Publications by authors named "Tai Yin"

50 Publications

Phospholipid Screening Postcardiac Arrest Detects Decreased Plasma Lysophosphatidylcholine: Supplementation as a New Therapeutic Approach.

Crit Care Med 2021 Jul 2. Epub 2021 Jul 2.

1 Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Manhasset, NY. 2 Department of Emergency Medicine, Northshore University Hospital, Manhasset, NY. 3 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY. 4 Biostatistics Unit, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY.

Objectives: Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival.

Design: Clinical case control study followed by translational laboratory study.

Setting: Research institution.

Patients/subjects: Adult cardiac arrest patients and male Sprague-Dawley rats.

Interventions: Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle.

Measurements And Main Results: We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect.

Conclusions: Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach.
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http://dx.doi.org/10.1097/CCM.0000000000005180DOI Listing
July 2021

A method for measuring the molecular ratio of inhalation to exhalation and effect of inspired oxygen levels on oxygen consumption.

Sci Rep 2021 Jun 17;11(1):12815. Epub 2021 Jun 17.

The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.

Using a new method for measuring the molecular ratio (R) of inhalation to exhalation, we investigated the effect of high fraction of inspired oxygen (FIO2) on oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ) in mechanically ventilated rats. Twelve rats were equally assigned into two groups by anesthetics: intravenous midazolam/fentanyl vs. inhaled isoflurane. R, VO2, VCO2, and RQ were measured at FIO2 0.3 or 1.0. R error was ± 0.003. R was 1.0099 ± 0.0023 with isoflurane and 1.0074 ± 0.0018 with midazolam/fentanyl. R was 1.0081 ± 0.0017 at an FIO2 of 0.3 and 1.0092 ± 0.0029 at an FIO2 of 1.0. There were no differences in VCO2 among the groups. VO2 increased at FIO2 1.0, which was more notable when midazolam/fentanyl was used (isoflurane-FIO2 0.3: 15.4 ± 1.1; isoflurane-FIO2 1.0: 17.2 ± 1.8; midazolam/fentanyl-FIO2 0.3: 15.4 ± 1.1; midazolam/fentanyl-FIO2 1.0: 21.0 ± 2.2 mL/kg/min at STP). The RQ was lower at FIO2 1.0 than FIO2 0.3 (isoflurane-FIO2 0.3: 0.80 ± 0.07; isoflurane-FIO2 1.0: 0.71 ± 0.05; midazolam/fentanyl-FIO2 0.3: 0.79 ± 0.03; midazolam/fentanyl-FIO2 1.0: 0.59 ± 0.04). R was not affected by either anesthetics or FIO2. Inspired 100% O2 increased VO2 and decreased RQ, which might be more remarkable when midazolam/fentanyl was used.
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http://dx.doi.org/10.1038/s41598-021-91246-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211831PMC
June 2021

Assessment of Cerebral Blood Oxygenation by Near-Infrared Spectroscopy before and after Resuscitation in a Rat Asphyxia Cardiac Arrest Model.

Adv Exp Med Biol 2021 ;1269:311-315

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

Clinical investigators have focused on the real-time evaluation of cerebral blood oxygenation (CBO) by near-infrared spectroscopy (NIRS) during cardiopulmonary resuscitation (CPR). A previous study showed that an abrupt increase of oxy-hemoglobin (Hb) level and tissue oxygenation index (TOI) was associated with the timing of return of spontaneous circulation (ROSC). However, it is not clear how TOI alters before and after CPR including a period of cardiac arrest (CA). Therefore, this study aimed to assess CBO with asphyxia CA and its association with CPR to ROSC in rats. Male Sprague-Dawley rats were used. We attached NIRS (NIRO-200NX, Hamamatsu Photonics, Japan) from the nasion to the upper cervical spine in rats. A ten-minute asphyxia was given to induce CA. After CA, mechanical ventilation was restarted, and manual CPR was performed. We examined the mean arterial pressure (MAP), end-tidal carbon dioxide (ETCO), and Oxy/Deoxy-Hb and TOI. Out of 14 rats, 11 obtained sustained ROSC. After the induction of asphyxia, a rapid drop of TOI was observed, followed by a subsequent increase of Oxy-Hb, Deoxy-Hb, and TOI with CPR. Recent CPR guidelines suggest the use of ETCO during CPR since its abrupt increase is a reasonable indicator of ROSC. In this study, abrupt increases in MAP, ETCO, and TOI were observed at the time of ROSC. TOI can be an alternative to ETCO for identifying ROSC after CA, and it also has the capability of monitoring CBO during and after CPR.
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http://dx.doi.org/10.1007/978-3-030-48238-1_49DOI Listing
May 2021

Effect of Adrenaline on Cerebral Blood Oxygenation Measured by NIRS in a Rat Asphyxia Cardiac Arrest Model.

Adv Exp Med Biol 2021 ;1269:277-281

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

Adrenaline is an important pharmacologic treatment during cardiac arrest (CA) for resuscitation. Recent studies suggest that adrenaline increases the likelihood of return of spontaneous circulation (ROSC) but does not contribute to improving neurological outcomes of CA. The mechanisms have not been elucidated yet. A bimodal increase in mean arterial pressure (MAP) is observed after adrenaline injection in rodent CA models (Okuma et al. Intensive Care Med Exp 7(1), 2019). In this study, we focused on alteration of systemic arterial pressure in conjunction with the measurement of cerebral blood oxygenation (CBO) such as oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) by near-infrared spectroscopy (NIRS). Male Sprague-Dawley rats were used. We attached NIRS between the nasion and the upper cervical spine. Rats underwent 10 minute asphyxia to induce CA. Then, cardiopulmonary resuscitation (CPR) was started, followed by a 20 μg/kg of bolus adrenaline injection at 30 seconds of CPR. This injection accelerated the first increase in MAP, and ROSC was observed with an abrupt increase in CBO. Interestingly, the second increase in MAP, once it exceeded a certain value, was accompanied by paradoxical decreases of Oxy-Hb and TOI while Deoxy-Hb increased. Based on this finding, we compared Oxy-Hb, Deoxy-Hb, and TOI at the first MAP ≈ 100 mmHg and the second MAP ≈ 100 mmHg. The average of Oxy-Hb and TOI from the 13 animals significantly decreased at the second increase in MAP over 100 mmHg while Deoxy-Hb significantly increased. NIRS identified a decrease in Oxy-Hb after ROSC. These findings may be a clue in understanding the mechanism of how and why adrenaline alters the neurological outcomes of CA post resuscitation.
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http://dx.doi.org/10.1007/978-3-030-48238-1_44DOI Listing
May 2021

Evaluation of the Quality of Chest Compression with Oxyhemoglobin Level by Near-Infrared Spectroscopy in a Rat Asphyxia Cardiac Arrest Model.

Adv Exp Med Biol 2021 ;1269:265-269

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

The real-time evaluation of chest compression during cardiopulmonary resuscitation is important to increase the chances of survival from a cardiac arrest (CA). In addition, cerebral oxygen level measured by near-infrared spectroscopy (NIRS) plays an important role as an indicator of return of spontaneous circulation. Recently, we developed a new method to improve the quality of chest compression using a thoracic pump in conjunction with the classic cardiac pump in a rat asphyxia CA model. This study evaluated the quality of chest compression using NIRS in male Sprague-Dawley rats. NIRS was attached between the nasion and the upper cervical spine, and rats underwent 10 minute asphyxia CA. After CA, we alternately performed three different types of chest compression (cardiac, thoracic, and cardiac plus thoracic pumps) every 30 seconds for up to 4 and a half minutes. We measured the oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) and compared these values between the groups. Oxy-Hb was significantly different among the groups (cardiac, thoracic, and cardiac plus thoracic, 1.5 ± 0.9, 4.4 ± 0.7, and 5.9 ± 2.1 μmol/L, p < 0.01, respectively), while Deoxy-Hb and TOI were not (Deoxy-HB -2.7 ± 1.2, -1.1 ± 3.2, and -1.6 ± 10.1 μmol/L; TOI, 1.8 ± 1.8, 5.5 ± 1.3, and 9.5 ± 8.0%, respectively). Oxy-Hb showed potential to evaluate the quality of chest compression in a rat asphyxia CA model.
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http://dx.doi.org/10.1007/978-3-030-48238-1_42DOI Listing
May 2021

Effect of Adrenaline on Cerebral Blood Oxygenation Measured by NIRS in a Rat Asphyxia Cardiac Arrest Model.

Adv Exp Med Biol 2021 ;1269:39-43

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

Adrenaline is an important pharmacologic treatment during cardiac arrest (CA) for resuscitation. Recent studies suggest that adrenaline increases the likelihood of return of spontaneous circulation (ROSC) but does not contribute to improving neurological outcomes of CA. The mechanisms have not been elucidated yet. A bimodal increase in mean arterial pressure (MAP) is observed after adrenaline injection in rodent CA models [17]. In this study, we focused on alteration of systemic arterial pressure in conjunction with the measurement of cerebral blood oxygenation (CBO) such as oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) by near-infrared spectroscopy (NIRS). Male Sprague-Dawley rats were used. We attached NIRS between the nasion and the upper cervical spine. Rats underwent 10-minute asphyxia to induce CA. Then, cardiopulmonary resuscitation (CPR) was started, followed by a 20 μg/kg of bolus adrenaline injection at 30 seconds of CPR. This injection accelerated the first increase in MAP, and ROSC was observed with an abrupt increase in CBO. Interestingly, the second increase in MAP, once it exceeded a certain value, was accompanied by paradoxical decreases of Oxy-Hb and TOI, while Deoxy-Hb increased. Based on this finding, we compared Oxy-Hb, Deoxy-Hb, and TOI at the first MAP ≈ 100 mmHg and the second MAP ≈ 100 mmHg. The average of Oxy-Hb and TOI from the 13 animals significantly decreased at the second increase in MAP over 100 mmHg, while Deoxy-Hb significantly increased. NIRS identified a decrease in Oxy-Hb after ROSC. These findings may be a clue to understanding the mechanism of how and why adrenaline alters the neurological outcomes of CA post-resuscitation.
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http://dx.doi.org/10.1007/978-3-030-48238-1_6DOI Listing
May 2021

Effects of Post-Resuscitation Normoxic Therapy on Oxygen-Sensitive Oxidative Stress in a Rat Model of Cardiac Arrest.

J Am Heart Assoc 2021 Apr 28;10(7):e018773. Epub 2021 Mar 28.

The Feinstein Institutes for Medical ResearchNorthwell Manhasset NY.

Background Cardiac arrest (CA) can induce oxidative stress after resuscitation, which causes cellular and organ damage. We hypothesized that post-resuscitation normoxic therapy would protect organs against oxidative stress and improve oxygen metabolism and survival. We tested the oxygen-sensitive reactive oxygen species from mitochondria to determine the association with hyperoxia-induced oxidative stress. Methods and Results Sprague-Dawley rats were subjected to 10-minute asphyxia-induced CA with a fraction of inspired O of 0.3 or 1.0 (normoxia versus hyperoxia, respectively) after resuscitation. The survival rate at 48 hours was higher in the normoxia group than in the hyperoxia group (77% versus 28%, <0.01), and normoxia gave a lower neurological deficit score (359±140 versus 452±85, <0.05) and wet to dry weight ratio (4.6±0.4 versus 5.6±0.5, <0.01). Oxidative stress was correlated with increased oxygen levels: normoxia resulted in a significant decrease in oxidative stress across multiple organs and lower oxygen consumption resulting in normalized respiratory quotient (0.81±0.05 versus 0.58±0.03, <0.01). After CA, mitochondrial reactive oxygen species increased by ≈2-fold under hyperoxia. Heme oxygenase expression was also oxygen-sensitive, but it was paradoxically low in the lung after CA. In contrast, the HMGB-1 (high mobility group box-1) protein was not oxygen-sensitive and was induced by CA. Conclusions Post-resuscitation normoxic therapy attenuated the oxidative stress in multiple organs and improved post-CA organ injury, oxygen metabolism, and survival. Additionally, post-CA hyperoxia increased the mitochondrial reactive oxygen species and activated the antioxidation system.
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http://dx.doi.org/10.1161/JAHA.120.018773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174361PMC
April 2021

Inhaled Gases as Therapies for Post-Cardiac Arrest Syndrome: A Narrative Review of Recent Developments.

Front Med (Lausanne) 2020 14;7:586229. Epub 2021 Jan 14.

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health System, Manhasset, NY, United States.

Despite recent advances in the management of post-cardiac arrest syndrome (PCAS), the survival rate, without neurologic sequelae after resuscitation, remains very low. Whole-body ischemia, followed by reperfusion after cardiac arrest (CA), contributes to PCAS, for which established pharmaceutical interventions are still lacking. It has been shown that a number of different processes can ultimately lead to neuronal injury and cell death in the pathology of PCAS, including vasoconstriction, protein modification, impaired mitochondrial respiration, cell death signaling, inflammation, and excessive oxidative stress. Recently, the pathophysiological effects of inhaled gases including nitric oxide (NO), molecular hydrogen (H), and xenon (Xe) have attracted much attention. Herein, we summarize recent literature on the application of NO, H, and Xe for treating PCAS. Recent basic and clinical research has shown that these gases have cytoprotective effects against PCAS. Nevertheless, there are likely differences in the mechanisms by which these gases modulate reperfusion injury after CA. Further preclinical and clinical studies examining the combinations of standard post-CA care and inhaled gas treatment to prevent ischemia-reperfusion injury are warranted to improve outcomes in patients who are being failed by our current therapies.
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http://dx.doi.org/10.3389/fmed.2020.586229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873953PMC
January 2021

The evaluation of pituitary damage associated with cardiac arrest: An experimental rodent model.

Sci Rep 2021 01 12;11(1):629. Epub 2021 Jan 12.

The Feinstein Institutes for Medical Research, Northwell Health, 350 Community Dr., Manhasset, NY, 11030, USA.

The pituitary gland plays an important endocrinal role, however its damage after cardiac arrest (CA) has not been well elucidated. The aim of this study was to determine a pituitary gland damage induced by CA. Rats were subjected to 10-min asphyxia and cardiopulmonary resuscitation (CPR). Immunohistochemistry and ELISA assays were used to evaluate the pituitary damage and endocrine function. Samples were collected at pre-CA, and 30 and 120 min after cardio pulmonary resuscitation. Triphenyltetrazolium chloride (TTC) staining demonstrated the expansion of the pituitary damage over time. There was phenotypic validity between the pars distalis and nervosa. Both CT-proAVP (pars nervosa hormone) and GH/IGF-1 (pars distalis hormone) decreased over time, and a different expression pattern corresponding to the damaged areas was noted (CT-proAVP, 30.2 ± 6.2, 31.5 ± 5.9, and 16.3 ± 7.6 pg/mg protein, p < 0.01; GH/IGF-1, 2.63 ± 0.61, 0.62 ± 0.36, and 2.01 ± 0.41 ng/mg protein, p < 0.01 respectively). Similarly, the expression pattern between these hormones in the end-organ systems showed phenotypic validity. Plasma CT-proAVP (r = 0.771, p = 0.025) and IGF-1 (r = -0.775, p = 0.024) demonstrated a strong correlation with TTC staining area. Our data suggested that CA induces pathological and functional damage to the pituitary gland.
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http://dx.doi.org/10.1038/s41598-020-79780-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804952PMC
January 2021

Plasma metabolomics supports the use of long-duration cardiac arrest rodent model to study human disease by demonstrating similar metabolic alterations.

Sci Rep 2020 11 12;10(1):19707. Epub 2020 Nov 12.

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA.

Cardiac arrest (CA) is a leading cause of death and there is a necessity for animal models that accurately represent human injury severity. We evaluated a rat model of severe CA injury by comparing plasma metabolic alterations to human patients. Plasma was obtained from adult human control and CA patients post-resuscitation, and from male Sprague-Dawley rats at baseline and after 20 min CA followed by 30 min cardiopulmonary bypass resuscitation. An untargeted metabolomics evaluation using UPLC-QTOF-MS/MS was performed for plasma metabolome comparison. Here we show the metabolic commonality between humans and our severe injury rat model, highlighting significant metabolic dysfunction as seen by similar alterations in (1) TCA cycle metabolites, (2) tryptophan and kynurenic acid metabolites, and (3) acylcarnitine, fatty acid, and phospholipid metabolites. With substantial interspecies metabolic similarity in post-resuscitation plasma, our long duration CA rat model metabolically replicates human disease and is a suitable model for translational CA research.
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http://dx.doi.org/10.1038/s41598-020-76401-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665036PMC
November 2020

Combination of cardiac and thoracic pump theories in rodent cardiopulmonary resuscitation: a new method of three-side chest compression.

Intensive Care Med Exp 2019 Dec 2;7(1):62. Epub 2019 Dec 2.

The Feinstein Institute for Medical Research, Northwell Health System, 350 Community Dr. Manhasset, Manhasset, NY, 11030, USA.

Background: High-quality cardiopulmonary resuscitation (HQ-CPR) is of paramount importance to improve neurological outcomes of cardiac arrest (CA). The purpose of this study was to evaluate chest compression methods by combining two theories: cardiac and thoracic pumps.

Methods: Male Sprague-Dawley rats were used. Three types of chest compression methods were studied. The 1-side method was performed vertically with 2 fingers over the sternum. The 2-side method was performed horizontally with 2 fingers, bilaterally squeezing the chest wall. The 3-side method combined the 1-side and the 2-side methods. Rats underwent 10 min of asphyxial CA. We examined ROSC rates, the left ventricular functions, several arterial pressures, intrathoracic pressure, and brain tissue oxygen.

Results: The 3-side group achieved 100% return of spontaneous circulation (ROSC) from asphyxial CA, while the 1-side group and 2-side group achieved 80% and 60% ROSC, respectively. Three-side chest compression significantly shortened the time for ROSC among the groups (1-side, 105 ± 36.0; 2-side, 141 ± 21.7; 3-side, 57.8 ± 12.3 s, respectively, P < 0.05). Three-side significantly increased the intrathoracic pressure (esophagus, 7.6 ± 1.9, 7.3 ± 2.8, vs. 12.7 ± 2.2; mmHg, P < 0.01), the cardiac stroke volume (the ratio of the baseline 1.2 ± 0.6, 1.3 ± 0.1, vs. 2.1 ± 0.6, P < 0.05), and the common carotid arterial pressure (subtracted by femoral arterial pressure 4.0 ± 2.5, 0.3 ± 1.6, vs. 8.4 ± 2.6; mmHg, P < 0.01). Three-side significantly increased the brain tissue oxygen (the ratio of baseline 1.4±0.1, 1.3±0.2, vs. 1.6 ± 0.04, P < 0.05).

Conclusions: These results suggest that increased intrathoracic pressure by 3-side CPR improves the cardiac output, which may in turn help brain oxygenation during CPR.
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http://dx.doi.org/10.1186/s40635-019-0275-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889262PMC
December 2019

Tissue-Specific Metabolic Profiles After Prolonged Cardiac Arrest Reveal Brain Metabolome Dysfunction Predominantly After Resuscitation.

J Am Heart Assoc 2019 09 31;8(17):e012809. Epub 2019 Aug 31.

Laboratory for Critical Care Physiology Feinstein Institute for Medical Research Manhasset NY.

Background Cardiac arrest (CA) has been a leading cause of death for many decades. Despite years of research, we still do not understand how each organ responds to the reintroduction of blood flow after prolonged CA. Following changes in metabolites of individual organs after CA and resuscitation gives context to the efficiency and limitations of current resuscitation protocols. Methods and Results Adult male Sprague-Dawley rats were arbitrarily assigned into 3 groups: control, 20 minutes of CA, or 20 minutes of CA followed by 30 minutes of cardiopulmonary bypass resuscitation. The rats were euthanized by decapitation to harvest brain, heart, kidney, and liver tissues. The obtained tissue samples were analyzed by ultra-high-performance liquid chromatography-high-accuracy mass spectrometry for comprehensive metabolomics evaluation. After resuscitation, the brain showed decreased glycolysis metabolites and fatty acids and increased amino acids compared with control. Similarly, the heart displayed alterations mostly in amino acids. The kidney showed decreased amino acid and fatty acid pools with severely increased tricarboxylic acid cycle metabolites following resuscitation, while the liver showed minimal alterations with slight changes in the lipid pool. Each tissue has a distinct pattern of metabolite changes after ischemia/reperfusion. Furthermore, resuscitation worsens the metabolic dysregulation in the brain and kidney, while it normalizes metabolism in the heart. Conclusions Developing metabolic profiles using a global metabolome analysis identifies the variable nature of metabolites in individual organs after CA and reperfusion, establishing a stark contrast between the normalized heart and liver and the exacerbated brain and kidney, only after the reestablishment of blood circulation.
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http://dx.doi.org/10.1161/JAHA.119.012809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755859PMC
September 2019

The role of decreased cardiolipin and impaired electron transport chain in brain damage due to cardiac arrest.

Neurochem Int 2018 11 1;120:200-205. Epub 2018 Sep 1.

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Department of Emergency Medicine, The Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA. Electronic address:

Ischemic brain damage is the major cause of mortality in cardiac arrest (CA). However, the molecular mechanism responsible for brain damage is not well understood. We previously found that mitochondrial state-3 respiration, which had been decreased following CA, was recovered in the kidney and liver, but not in the brain following cardiopulmonary bypass (CPB) resuscitation. Examination of mitochondria from these tissues may shed light on why the brain is the most vulnerable. In this study, adult male Sprague-Dawley rats were subjected to asphyxia-induced CA for 30 min or 30 min followed by 60 min CPB resuscitation. Mitochondria were then isolated from brain, heart, kidney, and liver tissues for examination using spectrophotometry and mass spectrometry to measure the activities of mitochondrial electron transport complexes and the cardiolipin content. We found significantly decreased complex I activity in mitochondria isolated from all four organs following CA, while complex III and IV activities remained intact. Following CPB resuscitation, complex I activity was normalized in kidney and liver, but unrecovered in brain and heart mitochondria. In addition, complex III activity in brain mitochondria was decreased by 22% with a concomitant decrease in cardiolipin following CPB resuscitation. These results suggest that of the tissues tested only brain mitochondria suffer reperfusion injury in addition to ischemic alterations, resulting in diminished overall mitochondrial respiration following resuscitation.
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http://dx.doi.org/10.1016/j.neuint.2018.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953615PMC
November 2018

Effect of compression waveform and resuscitation duration on blood flow and pressure in swine: One waveform does not optimally serve.

Resuscitation 2018 10 6;131:55-62. Epub 2018 Aug 6.

The Feinstein Institute for Medical Research, Department of Emergency Medicine, Northwell Health, Manhasset, NY, United States. Electronic address:

Background: Chest compression (CC) research primarily focuses on finding the 'optimum' compression waveform using a variety of compression efficacy metrics. Blood flow is rarely measured systematically with high fidelity. Using a programmable mechanical chest compression device, we studied the effect of inter-compression pauses in a swine model of cardiac arrest, testing the hypothesis that a single 'optimal' CC waveform exists based on measurements of resulting blood flow.

Methods: Hemodynamics were studied in 9 domestic swine (∼30 kg) using multiple flow probes and standard physiological monitoring. After 10 min of ventricular fibrillation, five mechanical chest compression waveforms (5.1 cm, varying inter-compression pauses) were delivered for 2 min each in a semi-random pattern, totaling 50 compression minutes. Linear Mixed Models were used to estimate the effect of compression waveform on hemodynamics.

Results: Blood flow and pressure decayed significantly with time in both arteries and veins. No waveform maximized blood flow in all vessels simultaneously and the waveform generating maximal blood flow in a specific vessel changed over time in all vessels. A flow mismatch between paired arteries and veins, e.g. abdominal aorta and inferior vena cava, also developed over time. The waveform with the slowest rate and shortest duty cycle had the smallest mismatch between flows after about 30 min of CPR.

Conclusions: This data challenges the concept of a single optimal CC waveform. Time dependent physiological response to compressions and no single compression waveform optimizing flow in all vessels indicate that current descriptions of CPR don't reflect patient physiology.
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http://dx.doi.org/10.1016/j.resuscitation.2018.08.005DOI Listing
October 2018

Comparing phospholipid profiles of mitochondria and whole tissue: Higher PUFA content in mitochondria is driven by increased phosphatidylcholine unsaturation.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Sep 10;1093-1094:147-157. Epub 2018 Jul 10.

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Department of Emergency Medicine, Feinstein Institute for Medical Research, Manhasset, NY, USA. Electronic address:

Phospholipids content in cellular and mitochondrial membranes is essential for maintaining normal function. Previous studies have found a lower polyunsaturated fatty acid (PUFA) content in mitochondria than whole tissue, theorizing decreased PUFA protects against oxidative injury. However, phospholipids (PPLs) are uniquely difficult to quantify without class separation and, as prior approaches have predominately used reverse-phase HPLC or shotgun analysis, quantitation of PPL classes may have been complicated due to the existence of numerous isobaric and isomeric species. We apply normal-phase HPLC with class separation to compare whole tissue and mitochondrial PPL profiles in rat brain, heart, kidney, and liver. In addition, we establish a novel method to ascertain PPL origin, using cardiolipin as a comparator to establish relative cardiolipin /PPL ratios. We report a higher PUFA content in tissue mitochondria driven by increased phosphatidylcholine unsaturation, suggesting mitochondria purposefully incorporate higher PUFA PPLs.
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http://dx.doi.org/10.1016/j.jchromb.2018.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299238PMC
September 2018

Dissociated Oxygen Consumption and Carbon Dioxide Production in the Post-Cardiac Arrest Rat: A Novel Metabolic Phenotype.

J Am Heart Assoc 2018 06 29;7(13). Epub 2018 Jun 29.

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY.

Background: The concept that resuscitation from cardiac arrest (CA) results in a metabolic injury is broadly accepted, yet patients never receive this diagnosis. We sought to find evidence of metabolic injuries after CA by measuring O consumption and CO production (VCO) in a rodent model. In addition, we tested the effect of inspired 100% O on the metabolism.

Methods And Results: Rats were anesthetized and randomized into 3 groups: resuscitation from 10-minute asphyxia with inhaled 100% O (CA-fraction of inspired O [FIO] 1.0), with 30% O (CA-FIO 0.3), and sham with 30% O (sham-FIO 0.3). Animals were resuscitated with manual cardiopulmonary resuscitation. The volume of extracted O (VO) and VCO were measured for a 2-hour period after resuscitation. The respiratory quotient (RQ) was RQ=VCO/VO. VCO was elevated in CA-FIO 1.0 and CA-FIO 0.3 when compared with sham-FIO 0.3 in minutes 5 to 40 after resuscitation (CA-FIO 1.0: 16.7±2.2, <0.01; CA-FIO 0.3: 17.4±1.4, <0.01; versus sham-FIO 0.3: 13.6±1.1 mL/kg per minute), and then returned to normal. VO in CA-FIO 1.0 and CA-FIO 0.3 increased gradually and was significantly higher than sham-FIO 0.3 2 hours after resuscitation (CA-FIO 1.0: 28.7±6.7, <0.01; CA-FIO 0.3: 24.4±2.3, <0.01; versus sham-FIO 0.3: 15.8±2.4 mL/kg per minute). The RQ of CA animals persistently decreased (CA-FIO 1.0: 0.54±0.12 versus CA-FIO 0.3: 0.68±0.05 versus sham-FIO 0.3: 0.93±0.11, <0.01 overall).

Conclusions: CA altered cellular metabolism resulting in increased VO with normal VCO. Normal VCO suggests that the postresuscitation Krebs cycle is operating at a presumably healthy rate. Increased VO in the face of normal VCO suggests a significant alteration in O utilization in postresuscitation. Several RQ values fell well outside the normally cited range of 0.7 to 1.0. Higher FIO may increase VO, leading to even lower RQ values.
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http://dx.doi.org/10.1161/JAHA.117.007721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064898PMC
June 2018

Increased Survival Time With SS-31 After Prolonged Cardiac Arrest in Rats.

Heart Lung Circ 2019 Mar 7;28(3):505-508. Epub 2018 Feb 7.

Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Department of Emergency Medicine, Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA. Electronic address:

Background: Cardiac arrest is one of the leading causes of death with a very high mortality rate. No therapeutic drug that can be administered during resuscitation has been reported. Mitochondrial dysfunction is believed to play an important role for the pathogenesis of cardiac arrest. SS-31, a tetra-peptide, has been shown to protect mitochondria from ischaemia/reperfusion injury. Therefore, we tested whether SS-31 improves rat survival after prolonged cardiac arrest.

Methods: Rats were randomised into two groups. After 25minutes of asphyxia-induced cardiac arrest, rats were resuscitated with or without SS-31 using cardiopulmonary bypass resuscitation. Rat survival was followed for additional 4.5hours using haemodynamic monitoring. The blood gas was analysed for surviving rats at multiple time points.

Results And Conclusions: After 5hours, 5 of 10 rats survived in the SS-31 group whereas only 1 of 10 rats survived in the control group (p=0.026). At 90minutes after resuscitation, the blood lactate level in the SS-31 treated rats (4.29±2.5mmol/L) was significantly lower than in control rats (7.36±3.1mmol/L, p=0.026), suggesting mitochondrial aerobic respiration was improved with SS-31 treatment. Overall, our data show the potential of SS-31 as a novel therapeutic in cardiac arrest.
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http://dx.doi.org/10.1016/j.hlc.2018.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081272PMC
March 2019

Comprehensive analysis of phospholipids in the brain, heart, kidney, and liver: brain phospholipids are least enriched with polyunsaturated fatty acids.

Mol Cell Biochem 2018 May 9;442(1-2):187-201. Epub 2017 Oct 9.

Department of Emergency Medicine, Feinstein Institute for Medical Research, Northwell Health System, 350 Community Dr, Manhasset, NY, 11030, USA.

It is commonly accepted that brain phospholipids are highly enriched with long-chain polyunsaturated fatty acids (PUFAs). However, the evidence for this remains unclear. We used HPLC-MS to analyze the content and composition of phospholipids in rat brain and compared it to the heart, kidney, and liver. Phospholipids typically contain one PUFA, such as 18:2, 20:4, or 22:6, and one saturated fatty acid, such as 16:0 or 18:0. However, we found that brain phospholipids containing monounsaturated fatty acids in the place of PUFAs are highly elevated compared to phospholipids in the heart, kidney, and liver. The relative content of phospholipid containing PUFAs is ~ 60% in the brain, whereas it is over 90% in other tissues. The most abundant species of phosphatidylcholine (PC) is PC(16:0/18:1) in the brain, whereas PC(18:0/20:4) and PC(16:0/20:4) are predominated in other tissues. Moreover, several major species of plasmanyl and plasmenyl phosphatidylethanolamine are found to contain monounsaturated fatty acid in the brain only. Overall, our data clearly show that brain phospholipids are the least enriched with PUFAs of the four major organs, challenging the common belief that the brain is highly enriched with PUFAs.
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http://dx.doi.org/10.1007/s11010-017-3203-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882520PMC
May 2018

Potential of lysophosphatidylinositol as a prognostic indicator of cardiac arrest using a rat model.

Biomarkers 2017 Dec 8;22(8):755-763. Epub 2016 Dec 8.

a Laboratory for Critical Care Physiology, Department of Emergency Medicine , Feinstein Institute for Medical Research, Northwell Health System , Manhasset , NY , USA.

Aims: The potential of a lysophosphatidylinositol species, LPI(18:0), as a biomarker of ischaemia was tested using a rat model of cardiac arrest (CA).

Methods: Male Sprague-Dawley rats were subjected to asphyxia-induced CA or CA followed by cardiopulmonary bypass (CPB) resuscitation. The brain, heart, kidney and liver tissues were harvested from rats after 0, 5, 10, 20, 30 and 60 min CA and 30 min CA followed by 60 min CPB resuscitation. Blood samples were collected from inferior vena cava and hepatic veins following 30 min CA. Phospholipids were extracted from the four tissues and blood and analysed by HPLC-MS.

Results: The relative content of LPI(18:0) compared to a phosphatidylinositol species, PI(18:0,22:4), was significantly increased in the brain, heart, liver and kidney following 30 min CA and decreased following CPB resuscitation. In addition, the increase of the LPI(18:0)/PI(18:0,22:4) ratio in the four tissues was proportional to the duration of ischaemia for CA lasting up to 60 min. The ratio was also found to be increased in plasma from the hepatic vein following 30 min CA.

Conclusion: LPI(18:0) is a good indicator of CA downtime and has a potential to be used for early prognostication of outcome in CA.
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http://dx.doi.org/10.1080/1354750X.2016.1265002DOI Listing
December 2017

DHA-supplemented diet increases the survival of rats following asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation.

Sci Rep 2016 11 4;6:36545. Epub 2016 Nov 4.

Laboratory for Critical Care Physiology, Department of Emergency Medicine, Feinstein Institute for Medical Research, Northwell Health System, Manhasset, New York, 11030, United States of America.

Accumulating evidence illustrates the beneficial effects of dietary docosahexaenoic acid (DHA) on cardiovascular diseases. However, its effects on cardiac arrest (CA) remain controversial in epidemiological studies and have not been reported in controlled animal studies. Here, we examined whether dietary DHA can improve survival, the most important endpoint in CA. Male Sprague-Dawley rats were randomized into two groups and received either a control diet or a DHA-supplemented diet for 7-8 weeks. Rats were then subjected to 20 min asphyxia-induced cardiac arrest followed by 30 min cardiopulmonary bypass resuscitation. Rat survival was monitored for additional 3.5 h following resuscitation. In the control group, 1 of 9 rats survived for 4 h, whereas 6 of 9 rats survived in the DHA-treated group. Surviving rats in the DHA-treated group displayed moderately improved hemodynamics compared to rats in the control group 1 h after the start of resuscitation. Rats in the control group showed no sign of brain function whereas rats in the DHA-treated group had recurrent seizures and spontaneous respiration, suggesting dietary DHA also protects the brain. Overall, our study shows that dietary DHA significantly improves rat survival following 20 min of severe CA.
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http://dx.doi.org/10.1038/srep36545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109906PMC
November 2016

The effects of early high-volume hemofiltration on prolonged cardiac arrest in rats with reperfusion by cardiopulmonary bypass: a randomized controlled animal study.

Intensive Care Med Exp 2016 Dec 9;4(1):25. Epub 2016 Sep 9.

The Feinstein Institute for Medical Research, Northwell Health System, 350 Community Dr., Manhasset, NY, 11030, USA.

Background: It is not yet clear whether hemofiltration can reduce blood cytokine levels sufficiently to benefit patients who suffer prolonged cardiac arrest (CA) treated with cardiopulmonary bypass (CPB). We sought to assess effects of high-volume and standard volume continuous veno-venous hemofiltration (CVVH) on blood cytokine levels and survival in a rat model of prolonged CA treated with CPB.

Methods: Sprague-Dawley male rats were subjected to 12 min of asphyxia to induce CA. CPB was initiated for resuscitation of animals and maintained for 30 min. Twenty-four rats were randomly assigned into three groups: without CVVH treatment (sham); standard volume CVVH at a filtration rate of 35-45 mL/kg/h; and high-volume hemofiltration (HVHF, 105-135 mL/kg/h). Hemofiltration was started simultaneously with CPB and maintained for 6 h. Plasma TNFα and IL-6 levels were measured at baseline, 0.5, 1, 2, 3, and 6 h after reperfusion. Survival time, neurological deficit score, and hemodynamic status were assessed.

Results: All animals survived over 6 h and died within 24 h. There were no significant differences in survival time (log-rank test, sham vs. CVVH; p = 0.49, sham vs. HVHF; p = 0.33) or neurological deficit scores (ANOVA, p = 0.14) between the groups. There were no significant differences in blood cytokine levels between the groups. Mean blood pressure in sham group animals increased to 1.5-fold higher than baseline levels at 30 min. HVHF significantly reduced blood pressure to 0.7-fold of sham group (p < 0.01).

Conclusions: There was no improvement in mortality, neurological dysfunction, TNFα, or IL-6 levels in rats after prolonged CA with CPB on either hemofiltration group when compared to the sham group.
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http://dx.doi.org/10.1186/s40635-016-0101-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017966PMC
December 2016

Computed Tomography Angiography in Diagnosis and Treatment of Splenic Artery Aneurysm.

Chin Med J (Engl) 2016 Feb;129(3):367-9

Department of Cardiovascular Internal Medicine, Nanlou Branch of Chinese PLA General Hospital, Beijing 100853, China.

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http://dx.doi.org/10.4103/0366-6999.174506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799585PMC
February 2016

The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

Oxid Med Cell Longev 2016 7;2016:7463407. Epub 2015 Dec 7.

Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.
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http://dx.doi.org/10.1155/2016/7463407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685127PMC
October 2016

Developing a kinematic understanding of chest compressions: the impact of depth and release time on blood flow during cardiopulmonary resuscitation.

Biomed Eng Online 2015 Nov 4;14:102. Epub 2015 Nov 4.

The Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, 3501 Civic Center Blvd, Suite 6026, Philadelphia, PA, 19104, USA.

Background: Effective cardiopulmonary resuscitation is a critical component of the pre-hospital treatment of cardiac arrest victims. Mechanical chest compression (MCC) devices enable the delivery of MCC waveforms that could not be delivered effectively by hand. While chest compression generated blood flow has been studied for more than 50 years, the relation between sternum kinematics (depth over time) and the resulting blood flow have not been well described. Using a five parameter MCC model, we studied the effect of MCC depth, MCC release time, and their interaction on MCC generated blood flow in a highly instrumented swine model of cardiac arrest.

Methods: MCC hemodynamics were studied in 17 domestic swine (~30 kg) using multiple extra-vascular flow probes and standard physiological monitoring. After 10 min of untreated ventricular fibrillation, mechanical MCC were started. MCC varied such that sternal release occurred over 100, 200, or 300 ms. MCC were delivered at a rate of 100 per min and at a depth of 1.25″ (n = 9) or at a depth of 1.9″ (n = 8) for a total of 18 min. Transitions between release times occurred every 2 min and were randomized. Linear Mixed Models were used to estimate the effect of MCC depth, MCC release time, and the interaction between MCC depth and release time on physiological outcomes.

Results: Blood pressures were optimized by a 200 ms release. End tidal carbon dioxide (EtCO2) was optimized by a 100 ms release. Blood flows were significantly lower at a 300 ms release than at either a 100 or 200 ms release (p < 0.05). 1.9″ deep MCC improved EtCO2, right atrial pressure, coronary perfusion pressure, inferior vena cava blood flow, carotid blood flow, and renal vein blood flow relative to 1.25″ MCC.

Conclusions: Deeper MCC improved several hemodynamic parameters. Chest compressions with a 300 ms release time generated less blood flow than chest compressions with faster release times. MCC release time is an important quantitative metric of MCC quality and, if optimized, could improve MCC generated blood flows and pressures.
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http://dx.doi.org/10.1186/s12938-015-0095-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634731PMC
November 2015

Phospholipid alterations in the brain and heart in a rat model of asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation.

Mol Cell Biochem 2015 Oct 10;408(1-2):273-81. Epub 2015 Jul 10.

Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, 3501 Civic Center Boulevard, Suite 6023, Philadelphia, PA, 19104-4399, USA.

Cardiac arrest (CA) induces whole-body ischemia, causing damage to multiple organs. Ischemic damage to the brain is mainly responsible for patient mortality. However, the molecular mechanism responsible for brain damage is not understood. Prior studies have provided evidence that degradation of membrane phospholipids plays key roles in ischemia/reperfusion injury. The aim of this study is to correlate organ damage to phospholipid alterations following 30 min asphyxia-induced CA or CA followed by cardiopulmonary bypass (CPB) resuscitation using a rat model. Following 30 min CA and CPB resuscitation, rats showed no brain function, moderately compromised heart function, and died within a few hours; typical outcomes of severe CA. However, we did not find any significant change in the content or composition of phospholipids in either tissue following 30 min CA or CA followed by CPB resuscitation. We found a substantial increase in lysophosphatidylinositol in both tissues, and a small increase in lysophosphatidylethanolamine and lysophosphatidylcholine only in brain tissue following CA. CPB resuscitation significantly decreased lysophosphatidylinositol but did not alter the other lyso species. These results indicate that a decrease in phospholipids is not a cause of brain damage in CA or a characteristic of brain ischemia. However, a significant increase in lysophosphatidylcholine and lysophosphatidylethanolamine found only in the brain with more damage suggests that impaired phospholipid metabolism may be correlated with the severity of ischemia in CA. In addition, the unique response of lysophosphatidylinositol suggests that phosphatidylinositol metabolism is highly sensitive to cellular conditions altered by ischemia and resuscitation.
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http://dx.doi.org/10.1007/s11010-015-2505-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573890PMC
October 2015

Developing dual hemofiltration plus cardiopulmonary bypass in rodents.

J Surg Res 2015 May 9;195(1):196-203. Epub 2014 Dec 9.

Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA.

Background: Emerging therapies for prolonged cardiac arrest (CA) include advanced circulatory interventions like emergency cardiopulmonary bypass (ECPB) and continuous venovenous hemofiltration (CVVHF). However, preclinical studies are limited because of the absence of a practical method of using CVVHF along with ECPB in rodents.

Methods: We modified a CA model with ECPB resuscitation to include the CVVHF circuit. Adult rats were cannulated via the femoral artery or vein and the jugular vein for the ECPB circuit. A new circuit for CVVHF was added to allow ECPB and CVVHF to be started simultaneously. CVVHF blood flow at 3 mL/min could be controlled with a screw clamp during ECPB. After cessation of ECPB, the CVVHF flow was maintained using a roller pump. The filtration rate was controlled at 40 mL/h/kg in the standard volume of CVVHF and 120 mL/h/kg in the high volume (HV) of CVVHF. The driving force of hemofiltration was evaluated by monitoring transmembrane pressure and filter clearance (FCL).

Results: Transmembrane pressure in both groups was stable for 6 h throughout CVVHF. FCL of blood urea nitrogen and potassium in the standard volume group was significantly less than the HV group (P < 0.01). FCL of blood urea nitrogen and potassium was stable throughout the CVVHF operation in both groups.

Conclusions: We developed a method of CVVHF along with ECPB in rodents after CA. We further demonstrated the ability to regulate both standard and HV filtration rates.
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http://dx.doi.org/10.1016/j.jss.2014.12.004DOI Listing
May 2015

Examination of physiological function and biochemical disorders in a rat model of prolonged asphyxia-induced cardiac arrest followed by cardio pulmonary bypass resuscitation.

PLoS One 2014 10;9(11):e112012. Epub 2014 Nov 10.

Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Background: Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion.

Method: A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition.

Results: After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue.

Conclusion: The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112012PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226499PMC
July 2015

[Treatment strategies of inflammatory abdominal aortic aneurysm].

Zhonghua Yi Xue Za Zhi 2014 Feb;94(5):348-51

Department of Vascular Surgery, General Hospital of People's Liberation Army, Beijing 100853, China.

Objective: Summarizes the treatment effect of inflammatory abdominal aortic aneurysm (inflammatory abdominal aortic aneurysm, IAAA), and explore its therapeutic strategy.

Methods: Retrospectively analysis 17 cases of IAAA in our center from January 2002 to August 2012, 16 males, 1 female, mean age 52-79 (67 ± 8). 4 cases were treated by conservative medical treatment, 5 cases treated by open surgery, 8 cases treated by EVAR.

Results: During follow-up no aneurysm-related death. Follow-up for the conservative medical treatment group was a mean of (10 ± 6) months, 1 case transit to EVAR, the aneurysm diameter of 2 cases decreased 2 mm and 4 mm, 1 case had no significant diameter change. The mean follow-up time of open group was (28 ± 23) months, mean operation time was (4.9 ± 0.7) hours, Mean operative blood loss was (3 300 ± 370) ml, 1 case with postoperative anastomotic pseudoaneurysm formation. The EVAR group followed up for (20 ± 14) months, without serious perioperative complications, 5 cases aneurysm diameter decreased (5.1 ± 1.5) mm.

Conclusion: Conservative medical treatment can improve clinical symptoms of IAAA, such as inflammation, abdominal/back pain and hydronephrosis.EVAR is gradually becoming a first-line treatment of IAAA.Open surgery is still the gold standard for treatment of IAAA. Therefore, definite conclusions should be drawn from further studies.
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February 2014

Catheter entrapment during cardiac electrophysiology study.

Ann Acad Med Singap 2013 Mar;42(3):161-2

Department of Cardiology, Tan Tock Seng Hospital, Singapore.

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March 2013

Early malperfusion, ischemia reperfusion injury, and respiratory failure in acute complicated type B aortic dissection after thoracic endovascular repair.

J Cardiothorac Surg 2013 Jan 23;8:17. Epub 2013 Jan 23.

Departments of Vascular Surgery, Clinical Division of Surgery, Chinese PLA General Hospital, Beijing, China.

Background: The aim of this study was to determine the early mortality and major complications of acute complicated type B aortic dissection (ACBD) after thoracic endovascular aortic repair (TEVAR).

Methods: Twenty-six consecutive patients with ACBD who underwent TEVAR were included. Clinical indications before TEVAR and in-hospital mortality and major complications after TEVAR were analyzed and compared with similar reports.

Results: TEVAR was technically successful in all cases. In-hospital mortality occurred in four patients (15%), and major complications occurred in an additional four patients (15%). Three of the four (75%) of the deaths were associated with malperfusion and ischemia reperfusion injury (IRI), and 3/4 (75%) of the major complications were caused by respiratory failure (RF).

Conclusions: In-hospital mortality associated strongly with severe end-organ malperfusion and IRI, while major complications associated with RF, during TEVAR. Our results indicate that malperfusion, IRI and respiratory failure during TEVAR should be carefully monitored and aggressively treated.
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http://dx.doi.org/10.1186/1749-8090-8-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639915PMC
January 2013
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