Abstract 177: A Multimodal Neuroprotection Strategy Using Ketamine, Melatonin, and Limited Initial Reoxygenation Following Cardiac Arrest Does Not Improve MRI Cytotoxic Injury in a Swine Model: A Pilot Study

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Miriam Peckham ◽  
Adam DeHavenon ◽  
Matthew D Alexander ◽  
Scott McNally ◽  
Jeffrey Anderson ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
White Matter ◽  
Pilot Study ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Temperature Management ◽  
Control Group ◽  
Swine Model ◽  
Neuroprotective Strategy

Introduction: Reperfusion/ischemic brain injury following arrest is a major cause of death/disability among patients surviving to admission. Aside from targeted temperature management, no proven neuroprotective strategies exist. Melatonin (anti-epileptic/antioxidant) and ketamine (glutamate inhibitor), along with controlled reintroduction of oxygenated blood have been proposed to reduce secondary injury. Hypothesis: We hypothesized that a combination of above therapies would reduce the ischemic burden measured on MRI following cardiac arrest if administered upon initial reperfusion. Methods: 6 swine underwent isoflurane anesthesia and control MRI (DTI b2000/20 directions, DSC). Swine were randomized to fixed periods of cardiac arrest (2 swine to 20 min and 1 to 30 min in both control and treated groups), and ECMO catheters placed in the distal aorta and right atrium, then ventricular fibrillation induced by a bipolar pacing catheter. Following ischemia, swine were reperfused at 2.8-3.5 L/min with either unblended oxygenated blood in the control group, or 21% oxygenated blood increased to 30% after 4 minutes and then titrated to maintain PaO2 of 80-100 mm Hg, melatonin 5 mg/kg bolus then 5 mg/kg/hr and ketamine 4 mg/kg/hr for 2 hours in the treated group. After 4 min swine were defibrillated until return of heartbeat. Animals were weaned from pump, decannulated, and epinephrine and fluid boluses administered for hemodynamic support, then re-imaged within 2 hours post-resuscitation using same protocol. Whole brain ADC measurements were performed on gray and white matter. Frontal lobe regions of interest drawn for DSC perfusion parameters. Results: Baseline hemodynamic parameters: BP, Heart Rate, End-Tidal CO2, and SpO2 were similar between animals. There was no difference in percent change ADC in gray or white matter between treated and untreated swine (p=0.9), or difference in CBV (p=0.67). CBF showed an upward trend in treated animals (p=0.17). Conclusions: A multimodal neuroprotective strategy of melatonin, ketamine, and controlled reoxygenation failed to demonstrate measurable impact on MRI markers of ischemia-reperfusion injury in this pilot study. The translation of promising neuroprotectants might be triaged using the employed model.

Abstract 138: Remote Ischemic Postconditioning Alleviates Postresuscitation Inflammatory Response and Pulmonary Edema in a Porcine Model of Cardiac Arrest

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jiefeng Xu ◽  
Sen Ye ◽  
Zilong Li ◽  
Moli Wang ◽  
Zhengquan Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Inflammatory Response ◽  
Pulmonary Edema ◽  
Porcine Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Limb Ischemia ◽  
Multiple Organ ◽  
Control Group ◽  
Lung Water

Introduction: Systemic ischemia-reperfusion injury produced by CA and resuscitation can result in severe post-cardiac arrest syndrome; which includes systemic inflammatory response and multiple organ dysfunction syndrome such as acute pulmonary edema. We previously demonstrated that remote ischemic post-conditioning (RIpostC) improved post-resuscitation myocardial and cerebral function in a rat model of CA. In this study, we investigated the effects of RIpostC on inflammatory response and pulmonary edema after CPR in a porcine model. Hypothesis: RIpostC would alleviate post-resuscitation inflammatory response and pulmonary edema in a porcine model of CA. Methods: Fourteen male domestic pigs weighing 37 ± 2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. The animals were then randomized to receive RIpostC or control. Coincident with the start of CPR, RIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results: Six of the seven animals in each group were successfully resuscitated. After resuscitation, significantly lower levels of tumor necrosis factor-α and interleukin-6 were measured in the animals that received RIpostC when compared with the control group. Post-resuscitation extra-vascular lung water index was lower in the RIpostC group than in the control group; in which the differences were significant at 2,3 and 4 hrs (Table). Conclusion: In a porcine model of CA, RIpostC significantly alleviates post-resuscitation inflammatory response and pulmonary edema.

scholarly journals Effects of Thyroid Hormone Analogue and a Leukotrienes Pathway-Blocker on Reperfusion Injury Attenuation after Heart Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Fadhil G. Al-Amran ◽  
Najah R. Hadi ◽  
Haider S. H. Al-Qassam
Keyword(s):  
Myocardial Ischemia ◽  
Heart Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Control Group ◽  
Group I ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Background. Global myocardial ischemia reperfusion injury after heart transplantation is believed to impair graft function and aggravate both acute and chronic rejection episodes. Objectives. To assess the possible protective potential of MK-886 and 3,5-diiodothyropropionic acid DITPA against global myocardial ischemia reperfusion injury after heart transplantation. Materials and Methods. Adult albino rats were randomized into 6 groups as follows: group I sham group; group II, control group; groups III and IV, control vehicles (1,2); group V, MK-886 treated group. Donor rats received MK-886 30 min before transplantation, and the same dose was repeated for recipients upon reperfusion; in group VI, DITPA treated group, donors and recipients rats were pretreated with DITPA for 7 days before transplantation. Results. Both MK-886 and DITPA significantly counteract the increase in the levels of cardiac TNF-α, IL-1β, and ICAM-1 and plasma level of cTnI (). Morphologic analysis showed that both MK-886 and DITPA markedly improved () the severity of cardiac injury in the heterotopically transplanted rats. Conclusions. The results of our study reveal that both MK-886 and DITPA may ameliorate global myocardial ischemia reperfusion injury after heart transplantation via interfering with inflammatory pathway.

scholarly journals Pediatric Cardiac Arrest

2020 ◽  
Author(s):  
Priscilla Yu ◽  
Ivie D. Esangbedo ◽  
Lakshmi Raman ◽  
Cindy Darnell Bowens
Keyword(s):  
Cardiac Arrest ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Temperature Management ◽  
Patient Centered ◽  
Recent Developments ◽  
Cpr Quality ◽  
Current Guidelines

This chapter will focus on four important topics in pediatric cardiac arrest. We will highlight recent developments in pediatric CPR quality, medications used in cardiac arrest, ECPR, and post-cardiac arrest care (PCAC) and discuss the existing literature behind AHA guidelines and gaps in knowledge. Optimization of CPR quality is critical during cardiac arrest. We will summarize literature regarding current guidelines which target provider-centered goals and discuss evidence behind patient-centered goals. We will also discuss the evidence behind drugs used in the PALS guidelines. In cases of refractory cardiac arrest, ECMO can be lifesaving; however, there are still many gaps in our knowledge of this field. We will summarize the literature regarding determination of candidacy, cannulation strategies, resuscitation practices during ECPR, and outcomes. After a cardiac arrest, PCAC is crucial to minimize further injury from post-cardiac arrest syndrome (PCAS). The main goals of PCAC are to prevent further brain injury, treat myocardial dysfunction, and systemic ischemia/reperfusion injury. We will discuss AHA guidelines on oxygenation and ventilation goals, targeted temperature management, hemodynamic monitoring, and neuromonitoring.

scholarly journals Change and significance of the expression of c-kit and SCF following recovery from unilateral testicular torsion in rats

2008 ◽  
Vol 31 (3) ◽  
pp. 98 ◽  
Author(s):  
Yi Guan ◽  
XinMin Zheng ◽  
ZhiWei Yang ◽  
ShiWen Li
Keyword(s):  
Germ Cells ◽  
Testicular Torsion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Torsion Group ◽  
Treated Group ◽  
Pcr Analysis ◽  
Control Group ◽  
Sham Operation ◽  
Expression Levels

Purpose: To investigate the change in expression levels of c-kit and SCF, and the protective effects of FSH on ischemia-reperfusion injury due to testicular torsion-detorsion. Methods: 24 adult male SD rats were divided into three groups of 8: control group, testicular torsion group and FSH-treated group. The control group was treated with sham-operation. Animals in the testicular torsion and FSH-treated groups were subjected to unilateral 720°counterclockwise testicular torsion for 2 hours and then reperfusion was allowed after detorsion. The FSH-treated group received intraperitoneal injection of FSH 15min before detorsion. Then, the rats were sacrificed and the testes were harvested. Histopathological changes were observed by light microscope, and the expression levels of c-kit, SCF in testicular tissue in the different groups were detected by Immunohistochemical assay and Quantitative Real-time RT-PCR analysis. Finally, the relative proportions of germ cells were measured by FCM. Results: c-kit and SCF were positive expressed in 52.58% and 61.16% of testicular cells of control tissues, respectively. Decreases of c-kit and SCF positive cells (15.01% and 9.18%) were found in the testicular torsion group. After being treated by FSH, the number of positive cells increased (31.25% and 20.01%). Moreover, the c-kit and SCF mRNA expression was increased dramatically (P < 0.01) in response to FSH stimulation. Furthermore, the number of haploid, diploid and tetraploid cells has also increased significantly in drug-treated testes (P < 0.01). Conclusion: The mechanism of tissue damage in the testicular torsion model, includes changes in the expression of c-kit and SCF following torsion. Also, FSH has a protective effect on germ cells after unilateral testicular torsion, which was reflected by increased c-kit and SCF levels.

Abstract 296: Adult Swine Model of Ventricular Fibrillation Arrest for Resuscitation with Perfluorocarbon Emulsions

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Travis W Murphy ◽  
Jiepei Zhu ◽  
Travis Parsons ◽  
Bruce D Spiess ◽  
Torben K Becker
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Minimally Invasive ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Circulatory Arrest ◽  
Spontaneous Circulation ◽  
Blood Levels ◽  
Swine Model ◽  
Initial Attempt

Background: The purpose of this study was to develop a model of ventricular fibrillation arrest with reliable outcomes and minimally invasive methods to study the use of perfluorocarbon emulsions (PFC) as agents to prevent ischemia-reperfusion injury after cardiac arrest as quantified by known biomarkers. Methods: Female Yorkshire swine underwent anesthesia and minimally invasive instrumentation for monitoring under ultrasound. Cardiac arrest was induced with spinal needle insertion at the apex and right parasternal space. Ventricular fibrillation was reliably obtained in all animals on initial attempts. A three-minute circulatory arrest state was observed. Administration of PFC was concurrent with resuscitation including closed chest compressions, epinephrine, amiodarone, and defibrillation at 1J/kg. Primary endpoint was induction of cardiac arrest and tolerance of PFC with return of spontaneous circulation. Blood levels of glial fibrillary acidic protein (GFAP) and ubiquitin C-Terminal Hydrolase-L1 (UCLH1) were secondary end points for three animals. Results: Six of six animals were induced into ventricular fibrillation on initial attempt and two of three survival experiments were able to obtain spontaneous circulation. PFC with pretreatment was tolerated well and no signs of increased pulmonary pressures. GFAP, UCHL1 were significantly lower in intervention animals compared to controls. Conclusions: The results obtained from this preliminary study and technical refinements via additional donated animals have allowed us to make modifications in the choice of PFC, vascular access, and anticoagulation plan. This model provides a consistent method for inducing ventricular fibrillation with minimally invasive techniques. The PFC tested was well tolerated. More robust evaluation of PFC as resuscitative agents is needed with appropriately powered studies.

Methionine protects from myocardial ischemia/reperfusion injury

2014 ◽  
Vol 2 (2) ◽  
pp. 87-97
Keyword(s):  
Reperfusion Injury ◽  
Surgical Procedure ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Treated Group ◽  
Control Group ◽  
Control Groups ◽  
Severity Scores

Ischemia-reperfusion of cardiac tissues may lead to a prominent damage of the myocyte through either necrosis or apoptosis that seems to be the predominant modes of death during this period. In this study, we investigated the effects of L-Methionine in regional ischemia/ reperfusion injury and apoptosis. Dwale-sprague rats were divided into four groups (six rats per group). Sham group, rats were subjected for all surgical procedure without ligation of the left interior descending coronary artery (LAD). Control group, in which LAD was ligated. Control vehicle and L-methionine treated groups, rats pretreated with normal saline and L-methionine (100 mg/kg, IP ), respectively, for 7 days then subjected to the surgical procedure with ligation of LAD for 25 minutes followed by 120 minutes reperfusion. At the end of reperfusion, cardiac tissue TNF-α, IL-1β, IL-6 and ssDNA, as well as plasma cardiac troponin I (cTnI) were measured. It has been found that L-methionine treated group showed significant reduction (P˂0.05) in TNFα, IL-1β, IL-6, ssDNA and cTnI with respect to the control groups. Histopathology study revealed that the treatment with L-methionine significantly (P˂0.05) improved cardiac injury as compared with control groups and the total severity scores showed that the cardiac injury was mild (score 1) in 50.0%, moderate (score 2) in 33.3% and sever (score 3) in 16.7% of L-methionine treated group. It is concluded that L-methionine reduces inflammatory reaction associated with ischemia/reperfusion injury induced by LAD ligation in addition to its reduction for cardiac injury induced by ischemia reperfusion.

The Role of Inflammatory Cytokines in Cardiac Arrest

2018 ◽  
Vol 35 (3) ◽  
pp. 219-224 ◽  
Author(s):  
Christopher Jou ◽  
Rian Shah ◽  
Andrew Figueroa ◽  
Jignesh K. Patel
Keyword(s):  
Cardiac Arrest ◽  
Reperfusion Injury ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Brain Dysfunction ◽  
Medical Intervention ◽  
Temperature Management

Introduction: Post-cardiac arrest syndrome (PCAS) is characterized by systemic ischemia/reperfusion injury, anoxic brain injury, and post-arrest myocardial dysfunction superimposed on a precipitating pathology. The role of inflammatory cytokines in cardiac arrest remains unclear. Aims: We aimed to describe, with an emphasis on clinical applications, what is known about the role of inflammatory cytokines in cardiac arrest. Data Sources: A PubMed literature review was performed for relevant articles. Only articles in English that studied cytokines in patients with cardiac arrest were included. Results: Cytokines play a crucial role in the pathogenesis of PCAS. Following cardiac arrest, the large release of circulating cytokines mediates the ischemia/reperfusion injury, brain dysfunction, and myocardial dysfunction seen. Interleukins, tumor necrosis factor, and matrix metalloproteinases all play a unique prognostic role in PCAS. High levels of inflammatory cytokines have been associated with mortality and/or poor neurologic outcomes. Interventions to modify the systemic inflammation seen in PCAS continue to be heavily studied. Currently, the only approved medical intervention for comatose patients following cardiac arrest is targeted temperature management. Medical agents, including minocycline and sodium sulfide, have demonstrated promise in animal models. Conclusions: The role of inflammatory cytokines for both short- and long-term outcomes is an important area for future investigation.

Protective Effects of Atractylodes macrocephala Polysaccharide on Liver Ischemia–Reperfusion Injury and Its Possible Mechanism in Rats

2011 ◽  
Vol 39 (03) ◽  
pp. 489-502 ◽  
Author(s):  
Cheng Jin ◽  
Pei-Jian Zhang ◽  
Chuan-Qing Bao ◽  
Yuan-Long Gu ◽  
Bing-Hua Xu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Normal Control ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Normal Control Group ◽  
Control Group ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Atractylodes Macrocephala

Atractylodes macrocephala polysaccharide (AMP), a traditional Chinese medicine, is thought to have protective effects against liver injury. Therefore, this study was designed to explore the effects of AMP on hepatic ischemia–reperfusion injury (IRI) and elucidate the possible mechanisms. Ninety-six Sprague-Dawley rats were randomly divided into four groups with 24 rats per group: a normal control group, an IRI group, an AMP-treated group (0.4 g/kg/d) and a bifendate-treated group (100 mg/kg). Rats were treated with AMP or bifendate once daily for seven days by gastric gavage. The normal control group and the IRI model group received an equivalent volume of physiological saline. At 1, 6 and 24 h after surgery, the rats were killed and liver tissue samples were obtained to determine interleukin-1 (IL-1) expression by Western blotting and nuclear factor-κB (NF-κB) expression by immunohistochemistry. Liver morphology was assessed by microscopy and transmission electron microscopy. Blood samples were obtained to measure liver function (alanine aminotransferase, aspartate aminotransferase, total bilirubin and direct bilirubin). AMP significantly reduced the elevated expression of markers of liver dysfunction and the hepatic morphologic changes induced by hepatic IRI in rats. AMP also markedly inhibited IRI-induced lipid peroxidation and altered the activities of the antioxidant enzyme superoxide dismutase and malondialdehyde levels. Moreover, pretreatment with AMP suppressed the expression of interleukin-1β and NF-kB in IRI-treated rats. These results suggest that AMP exerts protective and therapeutic effects against hepatic IRI in rats, which might be associated with its antioxidant properties and inhibition of NF-κB activation. More studies are needed to better understand the mechanisms underlying the protective effects of AMP on hepatic IRI.

scholarly journals Mild Hypothermia Inhibits Systemic and Cerebral Complement Activation in a Swine Model of Cardiac Arrest

2015 ◽  
Vol 35 (8) ◽  
pp. 1289-1295 ◽  
Author(s):  
Ping Gong ◽  
g Zhao ◽  
Rong Hua ◽  
Mingyue Zhang ◽  
Ziren Tang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Complement Activation ◽  
Ischemia Reperfusion Injury ◽  
Mild Hypothermia ◽  
Ischemia Reperfusion ◽  
Spontaneous Circulation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Swine Model ◽  
Factor Α ◽  
Necrosis Factor

Complement activation has been implicated in ischemia/reperfusion injury. This study aimed to determine whether mild hypothermia (HT) inhibits systemic and cerebral complement activation after resuscitation from cardiac arrest. Sixteen minipigs resuscitated from 8 minutes of untreated ventricular fibrillation were randomized into two groups: HT group ( n = 8), treated with HT (33 °C) for 12 hours; and normothermia group ( n = 8), treated similarly as HT group except for cooling. Blood samples were collected at baseline and 0.5, 6, 12, and 24 hours after return of spontaneous circulation (ROSC). The brain cortex was harvested 24 hours after ROSC. Complement and pro-inflammatory markers were detected using enzyme-linked immunosorbent assay. Neurologic deficit scores were evaluated 24 hours after ROSC. C1q, Bb, mannose-binding lectin (MBL), C3b, C3a, C5a, interleukin-6, and tumor necrosis factor- α levels were significantly increased under normothermia within 24 hours after ROSC. However, these increases were significantly reduced by HT. Hypothermia decreased brain C1q, MBL, C3b, and C5a contents 24 hours after ROSC. Hypothermic pigs had a better neurologic outcome than normothermic pigs. In conclusion, complement is activated through classic, alternative, and MBL pathways after ROSC. Hypothermia inhibits systemic and cerebral complement activation, which may provide an additional mechanism of cerebral protection.

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