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).

Conductance catheter measurement and effect of different anesthetics in a rat model of postresuscitation myocardial dysfunction.

We demonstrate the usefulness of left ventricular pressure-volume (PV) loops generated by the use of conductance catheter measurements and investigate the influence of the type of general anesthesia on postresuscitation myocardial dysfunction in a rat model of cardiac arrest (CA) and subsequent cardiopulmonary resuscitation. A total of 42 Wistar-Han rats were randomized to receive general anesthesia with sevoflurane and resuscitation after CA, general anesthesia with pentobarbital intraperitoneally and resuscitation after CA, or general anesthesia with pentobarbital without CA (sham group). Myocardial function, assessed by analysis of PV loops, was measured continuously and in real-time by using a PV-conductance catheter. Rats were monitored for 3 h after restoration of spontaneous circulation (ROSC). The use of PV-conductance catheters supported objective and reliable evaluation of myocardial function and proved feasible in this rat model of CA. End-diastolic volume increased in rats anesthetized with pentobarbital after ROSC (before CA, 237 ± 45 µL; after ROSC, 402 ± 64 µL). Preloadadjusted maximal power before CA was the same in all groups but decreased in both resuscitated groups. The decrease was less pronounced in rats anesthetized with sevoflurane compared with pentobarbital (11.8 ± 4.9 mW/µL(2) compared with 4.8 ± 1.9 mW/µL(2) at 3 h after ROSC). This finding indicates that the type of general anesthesia influences postresuscitation myocardial dysfunction in this rat model of experimentally induced CA and cardiopulmonary resuscitation. Rats that were anesthetized with sevoflurane exhibited less postresuscitation myocardial dysfunction than did those anesthetized with pentobarbital.

Effects of intracerebroventricular application of insulin-like growth factor 1 and its N-terminal tripeptide on cerebral recovery following cardiac arrest in rats.

BACKGROUND: Following global cerebral ischaemia due to cardiac arrest (CA), selective neuronal vulnerability and delayed neuronal death with distinct signs of apoptosis could be observed in certain areas of the brain. Growth hormones like the insulin-like growth factor 1 (IGF-1) and the bioactive N-terminal tripeptide of IGF-1, glycine-proline-glutamate (GPE), exhibit strong protective properties in focal ischaemia in vivo and in vitro. To examine these promising effects on neuronal survival and cerebral recovery after experimental cardiopulmonary resuscitation, the most vulnerable hippocampal CA-1 sector was investigated. METHODS: After 6 min of CA, 54 male Wistar rats were resuscitated and were randomly assigned to 3 groups (IGF-1, GPE vs. placebo; n=6 per group) and 3 different reperfusion periods. Intracerebroventricular application of IGF-1 (1.25 µgh(-1)), GPE (50 ngh(-1)) and placebo was performed using osmotic minipumps up to day 7 following reperfusion. After 3, 7 and 14 days, coronal brain sections were analysed by counting Nissl-positive (i.e. viable) neurons and TUNEL-positive (i.e., apoptotic) cells. All experiments were performed in a randomised and blinded setting. RESULTS: In all groups in the hippocampal CA-1 sector typical delayed neurodegeneration from day 3 to day 14 after CA could be found. No significant increase of the number of Nissl-positive neurons after IGF-1-treatment (p=0.18) as well as after GPE-treatment (p=0.14) could be observed. The number of TUNEL-positive cells could not be reduced significantly in the IGF-1 group (p=0.13), whereas GPE treatment revealed significant less TUNEL-positive cells (p=0.02). This was primarily an effect in the early phase (day 3: p=0.02) of reperfusion and was no more detectable 7 days (p=0.69) and 14 days after ROSC (p=0.30). CONCLUSION: Despite the well known neuroprotective properties of IGF-1 and GPE in ischaemic induced neuronal degeneration, this model could only reveal a short-term beneficial effect of GPE after experimental cardiac arrest in rats. (Institutional protocol number: 35-9185.81/43/00.).

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.

Facilitation of hypothermia by quinpirole and 8-OH-DPAT in a rat model of cardiac arrest.

AIM OF THE STUDY: Therapeutic hypothermia improves outcome after cardiac arrest. Dopamine D(2) agonists and serotonin 5-HT(1A) agonists lower body temperature by decreasing the set-point. We investigated the effect of these drugs on temperature and cerebral recovery of rats after cardiac arrest. METHODS: Male Wistar-Han rats were subjected to 6 min of cardiac arrest due to ventricular fibrillation. Following restoration of circulation, 1mg quinpirole, 1mg 8-OH-DPAT or vehicle were injected subcutaneously. Body temperature was monitored for 48 h. One additional group was kept normothermic. Animals were neurologically tested by a tape removal test. After 7 days, histology of hippocampal CA-1 sector was analysed with Nissl and TUNEL staining. RESULTS: Rats became spontaneously hypothermic after cardiac arrest. Induction of hypothermia was facilitated by both quinpirole (-0.033 ± 0.008°C/min) and 8-OH-DPAT (-0.029 ± 0.010°C/min) when compared to vehicle (-0.020 ± 0.005°C/min). Total 'dose' of hypothermia (area under the curve) was not different. All animals showed a neurological deficit, which improved with time; after 7 days, test results of the normothermic group (30 [11-88]s) still tended to be worse than those of the hypothermic groups (vehicle 8 [6-14]s, quinpirole 9 [4-17]s, 8-OH-DPAT 10 [8-22]s). There were no clear differences in Nissl or TUNEL histology after 7 days. CONCLUSION: Both quinpirole and 8-OH-DPAT led to faster induction of hypothermia. However, the outcome was not different from spontaneous hypothermia, probably because the total 'dose' of hypothermia was not influenced.

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.

Hypothermia and neuroprotection by sulfide after cardiac arrest and cardiopulmonary resuscitation.

BACKGROUND: Poor neurological outcome remains a major problem in patients suffering cardiac arrest. Recent data have demonstrated potent neuroprotective effects of the administration of sulfide donor compounds after ischaemia/reperfusion injury following cardiac arrest and resuscitation. Therefore, we sought to evaluate the impact of sodium sulfide (Na(2)S), a liquid hydrogen sulfide donor on core body temperature and neurological outcome after cardiac arrest in rats. METHODS: Fifty male Wistar rats were randomized into two groups (sulfide vs. placebo, n=25 per group). Cardiac arrest was induced by transoesophageal ventricular fibrillation during general anaesthesia. After 6 min of global cerebral ischaemia, animals were resuscitated by external chest compressions combined with defibrillation. An investigator blinded bolus of either Na(2)S (0.5 mg/kg body weight) or placebo 1 min before the beginning of CPR, followed by a continuous infusion of Na(2)S (1 mg/kg body weight/h) or placebo for 6 h, was administered intravenously. 1 day, 3 days, and 7 days after restoration of spontaneous circulation, neurological outcome was evaluated by a tape removal test. After 7 days of reperfusion, coronal brain sections were analyzed by TUNEL- and Nissl-staining. A caspase activity assay was used to determine antiapoptotic properties of Na(2)S. RESULTS: Temperature course was similar in both groups (mean minimal temperature in the sulfide group 31.3±1.2°C vs. 30.8±1.9°C in the placebo group; p=0.29). Despite significant neuroprotection demonstrated by the tape removal test after 3 days of reperfusion in the sulfide treated group, there was no significant difference in neuronal survival at day 7. Likewise results from TUNEL-staining revealed no differences in the amount of apoptotic cell death between the groups after 7 days of reperfusion. CONCLUSION: In our rat model of cardiac arrest, sulfide therapy was associated with only a short term beneficial effect on neurological outcome.

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.

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.

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.

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.

Effects of abciximab on postresuscitation microcirculatory dysfunction after experimental cardiac arrest in rats.

BACKGROUND: The term "postresuscitation syndrome" includes among other pathophysiology impaired microcirculation and endothelial leakage. GPIIb/IIIa receptor antagonists like abciximab have been shown to reduce endothelial leakage and to improve microcirculatory disturbances during experimental endotoxaemia where comparably similar endothelial dysfunction has been observed. Previous investigations on postresuscitation endothelial leakage have indicated a possible role of platelets. Therefore, we investigated effects of abciximab on postresuscitation microcirculation applying in vivo microscopy of postcapillary mesenteric venules after experimentally induced cardiac arrest and cardiopulmonary resuscitation in rats. METHODS: After 6 min of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), male Wistar rats were randomised into two groups (n=10) to receive abciximab (1mg/kg i.v.) or placebo (0.9% NaCl). Sham operated animals (n=10) served as non-ischaemic controls. At 360, 420 and 480 min after return of spontaneous circulation (ROSC) in vivo microscopy was performed to assess venular wall shear rate (WSR) and plasma extravasation (PE). RESULTS: Besides typical signs of severe endothelial leakage in both CA groups, no significant differences between the treatment groups were observed with regard to WSR and PE. CONCLUSION: In our study, a distinct postresuscitation microcirculatory splanchnic impairment after CA and successful CPR was observed. However, abciximab had no effects on WSR and PE. Our data does not support a valid resemblance between postresuscitation microcirculatory dysfunction observed in connection with experimental endotoxaemia. Furthermore, our data indicate that mechanisms other than GPIIb/IIIa mediated platelet activation play a role in postresuscitation syndrome. A better understanding of "postresuscitation disease" should enable the development of future therapeutic strategies for cardiac arrest survivors.

Effects of activated protein C on post cardiac arrest microcirculation: an in vivo microscopy study.

BACKGROUND: The clinical symptoms and pathophysiologic mechanisms during and after ischaemia-reperfusion following cardiac arrest (CA) and successful cardiopulmonary resuscitation (CPR) closely resemble those observed in patients with severe sepsis. Impairment of microcirculation and endothelial leakage seem to play key roles in the underlying pathophysiology. Recombinant human activated protein C (rhAPC) is the first drug being licensed for the treatment of severe sepsis in patients. Therefore, for the first time, we investigated effects of rhAPC on microhaemodynamic changes and endothelial leakage applying in vivo microscopy of postcapillary mesenteric venules after CA and CPR in rats. METHODS: After 6 min of CA, male Wistar rats were randomised into two groups (n=10) to receive rhAPC or placebo (0.9% NaCl). Sham-operated animals (n=10) served as non-ischaemic controls. At 360, 420, and 480 min after CA in vivo microscopy was performed to assess wall shear rate (WSR) and plasma extravasation (PE). RESULTS: Both treatment groups showed typical signs of impaired microcirculation and a severe endothelial leakage after CA at all time points studied when compared to the sham group. However, no significant differences between the treatment groups were observed with regard to WSR and PE. CONCLUSION: Our results show that CA with consecutive successful CPR leads to a microcirculatory impairment closely resembling experimentally induced sepsis. Intriguingly, despite these similarities, rhAPC had no significant effects on WSR and PE. Our results strongly suggest that further mechanisms such as mast cell activation might play an important role and have therefore to be studied to elucidate the pathophysiology of "postresuscitation disease".

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.