Abstract 273: Noninvasive Mitochondrial Modulation: Neuroprotection in a Translational Model of Cardiac Arrest and Resuscitation

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Joseph M Wider ◽  
Erin Gruley ◽  
Jennifer Mathieu ◽  
Emma Murphy ◽  
Rachel Mount ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Brain Injury ◽  
Near Infrared ◽  
Small Animal ◽  
Spontaneous Circulation ◽  
Infrared Light ◽  
Swine Model ◽  
Treatment Groups ◽  
The Brain ◽  
Neuroprotective Therapies

Background: Mitochondrial dysfunction contributes to cardiac arrest induced brain injury and has been a target for neuroprotective therapies. An emerging concept suggests that hyperactivation of neuronal mitochondria following resuscitation results in hyperpolarization of the mitochondrial membrane during reperfusion, which drives generation of excess reactive oxygen species. Previous studies from our group demonstrated that limiting mitochondrial hyperactivity by non-invasively modulating mitochondrial function with specific near infrared light (NIR) wavelengths can reduce brain injury in small animal models of global and focal ischemia. Hypothesis: Inhibitory wavelengths of NIR will reduce neuronal injury and improve neurocognitive outcome in a clinically relevant swine model of cardiac arrest. Methods: Twenty-eight male and female adult swine were enrolled (3 groups: Sham, CA/CPR, and CA/CPR + NIR). Cardiac arrest (8 minutes) was induced with a ventricular pacing wire and followed by manual CPR with defibrillation and epinephrine every 30 seconds until return of spontaneous circulation (ROSC), 2 of the 20 swine that underwent CA did not achieve ROSC and were not enrolled. Treatment groups were randomized prior to arrest and blinded to the CPR team. Treatment was applied at onset of ROSC by irradiating the scalp with 750 nm and 950 nm LEDs (5W) for 2 hours. Results: Sham-operated animals all survived (8/8), whereas 22% of untreated animals subjected to cardiac arrest died within 45 min of ROSC (CA/CPR, n= 7/9). All swine treated with NIR survived the duration of the study (CA/CPR + NIR, n=9/9). Four days following cardiac arrest, neurological deficit score was improved in the NIR treatment group (50 ± 21 CA/CPR vs. 0.8 ± 0.8 CA/CPR + NIR, p < 0.05). Additionally, neuronal death in the CA1/CA3 regions of the hippocampus, assessed by counting surviving neurons with stereology, was attenuated by treatment with NIR (17917 ± 5534 neurons/mm 3 CA/CPR vs. 44655 ± 5637 neurons/mm 3 CA/CPR + NIR, p < 0.05). All data is reported as mean ± SEM. Conclusions: These data provide evidence that noninvasive modulation of mitochondria, achieved by transcranial irradiation of the brain with NIR, mitigates post-cardiac arrest brain injury.

scholarly journals Real-Time Brain Monitoring by Near-Infrared Spectroscopy Predicts Neurological Outcome after Cardiac Arrest and Resuscitation in Rats: A Proof of Concept Study of a Novel Prognostic Measure after Cardiac Arrest

2021 ◽  
Vol 11 (1) ◽  
pp. 131
Author(s):  
Ryosuke Takegawa ◽  
Kei Hayashida ◽  
Tai Yin ◽  
Rishabh C. Choudhary ◽  
Santiago J. Miyara ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Brain Injury ◽  
Near Infrared ◽  
Mitochondrial Fission ◽  
Spontaneous Circulation ◽  
Gene Expressions ◽  
Dynamic Changes ◽  
Neurological Outcomes ◽  
Fluoro Jade B ◽  
The Brain

Clinical studies have demonstrated that dynamic changes in regional cerebral oxygen saturation (rSO2) after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) have a role in predicting neurological outcomes after the return of spontaneous circulation (ROSC). Our study evaluated whether the timing of rSO2 decline shortly after CPR reflects the severity of brain injury in a rat model of CA. Rats were subjected to different durations of asphyxia to produce variable severities of brain injury, due to CA. Time from ROSC to achieving the initial minimum rSO2 was defined as Tnadir. A Tnadir cut-off of 24 min had optimal sensitivity and specificity for predicting good neurological outcomes at 72 h after ROSC (AUC, 0.88; sensitivity, 89%; specificity, 86%; p < 0.01). Immunohistochemistry at 72 h post-CA revealed that the number of Fluoro-Jade B positive degenerating neurons in the hippocampus CA1 sector were markedly higher in animals with Tnadir > 24 min than that in animals with Tnadir ≤ 24 min. There was no difference in the gene expressions of cytokines and mitochondrial fission proteins in the brain at 2 h after ROSC between rats with Tnadir > 24 min and with Tnadir ≤ 24 min. In conclusion, Tnadir can be a novel predictor of good neurological outcomes after CA/CPR.

scholarly journals Foetal growth, birth transition, enteral nutrition and brain light scattering

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Osuke Iwata ◽  
Sachiko Iwata ◽  
Tsuyoshi Kurata ◽  
Kennosuke Tsuda ◽  
Koya Kawase ◽  
...  
Keyword(s):  
Brain Injury ◽  
Nutritional Status ◽  
Enteral Feeding ◽  
Near Infrared ◽  
Infrared Light ◽  
Apgar Scores ◽  
Near Infrared Light ◽  
Independent Variables ◽  
Foetal Growth ◽  
The Brain

AbstractIf the brain structure is assessed at neonatal intensive care units, covert clinical events related with subtle brain injury might be identified. The reduced scattering coefficient of near-infrared light (μS’) obtained using time-resolved near-infrared spectroscopy from the forehead of infants is associated with gestational age, body weight and Apgar scores, presumably reflecting subtle changes of the brain related to foetal growth and birth transition. One hundred twenty-eight preterm and term infants were studied to test whether μS’ obtained from the head at term-equivalent age is associated with foetal growth, birth transition and nutritional status after birth, which are key independent variables of developmental outcomes. As potential independent variables of μS’, birth weight, Apgar scores, age at full enteral feeding and post-conceptional age at the study were assessed to represent foetal growth, birth transition and nutritional status after birth. Subsequently, higher μS’ values were associated with higher Apgar scores (p = 0.003) and earlier establishment of enteral feeding (p < 0.001). The scattering property of near-infrared light within the neonatal brain might reflect changes associated with birth transition and nutritional status thereafter, which might be used as a non-invasive biomarker to identify covert independent variables of brain injury in preterm infants.

scholarly journals Photobiomodulation and the brain – has the light dawned?

2016 ◽  
Vol 38 (6) ◽  
pp. 24-28 ◽  
Author(s):  
Michael R. Hamblin
Keyword(s):  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
Near Infrared ◽  
Infrared Light ◽  
Great Promise ◽  
Brain Cells ◽  
Brain Disorders ◽  
Wide Range ◽  
The Brain

Evidence is mounting that photobiomodulation therapy (shining near-infrared light) can benefit a wide range of brain disorders. The photons can penetrate into the brain where they stimulate production of energy in brain cells, and trigger numerous signaling pathways. Acute ischaemic stroke was the first indication that progressed to human clinical trials. Acute and chronic stages of traumatic brain injury were then investigated. Currently, psychiatric disorders such as depression, and neurodegenerative diseases such as Alzheimer's and Parkinson's are under investigation. Although showing great promise, more trials are clearly needed before the therapy will be accepted.

scholarly journals Cerebrovascular autoregulation after rewarming from hypothermia in a neonatal swine model of asphyxic brain injury

2013 ◽  
Vol 115 (10) ◽  
pp. 1433-1442 ◽  
Author(s):  
Abby C. Larson ◽  
Jessica L. Jamrogowicz ◽  
Ewa Kulikowicz ◽  
Bing Wang ◽  
Zeng-Jin Yang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Brain Injury ◽  
Near Infrared ◽  
Swine Model ◽  
Secondary Brain Injury ◽  
Laser Doppler Flow ◽  
Cerebrovascular Autoregulation ◽  
Sham Surgery ◽  
Hypoxic Brain Injury ◽  
Hypoxic Brain

After hypoxic brain injury, maintaining blood pressure within the limits of cerebral blood flow autoregulation is critical to preventing secondary brain injury. Little is known about the effects of prolonged hypothermia or rewarming on autoregulation after cardiac arrest. We hypothesized that rewarming would shift the lower limit of autoregulation (LLA), that this shift would be detected by indices derived from near-infrared spectroscopy (NIRS), and that rewarming would impair autoregulation during hypertension. Anesthetized neonatal swine underwent sham surgery or hypoxic-asphyxic cardiac arrest, followed by 2 h of normothermia and 20 h of hypothermia, with or without rewarming. Piglets were further divided into cohorts for cortical laser-Doppler flow (LDF) measurements during induced hypotension or hypertension. We also tested whether indices derived from NIRS could identify the LDF-derived LLA. The LLA did not differ significantly among groups with sham surgery and hypothermia (29 ± 8 mmHg), sham surgery and rewarming (34 ± 7 mmHg), arrest and hypothermia (29 ± 10 mmHg), and arrest and rewarming (38 ± 11 mmHg). The LLA was not affected by arrest ( P = 0.60), temperature ( P = 0.08), or interaction between arrest and temperature ( P = 0.73). The NIRS-derived indices detected the LLA accurately, with the area under the receiver-operator characteristic curves of 0.81–0.96 among groups. In groups subjected to arrest and hypothermia, with or without rewarming, the slope of LDF relative to cerebral perfusion pressure during hypertension was not significantly different from zero ( P > 0.10). In conclusion, rewarming did not shift the LLA during hypotension or affect autoregulation during hypertension after asphyxic cardiac arrest. The NIRS-derived autoregulation indices identified the LLA accurately.

scholarly journals Near-Infrared Spectroscopy (NIRS) in Traumatic Brain Injury (TBI)

Sensors ◽  
2021 ◽  
Vol 21 (5) ◽  
pp. 1586
Author(s):  
María Roldán ◽  
Panayiotis A. Kyriacou
Keyword(s):  
Traumatic Brain Injury ◽  
Infrared Spectroscopy ◽  
Brain Injury ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Cerebral Oxygenation ◽  
Noninvasive Monitoring ◽  
Infrared Light ◽  
Cochrane Library ◽  
The Brain

Traumatic brain injury (TBI) occurs when a sudden trauma causes damage to the brain. TBI can result when the head suddenly and violently impacts an object or when an object pierces the skull and enters brain tissue. Secondary injuries after traumatic brain injury (TBI) can lead to impairments on cerebral oxygenation and autoregulation. Considering that secondary brain injuries often take place within the first hours after the trauma, noninvasive monitoring might be helpful in providing early information on the brain’s condition. Near-infrared spectroscopy (NIRS) is an emerging noninvasive monitoring modality based on chromophore absorption of infrared light with the capability of monitoring perfusion of the brain. This review investigates the main applications of NIRS in TBI monitoring and presents a thorough revision of those applications on oxygenation and autoregulation monitoring. Databases such as PubMed, EMBASE, Web of Science, Scopus, and Cochrane library were utilized in identifying 72 publications spanning between 1977 and 2020 which were directly relevant to this review. The majority of the evidence found used NIRS for diagnosis applications, especially in oxygenation and autoregulation monitoring (59%). It was not surprising that nearly all the patients were male adults with severe trauma who were monitored mostly with continue wave NIRS or spatially resolved spectroscopy NIRS and an invasive monitoring device. In general, a high proportion of the assessed papers have concluded that NIRS could be a potential noninvasive technique for assessing TBI, despite the various methodological and technological limitations of NIRS.

scholarly journals Non-invasive diffuse optical neuromonitoring during cardiopulmonary resuscitation predicts return of spontaneous circulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiffany S. Ko ◽  
Constantine D. Mavroudis ◽  
Ryan W. Morgan ◽  
Wesley B. Baker ◽  
Alexandra M. Marquez ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Hemoglobin Concentration ◽  
Spontaneous Circulation ◽  
Youden Index ◽  
Swine Model ◽  
Return Of Spontaneous Circulation ◽  
Non Invasive ◽  
Tissue Optical Properties ◽  
Tenfold Cross Validation

AbstractNeurologic injury is a leading cause of morbidity and mortality following pediatric cardiac arrest. In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO2], [Hb]), oxygen saturation (StO2) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8–11 kg; n = 52) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (< 10 min), were assessed by the weighted Youden index (Jw, w = 0.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48/52 animals; 37/48 achieved ROSC. Changes in scattering coefficient (785 nm), [HbO2], StO2 and THC from baseline were significantly different in ROSC versus No-ROSC subjects (p < 0.01) after 10 min of CPR. Change in [HbO2] of + 1.3 µmol/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, early ROSC prediction from the third minute of CPR.

Use of hemoglobin-based oxygen-carrying solution–201 to improve resuscitation parameters and prevent secondary brain injury in a swine model of traumatic brain injury and hemorrhage

2008 ◽  
Vol 108 (3) ◽  
pp. 575-587 ◽  
Author(s):  
Guy Rosenthal ◽  
Diane Morabito ◽  
Mitchell Cohen ◽  
Annina Roeytenberg ◽  
Nikita Derugin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mr Imaging ◽  
Swine Model ◽  
Secondary Brain Injury ◽  
Large Animal ◽  
Fluoro Jade B ◽  
Significant Difference ◽  
Impact Injury ◽  
The Brain

Object Traumatic brain injury (TBI) often occurs as part of a multisystem trauma that may lead to hemorrhagic shock. Effective resuscitation and restoration of oxygen delivery to the brain is important in patients with TBI because hypotension and hypoxia are associated with poor outcome in head injury. We studied the effects of hemoglobin-based oxygen-carrying (HBOC)–201 solution compared with lactated Ringer (LR) solution in a large animal model of brain injury and hemorrhage, in a blinded prospective randomized study. Methods Swine underwent brain impact injury and hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Twenty swine were randomized to undergo resuscitation with HBOC-201 (6 ml/kg) or LR solution (12 ml/kg) and were observed for an average of 6.5 ± 0.5 hours following resuscitation. At the end of the observation period, magnetic resonance (MR) imaging was performed. Histological studies of swine brains were performed using Fluoro-Jade B, a marker of early neuronal degeneration. Results Swine resuscitated with HBOC-201 had higher MAP, higher cerebral perfusion pressure (CPP), improved base deficit, and higher brain tissue oxygen tension (PbtO2) than animals resuscitated with LR solution. No significant difference in total injury volume on T2-weighted MR imaging was observed between animals resuscitated with HBOC-201 solution (1155 ± 374 mm3) or LR solution (1246 ± 279 mm3; p = 0.55). On the side of impact injury, no significant difference in the mean number of Fluoro-Jade B–positive cells/hpf was seen between HBOC-201 solution (61.5 ± 14.7) and LR solution (48.9 ± 17.7; p = 0.13). Surprisingly, on the side opposite impact injury, a significant increase in Fluoro-Jade B–positive cells/hpf was seen in animals resuscitated with LR solution (42.8 ± 28.3) compared with those resuscitated with HBOC-201 solution (5.6 ± 8.1; p < 0.05), implying greater neuronal injury in LR-treated swine. Conclusions The improved MAP, CPP, and PbtO2 observed with HBOC-201 solution in comparison with LR solution indicates that HBOC-201 solution may be a preferable agent for small-volume resuscitation in brain-injured patients with hemorrhage. The use of HBOC-201 solution appears to decrease cellular degeneration in the brain area not directly impacted by the primary injury. Hemoglobin-based oxygen-carrying–201 solution may act by improving cerebral blood flow or increasing the oxygen-carrying capacity of blood, mitigating a second insult to the injured brain.

Transcranial, Red/Near-Infrared Light-Emitting Diode Therapy to Improve Cognition in Chronic Traumatic Brain Injury

2016 ◽  
Vol 34 (12) ◽  
pp. 610-626 ◽  
Author(s):  
Margaret A. Naeser ◽  
Paula I. Martin ◽  
Michael D. Ho ◽  
Maxine H. Krengel ◽  
Yelena Bogdanova ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Near Infrared ◽  
Light Emitting Diode ◽  
Infrared Light ◽  
Near Infrared Light ◽  
Light Emitting

Abstract 65: Evaluating the Role of Continuously Monitoring Regional Cerebral Oxygen Saturation in Predicting the Return of Spontaneous Circulation in Cardiac Arrest Patients: Does the Use of an Electrocardiogram Alone Provide Adequate Information During Cardiopulmonary Resuscitation?

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Hitoshi Kano ◽  
Tomoyo Saito ◽  
Toshihisa Matsui ◽  
Akio Endo ◽  
Masaki Nagama ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Oxygen Saturation ◽  
Near Infrared ◽  
Tissue Oxygenation ◽  
Oxygenation Index ◽  
Cerebral Oxygen Saturation ◽  
Infrared Light ◽  
Cerebral Oxygen ◽  
Regional Cerebral Oxygen Saturation ◽  
Brain Tissue Oxygenation

During CPR as it is currently administered, treatments are selected from an algorithm derived by monitoring with ECG alone. One of the reasons for this is that no other devices are presently thought to be effective in helping to make treatment determinations. Monitoring of regional cerebral oxygen saturation with near infrared light is non-invasive and provides information on brain tissue oxygenation and hemodynamics. The results of our study suggest that measurements derived from continuously monitoring regional cerebral oxygen saturation during CPR can be considered an effective method of predicting the ROSC in cardiac arrest patients. Methods: In 95 patients with out-of-hospital cardiac arrest, the tissue oxygenation index (TOI) was continuously monitored (NIRO-200NX, Hamamatsu Photonics). We investigated the following parameters with respect to whether or not ROSC was achieved: TOI value at the contact of patients (initial TOI); TOI value just before ROSC (pre-ROSC TOI); and the maximum TOI during CPR (maximum TOI). Results: All the patients monitored received treatment with shocks or drugs and the initial TOI was 35.3±7.3%. For 74 patients who did not achieve ROSC, the maximum TOI was 41.0±7.4%, whereas for 21 patients who did achieve ROSC, the pre-ROSC TOI was 51.3±3.6% and the maximum TOI was 64.3±11.4%. ROSC was not achieved in the patients with maximum TOI below 45%. Conclusion: The pre-ROSC TOI was significantly higher than the maximum TOI in the patients who did not achieve ROSC which suggests the possibility of predicting ROSC by monitoring the increase in TOI. In cases where the TOI remains low, there is a possibility that ROSC should not be expected. In such cases, it may be desirable to attempt to improve the quality of CPR to increase the TOI before delivering shocks or administering drugs.

Abstract 246: Therapeutic Hypothermia Mimicking Peptide Administration During Cardiopulmonary Resuscitation Improved Cardiac Arrest Survival in Swine

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Matt Oberdier ◽  
Jing Li ◽  
Dan Ambinder ◽  
Xiangdong Zhu ◽  
Sarah Fink ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Therapeutic Hypothermia ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Sudden Cardiac Arrest ◽  
The United States ◽  
Rapid Onset ◽  
Spontaneous Circulation ◽  
Control Group ◽  
Swine Model

Background: Out-of-hospital sudden cardiac arrest is a leading cause of death in the United States, affecting over 350,000 people per year with an overall survival rate around 10%. CPR, defibrillation, and therapeutic hypothermia are common resuscitation strategies, but hypothermia is difficult to implement timely to achieve survival benefit. A cell-permeable peptide TAT-PHLPP9c has been shown to alter metabolic pathways similar to hypothermia, and decreases the release of two biomarkers, taurine and glutamate, during the high osmotic stress of heart stunning and brain injury in a mouse arrest model. Hypothesis: TAT-PHLPP9c, given during CPR, enhances 24-hour survival in a swine ventricular fibrillation (VF) model. Methods: In 14 (8 controls and 6 treated) sedated, intubated, and mechanically ventilated swine, after 5 min of VF, ACLS with vest CPR and periodic defibrillations was performed. Venous blood samples were collected at baseline, after 2 min of CPR, and at 2 and 30 min after return of spontaneous circulation (ROSC). The animals were survived up to 24 hrs and plasma samples were analyzed for glutamate and taurine in 2 controls and 1 animal given peptide. Results: Three of the control animals had ROSC, but none survived for 24 hrs, while 4 of 6 treated animals achieved neurologically intact survival at 24 hrs (p < 0.02). Compared to baseline, both taurine and glutamate plasma concentrations increased in the control group, but the increase was reduced substantially by the peptide treatment at 30 min after ROSC (Figure). Conclusion: The use of the cooling mimicking peptide TAT-PHLPP9c administered during CPR significantly improved 24-hour survival in this swine model of cardiac arrest. It reduced the increase of cerebral and myocardial metabolic biomarkers, which encourages utilizing a strategy of cell-permeable peptides for intravenous administration for more rapid onset of hypothermia-like salutary effects than are possible with current CPR cooling devices.

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