scholarly journals D-Cycloserine 24 and 48 Hours after Asphyxial Cardiac Arrest has No Effect on Hippocampal CA1 Neuropathology

2014 ◽  
Vol 34 (10) ◽  
pp. e1-e8 ◽  
Author(s):  
Vélvá M Combs ◽  
Heather D Crispell ◽  
Kelly L Drew
Keyword(s):  
Cardiac Arrest ◽  
Closed Head Injury ◽  
Spontaneous Circulation ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Cell Counts ◽  
Sprague Dawley Rats ◽  
Hippocampal Ca1 ◽  
Asphyxial Cardiac Arrest ◽  
Stimulation Of

Stimulation of N-methyl-D-aspartate receptors (NMDAR) contributes to regenerative neuroplasticity following the initial excitotoxic insult during cerebral ischemia. Stimulation of NMDAR with the partial NMDAR agonist D-cycloserine (DCS) improves outcome and restores hippocampal synaptic plasticity in models of closed head injury. We thus hypothesized that DCS would improve outcome following restoration of spontaneous circulation (ROSC) from cardiac arrest (CA). DCS (10 mg/kg, IP) was administered to Sprague-Dawley rats (male, 250–330 g; 63–84 days old) 24 and 48 hours after 6 or 8 minutes of asphyxial CA. Heart rate and blood pressure declined similarly in all groups. Animals showed neurological deficits after 6 and 8 minutes CA ( P < 0.05, Tukey) and these deficits recovered more quickly after 6 minutes than after 8 minutes of CA. CA decreased the number of healthy neurons within CA1 with no difference between 6 and 8 minutes duration of CA (180.8 ± 27.6 (naïve, n = 5) versus 46.3 ± 33.8 (all CA groups, n = 27) neurons per mm CA1). DCS had no effect on neurological deficits or CA1 hippocampal cell counts ( P > 0.05, Tukey).

Abstract 80: Development of CA1 Damage: Different Cell Counts in CA1 Region of Rats Resuscitated from 8-Minute Ventricular Fibrillation Cardiac Arrest After 2 Weeks of Survival Compared with 20 Weeks of Survival

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Wolfgang Weihs ◽  
Fritz Sterz ◽  
Florian Ettl ◽  
Ingrid A M Magnet ◽  
Alexandra-Maria Warenits ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Spontaneous Circulation ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Neurologic Recovery ◽  
Ca1 Region ◽  
Cell Counts ◽  
Viable Cells ◽  
Long Time

Background: Rodent models of cardiac arrest (CA) help to investigate mechanisms and therapy of cerebral ischemia and reperfusion. The CA1 region of hippocampus is specifically vulnerable to global ischemia and is considered to play an important role in neurological deficits of patients surviving cardiac arrests. Methods: Male 350g Sprague-Dawley rats were put into ventricular fibrillation (VF) CA. After 8 min of CA the animals received mechanical chest compressions for 2 min and epinephrine 20 μg/kg. The animals were defibrillated thereafter every 2 min to achieve return of spontaneous circulation. Six animals surviving with favorable neurologic recovery were sacrificed after 2 weeks and 11 after 20 and compared to 4 sham rats. For histological examination brains were fixed in formalin, paraffin-embedded and cut into coronary sections of 3 μm thickness. In Hematoxylin- Eosin-stained sections viable neurons were counted in a 500 μm sector of the CA1 region. Results: In sham animals 84±12 viable cells were counted in CA1 region. Two week survivors had 16±8 cells (p< 0.001), whereas 20 week survivors had 37±31 (p=0.018 vs sham, p=0.084 vs 2 weeks survivors) cells. The latter showed in 7 animals many viable cells (60±15) compared to 2 weeks survivors and in 4 animals very few cells 4±3 cells. Conclusions: A repopulation within week 2 and 20 of pyramid cells in the CA1 region of the hippocampus seems to have taken place in 7 of 11 rats resuscitated from 8 min VFCA whereas in others not. To discover the mechanism responsible for this huge difference in cell counts of the CA1 region in long time survivors of CA might help to understand the pathological mechanisms of the global ischemic insult.

Abstract 56: Ventilation Is Necessary During Cardiopulmonary Resuscitation In A Rat Model Of Cardiac Arrest Induced By Airway Obstruction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Akihide Kurita ◽  
Takumi Taniguchi ◽  
Ken Yamamoto
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Airway Obstruction ◽  
Survival Rates ◽  
Spontaneous Circulation ◽  
Sprague Dawley ◽  
Plasma Cytokine ◽  
Sprague Dawley Rats ◽  
Ventilation Strategies ◽  
Lactate Levels

Recent studies have showed that hypoventilation during cardiopulmonary resuscitation (CPR) improved the rates of return of spontaneous circulation (ROSC) and prognosis. However, there are few studies about the ventilation strategies during CPR in cardiac arrest caused by airway obstruction. To compare the effects of the three ventilation strategies during CPR in an animal model of cardiac arrest induced by airway obstruction, we investigated the rates of ROSC, survival rates, plasma cytokine levels, and lactate levels. thirty-six male Sprague Dawley rats were anesthetized with intraperitoneal injection of pentobarbital. Cardiac arrest was induced by airway obstruction. After 3 minutes of cardiac arrest, animals were randomized to receive one of the three ventilation strategies during CPR (n = 12 per group): normoventiraion (28 breaths/min), hypoventilation (14 breaths/min), or no-ventilation. The rates of chest compression (CC) was 240 –260 compressions/min and the depth of CC adjusted to maintain mean arterial pressure more than 25 mmHg in all groups. After 5 minutes of CPR, epinephrine (0.02 mg/kg) was administered, and all rats were ventilated at the rates of 28 breaths/min in FiO2 1.0. The rates of ROSC were 83%, 58%, 0% for the normoventilation, hypoventilation, and no-ventilation groups, respectively. The PaCO2 levels immediately after ROSC were 74mmHg and 88 mmHg for the normoventilation, and hypoventilation groups, respectively. The increases of plasma cytokine (TNF-a, and IL-6) levels and lactate levels after ROSC in the normoventilation group were significantly less than those in the hypoventilation group. The present study showed that normoventilation during CPR improved the rates of ROSC and the survival rates after ROSC in the animal cardiac arrest model induced by airway obstruction. Moreover, normoventilation attenuated the elevation of cytokine and lactate responses. These findings suggest that ventilation may be necessary during CPR in cardiac arrest caused by airway obstruction.

Abstract 211: Delayed Cell Death in CA1 Region in a Cardiac Arrest Rat Model: Continuing After 2 Weeks of Survival?

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sandra Högler ◽  
Ursula Teubenbacher ◽  
Wolfgang Weihs ◽  
Fritz Sterz ◽  
Ingrid A M Magnet ◽  
...  
Keyword(s):  
Cell Death ◽  
Cardiac Arrest ◽  
Brain Regions ◽  
Spontaneous Circulation ◽  
Sprague Dawley ◽  
Ca1 Region ◽  
Delayed Cell Death ◽  
Time Period ◽  
Sprague Dawley Rats ◽  
Hematoxylin Eosin

Background: Evolution of histological lesions in selectively vulnerable brain regions in animal models of cardiac arrest (CA)give evidence of potential therapeutic windows. Delayed cell death is of special interest in this regard. Methods: In male Sprague-Dawley rats (350g) ventricular fibrillation (VF) CA was induced for 6 min followed by chest compressions, ventilation and drugs for 2 min. To achieve return of spontaneous circulation animals were defibrillated every 2 min. Animals were sacrificed after one week (n=5) or two weeks (n=7) of survival and compared to four sham animals. Brains were fixed in formalin, embedded in paraffin wax and cut into 3 μm thick coronary sections for histological examination. Viable neurons with nucleolus were counted in Hematoxylin-Eosin (HE)-stained sections in a 250 μm sector of the medial CA1 region. FluoroJade B staining was applied to count dying neurons in the same sector. Results: In HE-staining sham animals had 31±4 viable neurons. In one week survivors 11±9 viable neurons (p=0.003) and in two week survivors 7±7 viable neurons (p=0.001 vs sham, p=0.49 vs one week survivors) were counted. Furthermore, a lot of degenerated hypereosinophilic neurons were present in HE-staining in both CA-groups. FluoroJade B-staining was negative in sham animals. In one week survivors 29±8 dying neurons (p=0.006) and in two week survivors 33±13 dying neurons (p= 0.016 vs sham, p=0.343 vs one week survivors) were detectable. Conclusions: Consistent damage in the medial CA1 region was present after 6 min VFCA in both survival time groups. Lesions seemed to be constant, with no significant differences between time points. Contrary to expectations, FluoroJade B-staining was still positive after two weeks of survival, suggesting that delayed cell death might go on for a longer time period than assumed so far.

scholarly journals Effects of the duration of postresuscitation hyperoxic ventilation on neurological outcome and survival in an asphyxial cardiac arrest rat model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tongyi Hu ◽  
Jianjie Wang ◽  
Shuangwei Wang ◽  
Jingru Li ◽  
Bihua Chen ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Survival Rates ◽  
Spontaneous Circulation ◽  
Temperature Management ◽  
Sprague Dawley ◽  
High Concentration ◽  
Neurologic Recovery ◽  
Physiological Variables ◽  
Hyperoxic Ventilation ◽  
Asphyxial Cardiac Arrest

Abstract Cardiac arrest leads to sudden cessation of oxygen supply and cerebral hypoxia occurs when there is not sufficient oxygen supplied to the brain. Current Guidelines for adult cardiopulmonary resuscitation (CPR) and emergency cardiovascular care recommend the use of 100% oxygen during resuscitative efforts to maximize the probability of achieving the return of spontaneous circulation (ROSC). However, the optimal strategy for oxygen management after ROSC is still debatable. The aim of the present study was to evaluate the effects of the duration of post-resuscitation hyperoxic ventilation on neurological outcomes in asphyxial cardiac arrest rats treated with targeted temperature management (TTM). Asphyxia was induced by blocking the endotracheal tube in 80 adult male Sprague-Dawley rats. CPR begun after 7 min of untreated cardiac arrest. Animals were randomized to either the normoxic control under normothermia (NNC) group or to one of the 4 experimental groups (n = 16 each) immediately after ROSC: ventilated with 100% oxygen for 0 (O2_0h), 1 (O2_1h), 3 (O2_3h), or 5 (O2_5h) h and ventilated with room air thereafter under TTM. Physiological variables were recorded at baseline and during the 6 h postresuscitation monitoring period. Animals were closely observed for 96 h to assess neurologic recovery and survival. There were no significant differences in baseline measurements between groups, and all animals were successfully resuscitated. There were significant interactions between the duration of 100% oxygen administration and hemodynamics as well as, myocardial and cerebral injuries. Among all the durations of hyperoxic ventilation investigated, significantly lower neurological deficit scores and higher survival rates were observed in the O2_3h group than in the NNC group. In conclusion, postresuscitation hyperoxic ventilation leads to improved PaO2, PaCO2, hemodynamic, myocardial and cerebral recovery in asphyxial cardiac arrest rats treated with TTM. However, the beneficial effects of high concentration-oxygen are duration dependent and ventilation with 100% oxygen during induced hypothermia contributes to improved neurological recovery and survival after 96 h.

Vagal stimulation-induced gastric damage in rats

1991 ◽  
Vol 261 (1) ◽  
pp. G104-G110
Author(s):  
L. E. Hierlihy ◽  
J. L. Wallace ◽  
A. V. Ferguson
Keyword(s):  
Vagal Stimulation ◽  
Mucosal Damage ◽  
Vagal Afferents ◽  
Gastric Damage ◽  
Gastric Mucosal Damage ◽  
Sprague Dawley ◽  
Vagus Nerves ◽  
Sprague Dawley Rats ◽  
Series Of Experiments ◽  
Stimulation Of

The role of the vagus nerve in the development of gastric mucosal damage was examined in urethan-anesthetized male Sprague-Dawley rats. Electrical stimulation was applied to the vagus nerves for a period of 60 min, after which macroscopic gastric damage was scored and samples of the stomach were fixed for later histological assessment. Damage scores were assigned blindly based on a 0 (normal) to 3 (severe) scale. Stimulation of vagal afferents or efferents in isolation did not result in significant damage to the gastric mucosa (P greater than 0.1). In contrast, stimulation of both intact vagus nerves resulted in significant gastric mucosal damage (mean damage score, 2.0 +/- 0.33, P less than 0.01). A second series of experiments demonstrated this gastric damage to be induced within 30-60 min; extending the stimulation period to 120 min did not worsen the gastric damage scores significantly (P greater than 0.1). In a third study, stimulation of both intact vagus nerves after paraventricular nucleus (PVN) lesion resulted in damage scores (0.33 +/- 0.17) that were significantly reduced compared with intact PVN and non-PVN-lesioned animals (P less than 0.01). These results indicate that the development of vagal stimulation-induced gastric damage requires the activation of both afferent and efferent vagal components and suggest further that such damage is dependent upon an intact PVN.

Endogenous CCK disrupts the MMC pattern via capsaicin-sensitive vagal afferent fibers in the rat

1997 ◽  
Vol 272 (1) ◽  
pp. G100-G105 ◽  
Author(s):  
A. Rodriguez-Membrilla ◽  
P. Vergara
Keyword(s):  
Intravenous Infusion ◽  
Sprague Dawley ◽  
Rat Intestine ◽  
Intracerebroventricular Infusion ◽  
C Fibers ◽  
Afferent Fibers ◽  
Sprague Dawley Rats ◽  
Vagal Afferent ◽  
Endogenous Release ◽  
Stimulation Of

A meal disrupts migrating motor complexes (MMC) in the rat intestine through stimulation of peripheral cholecystokinin (CCK)-B and central CCK-A receptors. The aim of this study was to determine pathways implicated in postprandial disruption of the MMC mediated by CCK. Sprague-Dawley rats were prepared with electrodes for electromyography in the small intestine, and ablation of vagal afferent C-fibers by capsaicin was carried out. Endogenous release of CCK was induced by oral administration of soybean trypsin inhibitor (SBTI). In control rats SBTI disrupted MMC and generated an irregular spiking activity that lasted longer than 3 h. Intravenous infusion of L-365,260 (2 x 10(-7) mol/kg) but not of L-364,718 (3 x 10(-9) mol/kg) restored the MMC pattern. In capsaicin-treated rats, SBTI did not modify fasting activity. Infusion of CCK octapeptide (CCK-8) at 3 x 10(-9) mol.kg-1.h-1 disrupted the MMC, although the response was quantitatively and qualitatively different from SBTI. The effect was reversed by intravenous infusion of L-364,718 or L-365,260 and intracerebroventricular infusion of L-364,718. In capsaicin-treated rats, the intracerebroventricular or intravenous infusion of L-364,718 inhibited CCK-8 effects. However, the intravenous infusion of L-365,260 did not reverse the MMC pattern. These results suggest that the disruption of the MMC mediated by CCK is due to stimulation of peripheral CCK-B receptors located in vagal afferent fibers. This initiates a reflex including stimulation of central CCK-A receptors. Exogenous CCK also stimulates peripheral CCK-A receptors not located in capsaicin-sensitive vagal afferent fibers.

Expression of Glucocorticoid Receptors in the Early Period After the Return of Spontaneous Circulation Among Patients Who Experienced Cardiac Arrest : A Retrospective Observational Study

2021 ◽  
Author(s):  
Yanan Yu ◽  
Ziren Tang ◽  
Jiabao Li ◽  
Miaorong Xie ◽  
Chenchen Hang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Glucocorticoid Receptors ◽  
Early Period ◽  
Treg Cells ◽  
Spontaneous Circulation ◽  
Skewed Distribution ◽  
Control Group ◽  
Total Cortisol ◽  
Cell Counts ◽  
Healthy Control

Abstract Background: Rapid changes in glucocorticoid (GC) levels and adrenal insufficiency are related to the development of post-cardiac arrest syndrome. However, changes in glucocorticoid receptors (GR) have not been studied. Hence, this study aimed to investigate the association of early changes in GR and prognosis and immune response in patients who experienced cardiac arrest (CA). Methods: In this observational single-center case-control study, we enrolled patients who were in the early period of return of spontaneous circulation after CA and were admitted to the emergency department of the Beijing Chaoyang Hospital between October 2018 and October 2019. Age- and sex-matched healthy individuals were recruited for the control group after a physical examination.GR expression and cell counts of circulatory T and B lymphocytes, natural killer, and regulatory T (Treg) cells were assessed. Plasma total cortisol and adrenocorticotrophic hormone (ACTH) levels were tested. Since the data for total cortisol and ACTH levels had a skewed distribution, we compared our results with the natural logarithmic conversion values after adding 1 (ln [total cortisol+ 1], ln [ACTH+ 1]). Measurement data with a skewed distribution are expressed as medians (25th and 75th percentiles). The Mann–Whitney U test was used to compare variables between groups. The qualitative parameters in the 2 × 2 contingency table were used for analysis.Results: Overall, 85 patients who experienced CA and 40 healthy individuals were enrolled. All cell counts were lower and plasma total cortisol levels were higher (P<0.001) in patients who experienced CA than those in the healthy control group. GR expression in Treg cells and CD3+CD4+ T lymphocytes was not significantly different, but the mean fluorescence intensity and GR expression in other cells were lower in patients who experienced CA (P<0.05) than those in the healthy control group. ACTH levels did not show any difference. There were no significant differences between survivors and non-survivors. Conclusion: Our findings provide insights into GC sensitivity and immunosuppressive status in these patients, and a new perspective for GC targeted treatment.

Abstract 148: Zoniporide Combined with α-Methylnorepinephrine Appears Highly Effective for Resuscitation from Cardiac Arrest in a Rat Model of Ventricular Fibrillation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Lorissa Lamoureux ◽  
Herbert K Whitehouse ◽  
Jeejabai Radhakrishnan ◽  
Raúl J Gazmuri
Keyword(s):  
Cardiac Arrest ◽  
Chest Compression ◽  
Rat Model ◽  
Myocardial Dysfunction ◽  
Spontaneous Circulation ◽  
Sprague Dawley ◽  
Survival Times ◽  
Highly Effective ◽  
Electrical Shocks ◽  
Novel Strategy

Background: We have reported in rat and swine models of cardiac arrest that sodium hydrogen exchanger isoform-1 (NHE-1) inhibition facilitates resuscitation, ameliorates myocardial dysfunction, and improves survival. Others have reported that α-methylnorepinephrine (α-MNE) - a selective α2-adrenoreceptor agonist - is superior to epinephrine given its lack of β-agonist effects. We examined in a rat model of VF and closed-chest resuscitation the effects of combining the NHE-1 inhibitor zoniporide (ZNP) with α-MNE. Methods: VF was electrically induced in 32 male retired breeder Sprague-Dawley rats and left untreated for 8 minutes after which resuscitation was attempted by an 8 minute interval of chest compression and delivery of electrical shocks. Rats were randomized 1:1:1:1 to receive a 3 mg/kg bolus of ZNP or 0.9% NaCl before starting chest compression and a 100 μg/kg bolus of α-MNE or its vehicle at minute 2 of chest-compressions establishing 4 groups of 8 rats each. Successfully resuscitated rats were monitored for 240 minutes. Results: The number of rats that had return of spontaneous circulation and then survived 240 min were: α-MNE(-)/ZNP(-) 4 and 2; α-MNE(-)/ZNP(+) 5 and 5; α-MNE(+)/ZNP(-) 2 and 1; and α-MNE(+)/ZNP(+) 7 and 7 yielding a statistically significant effect on overall survival times corresponding to 105 ± 114, 150 ± 124, 58 ± 108, and 210 ± 85 min, respectively (p < 0.045). Post-resuscitation lactate levels were attenuated in all treatment groups with the greatest effect by the α-MNE(+)/ZNP(+) combination without major differences in hemodynamic function (Table). Conclusion: We confirm a beneficial effect resulting from the combination of ZNP (given to attenuate myocardial reperfusion injury) and α-MNE (given to augment peripheral vascular resistance during chest compression without the detrimental actions of epinephrine). The proposed combination may prove to be a highly effective novel strategy for resuscitation from cardiac arrest.

Abstract 327: Asphyxial Cardiac Arrest Induces Dynamic Changes in Dopamine Neurotransmission and Linked Behavioral Deficits

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Aaron R Braverman ◽  
David F Fine ◽  
Tyler J Shick ◽  
Jason P Stezoski ◽  
Rehana K Leak ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Acoustic Startle ◽  
Dorsal Striatum ◽  
Sprague Dawley ◽  
Behavioral Deficits ◽  
Fast Scan Cyclic Voltammetry ◽  
Preference Testing ◽  
Sensorimotor Processing ◽  
Future Work ◽  
Asphyxial Cardiac Arrest

Introduction: Cardiac arrest survival has improved with advances in resuscitation care, but survivors face impairments from the resulting hypoxic-ischemic brain injury (HIBI). Given the popular clinical use of DA modulators, despite limited understanding of disturbances in DA neurotransmission after HIBI, we characterized striatal DA signaling and behavioral deficits in a rat model of asphyxial cardiac arrest (ACA). Hypothesis: ACA-induced HIBI alters DA neurotransmission linked to behavioral deficits. Methods: Adult male Sprague-Dawley rats (n=41) underwent either Sham procedures (n=10) or 5-min no-flow ACA (n=28) insult. Fast-scan cyclic voltammetry (FSCV) and maximal medial forebrain bundle stimulations (60Hz, 10s) were used to characterize presynaptic DA signaling in dorsal striatum (D-Str). FSCV findings were compared with sensorimotor processing [acoustic startle responses (ASR)], open field exploration (total distance & exploratory zone entries), myoclonus, and anhedonia (sucrose preference testing). Results: ACA increased maximum evoked overflow (fig 1) and several DA release-based kinetic metrics. ACA hindered sensorimotor processing via increased ASR %change, elicited myoclonic responses to auditory stimuli, reduced mobility & exploration, and increased anhedonia. Many behavioral measures correlated with D-Str neurotransmission ( fig 2 ). Conclusions: ACA causes early hypodopaminergia that evolves to a hyperdopaminergic state by 2 weeks that is associated with behavioral dysfunction. Future work should further characterize striatal pathology post-ACA and identify treatments to resolve altered DA signaling and behavioral deficits.

Sign in / Sign up

Export Citation Format

Share Document