These states are all characterized by marked decreases in metabolic rate, followed by a loss of homeothermic control in which the animal's CBT approaches that of the environment. We report that hydrogen sulfide can induce a Suspended Animation-like state in a nonhibernating species, the house mouse (Mus musculus). This state is readily reversible and does not appear to harm the animal. This suggests the possibility of inducing Suspended Animation-like states for medical applications.
Peter Safar - One of the best experts on this subject based on the ideXlab platform.
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Suspended Animation can allow survival without brain damage after traumatic exsanguination cardiac arrest of 60 minutes in dogs
Journal of Trauma-injury Infection and Critical Care, 2004Co-Authors: Ala Nozari, Patrick M. Kochanek, Peter Safar, Ann Radovsky, William Stezoski, Jeremy Henchir, Miroslav Klain, Samuel A. TishermanAbstract:BACKGROUND We have previously shown in dogs that exsanguination cardiac arrest of up to 120 minutes without trauma under profound hypothermia induced by aortic flush (Suspended Animation) can be survived without neurologic deficit. In the present study, the effects of major trauma (laparotomy, thoracotomy) are explored. This study is designed to better mimic the clinical scenario of an exsanguinating trauma victim, for whom Suspended Animation may buy time for resuscitative surgery and delayed resuscitation. METHODS Fourteen dogs were exsanguinated over 5 minutes to cardiac arrest. Flush of saline at 2 degrees C into the femoral artery was initiated at 2 minutes of cardiac arrest and continued until a tympanic temperature of 10 degrees C was achieved. The dogs were then randomized into a control group without trauma (n = 6) or a trauma group (n = 8) that underwent a laparotomy and isolation of the spleen before hemorrhage and then, at the start of cardiac arrest, spleen transection and left thoracotomy. During cardiac arrest, splenectomy was performed. After 60 minutes of no-flow cardiac arrest, reperfusion with cardiopulmonary bypass was followed by intensive care to 72 hours. RESULTS All 14 dogs survived to 72 hours with histologically normal brains. All control dogs were functionally neurologically intact. Four of eight trauma dogs were also functionally normal. Four had neurologic deficits, although three required prolonged mechanical ventilation because of airway edema and evidence of multiple organ failure. Blood loss from the chest and abdomen was variable and was associated with poor functional outcomes. CONCLUSION Rapid induction of profound hypothermic Suspended Animation (tympanic temperature, 10 degrees C) can enable survival without brain damage after exsanguination cardiac arrest of 60 minutes even in the presence of trauma, although prolonged intensive care may be required. This technique may allow survival of exsanguinated trauma victims, who now have almost no chance of survival.
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Novel Potentials for Emergency Hypothermia: Suspended Animation with Delayed Resuscitation from Exsanguination Cardiac Arrest
Hypothermia for Acute Brain Damage, 2004Co-Authors: Patrick M. Kochanek, Samuel A. Tisherman, S. William Stezoski, Ala Nozari, Peter SafarAbstract:Most combat fatalities result from rapid exsanguination in the field and resuscitation via fluid administration is generally unsuccessful. In a series of experiments over the past 5 years, we have developed a novel approach targeting the use of rapid induction of profound hypothermia by aortic flush to produce a state of Suspended Animation for delayed resuscitation after experimental exsanguination cardiac arrest in dogs. In over 200 experiments in dogs, exsanguination cardiac arrest was induced by rapid hemorrhage over ~5 min. After the 5-min hemorrhage and an additional 2 min of cardiac arrest, hypothermia (8°–34°C, tympanic temperature) was induced by aortic or femoral flush of ice-cold saline via a balloon catheter. Cardiac arrest was then continued for durations ranging between 15 and 120 min. The specific duration and temperature selected depended on the goals of the specific study. Delayed resuscitation after the predefined Suspended Animation interval was achieved using cardiopulmonary bypass (for 1–2h), mild hypothermia (34°C to 12h), and 72–90 h of continuous intensive care. In some studies, the insult also included laparotomy, splenectomy, and thoracotomy, to simulate trauma. In other studies, pharmacological agents were combined with hypothermia to test for therapeutic synergy. Final neurologic outcome was assessed at 72–96 h by overall performance category and neurological deficit scores. Brain histopathology was also evaluated. Normal neurologic outcome with minimal histopathologic damage was routinely achieved after a cardiac arrest of 90 min using this Suspended Animation approach. In some dogs, good neurologic outcome was achieved even after a cardiac arrest of 120 min. A delay of 5–8 min in the induction of Suspended Animation attenuated its preservative effect. Of 14 drugs tested, only the antioxidant tempol produced a synergistic effect with hypothermia. The addition of trauma worsened organ function without affecting brain histopathology. Suspended Animation with delayed resuscitation represents a revolutionary approach to resuscitation of the trauma victim with otherwise lethal exsanguination cardiac arrest. Our studies suggest additional benefit from the combination of antioxidants with hypothermia, and challenge the previously posed limits of hypothermic protection and preservation of the brain. In ongoing studies we are testing Suspended Animation after prolonged shock, evaluating the mechanisms of hypothermic protection using proteomics, and probing beyond the 2-h theoretical limit for cardiac arrest duration with intact survival.
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Suspended Animation can allow survival without brain damage after traumatic exsanguination cardiac arrest of 60 minutes in dogs.
The Journal of trauma, 2004Co-Authors: Ala Nozari, Patrick M. Kochanek, Peter Safar, Ann Radovsky, William Stezoski, Jeremy Henchir, Miroslav Klain, Samuel A. TishermanAbstract:We have previously shown in dogs that exsanguination cardiac arrest of up to 120 minutes without trauma under profound hypothermia induced by aortic flush (Suspended Animation) can be survived without neurologic deficit. In the present study, the effects of major trauma (laparotomy, thoracotomy) are explored. This study is designed to better mimic the clinical scenario of an exsanguinating trauma victim, for whom Suspended Animation may buy time for resuscitative surgery and delayed resuscitation. Fourteen dogs were exsanguinated over 5 minutes to cardiac arrest. Flush of saline at 2 degrees C into the femoral artery was initiated at 2 minutes of cardiac arrest and continued until a tympanic temperature of 10 degrees C was achieved. The dogs were then randomized into a control group without trauma (n = 6) or a trauma group (n = 8) that underwent a laparotomy and isolation of the spleen before hemorrhage and then, at the start of cardiac arrest, spleen transection and left thoracotomy. During cardiac arrest, splenectomy was performed. After 60 minutes of no-flow cardiac arrest, reperfusion with cardiopulmonary bypass was followed by intensive care to 72 hours. All 14 dogs survived to 72 hours with histologically normal brains. All control dogs were functionally neurologically intact. Four of eight trauma dogs were also functionally normal. Four had neurologic deficits, although three required prolonged mechanical ventilation because of airway edema and evidence of multiple organ failure. Blood loss from the chest and abdomen was variable and was associated with poor functional outcomes. Rapid induction of profound hypothermic Suspended Animation (tympanic temperature, 10 degrees C) can enable survival without brain damage after exsanguination cardiac arrest of 60 minutes even in the presence of trauma, although prolonged intensive care may be required. This technique may allow survival of exsanguinated trauma victims, who now have almost no chance of survival.
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Suspended Animation can allow survival without brain damage after traumatic exsanguination cardiac arrest of 60 minutes in dogs
American Society of Anesthesiologists' Annual Meeting, 2004Co-Authors: Ala Nozari, Patrick M. Kochanek, Peter Safar, Ann Radovsky, William Stezoski, Jeremy Henchir, Miroslav Klain, Samuel A. TishermanAbstract:Background: We have previously shown in dogs that exsanguination cardiac arrest of up to 120 minutes without trauma under profound hypothermia induced by aortic flush (Suspended Animation) can be survived without neurologic deficit. In the present study, the effects of major trauma (laparotomy, thoracotomy) are explored. This study is designed to better mimic the clinical scenario of an exsanguinating trauma victim, for whom Suspended Animation may buy time for resuscitative surgery and delayed resuscitation. Methods: Fourteen dogs were exsanguinated over 5 minutes to cardiac arrest. Flush of saline at 2°C into the femoral artery was initiated at 2 minutes of cardiac arrest and continued until a tympanic temperature of 10°C was achieved. The dogs were then randomized into a control group without trauma (n = 6) or a trauma group (n = 8) that underwent a laparotomy and isolation of the spleen before hemorrhage and then, at the start of cardiac arrest, spleen transection and left thoracotomy. During cardiac arrest, splenectomy was performed. After 60 minutes of no-flow cardiac arrest, reperfusion with cardiopulmonary bypass was followed by intensive care to 72 hours. Results: All 14 dogs survived to 72 hours with histologically normal brains. All control dogs were functionally neurologically intact. Four of eight trauma dogs were also functionally normal. Four had neurologic deficits, although three required prolonged mechanical ventilation because of airway edema and evidence of multiple organ failure. Blood loss from the chest and abdomen was variable and was associated with poor functional outcomes. Conclusion: Rapid induction of profound hypothermic Suspended Animation (tympanic temperature, 10°C) can enable survival without brain damage after exsanguination cardiac arrest of 60 minutes even in the presence of trauma, although prolonged intensive care may be required. This technique may allow survival of exsanguinated trauma victims, who now have almost no chance of survival.
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Survival without brain damage after clinical death of 60-120 mins in dogs using Suspended Animation by profound hypothermia.
Critical care medicine, 2003Co-Authors: Wilhelm Behringer, Patrick M. Kochanek, Peter Safar, Ann Radovsky, Rainer Kentner, C. Dixon, Samuel A. TishermanAbstract:ObjectivesThis study explored the limits of good outcome of brain and organism achievable after cardiac arrest (no blood flow) of 60–120 mins, with preservation (Suspended Animation) induced immediately after the start of exsanguination cardiac arrest.DesignProspective experimental comparison of thr
Wilhelm Behringer - One of the best experts on this subject based on the ideXlab platform.
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Therapeutic hypothermia after cardiac arrest.
Current opinion in anaesthesiology, 2005Co-Authors: Michael Holzer, Wilhelm BehringerAbstract:Most patients who suffer a cardiac arrest die after the event. Full neurological recovery occurs in only 6-23%. Until recently no specific post-arrest therapy was available to improve outcome. Application of therapeutic hypothermia (32-34 degrees C for 12-24 h) applied after cardiac arrest could help to improve this dreadful situation. This review covers the background of and recent clinical studies into hypothermia after cardiac arrest, and gives some insights into the future of resuscitation, namely Suspended Animation. Two randomized clinical trials of mild therapeutic hypothermia applied after successful resuscitation from cardiac arrest showed that hypothermia after cardiac arrest improves neurological outcome as well as overall mortality. The introduction of therapeutic hypothermia after cardiac arrest into routine intensive care practice could save thousands of lives worldwide, because only six patients must be treated to yield one additional patient with favourable neurological recovery. New developments in cooling techniques will make early induction of therapeutic hypothermia simple and convenient. The optimal duration and depth of hypothermia will be determined by future trials. Suspended Animation is cooling during cardiac arrest to preserve the organism under conditions of prolonged controlled clinical death, followed by delayed resuscitation, resulting in survival without brain damage. This concept was initially introduced for trauma victims who rapidly bleed to death, and proved to be feasible in studies evaluating outcomes following exsanguination cardiac arrest in large animals. Whether the concept of Suspended Animation is applicable to normovolemic cardiac arrest is under investigation.
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Survival without brain damage after clinical death of 60-120 mins in dogs using Suspended Animation by profound hypothermia.
Critical care medicine, 2003Co-Authors: Wilhelm Behringer, Patrick M. Kochanek, Peter Safar, Ann Radovsky, Rainer Kentner, C. Dixon, Samuel A. TishermanAbstract:ObjectivesThis study explored the limits of good outcome of brain and organism achievable after cardiac arrest (no blood flow) of 60–120 mins, with preservation (Suspended Animation) induced immediately after the start of exsanguination cardiac arrest.DesignProspective experimental comparison of thr
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Suspended Animation for delayed resuscitation from prolonged cardiac arrest that is unresuscitable by standard cardiopulmonary-cerebral resuscitation.
Critical Care Medicine, 2000Co-Authors: Peter Safar, Samuel A. Tisherman, A Capone, Wilhelm Behringer, Stephan Prueckner, Ann Radovsky, William Stezoski, Randy J. WoodsAbstract:Standard cardiopulmonary-cerebral resuscitation fails to achieve restoration of spontaneous circulation in approximately 50% of normovolemic sudden cardiac arrests outside hospitals and in essentially all victims of penetrating truncal trauma who exsanguinate rapidly to cardiac arrest. Among cardiopulmonary-cerebral resuscitation innovations since the 1960s, automatic external defibrillation, mild hypothermia, emergency (portable) cardiopulmonary bypass, and Suspended Animation have potentials for clinical breakthrough effects. Suspended Animation has been suggested for presently unresuscitable conditions and consists of the rapid induction of preservation (using hypothermia with or without drugs) of viability of the brain, heart, and organism (within 5 mins of normothermic cardiac arrest no-flow), which increases the time available for transport and resuscitative surgery, followed by delayed resuscitation. Since 1988, we have developed and used novel dog models of exsanguination cardiac arrest to explore Suspended Animation potentials with hypothermic and pharmacologic strategies using aortic cold flush and emergency portable cardiopulmonary bypass. Outcome evaluation was at 72 or 96 hrs after cardiac arrest. Cardiopulmonary bypass cannot be initiated rapidly. A single aortic flush of cold saline (4 degrees C) at the start of cardiac arrest rapidly induced (depending on flush volume) mild-to-deep cerebral hypothermia (35 degrees to 10 degrees C), without cardiopulmonary bypass, and preserved viability during a cardiac arrest no-flow period of up to 120 mins. In contrast, except for one antioxidant (Tempol), explorations of 14 different drugs added to the aortic flush at room temperature (24 degrees C) have thus far had disappointing outcome results. Profound hypothermia (10 degrees C) during 60-min cardiac arrest induced and reversed with cardiopulmonary bypass achieved survival without functional or histologic brain damage. Further plans for the systematic development of Suspended Animation include the following: a) aortic flush, combining hypothermia with mechanism-specific drugs and novel fluids; b) extension of Suspended Animation by ultraprofound hypothermic preservation (0 degrees to 5 degrees C) with cardiopulmonary bypass; c) development of the most effective Suspended Animation protocol for clinical trials in trauma patients with cardiac arrest; and d) modification of Suspended Animation protocols for possible use in normovolemic ventricular fibrillation cardiac arrest, in which attempts to achieve restoration of spontaneous circulation by standard external cardiopulmonary resuscitation-advanced life support have failed.
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Global Brain Ischemia: Animal Studies
Therapeutic Hypothermia, 1Co-Authors: Wilhelm BehringerAbstract:This chapter will describe the background of therapeutic hypothermia with regard to animal models with cardiac arrest or vessel occlusion that led to the recent trials of therapeutic hypothermia after cardiac arrest in humans (1, 2, 3, 4, 5, 6, 7). In addition, future potentials of intra-ischemic hypothermia (Suspended Animation) are discussed.
Randy J. Woods - One of the best experts on this subject based on the ideXlab platform.
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Suspended Animation for delayed resuscitation from prolonged cardiac arrest that is unresuscitable by standard cardiopulmonary-cerebral resuscitation.
Critical Care Medicine, 2000Co-Authors: Peter Safar, Samuel A. Tisherman, A Capone, Wilhelm Behringer, Stephan Prueckner, Ann Radovsky, William Stezoski, Randy J. WoodsAbstract:Standard cardiopulmonary-cerebral resuscitation fails to achieve restoration of spontaneous circulation in approximately 50% of normovolemic sudden cardiac arrests outside hospitals and in essentially all victims of penetrating truncal trauma who exsanguinate rapidly to cardiac arrest. Among cardiopulmonary-cerebral resuscitation innovations since the 1960s, automatic external defibrillation, mild hypothermia, emergency (portable) cardiopulmonary bypass, and Suspended Animation have potentials for clinical breakthrough effects. Suspended Animation has been suggested for presently unresuscitable conditions and consists of the rapid induction of preservation (using hypothermia with or without drugs) of viability of the brain, heart, and organism (within 5 mins of normothermic cardiac arrest no-flow), which increases the time available for transport and resuscitative surgery, followed by delayed resuscitation. Since 1988, we have developed and used novel dog models of exsanguination cardiac arrest to explore Suspended Animation potentials with hypothermic and pharmacologic strategies using aortic cold flush and emergency portable cardiopulmonary bypass. Outcome evaluation was at 72 or 96 hrs after cardiac arrest. Cardiopulmonary bypass cannot be initiated rapidly. A single aortic flush of cold saline (4 degrees C) at the start of cardiac arrest rapidly induced (depending on flush volume) mild-to-deep cerebral hypothermia (35 degrees to 10 degrees C), without cardiopulmonary bypass, and preserved viability during a cardiac arrest no-flow period of up to 120 mins. In contrast, except for one antioxidant (Tempol), explorations of 14 different drugs added to the aortic flush at room temperature (24 degrees C) have thus far had disappointing outcome results. Profound hypothermia (10 degrees C) during 60-min cardiac arrest induced and reversed with cardiopulmonary bypass achieved survival without functional or histologic brain damage. Further plans for the systematic development of Suspended Animation include the following: a) aortic flush, combining hypothermia with mechanism-specific drugs and novel fluids; b) extension of Suspended Animation by ultraprofound hypothermic preservation (0 degrees to 5 degrees C) with cardiopulmonary bypass; c) development of the most effective Suspended Animation protocol for clinical trials in trauma patients with cardiac arrest; and d) modification of Suspended Animation protocols for possible use in normovolemic ventricular fibrillation cardiac arrest, in which attempts to achieve restoration of spontaneous circulation by standard external cardiopulmonary resuscitation-advanced life support have failed.
