Search

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.

BACKGROUND Susceptibility differences between fat and water can cause changes in the water-fat frequency separation that can negatively affect the accuracy of fat fraction techniques. This may be especially relevant for brown adipose tissue, as MRI fat fraction techniques have been proposed for its detection. PURPOSE To assess the effect of microscopic magnetic susceptibility gradients on the water-fat frequency separation and its impact on chemical-shift-based fat fraction quantification techniques in the supraclavicular fat, where brown adipose tissue is commonly found in humans. STUDY TYPE Prospective. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL Subjects: 11 healthy volunteers, mean age of 26 and mean BMI of 23, three overweight volunteers, mean age of 38 and mean BMI of 33. Phantoms: bovine phantom and intralipid fat emulsion. Simulations: various water-fat distributions. FIELD STRENGTH/SEQUENCE Six-echo gradient echo chemical-shift-encoded sequence at 3T. ASSESSMENT Fat fraction values as obtained from a water-fat spectral model accounting for susceptibility-induced water-fat frequency variations were directly compared to traditional spectral models that assume constant water-fat frequency separation. STATISTICAL TESTS Two-tail t-tests were used for significance testing (p

PURPOSE To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. METHODS In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. RESULTS Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. CONCLUSION MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med 78:1922-1932, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

“I am not young enough to know everything.” Oscar Wilde Background: There is insufficient knowledge among providers and patients/caregivers of ionizing radiation exposure from medical imaging examinations. This study used a brief, interactive educational intervention targeting the topics of best imaging practices and radiation safety early in health professions students’ training. The authors hypothesized that public health, medical, and physician assistant students who receive early education for imaging appropriateness and radiation safety will undergo a change in attitude and have increased awareness and knowledge of these topics. Materials and methods: The authors conducted a 1.5-hour interactive educational intervention focusing on medical imaging utilization and radiation safety. Students were presented with a pre/postquestionnaire and data were analyzed using t tests and multivariate analysis of variance. Results: A total of 301 students were enrolled in the study. There was 58% ( P Conclusions: A brief educational session provided to health professions students early in their education showed an increased awareness and knowledge of the utility, limitations, and risks associated with medical imaging. Incorporation of a best imagining practice educational session early during medical education may promote more thoughtful imaging decisions for future medical providers.

Background Hypothermia is a problem for very premature infants after birth and leads to increased morbidity and mortality. Previously we found very premature infants exhibit abnormal thermal patterns, keeping foot temperatures warmer than abdominal temperatures for their first 12 h of life. Purpose We explored the utility of infrared thermography as a non-invasive method for measuring body temperature in premature infants in an attempt to regionally examine differential temperatures. Results Our use of infrared imaging to measure abdominal and foot temperature for extremely premature infants in heated, humid incubators was successful and in close agreement using Bland and Altman technique with temperatures measured by skin thermistors. Conclusions Our study methods demonstrated that it was feasible to capture full body temperatures of extremely premature infants while they were resting in a heated, humid incubator using a Flir SC640 infrared camera. This technology offers researchers and clinicians a method to examine acute changes in perfusion differentials in premature infants which may lead to morbidity.

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.

Objective To test instrumentation and develop analytic models to use in a larger study to examine developmental trajectories of body temperature and peripheral perfusion from birth in extremely low‐birth‐weight (EBLW) infants. Design A case study design. Setting The study took place in a Level 4 neonatal intensive care unit (NICU) in North Carolina. Participants Four ELBW infants, fewer than 29 weeks gestational age at birth. Methods Physiologic data were measured every minute for the first 5 days of life: peripheral perfusion using perfusion index by Masimo and body temperature using thermistors. Body temperature was also measured using infrared thermal imaging. Stimulation and care events were recorded over the first 5 days using video which was coded with Noldus Observer software. Novel analytical models using the state space approach to time‐series analysis were developed to explore maturation of neural control over central and peripheral body temperature. Results/Conclusion Results from this pilot study confirmed the feasibility of using multiple instruments to measure temperature and perfusion in ELBW infants. This approach added rich data to our case study design and set a clinical context with which to interpret longitudinal physiological data.

A feasibility study was performed to compare an investigational drug, HBN-1, to forced cooling to induce hypothermia after resuscitation in a translation model of asphyxial cardiac arrest in swine. Serum and cerebral spinal fluid neuron-specific enolase activity (sNSE and csfNSE) were measured after cardiac arrest as surrogate markers of brain injury. In a block design, swine resuscitated from 10 minutes of asphyxial cardiac arrest were infused intravenously with HBN-1 or iced saline vehicle (forced hypothermia [FH]) 5 to 45 minutes after return of spontaneous circulation (ROSC). External cooling in both groups was added 45 minutes after ROSC until hypothermia (T=4°C below baseline) was attained. Esophageal (core) temperature, shivering, cardiopulmonary parameters, and time to hypothermia after ROSC were monitored. sNSE and csfNSE were measured 180 minutes after ROSC. HBN-1 induced hypothermia significantly lowered temperature compared to FH 5-45 minutes after ROSC (p

Diffusion Tensor Imaging (DTI) has become a widely used MR modality to investigate white matter integrity in the brain. This paper presents the application of an automated method for voxel-wise group comparisons of DTI images in a study of fitness and aging. The automated processing method consists of 3 steps: 1) preprocessing including image format converting, image quality control, eddy-current and motion artifact correction, skull stripping and tensor image estimation, 2) study-specific unbiased DTI atlas computation via diffeomorphic fluid-based and demons deformable registration and 3) voxel-wise statistical analysis via heterogeneous linear regression and a wild bootstrap technique for correcting for multiple comparisons. Our results show that this fully automated method is suitable for voxel-wise group DTI analysis. Furthermore, in older adults, the results suggest a strong link between reduced fractional anisotropy (FA) values, fitness and aging.

Objective Aerobic fitness (VO 2 peak) and obesity risk (OR) may impact brain health. This study examined hemispheric and segment specific relationships between VO 2 peak, OR and cerebral white-matter (CWM) integrity in the cingulum brain region in healthy older adults. Methods Fifteen subjects (66±6 years) completed VO 2 peak testing and MRI of the brain. OR was determined via body mass index (BMI) and abdominal girth. MRI analysis was performed with a structural 3D T1 MP-Rage and diffusion tensor imaging technique (DTI, 21 directions, repeated four times) on a 3.0 T MR imaging unit. CWM integrity indices, fractional anisotropy (FA) and mean diffusivity (MD), were computed from the tensors. The anterior, middle and posterior cingulum segments were analysed on both sides of the brain. Partial correlations (age and gender controlled) and standard multiple regressions were used to determine significant associations and unique contributions to CWM integrity. Results VO 2 peak was moderately related to FA in the left middle cingulum segment (r partial=0.573, p=0.041) and explained 28.5% of FA9s total variance (p=0.10). Abdominal girth (r partial=−0.764, p=0.002) and BMI (r partial=−0.690, p=0.009) were inversely related to FA in the right posterior cingulum (RPC) segment. Abdominal girth and BMI uniquely explained 53.9% of FA9s total variance (p=0.012) and 43.9% (p=0.040), respectively, in the RPC. Conclusion Higher aerobic fitness and lower obesity risk are related to greater CWM integrity but not in the same cingulum segments.

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 Vasoconstriction, an inherent property of Hemoglobin Based Oxygen Carriers (HBOC) potentially due to nitric oxide (NO) scavenging, may increase cardiovascular complications in HBOC resuscitated trauma patients. The purpose of this study was to determine if co-administration of a weak NO donor, intravenous nitroglycerin (NTG), with HBOC-201 during resuscitation from hemorrhagic shock could safely attenuate HBOC-201 vasoconstriction. Methods and results Hemorrhagic shock was induced in 44 swine randomized to receive fluid resuscitation with HBOC, HBOC+NTG10mcg/kg/min, HBOC+NTG20mcg/kg/min, HBOC+NTG40mcg/kg/min, Hetastarch (HES), HES+NTG20mcg/kg/min, NTG20mcg/kg/min and Lactated Ringers (LR). HBOC resuscitation from hemorrhagic shock increased mean arterial pressure (MAP=94±33mmHg), mean pulmonary artery pressure (MPAP=29±11mmHg) and systemic vascular resistance (SVR=2684±871dyns/cm 5 ) in comparison to HES. Co-administration of NTG during HBOC resuscitation attenuated vasoconstriction with HBOC+40mcg/kg/min demonstrating the most robust reduction in vasoconstriction (MAP=59±23mmHg, MPAP=18±7mmHg, and SVR=1827±511dyns/cm 5 ), although the effects were transient. Co-administration of NTG with HBOC did not alter base deficit, lactate, methemoglobin levels, nor cause profound hypotension during resuscitation. Conclusion Nitroglycerin attenuates vasoconstrictive properties of HBOC when co-administered during resuscitation in this swine model of hemorrhagic shock. Translational survival studies are required to determine if this strategy of attenuation of the vasoconstriction of HBOC-201 reduces cardiovascular complications and improves outcome with HBOC fluid resuscitation for hemorrhagic shock.

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.

Hypothermia is recommended by international guidelines for treatment of unconscious survivors of cardiac arrest to improve neurologic outcomes. However, temperature management is often underutilized because it may be difficult to implement. The present study evaluated the efficacy of pharmacologically induced hypothermia on survival and neurological outcome in rats resuscitated from cardiac arrest.Cardiac arrest was induced for 10 min in 120 rats. Sixty-one rats were resuscitated and randomized to normothermia, physical cooling or pharmacological hypothermia 5 min after resuscitation. Pharmacological hypothermia rats received a combination of ethanol, vasopressin and lidocaine (HBN-1). Physical hypothermia rats were cooled with intravenous iced saline and cooling pads. Rats in the pharmacological hypothermia group received HBN-1 at ambient temperature (20 °C). Normothermic rats were maintained at 37.3 ± 0.2 °C.HBN-1 (p0.0001) shortened the time (85 ± 71 min) to target temperature (33.5 °C) versus physical hypothermia (247 ± 142 min). The duration of hypothermia was 17.0 ± 6.8h in the HBN-1 group and 17.3 ± 7.5h in the physical hypothermia group (p = 0.918). Survival (p = 0.034), neurological deficit scores (p0.0001) and Morris Water Maze performance after resuscitation (p = 0.041) was improved in the HBN-1 versus the normothermic group. HBN-1 improved survival and early neurological outcome compared to the physical hypothermia group while there was no significant difference in performance in the Morris water maze.HBN-1 induced rapid and prolonged hypothermia improved survival with good neurological outcomes after cardiac arrest suggesting that pharmacologically induced regulated hypothermia may provide a practical alternative to physical cooling.

Objective This study evaluates the effect of early administration of an empirical (1 mEq/kg) sodium bicarbonate dose on survival from prehospital cardiac arrest within brief ( 15 minutes) down time. Methods Prospective randomized, double-blinded clinical intervention trial that enrolled 874 prehospital cardiopulmonary arrest patients managed by prehospital, suburban, and rural regional emergency medical services. Over a 4-year period, the randomized experimental group received an empirical dose of bicarbonate (1 mEq/kg) after standard advanced cardiac life support interventions. Outcome was measured as survival to emergency department, as this was a prehospital study. Results The overall survival rate was 13.9% (110/792) for prehospital arrest patients. There was no difference in the amount of sodium bicarbonate administered to nonsurvivors (0.859 ± 0.284 mEq/kg) and survivors (0.8683 ± 0.284 mEq/kg) ( P = .199). Overall, there was no difference in survival in those who received bicarbonate (7.4% [58/420]), compared with those who received placebo (6.7% [52/372]) ( P = .88; risk ratio, 1.0236; 0.142-0.1387). There was, however, a trend toward improved outcome with bicarbonate in prolonged (>15 minute) arrest with a 2-fold increase in survival (32.8% vs 15.4%; P = .007). Conclusion The empirical early administration of sodium bicarbonate (1 mEq/kg) has no effect on the overall outcome in prehospital cardiac arrest. However, a trend toward improvement in prolonged (>15 minutes) arrest outcome was noted.

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 potential use of hypothermia as a therapeutic treatment for stroke and other pathological insults has prompted the search for drugs that can lower core temperature. Ideally, a drug is needed that reduces the set-point for control of core temperature (T(c)) and thereby induces a regulated reduction in T(c). To this end, a neurotensin analog (NT77) that crosses the blood brain barrier and induces hypothermia was assessed for its effects on the set-point for temperature regulation in the Sprague-Dawley rat by measuring behavioral and autonomic thermoregulatory responses. Following surgical implanation of radiotransmitters to monitor T(c), rats were placed in a temperature gradient and allowed to select from a range of ambient temperatures (T(a)) while T(c) was monitored by radiotelemetry. There was an abrupt decrease in selected T(a) from 29 to 16 degrees C and a concomitant reduction in T(c) from 37.4 to 34.0 degrees C 1 hr after IP injection of 5.0 mg/kg NT77. Selected T(a) and T(c) then recovered to control levels by 1.5 hr and 4 hr, respectively. Oxygen consumption (M) and heat loss (H) were measured in telemetered rats housed in a direct calorimeter maintained at a T(a) of 23.5 degrees C. Injection of NT77 initially led to a reduction in M, little change in H, and marked decrease in T(c). H initially rose but decreased around the time of the maximal decrease in T(c). Overall, NT77 appears to induce a regulated hypothermic response because the decrease in T(c) was preceded by a reduction in heat production, no change in heat loss, and preference for cold T(a)'s. Inducing a regulated hypothermic response with drugs such as NT77 may be an important therapy for ischemic disease and other insults.

Study Objective: Controversy surrounds the use of buffers during cardiac arrest to correct acidosis. The objective of this study was to determine whether attenuation or neutralization of cerebral acidosis by Carbicarb alters hippocampal glutamate levels, neuronal cell death, and neurologic deficits after reperfusion from asphyxial cardiac arrest in rats. Methods: Rats were prospectively randomized to either a control (n=45), low-dose Carbicarb (LDC; 3 mL/kg, n=45), or high-dose Carbicarb (HDC; 6 mL/kg, n=45) group in a blinded fashion during resuscitation after 8 minutes of asphyxial cardiac arrest. Microdialysis was used to assess brain pH and glutamate. A neurologic deficit score and neuronal cell death in the hippocampus were determined at day 7. Results: Resuscitation was greatest in LDC rats (42/45) and least in HDC rats (28/45) versus that in control rats (34/45). Brain pH was higher in the LDC and HDC rats 10 minutes after resuscitation and remained higher than that of control rats for 120 minutes after resuscitation. Glutamate levels at 10 to 120 minutes after reperfusion were lowest in the LDC rats. LDC rats had the lowest neurologic deficit score (1±2) versus that of control rats (13±8) and HDC rats (19±6). Hippocampal neuronal cell death was lowest in LDC rats (30±20) versus that in control rats (86±47) and HDC rats (233±85). Conclusion: LDC administered during resuscitation from asphyxial cardiac arrest attenuated acidosis, improved resuscitation, and reduced neurologic deficits and the number of dead hippocampal neurons. Neutralization of cerebral acidosis with HDC increased the number of dead hippocampal neurons and neurologic deficits after resuscitation from cardiac arrest in rats. [Katz LM, Wang Y, Rockoff S, Bouldin TW. Low-dose Carbicarb improves cerebral outcome after asphyxial cardiac arrest in rats. Ann Emerg Med. April 2002;39:359-365.]

Background: Medical students have limited confidence in performing procedural skills. A pilot study was conducted to evaluate the effect of a multifaceted Procedural Skills Lab (PSL) on the confidence of medical students to perform procedural skills. Methods: Twelve 2nd year medical students were randomly selected to participate in a pilot PSL. The PSL students met with an instructor for 2 h once a week for 4 weeks. Students participated in a flipped classroom and spaced education program before laboratory sessions that included a cadaver laboratory. Procedural skills included a focused assessment with sonography in trauma (FAST) scan, cardiac echocardiogram, lumbar puncture, arthrocentesis, and insertion of intraosseous and intravenous catheters. Students in the PSL were asked to rank their confidence in performing procedural skills before and after completion of the laboratory sessions (Wilcoxon ranked-sum test). A web-based questionnaire was also emailed to all 2nd year medical students to establish a baseline frequency for observing, performing, and confidence performing procedural skills (Mann–Whitney U-test). Results: Fifty-nine percent (n = 106) of 180 2nd year medical students (n = 12 PSL students [treatment group], n = 94 [control group]) completed the survey. Frequency of observation, performance, and confidence in performing procedural skills was similar between the control and treatment groups at baseline. There was an increased confidence level (p < 0.001) for performing all procedural skills for the treatment group after completion of the PSL. Discussion: An innovative PSL may increase students' confidence to perform procedural skills. Future studies will examine competency after a PSL.

OBJECTIVE To determine whether the neurotensin analog NT69L, administered systemically, could induce mild brain hypothermia after asphyxial cardiac arrest (ACA) in rats. METHODS The study design was experimental, blinded, randomized, and approved by the animal use committee. All rats had continuous monitoring of brain temperature and sustained 8 minutes of ACA, resuscitation, and either saline or NT69L intravenously after return of spontaneous circulation (ROSC). Rats surviving 14 days after ACA had a neurological deficit score (NDS) and a Morris Water Maze (MWM) test. RESULTS Seven of eight rats in each group survived 14 days. Brain temperature was less than 35 degrees C 13.1 +/- 3 minutes (mean +/- standard deviation) after NT69L vs controls that remained 37.5 degrees C at the same ambient temperature (p < 0.05 ANOVA). The NT69L group remained below 35 degrees C for 300 +/- 100 minutes while the controls remained at 37.5 +/- 0.5 degrees C. The NDS in the NT69L rats was 3 +/- 3% vs controls 26 +/- 8% (p < 0.05, Kruskal-Wallis, 0% = normal, 100% = brain dead). The NT69L rats performed better on the MWM vs the controls (22 +/- 8 sec vs 45 +/- 26 sec, respectively, p < 0.05 ANOVA). CONCLUSIONS NT69L induced rapid and prolonged mild brain hypothermia after ACA in this rat model and reduced neurological deficits.

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.

Over the past four decades, closed-chest cardiopulmonary resuscitation (CPR) and advanced cardiac life support (ACLS) interventions have saved many lives, but overall survival after cardiac arrest remains quite low, with survival rates of less than 5% reported in most studies. 3,15 The poor survival rates can be attributed to one or more of the following factors: (1) use of aggressive resuscitative measures in patients with end-stage disease processes for whom even optimal resuscitative efforts are unlikely to prove successful, (2) delays in initiation of effective therapies within the critical therapeutic window, and (3) ineffective or suboptimal therapeutic interventions. The first factor is complex and involves clinical judgment, advanced directives, medicolegal concerns, and societal expectations that are beyond the scope of this article. The second factor is primarily a problem for out-of-hospital victims and for nonmonitored in-hospital patients. The third factor is an ongoing challenge for the resuscitation research community. Resuscitative interventions can be classified as electrical therapy, artificial ventilation, artificial perfusion, or pharmacologic therapies. Although advances continue to be made in the areas of electrical therapy and artificial ventilation, presently available interventions are highly effective if they can be initiated in a timely manner. Thus, electrical therapy and artificial ventilation are usually not the limiting factors in a resuscitation. Pharmacologic agents given during cardiac arrest are primarily directed toward reversing the adverse effects of tissue hypoperfusion. The principal therapeutic effect of vasoconstrictor agents, traditionally epinephrine, is to restore peripheral arterial resistance to improve blood flow generated by closed-chest CPR. 29,38 The contributions of adrenergic agents and other drugs to improving survival from cardiac arrest have not been clearly demonstrated. Artificial perfusion is the principal weak link in the resuscitation armamentarium. Closed-chest CPR has been shown to generate blood flow equivalent to about 25% to 33% of normal cardiac output under optimal conditions. 4,13 If there is any time delay before the initiation of CPR, as commonly occurs, the progressive loss of peripheral arterial resistance substantially decreases the blood flow generated by CPR, even if performed well technically. 25 Thus, one of the greatest challenges in the development of better resuscitative interventions is to develop more effective methods of artificial perfusion support that can be initiated within the criticial time window allowing for return of spontaneous circulation (ROSC) with good neurologic recovery. Therefore, interventions to improve vital organ perfusion during cardiac arrest are the major focus of this article. Although significant underlying disease is prevalent in the general population of patients suffering cardiac arrest, this is especially true for patients in the intensive care unit setting. Myocardial dysfunction, pulmonary disease, metabolic disturbances, and sepsis only serve to complicate the task of the intensivist who is attempting to resuscitate patients in cardiac arrest. The monitoring sophistication of the ICU provides for early recognition of lethal dysrhythmias or other acute cardiovascular decompensation events. Also, patients in the ICU frequently have monitoring parameters available that can be used to guide the resuscitation. These parameters include arterial pressure, central venous pressure, central venous oximetry, and end-tidal carbon dioxide. This article discusses how these parameters can be used to optimize CPR techniques and to assess the effect of pharmacologic agents administered.

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

Noninvasive assessment of the immediate and delayed cardiopulmonary response to a 2% aminophylline-based topical thigh reducing cream.Prospective, double-blind, randomized, counterbalanced study with application of: no cream (NC), placebo cream (PC) or 2% aminophylline cream (AC).Nine healthy women (aged: 23+/-3 y; weight: 58+/-3 kg; height: 165+/-7 cm; body fat: 19+/-6%; estimated maximal aerobic fitness VO2max): 40+/-4 ml/kg/min).Medical history, skin patch test, skinfolds, YMCA submaximal cycle ergometry test, psychological evaluations (POMS and Speilberger STAI-1). Pulmonary function and spectral analysis on heart rate variability, measured immediately post-and 4 h post-treatment, on three separate days within a three-week period.Pulmonary function did not change. The averaged R-R interval (ms) was significantly lower for the immediate post AC treatment, but returned to baseline in 4 h.Application of a 2% aminophylline-based thigh cream does not affect pulmonary function, however, it may cause a temporary, transient reduction in the averaged R-R interval.

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.

Although high-dose epinephrine during CPR improves coronary perfusion pressure (CoPP) and rate of return of spontaneous circulation (ROSC) in some models, its impact on long term outcome (> or = 72 h) has not been evaluated. Previous studies of sodium bicarbonate (NaHCO3) therapy during CPR indicate that beneficial effects may be dependent on epinephrine (EPI) dose. We hypothesized that EPI and NaHCO3 given during CPR have a significant impact on long term outcome. One hundred male Sprague-Dawley rats were prospectively studied in a block randomized placebo controlled trial. Rats were anesthetized, paralyzed, mechanically ventilated, instrumented, and each underwent 10 min of asphyxia, resulting in 6.8 +/- 0.4 min of circulatory arrest. Resuscitation was performed by mechanical ventilation and manual external chest compressions. EPI 0.0 (placebo), 0.01, 0.1, or 1.0 mg/kg IV was given at the onset of CPR, followed by NaHCO3 0.0 (placebo) or 1.0 mEq/kg IV. Successfully resuscitated rats were monitored and ventilated for 1 h without hemodynamic support. Neurologic deficit scores (NDS), cerebral histopathologic damage scores (CHDS) and myocardial histopathologic damage scores (MHDS) were determined in rats that survived 72 h. EPI improved CoPP and ROSC in a dose-dependent manner up to 0.1 mg/kg. Rats receiving EPI 0.1 and 1.0 mg/kg during CPR exhibited prolonged post-ROSC hypertension and metabolic acidemia, increased A-a O2 gradient, and an increased incidence of post-ROSC ventricular tachycardia or fibrillation. Overall survival was lower with EPI 0.1 and 1.0 mg/kg compared to 0.01 mg/kg. Although NDS was significantly less with EPI 0.1 mg/kg compared to placebo, there was no difference in CHDS between groups. In contrast, MDS was significantly higher with EPI 0.1 mg/kg compared to placebo or EPI 0.01 mg/kg. There was an overall trend toward improved survival at 72 h in rats that received NaHCO3 which was most evident in the EPI 0.1 mg/kg group. We conclude that (1) EPI during CPR has a biphasic dose/response curve in terms of survival, when post-resuscitation effects are left untreated and (2) NaHCO3 doses greater than 1.0 mEq/kg may be necessary to treat the side-effects of high-dose EPI. Further work is needed to determine if treating the immediate post-resuscitation effects of high-dose EPI can prevent detrimental effects on long-term outcome.

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.

The aging human brain undergoes a variety of structural and metabolic changes, often coinciding with, or leading to, cognitive decline (Bullitt et al., 2009). Over the past decade, investigators have been searching for better methods to detect, treat, and prevent cognitive decline. This has lead to the development of a plethora of pharmaceutical approaches with limited success. Identifying non-pharmaceutical approaches for the prevention/treatment of cognitive decline is paramount. Because of its non-invasiveness, neuroimaging is fast becoming a preferred technology for evaluating brain structure and function. In addition, exercise is being recognized as a potential adjunct modality for preventing or reducing structural decline in the brain and perhaps attenuating corresponding cognitive decline. These two methodologies can work in tandem: first, for identification of subtle changes in the brain not detectable via standard cognitive testing and second, for application of appropriate exercise regimes shown to be associated with healthy brain aging. Taken together, disruptions in cognitive function may be delayed, or even halted, but only if intervention occurs “soon enough”. The obvious questions to answer are: 1) What is “soon enough”? 2) What type of neuroimaging might be “best”? and, 3) What kind of exercise? Simple questions with no simple answers. This chapter will begin with common, often overlooked issues regarding the use of exercise as a research modality and then progress to incorporating exercise into neuroimaging studies.

The marked improvement in outcome following induction of hypothermia after cardiac arrest has spurred the search for better methods to induce cooling. A regulated decrease in core temperature mediated by a drug-induced reduction in the set point for thermoregulation may be an ideal means of inducing hypothermia. To this end, the exploratory drug HBN-1 was assessed as a means to induce mild and prolonged hypothermia.Free moving rats were infused i.v. for 12 hours with: a vehicle at room temperature (normothermia), a vehicle chilled to 4°C (forced hypothermia), or HBN-1 (mixture of ethanol, lidocaine, and vasopressin) at room temperature. Core (intra-abdominal) temperature (Tc) was measured telemetrically, tail skin temperature (Ttail) by infrared thermography, metabolic rate (MR) was estimated with indirect calorimetery, and shivering was scored visually.HBN-1 elicited a reduction in Tc from 37.5°C to 34°C within 80 minutes after initiation of the infusion; Tc was maintained between 33°C and 34°C for more than 13 hours. HBN-1 infusion was associated with a reduction in MR (p=0.0006), a slight reduction in Ttail, and no evidence of shivering (p0.001). The forced hypothermia group displayed shivering (p0.001), a significant increase in MR, and a decrease in Ttail, indicative of peripheral vasoconstriction to reduce heat loss.HBN-1 infusion induced a mild and prolonged hypothermia in free moving, unanesthetized rats characterized by modulation of thermoeffectors to reduce heat gain and increase heat loss. HBN-1 thus appears to elicit regulated hypothermia and may provide a new method for achieving a prolonged state of therapeutic hypothermia.

Visual evoked potentials (VEPsX that provide unequivocal objective evidence of cortical binocularity have been recorded from adults and young infants using a new VEP system developed for this purpose. The system uses alternating field stereoscopy (AFS) to present separate visual stimuli to each eye. With this system, the binocular image pairs to the right and left eyes alternate at a high rate on a single video monitor. The subject wears spectacles incorporating lightscattering liquid crystal lenses which alternate electronically between opaque and clear modes in synchrony with the video monitor. To detect cortical binocularity, the system analyzes VEP activity mathematically and identifies significant responses at test frequencies reflecting binocular cortical interactions exclusively. Three types of binocular stimuli were presented: (1) dynamic random dot correlograms (correlograms); (2) dynamic random dot stereograms (stereograms); and (3) dichoptic checkerboard stimuli. The correlograms are generated when moving random dot patterns presented to each eye alternate between two phases, correlated and anticorrelated. With the stereograms, portions of random dot patterns presented to each eye are shifted horizontally relative to each other at a fixed rate, alternately producing crossed and uncrossed binocular disparities. Subjectively, these patterns appear to shift in depth. Dichoptic checkerboard stimuli are regular checkerboard patterns which reverse at different rates (frequencies) for each eye. Binocular VEPs are generated due to cortical interactions at the difference (beat) frequency. Using this VEP system, we have recorded binocular VEPs from 10 normal adults and more than 40 infant subjects. Responses to the correlograms, which we believe reflect binocular fusion, have been detected as early as 5 weeks of age, while responses to the stereograms, which require sensitivity to disparity changes, have been recorded in babies as young as 12 weeks.

Among the fears of aging are loss of memory, cognitive decline, and loss of independence. Baby boomers have entered the "aged" cohort and are actively seeking ways to maintain strong bodies and strong minds. Bench to clinical research suggests that keeping physically active and engaged in moderate to vigorous exercise may be vital to brain health. Because exercise promotes neurogenesis, increased brain volume, and improved cognitive function, it can help the aging brain to retain plasticity. However the precise mechanisms by which exercise accomplishes these changes in the brain are not clearly understood. This study argues that "what is good for the heart is good for the brain," although more research is needed to determine the optimal exercise prescription for brain health and successful cognitive aging.

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.

The proposal is based on a hypothesis that certain traumatic injuries produce unique skin temperature signatures that can be identified and quantified. The specific aims are to determine the efficacy of passive JR imaging in diagnosis of life-threatening pneumothoraces and related pulmonary injuries, and of limb-threatening traumatic injuries such as compartment syndrome. Following successful demonstration of effectiveness, specifications will be developed for field deployable JR imaging devices.

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.