[Effect of electroacupuncture at Baihui ameliorated neurologic deficit and hemodynamic stability in rat model of post-cardiac arrest syndrome].

OBJECTIVE: To observe the results of electroacupuncture (EA) on the resuscitation of a rat model of asphyxia cardiac arrest (CA). And to explore its effect on the neurologic deficits and hemodynamic instability of post-cardiac arrest syndrome (PCAS). METHODS: A total of 107 male SD rats were randomly divided into sham, CA, and EA groups. Each group received arterial catheterization and tracheal intubation. The sham group was not induced asphyxia. Asphyxial cardiac arrest was established by endotracheal tube clamping. Rats in the CA group received basic respiratory support and fluid resuscitation in return of spontaneous circulation (ROSC) and rats in the EA group received EA at Baihui based on the treatment of CA group after ROSC, with a dense-dispersed wave at frequencies of 4-20 Hz, while the current intensity was adjusted minimum to induce a twitch of the scalp, the course of treatment was 30 minutes. The baseline data, hemodynamics after ROSC, neurological deficit score (NDS), pathological changes of brain tissue, and levels of serum biomarker were recorded and compared among the three groups. The 72-hour survival of rats was analyzed by Kaplan-Meier survival curve. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of necrotic neurons in the hippocampal CA1 region of rat brain. Meanwhile, Nissl staining and TdT-mediated dUTP nick-end labeling (TUNEL) were used to detect cell apoptosis and injury. RESULTS: Compared with the CA group, the mean arterial pressure (MAP) in the EA group increased significantly at 15 minutes after ROSC [mmHg (1 mmHg ≈ 0.133 kPa): 125.00 (94.00, 136.25) vs. 92.00 (72.00, 122.50), P < 0.05]. There was no significant difference in the NDS score between the EA group and the sham group. Still, the NDS score of the rats in the CA group at 6 hours after ROSC were significantly lower than that in the sham group (46.00±10.61 vs. 80.00±0.00, P < 0.05). Kaplan-Meier survival curve analysis showed that EA did not improve the 72-hour survival rate of rats (100% in the sham group, 25% in the CA group, and 30% in the EA group, P > 0.05). The analysis by TUNEL showed that the apoptosis rate of neurons in CA1 region of the hippocampus in EA group at 6 hours after ROSC was significantly lower than that in CA group [(62.84±2.67)% vs. (71.29±3.70)%, P < 0.05]. Compared with the CA group, the level of serum S100 calcium binding protein B (S100B) in the EA group at 6 hours after ROSC was significantly lower (ng/L: 19.30±13.87 vs. 132.28±31.67, P < 0.05), but there were no significant differences in the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) between these two groups. CONCLUSIONS: In the present study, EA at Baihui can stabilize the hemodynamic, moreover, it has a particular neuroprotective effect on PCAS rats. Still, EA at Baihui does not reduce the systemic inflammatory response and improve the survival rate of rats, and its mechanism remains to be verified in further research.

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model.

With the current practice of therapeutic hypothermia for neonatal encephalopathy, disability rates and the severity spectrum of cerebral palsy are reduced. Nevertheless, safe and effective adjunct therapies are needed to optimize outcomes. This study's objective was to assess if 18 mg/kg melatonin given rapidly over 2 h at 1 h after hypoxia-ischemia with cooling from 1-13 h was safe, achieved therapeutic levels within 3 h and augmented hypothermic neuroprotection. Following hypoxia-ischemia, 20 newborn piglets were randomized to: (i) Cooling 1-13 h (HT; n = 6); (ii) HT+ 2.5% ethanol vehicle (HT+V; n = 7); (iii) HT + Melatonin (HT+M; n = 7). Intensive care was maintained for 48 h; aEEG was acquired throughout, brain MRS acquired at 24 and 48 h and cell death (TUNEL) evaluated at 48 h. There were no differences for insult severity. Core temperature was higher in HT group for first hour after HI. Comparing HT+M to HT, aEEG scores recovered more quickly by 19 h (p < 0.05); comparing HT+V to HT, aEEG recovered from 31 h (p < 0.05). Brain phosphocreatine/inorganic phosphate and NTP/exchangeable phosphate were higher at 48 h in HT+M versus HT (p = 0.036, p = 0.049 respectively). Including both 24 h and 48 h measurements, the rise in Lactate/N-acetyl aspartate was reduced in white (p = 0.030) and grey matter (p = 0.038) after HI. Reduced overall TUNEL positive cells were observed in HT+M (47.1 cells/mm2) compared to HT (123.8 cells/mm2) (p = 0.0003) and HT+V (97.5 cells/mm2) compared to HT (p = 0.012). Localized protection was seen in white matter for HT+M versus HT (p = 0.036) and internal capsule for HT+M compared to HT (p = 0.001) and HT+V versus HT (p = 0.006). Therapeutic melatonin levels (15-30mg/l) were achieved at 2 h and were neuroprotective following HI, but ethanol vehicle was partially protective.

Activation of Sigma-1 Receptor by Cutamesine Attenuates Neuronal Apoptosis by Inhibiting Endoplasmic Reticulum Stress and Mitochondrial Dysfunction in a Rat Model of Asphyxia Cardiac Arrest.

BACKGROUND: Global cerebral ischemic/reperfusion (I/R) injury after cardiac arrest (CA) is a major cause of mortality and morbidity in survivors of resuscitation. We utilized a rat model of asphyxia CA to explore the functional effects and mechanisms of Sigma-1 receptor (Sig-1R) activation in cerebral protection using the Sig-1R agonist cutamesine (SA-4503). METHODS: After resuscitation, the surviving rats were randomly divided into three groups (n = 18 each): the cardiopulmonary resuscitation (CPR) group (0.9% saline at 1 mL/kg); the SA4503 low-dose group (1 mg/kg SA4503); and the SA4503 high-dose group (2.5 mg/kg SA4503). The neurological deficit scores were recorded, and the cerebral cortex was harvested for western blotting. Mitochondrial transmembrane potential, adenosine triphosphate (ATP) concentrations, calcium homeostasis, and mitochondrial ultrastructure were also studied. RESULTS: The SA4503 treatment groups exhibited improved neurological outcomes compared with the CPR group. The protein levels of caspase-3 and the endoplasmic reticulum stress markers C/EBP homologous protein and caspase-12 were lower in the SA4503 treatment groups compared with the CPR group. SA4503 treatment also normalized mitochondrial membrane potential, tissue ATP concentrations, intracellular Ca overload, and upregulated Sig-1R protein level compared with the CPR group. The SA4503 high dose treatment showed significant cerebral protective effects compared with the SA4503 low dose treatment. The therapeutic effect of SA4503 was dose-dependent. CONCLUSIONS: CA downregulated Sig-1R protein expression. Activating Sig-1R using SA4503 protected against global cerebral I/R injury in a rat model of asphyxia CA by alleviating endoplasmic reticulum stress and mitochondrial dysfunction and eventually inhibiting neuronal apoptosis.

Enduring disturbances in regional cerebral blood flow and brain oxygenation at 24 h after asphyxial cardiac arrest in developing rats.

BACKGROUND: Disturbances in cerebral blood flow (CBF) and brain oxygenation (PbO2) are present early after pediatric cardiac arrest (CA). CBF-targeted therapies improved neurological outcome in our CA model. To assess the therapeutic window for CBF- and PbO2-targeted therapies, we propose to determine if CBF and PbO2 disturbances persist at 24 h after experimental pediatric CA. METHODS: Regional CBF and PbO2 were measured at 24 h after asphyxial CA in immature rats (n = 26, 6-8/group) using arterial spin label MRI and tissue electrodes, respectively. RESULTS: In all regions but the thalamus, CBF recovered to sham values by 24 h; thalamic CBF was >32% higher after CA vs. sham. PbO2 values at 24 h after CA in the cortex and thalamus were similar to shams in rats who received supplemental oxygen, however, on room air, cortical PbO2 was lower after CA vs. shams. CONCLUSION: CBF remains increased in the thalamus at 24 h after CA and PbO2 is decreased to hypoxic levels in cortex at 24 h after CA in rats who do not receive supplemental oxygen. Given the enduring disturbances in this model and the lack of routine CBF or PbO2 monitoring in patients, our data suggest the need for clinical correlation.

Brain cell death is reduced with cooling by 3.5°C to 5°C but increased with cooling by 8.5°C in a piglet asphyxia model.

BACKGROUND AND PURPOSE: In infants with moderate to severe neonatal encephalopathy, whole-body cooling at 33°C to 34°C for 72 hours is standard care with a number needed to treat to prevent a adverse outcome of 6 to 7. The precise brain temperature providing optimal neuroprotection is unknown. METHODS: After a quantified global cerebral hypoxic-ischemic insult, 28 piglets aged <24 hours were randomized (each group, n=7) to (1) normothermia (38.5°C throughout) or whole-body cooling 2 to 26 hours after insult to (2) 35°C, (3) 33.5°C, or (4) 30°C. At 48 hours after hypoxia-ischemia, delayed cell death (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling and cleaved caspase 3) and microglial ramification (ionized calcium-binding adapter molecule 1) were evaluated. RESULTS: At 48 hours after hypoxia-ischemia, substantial cerebral injury was found in the normothermia and 30°C hypothermia groups. However, with 35°C and 33.5°C cooling, a clear reduction in delayed cell death and microglial activation was observed in most brain regions (P<0.05), with no differences between 35°C and 33.5°C cooling groups. A protective pattern was observed, with U-shaped temperature dependence in delayed cell death in periventricular white matter, caudate nucleus, putamen, hippocampus, and thalamus. A microglial activation pattern was also seen, with inverted U-shaped temperature dependence in periventricular white matter, caudate nucleus, internal capsule, and hippocampus (all P<0.05). CONCLUSIONS: Cooling to 35°C (an absolute drop of 3.5°C as in therapeutic hypothermia protocols) or to 33.5°C provided protection in most brain regions after a cerebral hypoxic-ischemic insult in the newborn piglet. Although the relatively wide therapeutic range of a 3.5°C to 5°C drop in temperature reassured, overcooling (an 8.5°C drop) was clearly detrimental in some brain regions.

Hemodynamic rescue and ECG stability during chest compressions using adenosine and lidocaine after 8-minute asphyxial hypoxia in the rat.

INTRODUCTION: Sudden cardiac death generally arises from either ventricular fibrillation or asphyxial hypoxia. In an effort to translate the cardioprotective effects of adenosine and lidocaine (AL) from hemorrhagic shock to cardiopulmonary resuscitation, we examined the effect of AL on hemodynamics and electrocardiogram (ECG) stability in the rat model of asphyxial hypoxia. METHODS: Male Sprague-Dawley rats were randomly assigned to 1 of 4 groups (n = 8): saline (SAL), adenosine (ADO), lidocaine (LIDO), and AL. Cardiac arrest (mean arterial pressure <10 mm Hg) was induced by clamping the ventilator line for 8 minutes. A 0.5-mL intravenous drug bolus was injected followed by chest compressions (300 min(-1)), which were repeated every 5 minutes for 1 hour. RESULTS: Return of spontaneous circulation was achieved in 5 SAL (62.6%), 4 ADO (50%), 7 LIDO (87.5%), and 8 AL rats (100%) within 5 minutes but could not be sustained. During chest compressions, mean arterial pressure was consistently higher in the AL-treated rats compared with all groups (P < .05; 35-45 and 55 minutes) followed by the LIDO group and was lowest in the ADO and SAL groups (P < .05). Systolic pressure followed a similar pattern. In addition, diastolic pressure in the AL-treated rats was significantly higher from 25 to 60 minutes than LIDO and ADO alone or SAL, and heart rate was 30% to 40% lower. Improved ECG rhythm and R-R variability were apparent in AL-treated rats during early compressions and hands-off intervals. CONCLUSIONS: We conclude that a small bolus of 0.9% NaCl AL improved hemodynamics with possible diastolic rescue and ECG stabilization during chest compressions compared with ADO, LIDO, or SAL controls.

Extraction of tracheobronchial foreign bodies in children and adults with rigid and flexible bronchoscopy.

BACKGROUND: Tracheobronchial foreign bodies (TBFBs) due to accidental aspiration are seen in both children and adults and are usually extracted by flexible bronchoscopy (FB) or rigid bronchoscopy (RB). The experience over a decade of treating 214 patients with TBFBs has been analyzed retrospectively. METHODS: The records of all patients who presented with possible TBFB aspiration since 2001 were analyzed. A clinical profile of these patients was compiled. The method of extraction and its success was noted. Asphyxiating TBFBs were extracted straight away by RB, whereas for nonasphyxiating TBFBs, extraction was first attempted with FB and RB used only if the former failed. The success of the 2 procedures was compared. RESULTS: : Of a total of 266 patients in whom TBFBs were suspected, the diagnosis was confirmed by bronchoscopy in 214. TBFBs were more common in males, and in the age group between 1 and 2 years. Successful extraction could be achieved in 40% of the patients with FB and in 95% with RB where it was required. CONCLUSIONS: From our experience of extraction of TBFBs over more than a decade, we have drawn the following conclusions: (1) TBFBs present most frequently in the age group of 1 to 2 years, with cough and/or breathlessness commonly following a choking episode; (2) a high index of suspicion is essential and diagnostic FB should be performed in all such cases even though the chest radiograph is normal; (3) TBFBs can be life threatening and may require to be treated as an emergency; (4) FB may be used first for diagnosis and extraction under conscious sedation for nonasphyxiating TBFBs. It is usually more successful in adults and less so in children; (5) in these patients, if FB is unsuccessful, then RB may be used to extract the TBFB; (6) for asphyxiating TBFBs, RB is the procedure of choice; (7) pulmonologists who wish to practice extraction of TBFBs ought to be trained in both FB and RB and must possess adequate equipment and a skilled team to assist them.

Neonatal care in rural Karnataka: healthy and harmful practices, the potential for change.

BACKGROUND: Every year four million babies die in the first month of life and a quarter of these take place in India. A package of essential newborn care practices exists, which has a proven impact on reducing mortality, and can be implemented in low resource settings. However, childbirth and the neonatal period are culturally important times, during which there is strong adherence to traditional practices. Successful implementation of the package therefore requires in-depth knowledge of the local context and tailored behaviour change communication. METHODS: This study was carried out in rural Karnataka, India. It uses quantitative data from a prospective survey following mothers through their experience of pregnancy and the postnatal period; and qualitative data from in depth interviews and focus group discussions conducted with mothers, grandmothers and birth attendants. It explores local newborn care practices and beliefs, analyses their harmful or beneficial characteristics and elucidates areas of potential resistance to behaviour change and implementation of the essential newborn care package. RESULTS: Findings show that many potentially harmful newborn care practices are being carried out in the study area, such as unhygienic cord cutting, delayed breastfeeding and early bathing. Some are more amenable to change than others, depending on the strength of the underlying beliefs, and acceptability of alternative care. However, movement away from traditional practices is already taking place, particularly amongst the more educated and better off, and there is a clear opportunity to broaden, direct and accelerate this process. CONCLUSION: Community education should be a focus of the National Rural Health Mission (NRHM) and Integrated Management of Neonatal and Childhood Illness (IMNCI) program being implemented in Karnataka. The added capacity of the new Accredited Social Health Activists (ASHAs) could enable more women to be reached. With careful tailoring of behaviour change messages to the local context, government outreach workers can become effective brokers of positive change and significant improvements in home newborn care and neonatal mortality are possible.

[The treatment of posthypoxic encephalopathy in suicide patients by hyperbaric oxygenation]. / Lechenie postgipoksicheskoi éntsefalopatii u suitsidentov metodom giperbaricheskoi oksigenatsii.

Two groups of suicidants with residual posthypoxic encephalopathy (n = 324 and 120 respectively) were examined. The first group received treatment by hyperbaric oxigenation according to a specially designed methodology, the second one had conventional therapy. Marked improvement was found in intellectual and other mental functions in the patients on HBO treatment and practically no gain in those on conventional therapy. HBO was found to be well worth delivering to the above patients.

[The role of ear electroacupuncture on arterial pressure and respiration during asphyxia in rabbits].

This paper reports the study of the effect of ear electroacupuncture (EA) inserted in the "Er Jian" point on arterial pressure and integrated phrenic nerve discharge (IPND). The result showed that the arterial pressure was decreased and frequency of IPND was increased. The differences as follows: During spontaneous breathing, the blood pressure and IPND were -36.56 +/- 26.63 mmHg and, 2.42 +/- 1.42 spikes/10S (P less than 0.001); in excitatory period, -24.31 +/- 6.01 mmHg and, 2.16 +/- 1.12 spikes/10S (P less than 0.01) and in inhibitory period -18.26 +/- 7.04 mmHg (P less than 0.01) and, 2.07 +/- 1.07 spikes/10S (P less than 0.05). The lasting time was 26 min, 330S and 280S. We observed 20 cases with hypertension by ear electro-acupuncture. The systolic pressure and diastolic pressure of hypertension patients were decreased (P less than 0.001) and respiratory rate increased (P less than 0.05).

Novel pharmacologic approaches to brain resuscitation after cardiorespiratory arrest in the pediatric patient.

Although no specific pharmacologic therapy for clinical application to cerebral resuscitation after ischemia exists, biochemically guided mechanistic studies are under way to unravel what appears to be an extremely complex process. The evolution of the primary parenchymal insult after ischemia in the brain appears to be coupled to a multifactorial interaction between blood and damaged brain tissue that is initiated very rapidly during reperfusion and leads to further tissue injury (Fig. 8). Current studies implicate calcium, oxyradicals, phospholipid-derived metabolites, and blood elements as possible mediators of tissue injury during reperfusion. However, the optimal conditions for repair and ongoing metabolism after ischemia remain to be defined. In this regard, studies to investigate postischemic communication failure, optimal active and basal metabolic rate in the postischemic brain, and optimal pressure and flow patterns during reperfusion are needed to guide future therapies. Future therapies based on these alternative approaches could supplement refined versions of the regimens presented in this article--those that attempt to minimize reperfusion injury. Meaningful progress in the mitigation of postischemic encephalopathy is almost certain to require novel, specific therapies used in multimodal regimens with a significant fraction of the agents administered as near as possible to the onset of reperfusion. To develop these regimens to treat the pediatric arrest, studies in pediatric models or at least models of asphyxial arrest are essential.

[Pathophysiology and therapy of perinatal asphyxia in a mature newborn]. / Pathophysiologie und Therapie der perinatalen Asphyxie bei reifen Neugeborenen.

Based on modern knowledge about the pathophysiology of perinatal asphyxia a new concept of therapy is discussed. Besides cardiopulmonary resuscitation for the initial shock reaction the therapy of secondary complications according to the multi-system-reaction is emphasized. After the description of the correlation of partial asphyxia and the development of neurological defect syndromes in animal models the necessity of a "cerebral resuscitation" is mentioned.

Extrapulmonary Oxygenation by Giving Hydrogen Peroxide by Enema

An investigation of extrapulmonary oxygenation was made in dogs, rabbits and, finally, in a case of Tetralogy of Fallot using an intestinal perfusion of hydrogen peroxide (H2O2). For a single administration, 0.4 per cent H2O2 can be given safely by enema, in doses of 10ml./Kg. of body weight, this would give maximum oxygenation in both the portal vein and inferior vena cava without the formation of gas emboli. Concentrations higher than this caused gas bubbles in the portal vein. For serial administrations, 0.2 per cent H2O2 can be given by enema exchanging the intestinal contents at 10 to 15 minutes intervals. When given concomitantly with human whole blood, 1.0ml./Kg. of body weight, there is a prolonged higher oxygenation in the portal vein, inferior vena cava and femoral artery. This concentation of H2O2 would not cause gas emboli in the portal vein. Although extrapulmonary oxygenation is possible by giving oxygen by enema, this method would cause too much abdominal distension. In experiments of death by suffocation, the group given H2O2 had doubled the duration of E.K.G. activity when compared with controls. One patient with Tetralogy of Fallot, confirmed by clinical findings, X-ray studies, E.K.G. and cardiac catheterization, who was not suitable for cardiac surgery because of low mentality, was selected for this study. 0.2 per cent H2O2, 10ml. per Kg. of body weight by enema, exchanging intestinal contents at 30 minutes intervals, resulted in a marked elevation of the pO2 in the venous blood and in the inferior vena cava. There was a disappearance of finger tip and toe tip cyanosis and flushing of the soles and palms was noted during the procedure.