Regional ventilation in spontaneously breathing COVID-19 patients during postural maneuvers assessed by electrical impedance tomography.

BACKGROUND: Gravity-dependent positioning therapy is an established concept in the treatment of severe acute respiratory distress syndrome and improves oxygenation in spontaneously breathing patients with hypoxemic acute respiratory failure. In patients with coronavirus disease 2019, this therapy seems to be less effective. Electrical impedance tomography as a point-of-care functional imaging modality for visualizing regional ventilation can possibly help identify patients who might benefit from positioning therapy and guide those maneuvers in real-time. Therefore, in this prospective observational study, we aimed to discover typical patterns in response to positioning maneuvers. METHODS: Distribution of ventilation in 10 healthy volunteers and in 12 patients with hypoxemic respiratory failure due to coronavirus disease 2019 was measured in supine, left, and right lateral positions using electrical impedance tomography. RESULTS: In this study, patients with coronavirus disease 2019 showed a variety of ventilation patterns, which were not predictable, whereas all but one healthy volunteer showed a typical and expected gravity-dependent distribution of ventilation with the body positions. CONCLUSION: Distribution of ventilation and response to lateral positioning is variable and thus unpredictable in spontaneously breathing patients with coronavirus disease 2019. Electrical impedance tomography might add useful information on the immediate reaction to postural maneuvers and should be elucidated further in clinical studies. Therefore, we suggest a customized individualized positioning therapy guided by electrical impedance tomography.

Dynamic relative regional strain visualized by electrical impedance tomography in patients suffering from COVID-19.

Respiratory failure due to SARS-CoV-2 may progress rapidly. During the course of COVID-19, patients develop an increased respiratory drive, which may induce high mechanical strain a known risk factor for Patient Self-Inflicted Lung Injury (P-SILI). We developed a novel Electrical Impedance Tomography-based approach to visualize the Dynamic Relative Regional Strain (DRRS) in SARS-CoV-2 positive patients and compared these findings with measurements in lung healthy volunteers. DRRS was defined as the ratio of tidal impedance changes and end-expiratory lung impedance within each pixel of the lung region. DRRS values of the ten patients were considerably higher than those of the ten healthy volunteers. On repeated examination, patterns, magnitude and frequency distribution of DRRS were reproducible and in line with the clinical course of the patients. Lung ultrasound scores correlated with the number of pixels showing DRRS values above the derived threshold. Using Electrical Impedance Tomography we were able to generate, for the first time, images of DRRS which might indicate P-SILI in patients suffering from COVID-19.Trial Registration This observational study was registered 06.04.2020 in German Clinical Trials Register (DRKS00021276).

Massive macroglossia after palatoplasty: case report and review of the literature.

UNLABELLED: Cleft palates are among the most common birth defects. Serious complications in perioperative airway management after palatoplasty are rare and mostly described in children with preexisting compromise of airway due to craniofacial anomalies. A very uncommon but typical and frightening complication is postoperative extreme, very rapid emergence, and life-threatening macroglossia. While macroglossia usually has its peak within 24-48 h after palatoplasty and resolves spontaneously, we report a patient with massive lingual swelling with complete obstruction of the upper airway on the fifth postoperative day requiring tracheotomy. Swelling only resolved after removing the endotracheal tube after tracheotomy. Next to the description of our case, we discuss standard care procedure in perioperative management of patients with cleft palate to prevent this life-threatening complication after palatoplasty. CONCLUSION: Macroglossia can occur even 3-5 days after surgery and can be maintained by the pressure of the endotracheal tube to the tongue ground. Knowledge and avoidance of these risk factors are as important as early treatment of respiratory compromise.

Success rates and endotracheal tube insertion times of experienced emergency physicians using five video laryngoscopes: a randomised trial in a simulated trapped car accident victim.

CONTEXT: No randomised controlled trial has yet compared different video laryngoscopes in respect of the success rates and the time taken to achieve endotracheal intubation in trapped car accident victims. OBJECTIVE: The aim of the present study was to evaluate whether five video laryngoscopes facilitate tracheal intubation more quickly or more securely than conventional laryngoscopy. DESIGN: Prospective, controlled, randomised crossover trial. SETTING: An airway manikin was placed on the driver's seat of a compact car. Access was possible only through the opened driver's door. PARTICIPANTS: Twenty-five experienced anaesthetists. INTERVENTION: Tracheal intubation in a simulated trapped patient using video laryngoscopes in a typical out-of-hospital setting. MAIN OUTCOME MEASURES: Times to achievement of a view of the glottis, tracheal intubation, cuff inflation, first ventilation and tracheal tube position were compared using a standard Macintosh laryngoscope or Glidescope Ranger, Storz C-MAC, Ambu-Pentax AWS, Airtraq and McGrath Series 5 video laryngoscopes in a randomised order. Wilcoxon signed-rank test and McNemar test were used for statistical analysis. A P value of less than 0.05 was considered statistically significant. RESULTS: Twenty-five anaesthetists (35.1 ±â€Š7.3 years; 16 male, nine female) with an intubation experience of 374 ±â€Š96 intubations per year and an experience of 9.1 ±â€Š7.3 years participated. Glottic view, tracheal intubation, cuff inflation and first ventilation were achieved most rapidly with the Macintosh laryngoscope, although the Airtraq and Pentax AWS video laryngoscopes were not significantly slower. Times were significantly longer when the Glidescope Ranger, McGrath Series 5 or Storz C-MAC video laryngoscopes were used (P < 0.05), failure to place the endotracheal tube correctly was significantly commoner with the McGrath Series 5 than with the Macintosh (P = 0.031). CONCLUSION: When attempting to intubate a trapped car accident victim, video laryngoscopes provide a better view of the glottis, but some delay tracheal intubation significantly. The devices with a tube guide (Airtraq and Ambu Pentax AWS) enable tracheal intubation to be achieved significantly faster and with a lower failure rate than devices without a tube guide. No video laryngoscope outperformed direct laryngoscopy with a Macintosh laryngoscope in this simulation study.

The influence of pre-operative risk on the number of circulating endothelial progenitor cells during cardiopulmonary bypass.

BACKGROUND AIMS: The number of circulating endothelial progenitor cells (EPC) depends on cytokine release and is also associated with cardiovascular risk factors. During cardiopulmonary bypass (CPB) the endothelium is the first organ to be affected by mechanical and immunologic stimuli. We hypothesized that the magnitude of EPC mobilization by CPB correlates with the pre-operative cardiovascular morbidity profile. METHODS: EPC were quantified in blood samples from 30 patients who underwent cardiac surgery by magnetic bead isolation and fluorescence-activated cell sorting (FACS) analysis, based on concomitant expression of CD34, CD133 and CD309. Patients were divided into two groups based on the European System for Cardiac Operative Risk Evaluation (EuroSCORE): low risk (LR) and high risk (HR). Ten healthy volunteers served as controls. Samples were obtained before the start of CPB and at 1 and 24 h post-operatively. Plasma samples were collected for determination of release levels of cytokines and growth factors. RESULTS: All CPB patients showed a significantly reduced basal number of EPC compared with healthy individuals (LR 5.60 +/- 0.39/mL, HR 3.89 +/- 0.34/ mL, versus control 0.807 +/- 0.82/mL, P = 0.012 versus LR, P< 0.001 versus HR). CPB induced EPC release that peaked 1 h after surgery (pre-operative 4.79 +/- 0.32/mL, 1 h 57.49 +/- 5.31/mL, 24 h 6.67 +/- 1.05/mL, P< 0.001 pre-operative versus 1 h, P< 0.001 pre-operative versus 24 h) and was associated with the duration of CPB. However, EPC release was significantly attenuated in HR patients (33.09 +/- 3.58/mL versus 81.89 +/- 4.36/mL at 1 h after CPB, P < 0.0001) and inversely correlated with the pre-operative EuroSCORE. Serum granulocyte-colony-stimulating factor (G-CSF), stem cell factor (SCF) and vascular endothelial growth factor (VEGF) levels increased throughout the observation period and were also correlated with the EPC count. CONCLUSIONS: Cardiovascular risk factors influence the mobilization of EPC from the bone marrow after stimulation by CPB. This could be secondary to impaired mobilization or the result of increased EPC turnover, and may have implications for future cell therapy strategies in cardiac surgical patients.

Increased cortisol levels and anticholinergic activity in cognitively unimpaired patients.

Increased patients' serum anticholinergic activity (SAA) is described as a marker of cognitive dysfunction and can be influenced by different exogenous and endogenous factors. The role of cortisol in relation to SAA and cognition in perioperative conditions has not been investigated so far. In 30 men scheduled for urological surgery, the authors determined SAA and cortisol levels in blood and CSF and conducted neuropsychological testing in two subgroups with comparable pre- and intraoperative characteristics, one group with low SAA (mean=2.4 [SD=0.9], n=23) and the other with high SAA (mean=5.1 [SD=2.4], n=7) values. Increased SAA was associated with two times the number of anticholinergic medications but not with patients' age, medical history or impaired cognition. A significant linear correlation was detected between anticholinergic activities and cortisol levels. Thus, endogenous factors such as patients' stress levels should be taken into account for interpretation of the role of SAA.

Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist.

BACKGROUND: The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. METHODS: First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion. RESULTS: Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. CONCLUSIONS: Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.

The impact of Trendelenburg position and positive end-expiratory pressure on the internal jugular cross-sectional area.

BACKGROUND: Increasing the cross-sectional area (CSA) of the right internal jugular vein facilitates cannulation and decreases complications. Maneuvers such as the Trendelenburg tilt position and ventilation with a positive end-expiratory pressure (PEEP) may increase the CSA of the right internal jugular vein. We determined the changes in the CSA in response to different maneuvers. METHODS: The CSA (cm(2)) of the right internal jugular vein was assessed in 50 anesthetized adult cardiothoracic surgery patients using 2-dimensional ultrasound. First, the CSA was measured in response to supine position with no PEEP (control condition, S0) and compared with 5 different randomly ordered maneuvers: (1) PEEP ventilation with 5 cm H(2)O (S5), (2) PEEP with 10 cm H(2)O (S10), (3) a 20 degrees Trendelenburg tilt position with a PEEP of 0 cm H(2)O (T0), (4) a 20 degrees Trendelenburg tilt position combined with a PEEP of 5 cm H(2)O (T5), and (5) a 20 degrees Trendelenburg tilt position combined with a PEEP of 10 cm H(2)O (T10). RESULTS: All maneuvers increased the CSA of the right internal jugular vein with respect to the control condition S0 (all P < 0.05). S5 increased the CSA on average by 15.9%, S10 by 22.3%, T0 by 39.4%, T5 by 38.7%, and T10 by 49.7%. CONCLUSION: In a comparison of the effectiveness of applying different PEEP levels and/or the Trendelenburg tilt position on the CSA of the right internal jugular vein, the Trendelenburg tilt position was most effective.

Effects of hydroxyethyl starch, gelatin and dextran on endothelium-derived relaxation in porcine coronary arteries.

BACKGROUND: In a pilot study we could show that hydroxyethyl starch (HES) induced a significant reduction of endothelium-dependent relaxation (EDR) and the endothelium-derived hyperpolarizing factor (EDHF). In this follow-up study we investigated whether this effect of HES was dose-dependent and whether it could be replicated with other colloids like dextran (DX) and gelatin (GL). METHODS: Rings of fresh porcine coronary arteries were consecutively tested with or without HES, DX or GL (5, 10, or 20 mg/ml). Indomethacin was added in all measurements to eliminate prostacyclin effects. Prostaglandin F2α was used for contraction and bradykinin (BK, 10⁻¹° to 10⁻5 M) for inducing EDR. After blocking nitric oxide (NO) by N-nitro-L-arginine (L-NNA), the experiments were repeated to assess the EDHF-mediated relaxation response to BK. RESULTS: HES induced a reduction in EDR for the BK concentrations of 10⁻8 and 10⁻7 M (n = 10; p < 0.05). After NO blockage with L-NNA, the relaxation response was reduced especially for the BK concentrations of 10⁻6 and 10⁻5 M (p < 0.05). GL showed a reduction in EDR with or without NO blockage with L-NNA especially for the BK concentrations of 10⁻6 and 10⁻5 M (n = 14; p < 0.05). DX induced a significant reduction in EDR for the BK concentrations of 10⁻7 and 10⁻6 M (n = 12; p < 0.05). After NO blockage with L-NNA, the relaxation response was reduced especially for the BK concentrations of 10⁻6 and 10⁻5 M (p < 0.05). CONCLUSION: For clinically relevant concentrations of HES, DX and GL a significant reduction in both NO-induced and NO-/prostacyclin-independent EDR can be found in epicardial coronary arteries of the pig.

Intracerebroventricular application of granulocyte colony-stimulating factor after cardiac arrest does not promote beneficial effects on cerebral recovery after cardiac arrest in rats.

SUBJECT: Recent data demonstrated potent neuroprotective effects of growth hormones such as granulocyte colony-stimulating factor (G-CSF) after focal cerebral ischaemia. In order to assess possible effects of intracerebroventricular application of G-CSF on cerebral recovery after cardiac arrest (CA) in rats, neurological testing and histological analyses were performed. INTERVENTIONS: After 6 min of electrically induced CA, rats were resuscitated (CPR) and divided into two groups (G-CSF vs. placebo) with two different reperfusion times (7 and 14 days). G-CSF (3.84 microg) or placebo was applied 30 min after restoration of spontaneous circulation (ROSC). At 24h, 3, 7, 10 and 14 days, behavioural neurological testing was done (tape removal test, TRT). Neuronal degeneration of the hippocampal CA-1 sector was analyzed by TUNEL- and Nissl-staining. RESULTS: Before CA all animals passed the TRT (G-CSF 7 [4-12] s, placebo 9 [6-10] s). After ROSC both groups showed a clear neurological deficit (24h: G-CSF and placebo 180 [180-180] s), that improved with ongoing reperfusion times, without reaching baseline values (14 days: G-CSF 25 [21-59] s, placebo 34 [14-175] s). Survival rates did not differ between the groups. All animals showed massive neurodegeneration histologically without any differences between the groups 7 days after CA (TUNEL-positive: G-CSF 63.2 [53.8-72.1], placebo 72.6 [66.6-82.7]; Nissl-positive: G-CSF 2.5 [1.8-3.4], placebo 2.8 [2.0-5.1]). At 14 days, TUNEL-staining revealed no differences (G-CSF 45.2 [35.0-60.0], placebo 56.0 [37.6-63.4]), while G-CSF treatment led to fewer Nissl-positive neurons (G-CSF 1.5 [1.2-2.2], placebo 3.1 [2.1-4.2]; p=0.011). CONCLUSIONS: Despite promising experimental data concerning focal cerebral ischaemia, in this model of 6 min of normothermic CA no beneficial effects of G-CSF application could be demonstrated by behavioural testing and histological analyses of the hippocampal CA-1 sector.

Time course of caspase activation in selectively vulnerable brain areas following global cerebral ischemia due to cardiac arrest in rats.

This study evaluated the time course of caspase activation in selectively vulnerable brain areas (hippocampus, nucleus reticularis thalami (NRT), cortex and striatum) following cardiopulmonary resuscitation (CPR) after global cerebral ischemia due to cardiac arrest (CA) in rats. Caspases are well known to play a crucial role in the apoptotic cascade and inflammatory syndromes and, therefore, represent potential therapeutic postischemic targets. Given the delayed neurodegeneration following CA, it is highly important to study the time course of caspase activation in regard to therapeutic interventions after CA. To assess caspase activity, in situ staining was applied to detect general caspase activity at 6h, 3d and 7d and caspase-3 activity at 3d after return of spontaneous circulation (ROSC). For detection of neuronal apoptosis, TUNEL staining was applied at 7d after ROSC. Distinct patterns of early caspase activation were observed at 6h and 3d in the NRT and striatum and of late activation at 7d in the hippocampal CA-1 sector. General caspase and caspase-3 activity correlated strongly at 3d after ROSC in all areas studied. At 7d, the TUNEL-positive neuron counts in the hippocampal CA-1 sector correlated strongly with caspase activation. In conclusion, general caspase and caspase-3 activity after 6 min of CA and the delayed occurrence of TUNEL-positive neurons strongly indicate that neuronal degeneration after CA is at least strongly associated with apoptosis. Therefore, postischemic antiapoptotic interventions might offer potential future therapeutic opportunities global cerebral ischemia due to CA.

The effect of intracerebroventricular application of the caspase-3 inhibitor zDEVD-FMK on neurological outcome and neuronal cell death after global cerebral ischaemia due to cardiac arrest in rats.

BACKGROUND: Global cerebral ischaemia after cardiac arrest (CA) leads to programmed cell death (PCD) with characteristic signs of apoptosis in selectively vulnerable areas of the brain. The activation of caspase-3, an executioner caspase, plays a key role in the apoptotic cascade. We, therefore, studied the effects of the application of the specific caspase-3 inhibitor zDEVD-FMK on neurological outcome and neuronal cell death after experimental CA in rats. METHODS: A 6-min CA was induced in anaesthetised and mechanically ventilated male Wistar rats. After cardiopulmonary resuscitation (CPR) and restoration of spontaneous circulation (ROSC) the animals were randomised to two groups to receive a continuous intracerebroventricular (i.c.v.) infusion for 7 days of zDEVD-FMK or placebo (artificial cerebrospinal fluid, CSF). At 24h, 3 and 7 days after ROSC, animals were tested according to a neurological deficit score (NDS). Seven days after ROSC, coronal sections of the brain were taken at the dorsal hippocampal level and analysed with cresyl-violet staining, the TUNEL technique and a caspase activity assay. Viable and TUNEL-positive neurons were counted in the hippocampal CA-1 sector. RESULTS: The NDS demonstrated severe deficits 1 and 3 days after ROSC, which resolved by 7 days with no difference between the two groups. At 7 days after ROSC neuronal death could be detected using cresyl-violet and TUNEL staining with no difference between the groups. CONCLUSION: We conclude that zDEVD-FMK administration has no effect on neurological outcome and PCD after global cerebral ischaemia following CA in rats. Other mechanisms or pathways must be identified in the pathophysiology of PCD after CA.

Neurological outcome and inflammation after cardiac arrest--effects of protein C in rats.

BACKGROUND: The response of the human body to cardiac arrest (CA) and cardiopulmonary resuscitation is characterised by excessive coagulation, inadequate endogenous anti-coagulation and fibrinolysis as well as an inflammatory syndrome that closely resembles the immunological profile observed in patients with sepsis. Recombinant human activated protein C (rhAPC) has been found to be protective in severe sepsis and in animal models of stroke and spinal cord injury. In the present study, we evaluated the effects of rhAPC on neurological outcome after CA in rats. METHODS: After 6 min of CA and subsequent cardiopulmonary resuscitation, male Wistar rats were randomized into 3 treatment groups: high dose rhAPC (2 mg/kg bolus and 0.1 mg/(kg h) for 6 h), low dose rhAPC (0.5 mg/kg and 0.025 mg/(kg h) for 6 h), and placebo (n=12 per treatment and reperfusion time). Neurological outcome was determined using a tape removal test and a composite neurological deficit score (NDS). As secondary measurements, we evaluated overall and neuronal survival, hippocampal caspase activity and inflammatory markers. RESULTS: No difference between groups was found with the NDS. The tape removal test showed only a transitory improvement in the low dose group at 3 d after CA (P=0.041). No significant differences were observed for secondary measurements. CONCLUSION: A clear and lasting effect of rhAPC on neurological outcome or inflammation after CA could not be shown in this study but the detailed analysis of the postresuscitation syndrome given here builds a firm basis for further research.

Time course of the hypothermic response to continuously administered neurotensin.

Intracerebroventricular administration of the tridecapeptide neurotensin is known to elicit hypothermia in rodents for few hours. In the present study, we investigated a continuous intracerebroventricular infusion regimen for prolongation of the hypothermic effect. Male Wistar-Han rats (n=13) received neurotensin 10-50 microg/h for 48 h, while their body temperature was monitored continuously. This protocol led to a dose-dependent decrease of body temperature down to 35-36 degrees C. The nadir of hypothermia lasted for approximately 4h and normothermia was re-established after 12-24h. Furthermore, abundance of neurotensin in the hypothalamus was determined after 6 and 30 h by western blotting. High levels were still found at 30 h, while the rats had already become normothermic at that time. In summary, continuous infusion of neurotensin led to prolongation of the known hypothermic response, however resulted in development of tolerance.

Significant correlation between plasma and CSF anticholinergic activity in presurgical patients.

Previous studies have suggested a possible link between cognitive impairment and anticholinergic burden as reflected by high serum anticholinergic activity (SAA). Thus, we hypothesized a close relationship between anticholinergic activity in cerebral spinal fluid (CSF) and blood. However, it has never been convincingly demonstrated that peripheral anticholinergic activity correlates with central anticholinergic levels in presurgical patients. Therefore, anticholinergic activity was measured in blood and CSF from 15 patients with admission scheduled for urological surgery to compare peripheral and central anticholinergic level. Blood and CSF probes were taken after routine premedication and before spinal anesthesia. Anticholinergic activity was determined by competitive radioreceptor binding assay for muscarinergic receptors. Correlation analysis was conducted for peripheral and central anticholinergic levels. The mean anticholinergic levels were 2.4+/-1.7 in the patients' blood and 5.9+/-2.1 pmol/mL of atropine equivalents in CSF. Interestingly, the anticholinergic activity in CSF was about 2.5-fold higher than in patients' blood. A significant linear correlation was detected between blood and CSF levels. Therefore we conclude that SAA levels adequately reflect central anticholinergic activity. When patients receiving or not receiving anticholinergic medication were compared, anticholinergic activity tended to increase in blood and CSF after receiving anticholinergic medication > or =4 weeks (p>0.05).

Vasopressors are essential during cardiopulmonary resuscitation in rats: Is vasopressin superior to adrenaline?

BACKGROUND: Vasopressors are recommended for cardiopulmonary resuscitation (CPR) after cardiac arrest. In order to assess possible benefits regarding neurological recovery, vasopressin versus adrenaline and the combination of both was tested against placebo in a cardiac arrest model in rats. METHODS: Under anaesthesia with halothane and N2O, cardiac arrest was initiated via transoesophageal electrical fibrillation. After 7 min of global ischaemia, CPR was performed by external chest compression combined with defibrillation. Animals were randomly assigned to three groups receiving adrenaline, vasopressin and a combination of both (n = 15 per group) versus placebo (n = 8). At 1, 3 and 7 days animals were tested according to a neurological deficit score (NDS). After 7 days of reperfusion, coronal brain sections were analysed by Nissl- and TUNEL-staining. Viable as well as TUNEL-positive neurons were counted in the hippocampal CA-1 sector. For statistical analysis, the log rank and the Kruskal-Wallis ANOVA test were used. All data are given as mean+/-S.D.; a p-value <0.05 was considered significant. RESULTS: Mean arterial blood pressure (MAP) measured in the aorta did not differ between the vasopressor groups, whereas placebo animals had significantly lower levels. Survival to 7 days revealed significant differences between the placebo (n = 0/8) and all vasopressor groups (adrenaline, 10/15; adrenaline/vasopressin, 8/15; vasopressin, 12/15). Histological deficit scoring by quantitative analysis of the Nissl- and TUNEL-staining showed no difference in the amount of viable and apoptotic neurons in the vasopressin group (viable: 33+/-18; apoptotic: 63+/-23) versus the adrenaline group (viable: 21+/-12; apoptotic: 67+/-17) and the adrenaline/vasopressin group (viable: 31+/-26; apoptotic: 61+/-27). Neurological deficit scoring did not show any differences between the vasopressor groups. CONCLUSION: Administration of arginine-vasopressin during CPR does not improve behavioural and cerebral histopathological outcome, compared to the use of adrenaline or the combination of both vasopressors, after cardiac arrest in rats.

Effects of the application of erythropoietin on cerebral recovery after cardiac arrest in rats.

BACKGROUND: After transient global cerebral ischaemia, selectively vulnerable areas of the brain show delayed neuronal degeneration. Recent data have demonstrated potent neuroprotective effects of the application of growth hormones like erythropoietin (EPO) after focal cerebral ischaemia. In order to assess possible effects of the application of EPO on cerebral recovery after cardiac arrest in rats, the vulnerable hippocampal CA-1 sector was investigated. METHODS: Thirty male Wistar rats were randomised into two groups (EPO versus placebo; n=15 per group). Cardiac arrest was induced by ventricular fibrillation during general anaesthesia. After 6 min of global cerebral ischaemia, animals were resuscitated by external chest compressions combined with defibrillation. Investigator blinded bolus application of EPO (5000 IE/kg bodyweight) and placebo was performed at three different time points, respectively: 5 min before cardiac arrest (i.v.; intravenously), 24h (i.p.; intraperitoneally) and 72 h (i.p.) after ischaemia. At 24h, 72 h and 7 days, animals were tested according to a neurological deficit score. After of reperfusion, coronal brain sections were analysed by TUNEL- and Nissl-staining. A caspase activity assay was done to determine antiapoptotic properties of EPO. Statistical analyses were done using ANOVA. RESULTS: Neurological deficit scoring did not show differences between the groups. However, in all groups typical delayed neuronal degeneration could be found in the CA-1 sector. There was no difference in neuronal survival between the groups (viable neurons EPO (median [interquartile range]): 15.5 [10.1-21.3]; placebo: 16.8 [7.7-26.3]). Results from TUNEL-staining revealed no differences in the amount of apoptotic cell death between the groups (EPO: 71.2 [58.1-81.8]; placebo: 73.4 [67.8-78.2]). Caspase activity assays demonstrated a strong expression of general caspase activity as well as caspase-3 activity in the CA-1 sector and the nucleus reticularis thalami, without any differences between both groups. CONCLUSION: Despite the well known neuroprotective properties of EPO in ischaemia induced neuronal degeneration, this study could not reveal any beneficial effects of EPO after global cerebral ischaemia due to cardiac arrest in rats.

Evaluation of a tape removal test to assess neurological deficit after cardiac arrest in rats.

BACKGROUND: In animal models of cardiocirculatory arrest (CA) it is of major interest to establish tests that can assess neurological damage after global cerebral ischaemia following CA. We evaluated a tape removal test with regard to detection of sensorimotor deficit, comparing it to the Neurological Deficit Score (NDS) in an established model of global cerebral ischaemia after CA in rats. METHODS: Rats were subjected to either 6 min of CA followed by cardiopulmonary resuscitation (CPR) or a sham operation. At 1, 3 and 7 days from the intervention, two different neurological tests were applied to all animals: in the tape removal test, the time was measured from attachment of adhesive tapes to the front paws until the animals removed them using their teeth and compared to latencies in the sham group. The NDS assessed two parameters ("travel beam" and "stop at the edge of a table"). Receiver operating characteristic (ROC) analysis was used to compare tests. RESULTS: In the tape removal test, all animals of the CPR group showed a clear neurological deficit throughout the observation period with a marked recovery until day 7 (pre-CA: 4s, 1 day: 180 s, 3 days: 165 s, 7 days: 44 s; data are median values). Latencies differed significantly from those of sham-operated animals (1 day: P<0.001, 3 days: P=0.003, 7 days: P=0.006). ROC analysis showed that the tape removal test but not the NDS was appropriate for detecting neurological damage 3 and 7 days after restoration of spontaneous circulation (ROSC). Histological examination confirmed neuronal damage to the hippocampus, cortex, thalamus and striatum. CONCLUSION: In the present study, a clinically relevant sensorimotor deficit after global cerebral ischaemia following cardiac arrest in rats has been quantified for the first time by using a tape removal test. The tape removal test is a sensitive method that can be easily applied to test large numbers of animals in future studies.