Association of the time to first epinephrine administration and outcomes in out-of-hospital cardiac arrest: SOS-KANTO 2012 study

Objective

This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms.

Properties of neuronal activity related to a visual reaction time task in the monkey prefrontal cortex

1. Quantitative properties of neuronal activity related to a visual reaction time task were studied in the monkey prefrontal cortex. The task consisted of an initial waiting phase (3.0-s period), a warning phase (green lamp, a variable period of 1.5-3.5 s), a go phase (red lamp), and a reward phase. 2. A total of 189 task-related neurons showed 233 changes in discharge rates during the warning (n = 86), GO (n = 103), and reward (n = 44) phases of the task. Most of the task-related neurons (145/189, 77%) showed changes during only one of the task phases, and were designated W (warning phase)-type (n = 42), GO (go phase)-type (n = 59), and RE (reward phase)-type (n = 44) neurons. The remainder (n = 44, 23%) showed changes during both the warning and the go phases, and were designated WG (warning and go phase)-type neurons. In each phase, onset latencies, peak latencies, and decay times of each change were measured and compared. 3. The changes during the warning phase (n = 86) were separated into three groups based on decay time; that is, phasic changes (n = 31), phasic-tonic changes (n = 23), and tonic changes (n = 32). Onset latencies and peak latencies were homogeneously distributed, and there were no clear groupings, although phasic and phasic-tonic changes tended to show shorter latencies than tonic changes. 4. The changes during the go phase (n = 103) did not show distinct differences, either in terms of decay time or of latency. The changes during the go phase showed various degrees of coupling to both the visual go signal (GS) and lever-release hand movement. To quantitate the coupling, a value to indicate the degrees of coupling (coupling index) was calculated. The changes coupled more strongly to the GS (cue coupled), those coupled more closely to the lever release (movement coupled), and intermediate changes could be distinguished from each other. The cue-coupled changes showed shorter latencies from the time onset of the GS than the movement-coupled changes, and the intermediate changes showed intermediate latencies. The decay time and the duration of the intermediate changes were longer than those of the cue-coupled changes and the movement-coupled changes. 5. The properties of WG-type neurons were compared with those of W-type and GO-type neurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Met-RANTES ameliorates fibrous airway obliteration and decreases ERK expression in a murine model of bronchiolitis obliterans.

OBJECTIVES: Bronchiolitis obliterans (BO) is the main cause of late mortality among long-term survivors of lung transplantation. Chemokine-chemokine receptor (CCR) interaction and subsequent recruitment of infiltrating cells to the graft are early events in the development of chronic rejection of transplanted lungs. The present study investigated whether blockade of chemokine receptors CCR1 and CCR5 with Met-regulated-on-activation, normal T cells expressed and secreted (RANTES), an amino-terminal modified derivative of RANTES/CCL5, affects the development of BO in murine model and we sought to determine the expression of RANTES/CCL5 and their relationship with extracellular signal-regulated kinase (ERK). Materials and Methods: BALB/c mouse tracheas were heterotopically transplanted into C57Black6 recipients and treated for 21 days with either Met-RANTES at 20 microg/day or vehicle. Animals were killed at 21 days after transplantation for histologic examination of ERK expression. RESULTS: RANTES/CCL5 was highly expressed in allografts compare to isografts. Met-RANTES treatment ameliorated fibrous airway obliteration in a mouse model of BO and decreased ERK expression. CONCLUSION: Blockade of chemokine receptors by Met-RANTES ameliorated airway obliteration and decreased ERK expression. These findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in the development of chronic rejection and ERK may be a new molecular target for chronic rejection.     

Blocking effect of 1389-S on the sodium current in isolated guinea-pig ventricular myocytes

Under whole cell patch conditions, 1389-S blocked the INa in guinea-pig ventricular myocytes under steady state conditions (Kdrest = 30 microM, Kdi = 2.4 microM) with a shift of the inactivation curve to the hyperpolarizing direction. Both brief and long conditioning pulses could produce a use-dependent block of 1389-S. These results suggest that 1389-S had a higher affinity to the inactivated than to the rested state under steady state conditions and had a higher affinity to the activated state during train pulses as well as to the inactivated state, making channels unavailable for conduction upon activation.     

Catecholamine sensitivities of neurons related to a visual reaction time task in the monkey prefrontal cortex

1. Using microiontophoretic techniques and conscious monkeys, sensitivities to noradrenaline (NA) and dopamine (DA) of neurons of the prefrontal cortex (PFC), which showed changes in activity during a visual reaction time task, were investigated. The visual reaction time task was initiated by the pressing of a lever and consisted of four phases: an initial waiting phase of 3.0 s, a warning phase (green light of variable duration of 1.5-3.5 s), a lever release go phase (red light), and a final reward phase. 2. A total of 153 neurons, which showed changes in activity during one or two phase(s) of the task, were sampled. Of these neurons, 39 changed their activity during the warning phase, 48 changed their activity during the go phase, 38 changed their activity during both the warning and the go phases, and 28 changed their activity during the reward phase. 3. Iontophoretically applied NA and DA (with a current of 30-70 nA, but usually with a current of 50 nA) induced excitatory and/or inhibitory responses in 141 of the 153 task-related neurons. NA induced responses in 99 neurons, and these responses were predominantly inhibitory (n = 90). DA induced excitatory (n = 62) and inhibitory (n = 30) responses in 92 neurons. Fifty neurons were sensitive to both NA and DA. 4. The neurons showing changes in activity during different phases of the task showed different sensitivities to NA and DA applied with 50 nA. The warning phase-related neurons were primarily sensitive to NA (36/39), the go phase-related neurons were primarily sensitive to DA (44/48), neurons related to both the warning and go phases were sensitive to both NA and DA (33/38), and the reward phase-related neurons were primarily sensitive to NA (23/28). 5. In the neurons that showed increased changes in activity during the warning phase, NA reduced the background activity to a greater extent than the activity during the warning phase and increased the ratio of the warning phase-related activity to the background activity. In the neurons that showed decreased changes during the warning phase, NA reduced the activity during the warning phase to a great extent than the background activity, and increased ratio of the background activity to the warning phase-related activity. Furthermore, the latency of onset of the change in activity tended to become shorter by application of NA. Thus, NA enhanced the change in activity during the warning phase, irrespective of whether the direction of the change was toward an increase or a decrease.(ABSTRACT TRUNCATED AT 400 WORDS)     

Catecholaminergic neurons in the brain-stem and sleep apnea in SIDS victims

Background: Tyrosine hydroxylase (TH) is a specific marker for catecholaminergic neurones. Some reports have demonstrated a decrease of TH in the sudden infant death syndrome (SIDS) compared with controls. To further investigate this, the correlation between TH and sleep apnea was investigated here. Materials and methods: Among 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died under 6 months of age. They included 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and the duration of sleep apnea were analyzed. The brain-stem material was collected and subjected to immunohistochemical studies for TH. The density of TH-immunoreactive neurons was measured in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguus and the ventrolateral medulla (VLM) in the medulla oblongata. Correlation analyses were carried out between the density of TH-immunoreactive neurons and the data from the sleep apnea studies. Results: There was no SIDS specific correlation between TH-immunoreactive neurons in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguus and the ventrolateral medulla in the medulla oblongata and the frequency and duration of sleep apnea. Conclusions: No significant association between the pathological data and the physiological data refers to TH-positive neurons in the medulla oblongata in SIDS victims.     

Correlation between the Ki-67 antigen in the brainstem and physiological data on sleep apnea in SIDS victims

Background: The Ki-67 antigen appears in all human proliferating cells during late G1, S, M and G2 phases of the cell cycle, but is consistently absent in the G_o phase (noncycling) cells. The correlation between Ki-67 in the brainstem and sleep apnea in victims of the sudden infant death syndrome (SIDS) was investigated to elucidate cell kinetics in the brainstem of this condition, which is still the main cause of postneonatal infant death. Materials and methods: Twenty-six cases of SIDS occurred among 38 infants dying under 6 months of age in a cohort of 27,000 infants studied prospectively to characterize their sleep–wake behavior. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and duration of sleep apnea were analyzed. At autopsy, brainstem material was collected and immunohistochemistry for Ki-67 was carried out. The density of Ki-67-positive neurons was measured semiquantitatively. Correlation analyses were carried out between the density of Ki-67-positive neurons and the data on sleep apnea. Results: Except in two cases in SIDS victims and in one control, the detection of Ki-67 was negative. No correlation analysis between the Ki-67 and of sleep apnea was found. Conclusions: There were no abnormal cell kinetics detected by the demonstration of Ki-67 antigen in the brainstems of SIDS victims.