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Surgically treated hydrocephalus patients are frequently imaged with head computed tomography (CT), and risk/benefit communication with families is inconsistent and unknown. We aimed to educate patients and caregivers about radiation safety in CT and explore their communication preferences. We conducted a pediatric CT radiation safety and diagnostic imaging educational workshop for patients and caregivers at a national conference on hydrocephalus to characterize current practice and desired communication about CT imaging. Our workshop consisted of an interactive educational intervention with pre-/post-session surveys followed by feedback from participants. Our session included 34 participants (100% response rate for surveys) with 28 being parents of individuals with hydrocephalus. A total of 76% (n = 26) participants showed an increase in knowledge after the session (p 100 CT scans for shunt evaluation with the median being 25 scans (IQR 20). Caregivers desire and deserve to be empowered through education and social support, and continuously engaged through sharing decisions and co-designing care plans. The neurosurgical community is in an ideal position to collaborate with radiologists, primary care providers, and parents in the development and testing of credible, high-quality online and social media resources.

Therapeutic hypothermia (TH) and targeted temperature management improve neurologic recovery, and survival for patients resuscitated from witnessed out-of-hospital ventricular tachycardia (VT) and ventricular fibrillation (VF) cardiac arrest. The American Heart Association recently gave a class IIb recommendation for the use of TH for non-VT/VF and unwitnessed arrests. We explored changes in baseline characteristics, resource use, and outcomes after expanding indications for TH at our institution based on these guidelines. Fifty-six consecutive patients treated with TH for out-of-hospital cardiac arrest were retrospectively evaluated based on whether they received treatment before (protocol 1) or after (protocol 2) broadening inclusion criteria. In protocol 1, TH was indicated after a witnessed VT/VF arrest. In protocol 2, TH was indicated for unwitnessed arrests, pulseless electrical activity, or asystole. Both populations undergoing TH had similarly extensive medical comorbidities and consumed considerable hospital resources. Overall, 64% of the patients from both protocols died in the hospital, although nominally lower mortality was seen in patients treated under protocol 1 compared with protocol 2 (59% vs. 67%, P = 0.57). Lower mortality was observed after VT/VF than after pulseless electrical activity or asystole (47% vs. 93% vs. 56%, P = 0.017). No patient survived following an unwitnessed arrest, and age (odds ratio per 10 years = 2.59; 95% confidence interval, 1.34-4.81) was independently associated with increased mortality. In an evolving field where best practice is still poorly defined, these data, along with future prospective studies in larger populations, should help to enhance care delivery and optimize cost-effectiveness strategies.

The purpose of this study was to determine if mild hypothermia alters mitotic activity in normal and post-ischemic hippocampal slices. (1) Normothermic oxygen–glucose deprivation (OGD 60 min) increased mitotic activity in the hippocampus up to 4d post-OGD. (2) Mild hypothermia (33 °C for 24 h) initiated after OGD stress reduced mitotic activity compared to normothermic controls up to 8 d post-OGD. (3) Mild hypothermia stimulated mitotic activity in normal (no OGD stress) hippocampus up to 24 h post-hypothermia. In conclusion, mild transient hypothermia can increase or decrease mitotic activity depending upon the experimental condition of the hippocampal slices when hypothermia is induced.

BACKGROUND AND PURPOSE: Prior studies suggest that aerobic exercise may reduce both the brain atrophy and the decline in fractional anisotropy observed with advancing age. It is reasonable to hypothesize that exercise-induced changes to the vasculature may underlie these anatomic differences. The purpose of this blinded study was to compare high-activity and low-activity healthy elderly volunteers for differences in the cerebrovasculature as calculated from vessels extracted from noninvasive MR angiograms (MRAs). MATERIALS AND METHODS: Fourteen healthy elderly subjects underwent MRA. Seven subjects reported a high level of aerobic activity (64 ± 5 years of age; 5 men, 2 women) and 7, a low activity level (68 ± 6 years of age; 5 women, 2 men). Following vessel segmentation from MRA by an individual blinded to subject activity level, quantitative measures of vessel number, radius, and tortuosity were calculated and histogram analysis of vessel number and radius was performed. RESULTS: Aerobically active subjects exhibited statistically significant reductions in vessel tortuosity and an increased number of small vessels compared with less active subjects. CONCLUSIONS: Aerobic activity in elderly subjects is associated with lower vessel tortuosity values and an increase in the number of small-caliber vessels. It is possible that an aerobic exercise program may contribute to healthy brain aging. MRA offers a noninvasive approach to visualizing the cerebral vasculature and may prove useful in future longitudinal investigations.

Hypothermic preconditioning is rapid cooling and warming to induce tolerance to ischemia. The purpose of the study was to examine differences in brain and trunk temperature during hypothermic preconditioning.Rats (n=18) were implanted with telemetric probes for simultaneous measure of brain and trunk temperature. Hypothermic preconditioning was produced by exposing rats to cool and warm environments that produced rapid cooling to 30 degrees C and warming to 35 degrees C.Brain temperature was warmer (37.56+/-0.45 degrees C) than trunk (37.17+/-0.29 degrees C) temperature in unanesthetized, free roaming rats at room temperature (t-test p=0.04). The brain cooled (0.59+/-0.1 degrees C/min) quicker than the trunk (0.44+/-0.19 degrees C/min) during cooling cycles of hypothermic preconditioning and the brain (0.28+/-0.04 degrees C/min) warmed quicker than the trunk (0.18+/-0.07 degrees C/min) during the warming cycle of hypothermic preconditioning (t-test p0.0001). When the trunk temperature probe was designated to reach the target temperature of 35 degrees C during warming, the brain temperature (38.1+/-0.44 degrees C) was warmer than trunk temperature (34.95+/-0.16 degrees C) during the peak of warming (t-test p0.0001).The brain cools and warms quicker than the trunk during hypothermic preconditioning. Failure to anticipate these differences could lead to unrecognized brain hyperthermia during warming. Appreciation of differences in rates of change between brain and trunk temperature may be important when designing hypothermic preconditioning experiments.

Rationale and objective Pneumothorax (Ptx) is a life-threatening complication that can result from trauma, mechanical ventilation, and invasive procedures. Infrared thermography (IRT), a compact and portable technology, has become highly sensitive. We hypothesized that IRT could detect Ptx by identifying associated changes in skin temperature. Materials and methods Bilateral nonpenetrating chest incisions or needle punctures were performed in 21 anesthetized rats. Rats were then randomized to no, bilateral, left, or right Ptx by either open ( n = 16) or closed percutaneous ( n = 5) puncture through selected pleurae. Real-time thermographic images and surface temperature data were acquired with a noncooled infrared camera. Results In all cases, blinded observers correctly identified each Ptx with real-time grayscale image analysis. When compared to either the ipsilateral baseline or an abdominal reference, experimental Ptx produced a significantly greater decrease in surface temperature when compared to non-Ptx control. Conclusions These results demonstrate that portable infrared imaging can rapidly and accurately detect changes in thoracic surface temperature associated with experimental pneumothorax.

The aim of this study was to determine whether hypoxic-ischemia from asphyxial cardiac arrest activates brain caspases-1 and -3, and the anti-apoptotic protein, XIAP. Asphyxial cardiac arrest in rats was used to induce hypoxic-ischemia. A pan-caspase inhibitor (zVAD) was given in the treatment group. At 72 h after reperfusion, caspase-3 and XIAP expression were present in multiple vulnerable brain regions, whereas caspase-1 was predominantly found in the CA1 hippocampus. zVAD significantly reduced expression of caspases and XIAP and the number of ischemic neurons in the CA1 hippocampus while neurological deficit scores were improved. We conclude that hypoxic-ischemia increases caspases-1 and-3, and XIAP expression. Treatment with zVAD significantly decreases caspase and XIAP expression in these brain regions and improves neurological outcome.

Recovery of normal brain energetic conditions during and after resuscitation from cardiac arrest is critical for survival and good neurologic outcome. This review emphasizes the glucose-driven metabolic processes during and after ischemia and on the post-resuscitation development of secondary energy derangements. It also explores some potential therapeutic interventions designed to attenuate these energy derangements. The article summarizes some bench research and is not intended to provide treatment strategies for clinical application.

In the setting of rapidly exsanguinating hemorrhage, resuscitation with intravenous (i.v.) crystalloid solution may not sustain survival before availability of allogenic blood transfusion and surgery. This study tested the hypothesis that bovine hemoglobin-based oxygen carrier, HBOC-201, would improve resuscitation and extend early survival from exsanguinating hemorrhage. This study simulated the prehospital scenario of rapidly exsanguinating hemorrhage with prolonged prehospital time and lack of blood availability. Severe hemorrhagic shock was induced in swine by using multiple liver lacerations. At 9 min after the onset of bleeding, swine were randomized to receive approximately 10 mL/kg/min of i.v. lactated Ringer's solution (n = 10) or HBOC-201 (n = 7) to achieve a mean aortic pressure (MAP) of 60 mmHg. Thereafter, infusion rate was adjusted to maintain MAP at 60 mmHg for up to 2 h. All animals were initially successfully resuscitated. The results showed 2-h survival was 1 of 10 with lactated Ringer's and 7 of 7 with HBOC-201 (P = 0.0004). Nine lactated Ringer's swine had cardiovascular collapse at 36 +/- 10 min. Lactate at 30 min was 18 +/- 3 mmol/L with lactated Ringer's and 12 +/- 2 mmol/L with HBOC-201 (P < 0.05). Hematocrit was

Hyperglycemia before ischemia worsens cerebral outcome. The aim of this study was to determine the cerebral effects of giving glucose with or without insulin after asphyxial cardiac arrest. Rats underwent 8 min of asphyxial cardiac arrest. After arrest, Group 1 received NaCl; Group 2, insulin; Group 3, glucose; and Group 4, glucose plus insulin, all intravenously. Neurological deficit (ND) scores were 14+/-10%, 22+/-12%, 12+/-10% and 2+/-2% in Groups 1-4, respectively, 72 h after reperfusion. Overall histological damage (HD) scores were 4, 2, 3 and 1, respectively. Group 4 fared significantly better than group 1 on both scores. Glucose after asphyxial cardiac arrest in rats produces no increased brain damage while glucose plus insulin improves cerebral outcome.

The incidence and distribution of ischemic (necrotic) neurons in the brains of rats 72 hr after hypoxic ischemia induced via asphyxiation is described and scored. Anesthetized Sprague-Dawley rats (10/group) were endotracheally intubated and had their airways occluded for 6, 8, or 10 min, which resulted, respectively, in approximately 3, 5, or 7 min of pulselessness (MABP < 10 mm Hg). Survival was 10/10, 9/10, and 6/10 in the 6-, 8-, and 10-min groups: deaths occurred within 1 hr after resuscitation. At 72 hr, rats were reanesthetized and their brains were perfusion-fixed with 3% buffered paraformaldehyde. Paraffin-embedded, 5-μm-thick, H&E-stained sections at 5 coronal levels of the brain had shrunken, hypereosinophilic ischemic neurons in 12 anatomic regions. Ischemic neurons were most consistently found in the lateral reticular thalamic nucleus; lateral caudoputamen; CA1 region of the hippocampus; subiculum; and, with longer asphyxia times, among cerebellar Purkinje neurons. Categorical histologic damage scores were assigned to affected regions on the basis of manual counts of ischemic neurons and summed for the whole brain. Brain histologic damage scores were significantly (p < 0.01) different for the 6-, 8-, and 10-min groups (means of 8 ± 2; 14 ± 4; and 22 ± 4). Brain regions where both the number of rats affected and ranked categorical scores for ischemic neurons increased with asphyxia time were the lateral caudoputamen and cerebellar Purkinje neurons.

Survival after drowning depends on a well-functioning chain of survival, starting outside the hospital and continuing in-hospital during the post-resuscitation phase. Prehospital care personnel provide the opportunity to perform rapid rescue from submersion events. Reestablishing ventilation before cardiac arrest nearly assures no long-term neurological sequelae [1, 2]. However, if the drowning victim sustains cardiac arrest, CPR provides the best chance of neurological recovery. Controversy exists over the optimal method for performing CPR. Research suggests that bystander chest compressions alone may be better than rescue breathing combined with chest compressions (standard CPR) for resuscitating patients with sudden cardiac death [3]. These studies excluded drowning victims and others with an asphyxial cause of cardiac arrest. Unlike sudden cardiac death, drowning victims asphyxiate which leads to cardiac arrest, so maximizing oxygenation in addition to perfusion during CPR may improve outcome [4, 5]. Two prospective, population-based cohort studies support performing standard CPR for drowning victims (rescue breathing and chest compressions) [6, 7] and bystanders may play an important role [8]. Thus, it is recommended that drowning victims with no signs of life be provided chest compressions with rescue breathing rather than compression CPR alone.

Item does not contain fulltext Drowning is a leading cause of accidental death. Survivors may sustain severe neurologic morbidity. There is negligible research specific to brain injury in drowning making current clinical management non-specific to this disorder. This review represents an evidence-based consensus effort to provide recommendations for management and investigation of the drowning victim. Epidemiology, brain-oriented prehospital and intensive care, therapeutic hypothermia, neuroimaging/monitoring, biomarkers, and neuroresuscitative pharmacology are addressed. When cardiac arrest is present, chest compressions with rescue breathing are recommended due to the asphyxial insult. In the comatose patient with restoration of spontaneous circulation, hypoxemia and hyperoxemia should be avoided, hyperthermia treated, and induced hypothermia (32-34 degrees C) considered. Arterial hypotension/hypertension should be recognized and treated. Prevent hypoglycemia and treat hyperglycemia. Treat clinical seizures and consider treating non-convulsive status epilepticus. Serial neurologic examinations should be provided. Brain imaging and serial biomarker measurement may aid prognostication. Continuous electroencephalography and N20 somatosensory evoked potential monitoring may be considered. Serial biomarker measurement (e.g., neuron specific enolase) may aid prognostication. There is insufficient evidence to recommend use of any specific brain-oriented neuroresuscitative pharmacologic therapy other than that required to restore and maintain normal physiology. Following initial stabilization, victims should be transferred to centers with expertise in age-specific post-resuscitation neurocritical care. Care should be documented, reviewed, and quality improvement assessment performed. Preclinical research should focus on models of asphyxial cardiac arrest. Clinical research should focus on improved cardiopulmonary resuscitation, re-oxygenation/reperfusion strategies, therapeutic hypothermia, neuroprotection, neurorehabilitation, and consideration of drowning in advances made in treatment of other central nervous system disorders.

OBJECTIVE Early compartment syndrome is difficult to diagnose, and a delay in the diagnosis can result in amputation or death. Our objective was to explore the potential of infrared imaging, a portable and noninvasive technology, for detecting compartment syndrome in the legs of patients with multiple trauma. We hypothesized that development of compartment syndrome is associated with a reduction in surface temperature in the involved leg and that the temperature reduction can be detected by infrared imaging. DESIGN Observational clinical study. SETTING Level I trauma center between July 2006 and July 2007. PATIENTS Trauma patients presenting to the emergency department. INTERVENTIONS Average temperature of the anterior surface of the proximal and distal region of each leg was measured in the emergency department with a radiometrically calibrated, 320 x 240, uncooled microbolometer infrared camera. MEASUREMENTS AND MAIN RESULTS The difference in surface temperature between the thigh and foot regions (thigh-foot index) of the legs in trauma patients was determined by investigators blinded to injury pattern using thermographic image analysis software. The diagnosis of compartment syndrome was made intraoperatively. Thermographic images from 164 patients were analyzed. Eleven patients developed compartment syndrome, and four of those patients had bilateral compartment syndrome. Legs that developed compartment syndrome had a greater difference in proximal vs. distal surface temperature (8.80 +/- 2.05 degrees C) vs. legs without compartment syndrome (1.22 +/- 0.88 degrees C) (analysis of variance p < .01). Patients who developed unilateral compartment syndrome had a greater proximal vs. distal temperature difference in the leg with (8.57 +/- 2.37 degrees C) vs. the contralateral leg without (1.80 +/- 1.60 degrees C) development of compartment syndrome (analysis of variance p < .01). CONCLUSIONS Infrared imaging detected a difference in surface temperature between the proximal and distal leg of patients who developed compartment syndrome. This technology holds promise as a supportive tool for the early detection of acute compartment syndrome in trauma patients.

Protein kinase C (PKC) isozymes have been known to mediate a variety of complex and diverse cellular functions. deltaPKC has been implicated in mediating apoptosis. Using two models of cerebral ischemia, cardiac arrest in rats and oxygen glucose deprivation (OGD) in organotypic hippocampal slices, we tested whether an ischemic insult promoted deltaPKC cleavage during the reperfusion and whether the upstream pathway involved release of cytochrome c and caspase 3 cleavage. We showed that cardiac arrest/OGD significantly enhanced deltaPKC translocation and increased its cleavage at 3 h of reperfusion. Since deltaPKC is one of the substrates for caspase 3, we next determined caspase 3 activation after cardiac arrest and OGD. The maximum decrease in levels of procaspase 3 was observed at 3 h of reperfusion after cardiac arrest and OGD. We also determined cytochrome c release, since it is upstream of caspase 3 activation. Cytochrome c in cytosol increased at 1 h of reperfusion after cardiac arrest/OGD. Inhibition of either deltaPKC/caspase 3 during OGD and early reperfusion resulted in neuroprotection in CA1 region of hippocampus. Our results support the deleterious role of deltaPKC in reperfusion injury. We propose that early cytochrome c release and caspase 3 activation promote deltaPKC translocation/cleavage.

Cardiac arrest (CA) patients exhibit learning and memory disabilities. These deficits suggest that synaptic dysfunction may underlie such disabilities. The hypothesis of the present study was that synaptic dysfunction occurs following CA and that this precedes cell death. To test this hypothesis, we used histopathological and electrophysiological markers in the hippocampus of rats subjected to CA. Evoked potentials (EP) were determined in the CA1 region of hippocampal slices harvested from animals subjected to CA or sham-operated rats by stimulating the Schaffer collaterals and recording in the CA1 pyramidal region. EP amplitudes were significantly attenuated by approximately 60% in hippocampal slices harvested from animals subjected to CA. Hippocampal slices harvested from sham rats exhibited normal long-term potentiation (LTP). In contrast, hippocampal slices harvested 24 h after CA exhibited no LTP response, even when no histopathological abnormalities were observed. These data suggest that synaptic dysfunction occurs before and without overt histopathology. We suggest that the synaptic dysfunction precedes and may be an early marker for delayed neuronal cell death in the hippocampus after CA.

Regulated hypothermia produces a decrease in core temperature by lowering the brain's temperature set-point while maintaining thermoregulation at that lower set point. In contrast, forced hypothermia lowers core temperature by overwhelming the body's capacity to thermoregulate, but does not change the set-point. Regulated hypothermia has been shown to be cerebral protective in hibernating mammals. The effect of regulated hypothermia on the brain during reperfusion from hypoxic-ischemia has not been well studied. We induced regulated hypothermia with a neurotensin analogue (NT77) to determine whether it could reduce oxidative stress in the brain during reperfusion from asphyxial cardiac arrest (ACA) in rats. Mild hypothermia (32–34 °C) was induced by brief (4 h) external cooling (BC), NT77 or prolonged external cooling (24 h) (PC) 30 min after resuscitation from 8 min of ACA in rats. Malondialdehyde (MDA) levels in the brain were measured during reperfusion to quantitate oxidative stress. Results: MDA levels in the hippocampus were elevated at 16 h of normothermic reperfusion versus 48 h with BC reperfusion. There was no increase in hippocampal MDA levels in the NT77 and PC groups at 24–72 h of reperfusion. Regulated hypothermia induced by NT77 reduced oxidative stress in the hippocampus during reperfusion from hypoxic-ischemia in comparison to forced brief external cooling of the same duration. In addition, the duration of external cooling after resuscitation also alters oxidative stress in the brain during reperfusion.

External cooling is commonly used to force induction of mild hypothermia but requires equipment, has a slow onset of action, and must be prolonged to provide permanent neurologic benefits after hypoxic-ischemia. It is unknown whether the method for inducing mild hypothermia affects neurologic outcome after near-drowning. The objective of the study was to induce mild hypothermia with neurotensin analog NT77 or external cooling in a rat model of near-drowning. We hypothesize that NT77 would be more effective for improving neurologic outcome than external cooling of the same duration.Rats were randomized to a normothermic control, neurotensin-induced hypothermia, brief external cooling, or prolonged external cooling group after asphyxial cardiac arrest.Laboratory investigation.Forty-eight rats.Mild hypothermia was induced by external cooling for 4 hrs (brief external cooling) or 24 hrs (prolonged external cooling) or by neurotensin-induced hypothermia administration 30 mins after asphyxial cardiac arrest in rats.Outcome was assessed by a neurologic deficit score, the Morris water maze, and CA1 hippocampus histology 15 days after resuscitation.Neurologic deficit score at 72 hrs after asphyxial cardiac arrest was lower with neurotensin-induced hypothermia (score, 0) and prolonged external cooling (score, 0) vs. normothermic control (score, 20) and brief external cooling (score, 18; p.05). Latency time in the Morris water maze 15 days after asphyxial cardiac arrest was decreased with neurotensin-induced hypothermia (14+/-11 secs) and prolonged external cooling (18+/-9 secs) vs. normothermic control (74+/-17 secs) and brief external cooling (78+/-18 secs, p.05). There was less ischemic neuronal damage with neurotensin-induced hypothermia (28+/-24%) and prolonged external cooling (21+/-14%) vs. normothermic control (61+/-32%) and brief external cooling (51+/-32%).Neurotensin-induced hypothermia improved neurologic outcome after asphyxial cardiac arrest in rats vs. brief external cooling but was comparable to prolonged external cooling.

Blunt abdominal trauma that leads to hemorrhagic shock and cardiac arrest is almost always fatal in the prehospital setting. The current study investigated whether a hemoglobin-based oxygen carrier (HBOC-201) could maintain organ viability during an exsanguinating liver injury and allow for prolonged survival. This hypothesis was tested in a large animal model that simulated blunt abdominal trauma with major organ injury.Swine underwent a liver crush, laceration and 50 ml/kg initial blood loss. The liver bled at 3 ml/kg per min during the resuscitation phase. No fluid (NF=6), hetastarch (HES=8), or HBOC-201 (HBOC=8) was given during the resuscitation phase. Swine alive 60 min after the initial injury underwent liver repair and 96 h observation.All HBOC swine survived 60 min versus none of the NF or HES swine (P0.05). All HBOC swine survived 24 h and 7/8 survived 96 h with good functional recovery.HBOC resuscitation during liver bleeding in a swine model of hemorrhagic shock and liver injury allowed for 96 h survival. No fluid or HES in the same model was fatal.

Hypothermia during brain ischemia can improve neurological outcome. This study tested whether local cranial cooling during the low-flow state of cardiopulmonary resuscitation (CPR) could produce clinically significant cerebral cooling. Ice was applied to the heads and necks of subjects (hypothermia group) with out-of-hospital cardiac arrest (OOHCA) during CPR. Nasopharyngeal and tympanic temperatures were measured as surrogates for cerebral temperature. The rate of cranial cooling in the hypothermia group (-0.06 +/- 0.06 degrees C/min) was not significantly increased compared with a control group without ice (-0.04 +/- 0.07 degrees C/min), although older age was associated with more rapid cranial cooling. Of note, many subjects with OOHCA are already mildly hypothermic (mean cranial temperature= 35.0 +/- 1.2 degrees C) when they are first encountered in the field. This study suggests that brief cranial cooling is ineffective for rapidly lowering brain temperature. However, most cardiac arrest victims are spontaneously mildly hypothermic and preventing rewarming may provide some of the desired benefits of cerebral hypothermia.

Objective: The prospects for resuscitation after blunt traumatic cardiac arrest are dismal. Selective aortic arch perfusion (SAAP) with a hemoglobin-based oxygen carrier (HBOC-201) offers a potentially effective therapy. This study evaluated the acute cardiovascular and metabolic effects of SAAP with HBOC-201 in an exsanguination model of cardiac arrest. Design: Randomized, controlled, laboratory investigation. Setting: University research laboratory. Subjects: Domestic swine, 25-39 kg. Interventions: Partial resection of four liver lobes rapidly led to profound hemorrhagic shock and subsequent cardiac arrest at 10-13 mins. At 15 mins, swine were randomized to receive either SAAP with oxygenated lactated Ringer's (LR) solution (n = 6) or SAAP with oxygenated HBOC-201 (n = 6) at a rate of 10 mL.kg -1 .min -1 until return of spontaneous circulation with a mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved. Epinephrine (0.005 mglkg) was given via intra-aortic route every 30 secs as needed to promote return of spontaneous circulation beginning at 18 mins after onset of liver injury (3 mins after beginning SAAP). Measurements and Main Results: Mean aortic pressure, cardiac output, total blood loss, and time of arrest were similar for both groups before SAAP therapy. In the SAAP-HBOC group, return of spontaneous circulation with a sustained mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved in six of six swine at 1.9 ± 0.3 mins of SAAP, and none of these swine required epinephrine. In the SAAP-LR group, no swine (from a total of six) achieved return of spontaneous circulation before intra-aortic epinephrine administration, and only two of six swine had brief return of spontaneous circulation with an mean aortic pressure of 60 mm Hg (8.0 kPa) after intra-aortic epinephrine that was sustained for

An electron spin resonance technique was used to measure cerebral antioxidant activity during asphyxial cardiac arrest and reperfusion. There were significant decreases in ascorbate (48%), glutathione (44%), total thiols (42%), protein thiols (38%) and alpha-tocopherol (26%) in the hippocampus 10 min after reperfusion (p < 0.05 vs respective baselines) but not during asphyxial cardiac arrest. The levels of antioxidants returned to baseline values by 120 min after reperfusion. The results support the hypothesis that reperfusion from asphyxial cardiac arrest, but not arrest alone, produced a significant oxidative stress as reflected by a depletion of both water and lipid soluble antioxidants. Furthermore, antioxidant depletion was transient, with normal antioxidant levels observed 120 min, 24 h and 72 h after reperfusion.

In 1961, in Pittsburgh, PA, "cerebral" was added to the cardiopulmonary resuscitation system (CPR --> CPCR). Cerebral recovery is dependent on arrest and cardiopulmonary resuscitation times, and numerous factors related to basic, advanced, and prolonged life support. Postischemic-anoxic encephalopathy (the cerebral postresuscitation disease or syndrome) is complex and multifactorial. The prevention or mitigation of this syndrome requires that there be development and trials of special, multifaceted, combination treatments. The selection of therapies to mitigate the postresuscitation syndrome should continue to be based on mechanistic rationale. Therapy based on a single mechanism, however, is unlikely to be maximally effective. For logistic reasons, the limit for neurologic recovery after 5 mins of arrest must be extended to achieve functionally and histologically normal human brains after 10 to 20 mins of circulatory arrest. This goal has been approached, but not quite reached. Treatment effects on process variables give clues, but long-term outcome evaluation is needed for documentation of efficacy and to improve clinical results. Goals have crystallized for clinically relevant cardiac arrest-intensive care outcome models in large animals. These studies are expensive, but essential, because positive treatment effects cannot always be confirmed in the rat forebrain ischemia model. Except for a still-elusive breakthrough effect, randomized clinical trials of CPCR are limited in their ability to statistically document the effectiveness of treatments found to be beneficial in controlled outcome models in large animals. Clinical studies of feasibility, side effects, and acceptability are essential. Hypertensive reperfusion overcomes multifocal no-reflow and improves outcome. Physical combination treatments, such as mild resuscitative (early postarrest) hypothermia (34 degrees C) plus cerebral blood flow promotion (e.g., with hypertension, hemodilution, and normocapnia), each having multiple beneficial effects, achieved complete functional and near-complete histologic recovery of the dog brain after 11 mins of normothermic, ventricular fibrillation cardiac arrest. Calcium entry blockers appear promising as a treatment for postischemic-anoxic encephalopathy. However, the majority of single or multiple drug treatments explored so far have failed to improve neurologic outcome. Assembling and evaluating combination treatments in further animal studies and determining clinical feasibility inside and outside hospitals are challenges for the near future. Treatments without permanent beneficial effects may at least extend the therapeutic window. All of these investigations will require coordinated efforts by multiple research groups, pursuing systematic, multilevel research--from cell cultures to rats, to large animals, and to clinical trials. There are still many gaps in our knowledge about optimizing extracerebral life support for cerebral outcome.

An outcome model with asphyxial cardiac arrest in rats has been developed for quantifying brain damage. Twenty-two rats were randomized into three groups. Control group I was normal, was conscious, and had no asphyxia ( n = 6). Sham group II had anesthesia and surgery but no asphyxia ( n = 6). All 12 rats in groups I and II survived to 72 h and were functionally and histologically normal. Arrest group III (the model; n = 10) had light anesthesia and apneic asphyxia of 8 min, which led to cessation of circulation at 3–4 min of apnea, resulting in cardiac arrest (no flow) of 4–5 min. All 10 rats had spontaneous circulation restored by standard external cardiopulmonary resuscitation. Nine rats survived controlled ventilation for 1 h and observation to 72 h, while one rat died before extubation. All nine survivors were conscious at 72 h, with neurologic deficit scores (0% = best; 100% = worst) of 7 ± 69? (2–16%). All brain regions at five coronal levels were examined for ischemic neurons. The prevalence of ischemic neurons in five regions was categorically scored. The average total brain histopathologic damage score in group III ( n = 9) was 2.1 ( p < 0.05 vs. group I or II). A reproducible outcome model of cardiac arrest in rats was documented. It provides a tool for investigating pathophysiological mechanisms of neuronal death caused by a transient global hypoxic–ischemic brain insult.

Apneic asphyxia to cardiac arrest (CA) in rats of 10 min was reversed by cardiopulmonary resuscitation (CPR), and after controlled ventilation and controlled normotension for 20 min, was followed by decapitation and brain freezing, and determination of brain concentrations of cytosolic and lysosomal enzymes. Normal values came from a control group of 10 rats without CA. In 20 rats with CA brain cytosolic enzymes CK, LD, and ASAT decreased postarrest, while lysosomal enzyme changes were variable (Table D. Brain lactate increased 8–10-fold post-CA. To test the model, effect of methylprednisolone (MP) was studied. The 20 rats with CA were divided into 4 groups: Group I, received placebo pre-CA; Group II, MP 30 mg/kg i.v. pre-CA; Group III, placebo post-CA; and Group IV, MP post-CA. The post-CA MP Group IV was the only one without norepinephrine requirement and with return of EEG activity at 20 min. Brain CK, LD, and ASAT losses post-CA were not different between groups; and showed no differences between MP groups II and IV vs. placebo Groups I and III. When comparing both pre-CA Groups (I and II) with both post-CA Groups (III and IV), post-CA CK and ASAT levels were the same, but LD was higher in the post-CA treatment group. The lysosomal enzymes acid phosphatase, mannosidase, β-glucuronidase and hexosamidase showed variable concentration changes post-CA in the four groups, with a trend toward a lesser increase of some after MP or after post-treatment. Brain enzyme changes in our asphyxial CA rat model can serve as markers of brain damage. MP post-CA might enhance cardiovascular and EEG recovery, but does not seem to influence brain enzyme levels at 20 min post-CA.