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Wilhelm Behringer

Publications and source records attributed to Wilhelm Behringer.

At least 19 recordsLinked to original sources
PubMed2006

Small volume resuscitation with tempol is detrimental during uncontrolled hemorrhagic shock in rats.

BACKGROUND: In a previous study, titration of a hypertonic saline (HTS) solution during severe uncontrolled hemorrhagic shock (UHS) failed to reduce mortality. In a separate study, a novel antioxidant, polynitroxylated albumin (PNA) plus tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), infused during shock increased long-term survival. We hypothesized that combining potent antioxidants with a hypertonic solution during UHS would preserve the logistical advantage of small volume resuscitation and improve survival. METHODS: An UHS outcome model in rats was used. UHS phase I (90 min) included blood withdrawal of 30 ml/kg over 15 min, followed by tail amputation for uncontrolled bleeding. At 20 min, rats were randomized to four groups (n=10 each) for hypotensive resuscitation from 20 to 90 min (mean arterial pressure [MAP] > or = 40 mmHg): HTS/starch group received 7.2% NaCl/10% hydroxyethyl starch; HTS/albumin group received 7.5% NaCl/20% albumin; HTS/PNA group received 7.5% NaCl/20% PNA; HTS/albumin+tempol group received 7.5% NaCl/20% albumin plus tempol. Resuscitation phase II (180 min) included hemostasis, return of shed blood and administration of fluids to restore MAP > or = 80 mmHg. Observation phase III was to 72 h. RESULTS: The total amount of fluid required to maintain hypotensive MAP during HS was low and did not differ between groups (range: 3.4+/-1.9 to 5.3+/-2.5 ml/kg). The rate of fluid administration required was higher in the HTS/albumin+tempol group compared to all other groups (p=0.006). Additional uncontrolled blood loss was highest in the HTS/PNA group (16.2+/-5.7 ml/kg [p=0.01] versus 10.4+/-7.9 ml/kg in the HTS/starch group, 7.7+/-5.2 ml/kg in the HTS/albumin group and 8.2+/-7.1 ml/kg in the HTS/albumin+tempol group). MAP after start of resuscitation in phase I was lower in the HTS/albumin+tempol group than the HTS/albumin or HTS/PNA groups (p<0.01). This group was also less tachycardic. Long-term survival was low in all groups (2 of 10 after HTS/starch and 1 of 10 after HTS/albumin, 3 of 10 after HTS/PNA, 1 of 10 after HTS/albumin+tempol). Median survival time was shortest in the HTS/albumin+tempol group (72 min [CI 34-190]) compared to all other groups (p=0.01). CONCLUSIONS: Despite its benefits in other model systems, free tempol is potentially hazardous when combined with hypertonic fluids. PNA abrogates these deleterious effects on acute mortality but may lead to increased blood loss in the setting of UHS.

Albumins↗
PubMed2006

Rapid induction of cerebral hypothermia by aortic flush during normovolemic cardiac arrest in pigs.

OBJECTIVE: Induction of deep cerebral hypothermia before reperfusion might improve neurologic outcome after cardiac arrest. We hypothesized that an aortic flush with cold saline during cardiac arrest is able to induce deep cerebral hypothermia and that the cooling efficiency can be enhanced by a) increasing the arteriovenous pressure gradient during the flush with vasopressin; b) improving the cerebral microcirculation during the flush with the thrombolytic agent alteplase; and c) increasing the arteriovenous pressure gradient further with venting the right heart by draining blood during the flush. DESIGN: Prospective randomized experimental study. SETTING: University research laboratory. SUBJECTS: Twenty-four pigs Large White breed (31-42 kg). INTERVENTIONS: After 10 mins of ventricular fibrillation, pigs received an aortic flush (100 mL/kg, 4 degrees C, flow rate 35 mL/kg/min) into the descending aorta via a balloon catheter. The animals were subjected randomly to either an aortic flush with saline, saline plus vasopressin 1.2 IU/kg, saline plus alteplase 1 mg/kg, saline plus a combination of vasopressin 1.2 IU/kg and alteplase 1 mg/kg, or saline plus vasopressin 1.2 IU/kg and venting the right heart. Arterial and venous pressures and brain temperatures were recorded for an observation time of 10 mins after flush. MEASUREMENTS AND MAIN RESULTS: A sufficient arteriovenous pressure gradient and deep cerebral hypothermia were only achieved with a flush containing vasopressin (brain temperature 16.1+/-1.3 degrees C in the vasopressin group vs. 35.4+/-1.5 degrees C in the saline group, p<.001); combining vasopressin with alteplase, or venting the right heart, did not further enhance the cooling efficiency of the flush. CONCLUSIONS: A cold saline aortic flush with vasopressin rapidly decreases brain temperature during prolonged normovolemic cardiac arrest in pigs. Whether deep cerebral hypothermia induced before reperfusion can improve neurologic outcome after cardiac arrest needs further investigation in large animal outcome studies.

Animals↗
PubMed2005

Titrated hypertonic/hyperoncotic solution for hypotensive fluid resuscitation during uncontrolled hemorrhagic shock in rats.

BACKGROUND: In volume- or pressure-controlled hemorrhagic shock (HS) a bolus intravenous infusion of hypertonic/hyperoncotic solution (HHS) proved beneficial compared to isotonic crystalloid solutions. During uncontrolled HS in animals, however, HHS by bolus increased blood pressure unpredictably, and increased blood loss and mortality. We hypothesized that a titrated i.v. infusion of HHS, compared to titrated lactated Ringer's solution (LR), for hypotensive fluid resuscitation during uncontrolled HS reduces fluid requirement, does not increase blood loss, and improves survival. METHODS: We used our three-phased uncontrolled HS outcome model in rats. HS phase I began with blood withdrawal of 3 ml/100g over 15 min, followed by tail amputation. Then, hydroxyethyl starch 10% in NaCl 7.2% was given i.v. to the HHS group (n=10) and LR to the control group (n=10), both titrated to prevent mean arterial pressure (MAP) from falling below 40 mmHg during HS time 20-90 min. At HS 90 min, resuscitation phase II of 180 min began with hemostasis, return of all the blood initially shed, plus fluids i.v. as needed to maintain normotension (MAP>or=70 mmHg). Liver dysoxia was monitored as increase in liver surface pCO2 during phases I and II. Observation phase III was to 72 h. RESULTS: During HS, preventing a decrease in MAP below 40 mmHg required HHS 4.9+/-0.6 ml/kg (all data mean+/-S.E.M.), compared to LR 62.2+/-16.6 ml/kg (P<0.001), with no group difference in MAP. Uncontrolled blood loss during HS from the tail stump was 13.3+/-1.9 ml/kg with HHS infusion, versus 12.6+/-2.5 ml/kg with LR infusion (P=0.73). Serum sodium concentrations were moderately elevated at the end of HS in the HHS group (149+/-3 mmol/l) versus the LR group (139+/-1 mmol/l) (P=0.001), and remained elevated throughout. Liver pCO2 increased during HS in both groups equally (P<0.001 versus baseline), and tended to return to baseline levels at the end of HS. Blood gas and lactate values throughout did not differ between groups. During HS, 2 of 10 rats in the HHS group versus 0 of 10 in the LR group died (P=0.47). There was no difference between HHS and LR groups in survival rates to 72 h (3 of 10 in the HHS group versus 2 of 10 in the LR group) (P=1.0). Survival times, by life table analysis, were not different (P=0.75). CONCLUSION: In prolonged uncontrolled HS, a titrated i.v. infusion of HHS can maintain controlled hypotension with only one-tenth of the volume of LR required, without increasing blood loss. This titrated HHS strategy may not increase the chance of long-term survival.

Animals↗
PubMed2005

Therapeutic hypothermia after cardiac arrest.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

Journal Article↗
PubMed2005

Extracorporeal venovenous cooling for induction of mild hypothermia in human-sized swine.

OBJECTIVE: Several cooling methods have been investigated for inducing mild hypothermia (33-36 degrees C) after cardiac arrest, brain trauma, or stroke. To achieve its best effect, therapeutic hypothermia has to be applied very early after the ischemic insult; otherwise, the beneficial effect would be diminished or even abrogated. The aim of this study was to investigate the effectiveness and safety of extracorporeal venovenous cooling as compared with endovascular cooling. DESIGN: Swine were cooled in a randomized crossover design from 38 degrees C to 33 degrees C brain temperature, either with extracorporeal venovenous cooling or with endovascular cooling. SETTING: Laboratory investigation. SUBJECTS: Six swine of human size (85 to 101 kg). INTERVENTIONS: Swine were randomly cooled with the first device, and after achieving the target brain temperature, re-warmed via the same technique and with heating lamps to baseline temperature. Then the other catheter was inserted and cooling was performed with the second device. MEASUREMENTS: Brain, pulmonary artery and tympanic temperature, blood pressure, and heart rate were recorded continuously. Laboratory samples, including free hemoglobin, were taken at predefined temperature points during cooling. Comparisons between and within (baseline vs. 33 degrees C) the treatment groups were performed with the paired Student's t-test. MAIN RESULTS: The time needed to reduce brain temperature from 38.0 degrees C to 33.0 degrees C was 41 +/- 17 mins with venovenous cooling and 126 +/- 37 mins with endovascular cooling (p = .001). Heart rate and mean arterial pressure decreased moderately during cooling and were significantly lower at 33 degrees C than at baseline in both groups, without differences between groups. None of the swine developed significant hemolysis, arrhythmias, or bleeding. CONCLUSIONS: Extracorporeal venovenous cooling was an effective and safe method to rapidly induce therapeutic mild hypothermia in human-sized swine. It seems to be promising for further application and investigation in patients.

Animals↗
PubMed2004

Ventricular fibrillation median frequency may not be useful for monitoring during cardiac arrest treated with endothelin-1 or epinephrine.

In this study, we evaluated whether median fibrillation frequency (MF) and mean fibrillation amplitude (AMP) reflect coronary perfusion pressure (CoPP) and predict successful defibrillation. MF, AMP, and CoPP were measured during prolonged ventricular fibrillation (VF) cardiac arrest and resuscitation in pigs. After 5 min of VF, cardiopulmonary resuscitation was started. At 10 min, the pigs received randomly a single dose of endothelin-1 50 mug (n = 7), 100 mug (n = 7), or 200 mug (n = 5), or repeated doses of epinephrine 0.04 mg/kg (n = 6), or saline (n = 6) every 3 min. At 25 min, the pigs were defibrillated to achieve restoration of spontaneous circulation (ROSC). In a nonparametric spectral analysis of the individual MF versus CoPP and AMP versus CoPP curves, we found no link between the different curves in different animals or therapies. No difference was found in MF in pigs with ROSC (n = 8) compared with animals not achieving ROSC (n = 23) immediately before defibrillation (P = 0.85). Our data suggest that, in prolonged VF cardiac arrest, MF and AMP might not be useful tools to reflect myocardial perfusion.

Adrenergic alpha-Agonists↗
PubMed2003

Mild hypothermia during hemorrhagic shock in rats improves survival without significant effects on inflammatory responses.

OBJECTIVE: To explore the hypothesis that the survival benefit of mild, therapeutic hypothermia during hemorrhagic shock is associated with inhibition of lipid peroxidation and the acute inflammatory response. DESIGN: Prospective and randomized. SETTING: Animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats underwent pressure-controlled (mean arterial pressure 40 mm Hg) hemorrhagic shock for 90 mins. They were randomized to normothermia (38.0 +/- 0.5 degrees C) or mild hypothermia (33-34 degrees C from hemorrhagic shock 20 mins to resuscitation time 12 hrs). Rats were killed at resuscitation time 3 or 24 hrs. MEASUREMENTS AND MAIN RESULTS: All seven rats in the hypothermia group and seven of 15 rats in the normothermia group survived to 24 hrs (p <.05). Hypothermic rats had lower serum potassium and higher blood glucose concentrations at 90 mins of hemorrhagic shock (p <.05). At resuscitation time 24 hrs, the hypothermia group had less liver injury (based on serum concentrations of ornithine carbamolytransferase and liver histology) and higher blood glucose than the normothermia group (p <.05). There were no differences in serum free 8-isoprostane (a marker of lipid peroxidation by free radicals) between the two groups at either baseline or resuscitation time 1 hr. Serum concentrations of interleukin- 1 beta, interleukin-6, and tumor necrosis factor-alpha peaked at resuscitation time 1 hr. Tumor necrosis factor-alpha concentrations were higher (p <.05) at resuscitation time 1 hr in the hypothermia group compared with the normothermic group. Serum cytokine concentrations were not different between survivors and nonsurvivors in the normothermia group. Serum cytokine concentrations returned to baseline values in both groups by 24 hrs. There were no differences in the number of neutrophils in the lungs or the small intestine between the groups. More neutrophils were found in the lungs at resuscitation time 3 hrs than at resuscitation time 24 hrs in both groups (p <.01). CONCLUSIONS: These data suggest that lipid peroxidation and systemic inflammatory responses to hemorrhagic shock are minimally influenced by mild hypothermia, although liver injury is mitigated and survival improved. Other mechanisms of benefit from mild hypothermia need to be explored.

Animals↗
PubMed2003

Hypothermia after cardiac arrest: a treatment that works.

PURPOSE OF REVIEW: Sudden death from cardiac arrest is a major health problem that still receives too little publicity. Current therapy after cardiac arrest concentrates on resuscitation efforts because, until now, no specific therapy for brain protection after restoration of spontaneous circulation was available. Therapeutic mild or moderate resuscitative hypothermia is a novel therapy with multifaceted chemical and physical effects by preventing or mitigating the derangements seen in the postresuscitation syndrome. RECENT FINDINGS AND SUMMARY: In 2002, two prospective, randomized studies reported improved outcomes when deliberate hypothermia was induced in comatose survivors after resuscitation from cardiac arrest. However, several issues with regard to resuscitative cooling are still unanswered and should be studied further. These include the optimal timing to initiate cooling, the optimal cooling period, the optimal temperature level, and rewarming strategy. Even important questions, such as which cooling technique will be available in the near future that would combine ease of use with high efficacy, are not answered yet.

Heart Arrest↗
PubMed2003

Survival without brain damage after clinical death of 60-120 mins in dogs using suspended animation by profound hypothermia.

OBJECTIVES: This 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. DESIGN: Prospective experimental comparison of three arrest times, without randomization. SETTING: University research laboratory. SUBJECTS: Twenty-seven custom-bred hunting dogs (17-25 kg). INTERVENTIONS: Dogs were exsanguinated over 5 mins to cardiac arrest no-flow of 60 mins, 90 mins, or 120 mins. At 2 mins of cardiac arrest, the dogs received, via a balloon-tipped catheter, an aortic flush of isotonic saline at 2 degrees C (at a rate of 1 L/min), until tympanic temperature reached 20 degrees C (for 60 mins of cardiac arrest), 15 degrees C (for 60 mins of cardiac arrest), or 10 degrees C (for 60, 90, or 120 mins of cardiac arrest). Resuscitation was by closed-chest cardiopulmonary bypass, postcardiac arrest mild hypothermia (tympanic temperature 34 degrees C) to 12 hrs, controlled ventilation to 20 hrs, and intensive care to 72 hrs. MEASUREMENTS AND MAIN RESULTS: We assessed overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, death), neurologic deficit scores (NDS 0-10%, normal; 100%, brain death), regional and total brain histologic damage scores at 72 hrs (total HDS >0-40, mild; 40-100, moderate; >100, severe damage), and morphologic damage of extracerebral organs. For 60 mins of cardiac arrest (n = 14), tympanic temperature 20 degrees C (n = 6) was achieved after flush of 3 mins and resulted in two dogs with OPC 1 and four dogs with OPC 2: median NDS, 13% (range 0-27%); and median total HDS, 28 (range, 4-36). Tympanic temperature of 15 degrees C (n = 5) was achieved after flush of 7 mins and resulted in all five dogs with OPC 1, NDS 0% (0-3%), and HDS 8 (0-48). Tympanic temperature 10 degrees C (n = 3) was achieved after flush of 11 mins and resulted in all three dogs with OPC 1, NDS 0%, and HDS 16 (2-18). For 90 mins of cardiac arrest (n = 6), tympanic temperature 10 degrees C was achieved after flush of 15 mins and resulted in all six dogs with OPC 1, NDS 0%, and HDS 8 (0-37). For 120 mins of cardiac arrest (n = 7), three dogs had to be excluded. In the four dogs within protocol, tympanic temperature 10 degrees C was achieved after flush of 15 mins. This resulted in one dog with OPC 1, NDS 0%, and total HDS 14; one with OPC 1, NDS 6%, and total HDS 20; one with OPC 2, NDS 13%, and total HDS 10; and one with OPC 3, NDS 39%, and total HDS 22. CONCLUSIONS: In a systematic series of studies in dogs, the rapid induction of profound cerebral hypothermia (tympanic temperature 10 degrees C) by aortic flush of cold saline immediately after the start of exsanguination cardiac arrest-which rarely can be resuscitated effectively with current methods-can achieve survival without functional or histologic brain damage, after cardiac arrest no-flow of 60 or 90 mins and possibly 120 mins. The use of additional preservation strategies should be pursued in the 120-min arrest model.

Animals↗
PubMed2002

Veno-venous extracorporeal blood shunt cooling to induce mild hypothermia in dog experiments and review of cooling methods.

Mild hypothermia (33-36 degrees C) might be beneficial when induced during or after insults to the brain (cardiac arrest, brain trauma, stroke), spinal cord (trauma), heart (acute myocardial infarction), or viscera (hemorrhagic shock). Reaching the target temperature rapidly in patients inside and outside hospitals remains a challenge. This study was to test the feasibility of veno-venous extracorporeal blood cooling for the rapid induction of mild hypothermia in dogs, using a simple pumping-cooling device. Ten custom-bred hunting dogs (21-28 kg) were lightly anesthetized and mechanically ventilated. In five dogs, two catheters were inserted through femoral veins, one peripheral and the other into the inferior vena cava. The catheters were connected via a coiled plastic tube as heat exchanger (15 m long, 3 mm inside diameter, 120 ml priming volume), which was immersed in an ice-water bath. A small roller-pump produced a veno-venous flow of 200 ml/min (about 10% of cardiac output). In five additional dogs (control group), a clinically practiced external cooling method was employed, using alcohol over the skin of the trunk and fanning plus ice-bags. During spontaneous normotension, veno-venous cooling delivered blood into the vena cava at 6.2 degrees C standard deviation (SD 1.4) and decreased tympanic membrane (Tty) temperature from 37.5 to 34.0 degrees C at 5.2 min (SD 0.7), and to 32.0 degrees C at 7.9 min (SD 1.3). Skin surface cooling decreased tympanic temperature from 37.5 to 34.0 degrees C at 19.9 min (SD 3.7), and to 32.0 degrees C at 29.9 (SD 5.1) (P=0.001). Heart rates at Tty 34 and 32 degrees C were significantly lower than at baseline in both groups, but within physiological range, without difference between groups. There were no arrhythmias. We conclude that in large dogs the induction of mild systemic hypothermia with extracorporeal veno-venous blood shunt cooling is simple and four times more rapid than skin surface cooling.

Allied Health Personnel↗
PubMed2002

Endothelin-1 elevates regional cerebral perfusion during prolonged ventricular fibrillation cardiac arrest in pigs.

Since adrenaline (epinephrine) also has negative effects during and after cardiopulmonary resuscitation (CPR) a non-adrenergic vasoconstrictor like endothelin might be an alternative to increase vital organ blood flow. We studied the effect of different doses of endothelin-1 compared with adrenaline on the ability to resuscitate, cerebral and myocardial blood flow (MBF) in a closed chest cardiac arrest pig model. After 5 min of ventricular fibrillation, CPR with a ventilator and a mechanical compression device was started. At 10 min, 31 pigs were randomized to receive a single dose of endothelin-1 50, 100 or 200 microg or repeated doses of adrenaline 0.04 mg kg(-1) or saline every 3 min. After 25 min, the pigs were defibrillated to achieve restoration of spontaneous circulation. Blood flow was measured with the fluorescent microsphere method. In animals receiving endothelin-1 50, 100 and 200 microg the cerebral blood flow (CBF) increased from median 28 (25th; 75th quartile: 16; 40), 32 (15; 48) and 17 (4; 65) to 36 (31; 54), 47 (39; 57) and 63 (35; 83) ml min(-1) per 100 g, respectively, 6 min after drug administration (P<0.05 endothelin-1 50 microg vs. Control, P<0.01 endothelin-1 100 and 200 microg vs. Control). At the same time CBF decreased in the control and adrenaline group from 36 (21; 41) and 39 (15; 50) to 12 (2; 25) and 24 (15; 26) ml min(-1) per 100 g, respectively, (P<0.05 adrenaline vs. endothelin-1 200 microg). There was no difference in MBF between the treatment groups despite a higher coronary perfusion pressure (CoPP) in the endothelin-1 groups. Restoration of spontaneous circulation could be only achieved in the endothelin-1 50 microg (3 of 7; 43%) and 100 microg (5 of 7; 71%) group. This study suggests that endothelin-1 enhances CBF during CPR better than adrenaline and increases resuscitation success.

Animals↗
PubMed2002

Cerebral resuscitation potentials for cardiac arrest.

Permanent brain damage after cardiac arrest and resuscitation is determined by many factors, predominantly arrest (no-flow) time, cardiopulmonary resuscitation (low-flow) time, and temperature. Research since around 1970 into cardiopulmonary-cerebral resuscitation has attempted to mitigate the postischemic-anoxic encephalopathy. These efforts' results have recently shown outcome benefits as documented in clinically relevant outcome models in dogs and in clinical trials. Pharmacologic strategies have so far yielded relatively disappointing results. In a recent exploration of 14 drugs in dogs, only the antioxidant tempol administered at the start of prolonged cardiac arrest improved functional outcome in dogs. Cerebral blood flow promotion by hypertensive reperfusion and hemodilution has resulted in improved outcome in dogs, and brief hypertension after restoration of spontaneous circulation is associated with improved outcome in patients. Postarrest hypercoagulability of blood seems to yield to therapeutic thrombolysis, which is associated with improved cerebral outcome in animals and patients. In a clinically relevant dog outcome model, mild postarrest cerebral hypothermia (34 degrees C), initiated with reperfusion and continued for 12 hrs, combined with cerebral blood-flow promotion increased from 5 to >10 mins the previously longest normothermic no-flow time that could be reversed to complete cerebral recovery. Mild hypothermia by surface cooling after prolonged cardiac arrest in patients has been found effective in recent clinical studies in Australia and Europe. Preliminary data on the recent randomized study in Europe have been reported. For presently unresuscitable cardiac arrests, research since the 1980s in dog outcome models of prolonged exsanguination cardiac arrest has culminated in brain and organism preservation during cardiac arrest (no-flow) durations of up to 90 mins, perhaps 120 mins, at a tympanic temperature of 10 degrees C and complete recovery of function and normal histology. This "suspended animation for delayed resuscitation" strategy includes use of an aortic flush of cold saline (or preservation solution) within the first 5 mins of no flow. This strategy should also be explored for the larger number of patients with unresuscitable out-of-hospital cardiac arrests. Suspended animation for prolonged preservation of viability could buy time for transport and repair during hypothermic no flow followed by resuscitation, or it could serve as a bridge to prolonged cardiopulmonary bypass.

Animals↗
PubMed2002

Antioxidant Tempol enhances hypothermic cerebral preservation during prolonged cardiac arrest in dogs.

The authors are systematically exploring pharmacologic preservation for temporarily unresuscitable exsanguination cardiac arrest in dogs. They hypothesized that the antioxidant Tempol improves cerebral outcome when added to aortic saline flush at the start of cardiac arrest. In study A, no drug (n = 8), Tempol 150 mg/kg (n = 4), or Tempol 300 mg/kg (n = 4) was added to 25 mL/kg saline flush at 24 degrees C (achieving mild cerebral hypothermia) at the start of 20-minute cardiac arrest. In study B, no drug (n = 8) or Tempol 300 mg/kg (n = 7) was added to 50 mL/kg saline flush at 2 degrees C (achieving moderate cerebral hypothermia) at the start of 40-minute cardiac arrest. Cardiac arrest was reversed with cardiopulmonary bypass. Mild hypothermia lasted for 12 hours, controlled ventilation was sustained to 24 hours, and intensive care was provided for up to 72 hours. In study A, overall performance category 1 or 2 (good outcome) was achieved in all eight dogs treated with Tempol compared with three of eight dogs in the control group ( P = 0.03). In study B, good outcome was achieved in all seven dogs treated with Tempol versus only two of 8 dogs in the control group ( P = 0.007). In both studies, neurologic deficit scores were significantly better in the Tempol group, but not total histologic damage scores. At 72 hours, electron paramagnetic resonance spectroscopy of Tempol revealed direct evidence for its presence in the brain. Single- and double-strand DNA damage, nitrotyrosine immunostaining, total antioxidant reserve, and ascorbate acid levels were similar between groups, and thiol levels were decreased after Tempol in study B. The authors conclude that when added to aortic saline flush at the start of prolonged cardiac arrest, the antioxidant Tempol can enhance mild or moderate hypothermic cerebral preservation in terms of improved functional outcome. The mechanisms involved in this beneficial effect need further clarification.

Animals↗
PubMed2002

Systemic hypothermia, but not regional gut hypothermia, improves survival from prolonged hemorrhagic shock in rats.

BACKGROUND: Extracorporeal blood perfusion of the gut or enterectomy can improve survival during hemorrhagic shock (HS), suggesting that the gut may be of primary importance in resuscitation. We hypothesized that cooling the gut alone could improve survival in a rat HS model and avoid potential deleterious effects of systemic hypothermia. METHODS: Thirty-two Sprague-Dawley rats were anesthetized with halothane. The gut (small intestine, cecum, and colon) was exteriorized. The right atrial (T ), rectal, and gut (T ) intraluminal temperatures were monitored. HS was induced by withdrawal of 2 mL of blood per 100 g body weight over 10 minutes. Mean arterial pressure was then maintained at 35 to 40 mm Hg to HS 90 min. From HS 20 min to resuscitation time 1 h, rats were randomized into four groups (n = 8 each): normothermia (T and T approximately 38.0 degrees C), gut-25 degrees C (T approximately 38 degrees C, T approximately 25 degrees C, induced by rinsing the gut with cooled saline), gut-33 degrees C (T approximately 38 degrees C, T approximately 33 degrees C), and systemic hypothermia (T approximately 33 degrees C, T approximately 25 degrees C). At HS 90 min, shed blood and Ringer's solution were infused to restore normotension. Survival, metabolism, and tissue damage were observed to 72 hours. RESULTS: Blood pressure was not different between groups. Compared with the normothermia group, the systemic hypothermia group had lower base deficit and lactate, and needed less fluid during resuscitation for normotension (p < 0.05), but these values were not different in the gut hypothermia groups. In addition, there were no significant improvements in tissue protection induced by regional gut hypothermia, whereas the systemic hypothermia group had lower plasma potassium, lower ornithine carbamoyltransferase (marker of liver injury), and higher glucose levels after HS (all p < 0.05). All rats in the systemic hypothermia group survived to 72 hours, whereas there was only one survivor in the normothermia group, two in the gut-33 degrees C group, and none in the gut-25 degrees C group (all p < 0.05 vs. systemic hypothermia). CONCLUSION: Cooling the gut alone does not improve acute survival from HS, suggesting that early deaths are not secondary to gut ischemia. Mild systemic hypothermia allowed 100% survival from prolonged HS.

Animals↗
PubMed2002

Early antioxidant therapy with Tempol during hemorrhagic shock increases survival in rats.

BACKGROUND: Hemorrhagic shock (HS) is associated with the generation of reactive oxygen species, which may contribute to delayed multiple organ system failure and death. Previous studies have shown that the antioxidant Tempol improved physiologic variables, although not necessarily outcome, in septic shock and HS. We hypothesized that the combination of free Tempol with polynitroxylated albumin (PNA)-bound Tempol (which prolongs half-life and decreases toxicity) improves outcome after HS in rats. METHODS: In study 1, HS was induced by blood withdrawal of 3 mL/100 g over 15 minutes. Mean arterial pressure was maintained at 40 mm Hg with either infusion of normal saline or withdrawal of blood from 20 to 90 minutes. Resuscitation (90-270 minutes) was with infusion of shed blood. Observation was to 72 hours. At HS 45 min, albumin (ALB) (n = 10) or PNA + Tempol (n = 10) was infused slowly (1 mL/100 g/h) until 120 minutes. Study 2 was the same as study 1 (n = 6 per group), but terminated at 150 minutes. Study 3 was the same as study 1, but started with ALB or PNA + Tempol (n = 7 per group) at 20 minutes. The primary outcome variable in studies 1 and 3 was survival, whereas the primary outcome variables in study 2 were antioxidant reserve (ability of the serum or tissue homogenate to scavenge peroxyl radicals produced by 2,2'-azobis [2-aminodipropane]-dihydrochloride) in serum and small intestine, and low-molecular-weight thiols in tissues (liver, small intestine, and kidney). RESULTS: In study 1, 72-hour survival was 1 of 10 (ALB group) versus 2 of 10 (PNA + Tempol group). At 90 minutes, pH was lower in the ALB group versus the PNA + Tempol group (p = 0.02) and remained low. Arterial lactate increased to 8.9 +/- 3.2 (mean +/- SD) versus 6.5 +/- 1.8 mmol/L (p = 0.04) and base excess was -9.6 +/- 4.3 versus -5.2 +/- 3.2 mmol/L (p = 0.01) (ALB vs. PNA + Tempol groups, respectively). In study 2, antioxidant reserve in serum was lower in the ALB group versus the PNA + Tempol group (p = 0.002). There were no differences between groups in antioxidant reserve in the small intestine or low-molecular-weight thiols in liver, kidney, and small intestine. In study 3, 72-hour survival was zero of seven (ALB group) versus five of seven (PNA + Tempol group) (p = 0.02). Heart rate and systolic blood pressure during late HS were higher in the ALB group in studies 1 and 3 (p < 0.05). CONCLUSION: When infused early in HS, PNA + Tempol can increase survival. When given late, it significantly improves acid-base and serum antioxidant status, without an effect on survival. Additional studies will be required to determine whether early resuscitation with PNA + Tempol attenuates reactive oxygen species-mediated injury as the mechanism for preventing the progression toward multiple organ failure and death after HS. The results suggest that antioxidant therapy with Tempol deserves further study as a potential adjunct in the initial resuscitation from HS.

Acid-Base Equilibrium↗