Abstract 21: Remote Limb Ischemic Postconditioning Improves Postresuscitation Cerebrovascular Circulation and Survival/Neurological Prognoses via In Situ and Remote Activation of Akt-eNOS-NO Signaling Pathway

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Wei-Tien Chang ◽  
Woan-Yi Wang ◽  
Chun-Pei Lee ◽  
Hsiao-Ching Wei ◽  
Sung-Chun Tang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Femoral Artery ◽  
Cerebral Perfusion ◽  
Cerebrovascular Circulation ◽  
Neurological Outcomes ◽  
Arterial Blood ◽  
Left Femoral Artery ◽  
No Signaling ◽  
The Brain

Introduction: Cerebrovascular circulation is usually compromised after cardiac arrest and CPR. Remote limb ischemic post-conditioning (RLIP) is clinically feasible and can potentially mitigate post-resuscitation neurological deficits. Since nitric oxide (NO) is implicated in post-conditioning protection, we aim to investigate if RLIP impacts post-resuscitation cerebral perfusion and prognosis via NO-related mechanism. Hypothesis: RLIP improves post-CPR cerebral perfusion and prognosis through in situ and remote activation of Akt-eNOS-NO signaling. Methods: Using an established rat model of asphyxia cardiac arrest and CPR, we randomized the rats to the following groups: (1) sham, (2) standard CPR, (3) RLIP 5 min after return of spontaneous circulation (ROSC). RLIP was done by 3 cycles of 5 min of left hind limb ischemia followed by 5 min of reperfusion. Arterial blood was sampled for colorimetric determination of nitrate/nitrite. The cerebral perfusion was continuously recorded by OxyFLO probe. Two hours after ROSC, the brain and left femoral artery were harvested for measuring phosphorylated endothelial NO synthase (p-eNOS at Ser1177) and protein kinase B (p-Akt at Ser473). In a subgroup the survival and neurological outcomes were monitored up to 3 days. Results: The cerebral perfusion was significantly decreased (0.6-0.8 folds that of baseline) after ROSC in standard CPR group. If RLIP was employed, the cerebral perfusion was significantly augmented (up to 1.6 folds, P < 0.001) in the post-resuscitation phase. This was associated with improved survival (log-rank P < 0.05) and neurological scores at 6, 24, 48 and 72 h (all P < 0.05). Plasma NO as indicated by nitrate/nitrite was significantly increased in the RLIP group ( P < 0.05). Most of all, p-eNOS and p-Akt were significantly increased not only in left femoral artery but also in brain. If NOS inhibitor N ω -nitro-L-arginine methyl ester (10 mg/kg) was used, not only the NO increase was reversed, the improvement in survival and neurological outcomes were also abrogated. Conclusions: RLIP enhances post-resuscitation cerebral perfusion and improves survival and neurological prognoses not only via in situ limb artery derived NO but remote activation of Akt-eNOS signaling in the brain.

Abstract 103: Propofol Infusion in the Early Post-Cardiac Arrest Phase Improves Cerebral Perfusion and Confers Anti-Apoptotic Neuroprotection via Akt-eNOS-NO Signaling

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Wei-Tien Chang ◽  
Min-Hsuan Hsu ◽  
Woan-Yi Wang ◽  
Chunpei Lee ◽  
Chih-Hung Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cerebral Perfusion ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Temperature Management ◽  
Target Temperature Management ◽  
Arterial Blood ◽  
No Signaling ◽  
The Brain

Introduction: Neurological outcome after cardiac arrest (CA) and CPR is usually unsatisfactory even in this era of target temperature management (TTM). Propofol is not only a useful sedative drug for TTM but confers neuroprotective effect. We previously showed that propofol combined with TTM improves survival in patients resuscitated from CA. In this study we aimed to explore the underlying mechanism focusing on cerebrovascular circulation and anti-apoptosis signaling. Hypothesis: Infusion of propofol in the early post-CA phase improves cerebral perfusion and mitigates neuronal apoptosis via Akt-eNOS signaling. Methods: Using an established rat model of asphyxia cardiac arrest and CPR, propofol infusion (20 mg/kg/h) was instituted after return of spontaneous circulation (ROSC) and continued in the first 2 h. Hemodynamics were monitored and the cerebral perfusion was continuously recorded by OxyFLO probe. The arterial blood was regularly sampled for measurement of reactive oxygen species (ROS, chemiluminescence method) and NO (demonstrated by nitrate/nitrite). Two hours after ROSC, the brain was harvested for measurement of casepase-3, endothelial NO synthase (eNOS) and protein kinase B (Akt). Results: After CA and CPR, the cerebral perfusion was significantly reduced to ~0.5 folds that of baseline. With the infusion of propofol, the cerebral perfusion was significantly increased from the beginning after ROSC ( P < 0.01 vs. CPR control). The plasma NO indicated by nitrate/nitrite 2 h post-CPR was significantly increased ( P < 0.01) while ROS abrogated ( P < 0.05). The cleaved caspase-3/caspase-3 of the brain was markedly reduced ( P < 0.001), suggesting anti-apoptotic neuroprotection. When exploring the mechanism, the phosphorylated (p)-eNOS/eNOS and p-Akt/Akt were significantly increased (both P < 0.001), indicating activation of Akt-eNOS-NO signaling. Conclusions: Infusion of propofol in the early post-CA phase reduces oxidative stress, improves cerebral perfusion, and ameliorates neuronal apoptosis. The protection is, at least in part, mediated via activation of Akt-eNOS-NO signaling.

Abstract 2046: Hypercapnic Resuscitation Improves Survival and Neurological Outcomes by Nitric Oxide Synthase-Mediated Enhancement of Brain Perfusion

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Wei-Tien Chang ◽  
Lay-San Gan ◽  
Chiang-Ting Chien ◽  
Chien-Hua Huang ◽  
Huei-Wen Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Arrest ◽  
Apoptotic Cell ◽  
Brain Perfusion ◽  
No Synthase ◽  
Neurological Injury ◽  
Neurological Outcomes ◽  
Arterial Blood ◽  
The Brain

Neurological injury is one of the major causes of morbidity and mortality following cardiac arrest and cardiopulmonary resuscitation (CPR). Brain perfusion is usually compromised in the post-resuscitation phase, which inevitably lengthens the ischemic insult of the brain. Hypercapnia has been reported to cause cerebral vasodilatation. We therefore sought to study the potentials of hypercapnic resuscitation in improving the brain perfusion as well as survival and neurological prognoses. Using an established rat model of asphyxial cardiac arrest (6 min) and CPR, we employed hypercapnic (5% CO 2 , 95% O 2 ) ventilation during CPR and the first 2 h post-resuscitation, and compared the brain perfusion with normocapnia (5% N 2 , 95% O 2 ) control. The blood pressure was continuously monitored, with arterial blood sampled regularly for gas analysis. The tissue perfusion of the brain was measured by OxyLyte 2000E perfusion sensor. In a subgroup the survival and neurological outcomes were monitored up to 3 days. TdT-mediated dUTP nick-ends labeling (TUNEL) stain and Bax/Bcl2 of the brain were assessed as indicators of apoptotic cell death. The PaCO 2 was significantly higher ( P <0.001) and pH significantly lower ( P <0.001) in hypercapnia group during the first 2 h post-resuscitation. No difference was noted in PaO 2 or blood pressure. In normocapnia control, the brain perfusion was significantly reduced in the first 30 min post-resuscitation. Hypercapnic ventilation enhanced brain perfusion during this period ( P <0.05). The survival and neurological outcomes were also improved (LogRank P <0.05), which was consistent with the decrease in TUNEL stain and Bax/Bcl2. If nitric oxide (NO) synthase inhibitor N ω -nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) was cotreated with hypercapnia, the increased brain perfusion and reduced TUNEL and Bax/Bcl2 were reversed. The improved survival and neurological outcomes were also abrogated. Hypercapnic ventilation during CPR and early post-resuscitation phase improves brain perfusion and hence survival and neurological outcomes. This is in part mediated by NO synthase-related vasodilatation.

Abstract P790: Landiolol Attenuates Global Cerebral Edema Following Experimental Cardiac Arrest in Mice

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Tomoyuki Iwai ◽  
Shin Nakayama
Keyword(s):  
Cardiac Arrest ◽  
Water Content ◽  
Cerebral Edema ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
P Value ◽  
Brain Water Content ◽  
Arterial Blood ◽  
The Brain ◽  
Brain Water

Introduction: Cerebral edema following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) is associated with unfavorable neurologic outcome. The Na + -K + -2Cl - water cotransporter NKCC1 is suspected to be a critical mediator of edema formation after ischemia. It is reported that β1 adrenoreceptor antagonists protect neurons following brain ischemia in rodents. β1 adrenoreceptor antagonists inhibit the Na + -K + -ATPase, which can inhibit driving force of NKCC1 that theoretically reduces cerebral edema following ischemia-reperfusion injury. In this study, we examined whether landiolol, a selective β1 adrenoreceptor antagonist, attenuates cerebral edema following CA/CPR. Methods: Isoflurane-anesthetized adult male mice (C57BL/6J, 25-30g) were randomized into landiolol group or control group. After 7-min CA followed by CPR, landiolol (0.5ml, 830μg/ml) was administered by continuous infusion intravenously for 4 hours. Animals in control group were given normal saline (0.5ml) in the same manner. Twenty-four hours after CA/CPR, the brain was removed to assess brain water content using wet-to-dry method. The primary outcome was measurement of the brain water content. Heart rate and arterial blood pressure were recorded. Measured parameters were analyzed by one-way ANOVA with post hoc Tukey-Kramer test using SPSS® statistics 25. Differences were considered statistically significant at a P value < 0.05. Results: Brain water contents was increased in control group mice after CA/CPR (n=10) compared with those in sham operated mice (n=5) (79.5±0.85% vs 78.3±0.14%, P=0.003). Compared with control group, landiolol treatment significantly reduced brain water content in mice subjected to CA/CPR (n=12) (78.9±0.51% vs 79.5±0.85%, P=0.04). Conclusion: Landiolol attenuated brain edema following CA/CPR. These results may suggest selective β1-blocker could be alternative treatment for neuroprotection in patients who suffered CA/CPR.

Arterial Grafting with the Telescoping Anastomotic Technique for Arterial Defects

1994 ◽  
Vol 19 (4) ◽  
pp. 461-465 ◽  
Author(s):  
S. SAITOH ◽  
Y. NAKATSUCHI
Keyword(s):  
Femoral Artery ◽  
Patency Rate ◽  
Arterial Graft ◽  
Anastomotic Technique ◽  
Vein Grafts ◽  
Arterial Blood ◽  
Left Femoral Artery ◽  
Arterial Grafting ◽  
Time Required ◽  
The Right

An arterial graft was taken from the left femoral artery of the rat and grafted into the right femoral artery using the telescoping anastomotic technique at both the proximal and distal anastomoses to compare the patency rate with that of the vein grafts interposed into the arterial defect with the same telescoping technique. The time required for each anastomosis was about 10 minutes and all of the 31 grafts remained patent without application of xylocaine, yielding a higher patency rate than the vein grafts interposed in an arterial defect. The telescoping technique proved to be so dependable that it could be used at least twice in an artery. Inserting one vessel stump into another using the telescoping technique may not itself be responsible for the failure of vein grafts interposed in an arterial defect, but distortion of the slack venous wall of the graft by high arterial blood pressure is.

scholarly journals Levosimendan increases brain tissue oxygen levels after cardiopulmonary resuscitation independent of cardiac function and cerebral perfusion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andreas García-Bardon ◽  
Jens Kamuf ◽  
Alexander Ziebart ◽  
Tanghua Liu ◽  
Nadia Krebs ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiac Output ◽  
Brain Tissue ◽  
Cerebral Perfusion ◽  
Cerebral Oxygenation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Microcirculation ◽  
Arterial Blood ◽  
Promising Therapeutic Approach

AbstractPrompt reperfusion is important to rescue ischemic tissue; however, the process itself presents a key pathomechanism that contributes to a poor outcome following cardiac arrest. Experimental data have suggested the use of levosimendan to limit ischemia–reperfusion injury by improving cerebral microcirculation. However, recent studies have questioned this effect. The present study aimed to investigate the influence on hemodynamic parameters, cerebral perfusion and oxygenation following cardiac arrest by ventricular fibrillation in juvenile male pigs. Following the return of spontaneous circulation (ROSC), animals were randomly assigned to levosimendan (12 µg/kg, followed by 0.3 µg/kg/min) or vehicle treatment for 6 h. Levosimendan-treated animals showed significantly higher brain PbtO2 levels. This effect was not accompanied by changes in cardiac output, preload and afterload, arterial blood pressure, or cerebral microcirculation indicating a local effect. Cerebral oxygenation is key to minimizing damage, and thus, current concepts are aimed at improving impaired cardiac output or cerebral perfusion. In the present study, we showed that NIRS does not reliably detect low PbtO2 levels and that levosimendan increases brain oxygen content. Thus, levosimendan may present a promising therapeutic approach to rescue brain tissue at risk following cardiac arrest or ischemic events such as stroke or traumatic brain injury.

scholarly journals Alterations in Endothelin Receptors Following Hemorrhage and Resuscitation by Centhaquin

2018 ◽  
pp. S199-S214
Author(s):  
S. BRIYAL ◽  
R. GANDHAKWALA ◽  
M. KHAN ◽  
M. S. LAVHALE ◽  
A. GULATI
Keyword(s):  
Femoral Artery ◽  
Renal Medulla ◽  
Receptor Expression ◽  
Protein Levels ◽  
Left Femoral Artery ◽  
Etb Receptor ◽  
The Right ◽  
Induced Changes ◽  
The Brain ◽  
Pressure Catheter

Endothelin-1 (ET-1) acts on ETA and ETB receptors and has been implicated in hemorrhagic shock (shock). We determined effect of shock and resuscitation by hypertonic saline (saline) or centhaquin on ETA and ETB receptor expression. Rats were anesthetized, a pressure catheter was placed in the left femoral artery; blood was withdrawn from the right femoral artery to bring mean arterial pressure (MAP) to 35 mm Hg for 30 min, resuscitation was performed and 90 min later sacrificed to collect samples for biochemical estimations. Resuscitation with centhaquin decreased blood lactate and increased MAP. Protein levels of ETA or ETB receptor were unaltered in the brain, heart, lung and liver following shock or resuscitation. In the abdominal aorta, shock produced an increase (140 %) in ETA expression which was attenuated by saline and centhaquin; ETB expression was unaltered following shock but was increased (79 %) by centhaquin. In renal medulla, ETA expression was unaltered following shock, but was decreased (-61 %) by centhaquin; shock produced a decrease (-34 %) in ETB expression which was completely attenuated by centhaquin and not saline. Shock induced changes in ETA and ETB receptors in the aorta and renal medulla are reversed by centhaquin and may be contributing to its efficacy.

scholarly journals Association Between Neurological Outcomes and Extreme Hyperoxia in Patients with Out-of-Hospital Cardiac Arrest Who Underwent Extracorporeal Cardiopulmonary Resuscitation: A Retrospective Observational Study from a Multicenter Registry

2021 ◽  
Author(s):  
Masahiro Kashiura ◽  
Hideto Yasuda ◽  
Yuki Kishihara ◽  
Keiichiro Tominaga ◽  
Masaaki Nishihara ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Analysis Model ◽  
Neurological Outcomes ◽  
Arterial Blood ◽  
The Impact ◽  
Hospital Cardiac Arrest

Abstract Background: To investigate the impact of hyperoxia that developed immediately after extracorporeal membrane oxygenation (ECMO)-assisted cardiopulmonary resuscitation (ECPR) on patients’ 30-day neurological outcomes after out-of-hospital cardiac arrest (OHCA). Methods: This study retrospectively analyzed data from the Japanese OHCA registry from June 2014 to December 2017. We analyzed adult patients (18 years or older) who had undergone ECPR. Eligible patients were divided into the following three groups based on their initial partial pressure of oxygen in arterial blood (PaO2) levels after ECMO pump-on: normoxia group, PaO2 ≤ 200 mm Hg; moderate hyperoxia group, 200 mm Hg < PaO2 ≤ 400 mm Hg; and extreme hyperoxia group, PaO2 > 400 mm Hg. The primary and secondary outcomes were 30-day favorable neurological outcomes. Logistic regression statistical analysis model of 30-day favorable neurological outcomes was performed after adjusting for multiple propensity scores calculated using pre-ECPR covariates and for confounding factors post-ECPR.Results: Of the 34 754 patients with OHCA enrolled in the registry, 847 were included. The median PaO2 level was 300 mm Hg (interquartile range: 148–427 mm Hg). Among the eligible patients, 277, 313, and 257 were categorized as normoxic, moderately hyperoxic, and extremely hyperoxic, respectively. Moderate hyperoxia was not significantly associated with neurologically favorable outcomes compared with normoxia as a reference (adjusted odds ratio, 0.86; 95% confidence interval: 0.55–1.35; p = 0.51). However, extreme hyperoxia was associated with less neurologically favorable outcomes when compared with normoxia (adjusted odds ratio, 0.48; 95% confidence interval: 0.29–0.82; p = 0.007).Conclusions: For patients with OHCA who received ECPR, extreme hyperoxia (PaO2 > 400 mm Hg) was associated with poor neurological outcomes. Avoidance of extreme hyperoxia may improve neurological outcomes in patients with OHCA treated with ECPR.

scholarly journals Critical Closing Pressure: Comparison of Three Methods

2009 ◽  
Vol 29 (5) ◽  
pp. 987-993 ◽  
Author(s):  
Jorge A López-Magañna ◽  
Hugh K Richards ◽  
Danila K Radolovich ◽  
Dong-Joo Kim ◽  
Peter Smielewski ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Arrest ◽  
Arterial Blood Pressure ◽  
Transcranial Doppler ◽  
Cerebrovascular Circulation ◽  
Waveform Analysis ◽  
Arterial Blood ◽  
Pressure Threshold ◽  
Critical Closing Pressure ◽  
Closing Pressure

Critical closing pressure (CCP) is an arterial pressure threshold below which small arterial vessels collapse. Our aim was to compare different methods to estimate CCP in the cerebrovascular circulation using the relationships between transcranial Doppler flow velocity (FV), laser-Doppler flux (LDF), and arterial blood pressure (ABP). A total of 116 experiments in rabbits were analyzed retrospectively. At the end of each recording, cardiac arrest (CA) was induced. Arterial blood pressure in femoral artery, basilar artery FV, cortical blood LDF, intracranial pressure (ICP) was recorded. Critical closing pressure was estimated using linear regression between decreasing mean ABP values, FV, and LDF during CA. In addition, CCP was calculated from FV waveform just before CA. The correlation between CCP evaluated using LDF and FV during CA was 0.98 ( P < 0.0001). The correlation between CCP measured during CA and CCP estimated from the transcranial Doppler ultrasonography (TCD) waveform was weaker ( R=0.39; P <0.001), with CCP calculated from waveform being significantly greater than CCP from CA (median difference 9 mm Hg; P < 0.003). Critical closing pressures obtained from FV waveform and CA correlated with mean ICP before CA ( R = 0.40; P = 0.001). In conclusion strong correlation exists between CCP values obtained by means of FV and LDF during cardiac arrest. However, predictions of CCP using TCD waveform analysis show substantial differences from values of CCP recorded during cardiac arrest.

scholarly journals Clinical Trials in Cardiac Arrest and Subarachnoid Hemorrhage: Lessons from the Past and Ideas for the Future

2013 ◽  
Vol 2013 ◽  
pp. 1-42
Author(s):  
Jennifer A. Frontera
Keyword(s):  
Clinical Trials ◽  
Cardiac Arrest ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Randomized Clinical Trials ◽  
Early Brain Injury ◽  
Aneurysm Rupture ◽  
Neurological Outcomes ◽  
Injury Research ◽  
The Brain

Introduction. Elevated intracranial pressure that occurs at the time of cerebral aneurysm rupture can lead to inadequate cerebral blood flow, which may mimic the brain injury cascade that occurs after cardiac arrest. Insights from clinical trials in cardiac arrest may provide direction for future early brain injury research after subarachnoid hemorrhage (SAH).Methods. A search of PubMed from 1980 to 2012 and clinicaltrials.gov was conducted to identify published and ongoing randomized clinical trials in aneurysmal SAH and cardiac arrest patients. Only English, adult, human studies with primary or secondary mortality or neurological outcomes were included.Results. A total of 142 trials (82 SAH, 60 cardiac arrest) met the review criteria (103 published, 39 ongoing). The majority of both published and ongoing SAH trials focus on delayed secondary insults after SAH (70%), while 100% of cardiac arrest trials tested interventions within the first few hours of ictus. No SAH trials addressing treatment of early brain injury were identified. Twenty-nine percent of SAH and 13% of cardiac arrest trials showed outcome benefit, though there is no overlap mechanistically.Conclusions. Clinical trials in SAH assessing acute brain injury are warranted and successful interventions identified by the cardiac arrest literature may be reasonable targets of the study.

Sign in / Sign up

Export Citation Format

Share Document