Abstract 14456: Rethinking The Treatment Of Cardiac Arrest To Include Non-oxygen Metabolite Supplementation: Plasma Lysophosphatidylcholine Level Maintenance After Cardiac Arrest Is Critical For Survival

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Muhammad Shoaib ◽  
Mitsuaki Nishikimi ◽  
Rishabh Choudhary ◽  
Tai Yin ◽  
Kei Hayashida ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Membrane Integrity ◽  
Whole Body ◽  
Strongly Correlated ◽  
Oxygen Metabolites ◽  
Subsequent Resuscitation

Cardiac arrest (CA) is a loss of circulation that curtails the supply of oxygen and non-oxygen metabolites to the whole body resulting in ischemia and death. Subsequent resuscitation is vital for survival, but also causes reperfusion injury. Oxygen deprivation as one arm of ischemia-reperfusion injury and its relationship with death is well-established, but its counterpart, metabolite dysfunction, is overlooked and poorly understood. We have previously shown that many metabolites are not normalized as efficiently or rapidly after resuscitation especially, particularly those that are severely decreased after CA. As such, we hypothesize that appropriate replenishment of certain metabolites is essential for survival. Lysophosphatidylcholine (LPC), an important family of phospholipids, is an example of such non-oxygen metabolites required post-CA. With multifactorial roles for maintaining homeostasis, such as acting as an energy substrate, maintaining membrane integrity, and functioning in inter- and intra-cellular signaling, decreased levels of LPC post-CA disrupts the various physiologic responsibilities resulting in profound systemic effects causing cellular and organ system injury. In this analysis, 1) phospholipid screening using HPLS-MS on plasma samples obtained from asphyxial-CA rats and human CA patients shows that LPC significantly decreases post-CA, especially during the reperfusion phase, and is strongly correlated with the duration of preceding CA and poor neurological/survival outcomes, and 2) individual supplementation of three species of LPC (LPC 18:0, LPC 18:1, and LPC 22:6) following resuscitation after 10 and 12 min rat CA helps improve survival and brain function as compared with vehicle. Overall, our study highlights that LPC is an essential, non-oxygen metabolite that is necessary to help promote survival after CA in rats that has therapeutic potential for human translation.

scholarly journals Inhaled Gases as Therapies for Post–Cardiac Arrest Syndrome: A Narrative Review of Recent Developments

2021 ◽  
Vol 7 ◽  
Author(s):  
Kei Hayashida ◽  
Santiago J. Miyara ◽  
Koichiro Shinozaki ◽  
Ryosuke Takegawa ◽  
Tai Yin ◽  
...  
Keyword(s):  
Cell Death ◽  
Cardiac Arrest ◽  
Reperfusion Injury ◽  
Protein Modification ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Whole Body ◽  
Gas Treatment ◽  
Neurologic Sequelae ◽  
Post Cardiac Arrest Syndrome

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 (H2), and xenon (Xe) have attracted much attention. Herein, we summarize recent literature on the application of NO, H2, 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.

scholarly journals Therapeutic Potential of Selenium as a Component of Preservation Solutions for Kidney Transplantation

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3592
Author(s):  
Aneta Ostróżka-Cieślik ◽  
Barbara Dolińska ◽  
Florian Ryszka
Keyword(s):  
Reperfusion Injury ◽  
Activity Concentration ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Preservation Solution ◽  
Kidney Preservation ◽  
Preservation Solutions ◽  
Metabolic Reduction

Selenium has strong antioxidant properties and diverse effects on the immune system. The aim of the study was to analyse the protective effect of selenium as a component of a kidney preservation solution on the prevention of ischemia-reperfusion injury of nephrons. The solution was modified by the addition of Se (1 µg/L), prolactin (0.1 µg/L) and Se with prolactin (1 µg/L Se + 0.1 µg/L PRL). The study used a model for storing isolated porcine kidneys in Biolasol® (modified Biolasol®), which minimizes ischemia-reperfusion injury of grafts. The introduction of Se4+ ions at a dose of 1 µg/L into the Biolasol® preservation solution in the form of Na2SeO3 caused an increase in the activity/concentration of the analysed biochemical parameters: aspartate transaminase, alanine transaminase, urea and protein. This suggests an adverse effect of Se4+ on nephron function during ischemia-reperfusion. The best graft protection was obtained by using Biolasol® modified with the addition of selenium (IV) at a dose of 1 µg/L and prolactin at a concentration of 0.1 µg/L. We proposed the mechanism of prolactin action in the metabolic reduction of selenite (SO32−) during ischemia/reperfusion.

Effect of 3-aminotriazole on hyperthermia-mediated cardioprotection in rabbits

1996 ◽  
Vol 270 (4) ◽  
pp. H1165-H1171 ◽  
Author(s):  
J. G. Kingma ◽  
D. Simard ◽  
J. R. Rouleau ◽  
R. M. Tanguay ◽  
R. W. Currie
Keyword(s):  
Reperfusion Injury ◽  
Catalase Activity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Whole Body ◽  
Cellular Protection ◽  
Whole Body Hyperthermia ◽  
Tetrazolium Staining

Hyperthermia-induced cardioprotection during myocardial ischemia may involve increased activity of antioxidative enzymes. In this study we investigated the effects of 3-amino-1,2,4-triazole (3-AT), an irreversible catalase inhibitor, in heat-shocked (HS) rabbits subjected to ischemia-reperfusion injury. Rabbits underwent whole body hyperthermia at 42 degrees C for 15 min. Twenty-four hours later, rabbits were administered either saline vehicle or 3-AT (1 or 2 g/kg i.p.) 30 min before undergoing 30 min of regional coronary occlusion and 3 h reperfusion. Controls did not undergo whole body hyperthermia and were given either saline or 3-AT. Heart rate and left ventricular pressure were recorded continuously during these experiments. Infarct area (tetrazolium staining) was normalized to anatomic risk zone size (microsphere autoradiography). Expression of HSP 71 was verified using Western blot analysis; myocardial catalase activity was determined in tissue biopsies. Infarct size was significantly reduced in HS rabbits (25.1 +/- 2.8%, P = 0.2; means +/- SE) compared with controls (53.6 +/- 4.7%). Treatment with 1 g/kg 3-AT attenuated HS-mediated cardioprotection (36.9 +/- 4.9%, P = 0.063 vs. HS); protection was abolished with 2 g/kg 3-AT (48.9 +/- 6.6%). Myocardial catalase activities were higher in tissue biopsies from HS rabbits (47.0 +/- 4.5 U/mg protein, P < or = 0.02) compared with controls (33.4 +/- 1.9 U/mg protein); catalase activities were significantly reduced in rabbits treated with 3-AT. In conclusion, whole body hyperthermia increases expression levels of HSP 71; myocardial catalase activity is also significantly increased. Myocardial protection is HS rabbits subjected to ischemia-reperfusion injury was reversed with 3-AT. These data suggest that increased intracellular activities of catalase and possibly other antioxidant enzymes is an important mechanism for hyperthermia-mediated cellular protection.

scholarly journals Inhibition of Myocardial Ischemia/Reperfusion Injury by Exosomes Secreted from Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Heng Zhang ◽  
Meng Xiang ◽  
Dan Meng ◽  
Ning Sun ◽  
Sifeng Chen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Left Ventricle ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Area At Risk

Exosomes secreted by mesenchymal stem cells have shown great therapeutic potential in regenerative medicine. In this study, we performed meta-analysis to assess the clinical effectiveness of using exosomes in ischemia/reperfusion injury based on the reports published between January 2000 and September 2015 and indexed in the PUBMED and Web of Science databases. The effect of exosomes on heart function was evaluated according to the following parameters: the area at risk as a percentage of the left ventricle, infarct size as a percentage of the area at risk, infarct size as a percentage of the left ventricle, left ventricular ejection fraction, left ventricular fraction shortening, end-diastolic volume, and end-systolic volume. Our analysis indicated that the currently available evidence confirmed the therapeutic potential of mesenchymal stem cell-secreted exosomes in the improvement of heart function. However, further mechanistic studies, therapeutic safety, and clinical trials are required for optimization and validation of this approach to cardiac regeneration after ischemia/reperfusion injury.

Chronic activation of PPARα is detrimental to cardiac recovery after ischemia

2006 ◽  
Vol 290 (1) ◽  
pp. H87-H95 ◽  
Author(s):  
Nandakumar Sambandam ◽  
Dominique Morabito ◽  
Cory Wagg ◽  
Brian N. Finck ◽  
Daniel P. Kelly ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Glucose Oxidation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Fatty Acid ◽  
Whole Body ◽  
Cardiac Recovery ◽  
Oxidation Rates ◽  
Cardiac Power ◽  
Chronic Activation

High fatty acid oxidation (FAO) rates contribute to ischemia-reperfusion injury of the myocardium. Because peroxisome proliferator-activated receptor (PPAR)α regulates transcription of several FAO enzymes in the heart, we examined the response of mice with cardiac-restricted overexpression of PPARα (MHC-PPARα) or whole body PPARα deletion including the heart (PPARα−/−) to myocardial ischemia-reperfusion injury. Isolated working hearts from MHC-PPARα and nontransgenic (NTG) littermates were subjected to no-flow global ischemia followed by reperfusion. MHC-PPARα hearts had significantly higher FAO rates during aerobic and postischemic reperfusion (aerobic 1,479 ± 171 vs. 699 ± 117, reperfusion 1,062 ± 214 vs. 601 ± 70 nmol·g dry wt−1·min−1; P < 0.05) and significantly lower glucose oxidation rates compared with NTG hearts (aerobic 225 ± 36 vs. 1,563 ± 165, reperfusion 402 ± 54 vs. 1,758 ± 165 nmol·g dry wt−1·min−1; P < 0.05). In hearts from PPARα−/− mice, FAO was significantly lower during aerobic and reperfusion (aerobic 235 ± 36 vs. 442 ± 75, reperfusion 205 ± 25 vs. 346 ± 38 nmol·g dry wt−1·min−1; P < 0.05) whereas glucose oxidation was significantly higher compared with wild-type (WT) hearts (aerobic 2,491 ± 631 vs. 901 ± 119, reperfusion 2,690 ± 562 vs. 1,315 ± 172 nmol·g dry wt−1·min−1; P < 0.05). Increased FAO rates in MHC-PPARα hearts were associated with a markedly lower recovery of cardiac power (45 ± 9% vs. 71 ± 6% of preischemic levels in NTG hearts; P < 0.05). In contrast, the percent recovery of cardiac power of PPARα−/− hearts was not significantly different from that of WT hearts (80 ± 8% vs. 75 ± 9%). This study demonstrates that chronic activation of PPARα is detrimental to the cardiac recovery during reperfusion after ischemia.

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