The American Heart Association Emergency Cardiovascular Care 2030 Impact Goals and Call to Action to Improve Cardiac Arrest Outcomes: A Scientific Statement From the American Heart Association.

Every 10 years, the American Heart Association (AHA) Emergency Cardiovascular Care Committee establishes goals to improve survival from cardiac arrest. These goals align with broader AHA Impact Goals and support the AHA's advocacy efforts and strategic investments in research, education, clinical care, and quality improvement programs. This scientific statement focuses on 2030 AHA emergency cardiovascular care priorities, with a specific focus on bystander cardiopulmonary resuscitation, early defibrillation, and neurologically intact survival. This scientific statement also includes aspirational goals, such as establishing cardiac arrest as a reportable disease and mandating reporting of standardized outcomes from different sources; advancing recognition of and knowledge about cardiac arrest; improving dispatch system response, availability, and access to resuscitation training in multiple settings and at multiple time points; improving availability, access, and affordability of defibrillators; providing a focus on early defibrillation, in-hospital programs, and establishing champions for debriefing and review of cardiac arrest events; and expanding measures to track outcomes beyond survival. The ability to track and report data from these broader aspirational targets will potentially require expansion of existing data sets, development of new data sets, and enhanced integration of technology to collect process and outcome data, as well as partnerships of the AHA with national, state, and local organizations. The COVID-19 (coronavirus disease 2019) pandemic, disparities in COVID-19 outcomes for historically excluded racial and ethnic groups, and the longstanding disparities in cardiac arrest treatment and outcomes for Black and Hispanic or Latino populations also contributed to an explicit focus and target on equity for the AHA Emergency Cardiovascular Care 2030 Impact Goals.

Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

Therapeutic potential of mitochondrial transplantation in modulating immune responses post-cardiac arrest: a narrative review.

BACKGROUND: Mitochondrial transplantation (MTx) has emerged as a novel therapeutic strategy, particularly effective in diseases characterized by mitochondrial dysfunction. This review synthesizes current knowledge on MTx, focusing on its role in modulating immune responses and explores its potential in treating post-cardiac arrest syndrome (PCAS). METHODS: We conducted a comprehensive narrative review of animal and human studies that have investigated the effects of MTx in the context of immunomodulation. This included a review of the immune responses following critical condition such as ischemia reperfusion injury, the impact of MTx on these responses, and the therapeutic potential of MTx in various conditions. RESULTS: Recent studies indicate that MTx can modulate complex immune responses and reduce ischemia-reperfusion injury post-CA, suggesting MTx as a novel, potentially more effective approach. The review highlights the role of MTx in immune modulation, its potential synergistic effects with existing treatments such as therapeutic hypothermia, and the need for further research to optimize its application in PCAS. The safety and efficacy of autologous versus allogeneic MTx, particularly in the context of immune reactions, are critical areas for future investigation. CONCLUSION: MTx represents a promising frontier in the treatment of PCAS, offering a novel approach to modulate immune responses and restore cellular energetics. Future research should focus on long-term effects, combination therapies, and personalized medicine approaches to fully harness the potential of MTx in improving patient outcomes in PCAS.

Insufficient oxygen inhalation during cardiopulmonary resuscitation induces early changes in hemodynamics followed by late and unfavorable systemic responses in post-cardiac arrest rats.

Cardiac arrest (CA) and concomitant post-CA syndrome lead to a lethal condition characterized by systemic ischemia-reperfusion injury. Oxygen (O2 ) supply during cardiopulmonary resuscitation (CPR) is the key to success in resuscitation, but sustained hyperoxia can produce toxic effects post CA. However, only few studies have investigated the optimal duration and dosage of O2 administration. Herein, we aimed to determine whether high concentrations of O2 at resuscitation are beneficial or harmful. After rats were resuscitated from the 10-min asphyxia, mechanical ventilation was restarted at an FIO2 of 1.0 or 0.3. From 10 min after initiating CPR, FIO2 of both groups were maintained at 0.3. Bio-physiological parameters including O2 consumption (VO2 ) and mRNA gene expression in multiple organs were evaluated. The FIO2 0.3 group decreased VO2 , delayed the time required to achieve peak MAP, lowered ejection fraction (75.1 ± 3.3% and 59.0 ± 5.7% with FIO2 1.0 and 0.3, respectively; p < .05), and increased blood lactate levels (4.9 ± 0.2 mmol/L and 5.6 ± 0.2 mmol/L, respectively; p < .05) at 10 min after CPR. FIO2 0.3 group had significant increases in hypoxia-inducible factor, inflammatory, and apoptosis-related mRNA gene expression in the brain. Likewise, significant upregulations of hypoxia-inducible factor and apoptosis-related gene expression were observed in the FIO2 0.3 group in the heart and lungs. Insufficient O2 supplementation in the first 10 min of resuscitation could prolong ischemia, and may result in unfavorable biological responses 2 h after CA. Faster recovery from the impairment of O2 metabolism might contribute to the improvement of hemodynamics during the early post-resuscitation phase; therefore, it may be reasonable to provide the maximum feasible O2 concentrations during CPR.

Low respiratory quotient correlates with high mortality in patients undergoing mechanical ventilation.

OBJECTIVE: Oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), which is the ratio of VO2 to VCO2, are critical indicators of human metabolism. To seek a link between the patient's metabolism and pathophysiology of critical illness, we investigated the correlation of these values with mortality in critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older healthy volunteers and patients who underwent mechanical ventilation were enrolled. A high-fidelity automation device, which accuracy is equivalent to the gold standard Douglas Bag technique, was used to measure VO2, VCO2, and RQ at a wide range of fraction of inspired oxygen (FIO2). RESULTS: We included a total of 21 subjects including 8 post-cardiothoracic surgery patients, 7 intensive care patients, 3 patients from the emergency room, and 3 healthy volunteers. This study included 10 critical care patients, whose metabolic measurements were performed in the ER and ICU, and 6 died. VO2, VCO2, and RQ of survivors were 282 +/- 95 mL/min, 202 +/- 81 mL/min, and 0.70 +/- 0.10, and those of non-survivors were 240 +/- 87 mL/min, 140 +/- 66 mL/min, and 0.57 +/- 0.08 (p = 0.34, p = 0.10, and p < 0.01), respectively. The difference of RQ was statistically significant (p < 0.01) and it remained significant when the subjects with FIO2 < 0.5 were excluded (p < 0.05). CONCLUSIONS: Low RQ correlated with high mortality, which may potentially indicate a decompensation of the oxygen metabolism in critically ill patients.

Hyperoxia-Induced Secondary Respiratory Failure in a Systemic Ischaemia-Reperfusion Injury.

Recent studies revealed that excessive supplemental oxygen, such as inhaled 100% O2, damages various organ functions in post-cardiac arrest (CA) patients. Optimal indicators of supplemental oxygen are therefore important to prevent hyperoxic organ injuries. In this study, we evaluated a hyperoxic pulmonary injury and assessed the association between alveolar-arterial oxygen difference (AaDO2) and a degree of lung oedema. In this study, we focused on the hyperoxia-induced lung injury and its association with changes of gas-exchange parameters in post-CA rats. Rats were resuscitated from 10 min of asphyxial CA and stratified into two groups: those with inhaled 100% O2 (CA-FiO2 1.0) and those with 30% O2 (CA-FiO2 0.3). We prepared a sham surgery group for comparison (sham-FiO2 0.3). After 2 h, animals were sacrificed, and the lung wet-to-dry (W/D) weight ratio was measured. We collected blood gas results and measured the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (p/f ratio), and calculated AaDO2. The lung W/D ratio in the CA-FiO2 1.0 group (5.8 ± 0.26) was higher than in the CA-FiO2 0.3 (4.6 ± 0.42) and sham-FiO2 0.3 groups (4.6 ± 0.38, p < 0.01). There was a significant difference in AaDO2 between CA-FiO2 1.0 (215 ± 49.3) and, CA-FiO2 0.3 (36.8 ± 32.3), and sham-FiO2 0.3 groups (49.0 ± 20.5, p < 0.01). There were also significant changes in pH and blood lactate levels in the early phase among the three groups. AaDO2 showed the strongest correlation with W/D ratio (r = 0.9415, p < 0.0001), followed by pH (r = -0.5131, p = 0.0294) and p/f ratio (r = -0.3861, p = 0.1135). Hyperoxic injury might cause the pulmonary oedema after CA. Measuring respiratory quotient (RQ) in rodents enabled an accurate calculation for AaDO2 at a variety level of inhaled O2. Given that AaDO2 measurement is non-invasive, we therefore consider AaDO2 to be a potentially optimal indicator of post-CA hyperoxic pulmonary injury.

Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma-Brain Disjunction.

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models.

The Role of Phospholipid Alterations in Mitochondrial and Brain Dysfunction after Cardiac Arrest.

The human brain possesses three predominate phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS), which account for approximately 35-40%, 35-40%, and 20% of the brain's phospholipids, respectively. Mitochondrial membranes are relatively diverse, containing the aforementioned PC, PE, and PS, as well as phosphatidylinositol (PI) and phosphatidic acid (PA); however, cardiolipin (CL) and phosphatidylglycerol (PG) are exclusively present in mitochondrial membranes. These phospholipid interactions play an essential role in mitochondrial fusion and fission dynamics, leading to the maintenance of mitochondrial structural and signaling pathways. The essential nature of these phospholipids is demonstrated through the inability of mitochondria to tolerate alteration in these specific phospholipids, with changes leading to mitochondrial damage resulting in neural degeneration. This review will emphasize how the structure of phospholipids relates to their physiologic function, how their metabolism facilitates signaling, and the role of organ- and mitochondria-specific phospholipid compositions. Finally, we will discuss the effects of global ischemia and reperfusion on organ- and mitochondria-specific phospholipids alongside the novel therapeutics that may protect against injury.

Exogenous mitochondrial transplantation improves survival and neurological outcomes after resuscitation from cardiac arrest.

BACKGROUND: Mitochondrial transplantation (MTx) is an emerging but poorly understood technology with the potential to mitigate severe ischemia-reperfusion injuries after cardiac arrest (CA). To address critical gaps in the current knowledge, we test the hypothesis that MTx can improve outcomes after CA resuscitation. METHODS: This study consists of both in vitro and in vivo studies. We initially examined the migration of exogenous mitochondria into primary neural cell culture in vitro. Exogenous mitochondria extracted from the brain and muscle tissues of donor rats and endogenous mitochondria in the neural cells were separately labeled before co-culture. After a period of 24 h following co-culture, mitochondrial transfer was observed using microscopy. In vitro adenosine triphosphate (ATP) contents were assessed between freshly isolated and frozen-thawed mitochondria to compare their effects on survival. Our main study was an in vivo rat model of CA in which rats were subjected to 10 min of asphyxial CA followed by resuscitation. At the time of achieving successful resuscitation, rats were randomly assigned into one of three groups of intravenous injections: vehicle, frozen-thawed, or fresh viable mitochondria. During 72 h post-CA, the therapeutic efficacy of MTx was assessed by comparison of survival rates. The persistence of labeled donor mitochondria within critical organs of recipient animals 24 h post-CA was visualized via microscopy. RESULTS: The donated mitochondria were successfully taken up into cultured neural cells. Transferred exogenous mitochondria co-localized with endogenous mitochondria inside neural cells. ATP content in fresh mitochondria was approximately four times higher than in frozen-thawed mitochondria. In the in vivo survival study, freshly isolated functional mitochondria, but not frozen-thawed mitochondria, significantly increased 72-h survival from 55 to 91% (P = 0.048 vs. vehicle). The beneficial effects on survival were associated with improvements in rapid recovery of arterial lactate and glucose levels, cerebral microcirculation, lung edema, and neurological function. Labeled mitochondria were observed inside the vital organs of the surviving rats 24 h post-CA. CONCLUSIONS: MTx performed immediately after resuscitation improved survival and neurological recovery in post-CA rats. These results provide a foundation for future studies to promote the development of MTx as a novel therapeutic strategy to save lives currently lost after CA.

Preserving Brain LPC-DHA by Plasma Supplementation Attenuates Brain Injury after Cardiac Arrest.

OBJECTIVE: Cardiac arrest (CA) is a major health burden with brain damage being a significant contributor to mortality. We found lysophosphatidylcholine (LPC), including a species containing docosahexaenoic acid (LPC-DHA), was significantly decreased in plasma post-CA, supplementation of which significantly improved neurological outcomes. The aim of this study is to understand the protective role of LPC-DHA supplementation on the brain post-CA. METHODS: We first evaluated associations between the plasma level of LPC-DHA and neurological injury and outcomes of human patients with CA. We then utilized a rat CA model and cell cultures to investigate therapeutic and mechanistic aspects of plasma LPC-DHA supplementation. RESULTS: We found that decreased plasma LPC-DHA was strongly associated with neurological outcomes and disappearance of the difference between gray and white matter in the brain after CA in human patients. In rats, the decreased plasma LPC-DHA was associated with decreased levels of brain LPC-DHA after CA, and supplementing plasma LPC-DHA normalized brain levels of LPC-DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes. We also observed deceased severity of metabolic alterations with LPC-DHA supplementation using untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures. INTERPRETATION: The observed neuroprotection accompanied with normalized brain LPC-DHA level by plasma supplementation implicate the importance of preventing the decrease of brain LPC-DHA post-CA for attenuating brain injury. Furthermore, the data supports the causative role of decreased plasma LPC-DHA for brain damage after CA. ANN NEUROL 2022;91:389-403.

Metformin-mediated mitochondrial protection post-cardiac arrest improves EEG activity and confers neuroprotection and survival benefit.

Cardiac arrest (CA) produces global ischemia/reperfusion injury resulting in substantial multiorgan damage. There are limited efficacious therapies to save lives despite CA being such a lethal disease process. The small population of surviving patients suffer extensive brain damage that results in substantial morbidity. Mitochondrial dysfunction in most organs after CA has been implicated as a major source of injury. Metformin, a first-line treatment for diabetes, has shown promising results in the treatment for other diseases and is known to interact with the mitochondria. For the treatment of CA, prior studies have utilized metformin in a preconditioning manner such that animals are given metformin well before undergoing CA. As the timing of CA is quite difficult to predict, the present study, in a clinically relevant manner, sought to evaluate the therapeutic benefits of metformin administration immediately after resuscitation using a 10 min asphxyial-CA rat model. This is the first study to show that metformin treatment post-CA (a) improves 72 h survival and neurologic function, (b) protects mitochondrial function with a reduction in apoptotic brain injury without activating AMPK, and (c) potentiates earlier normalization of brain electrophysiologic activity. Overall, as an effective and safe drug, metformin has the potential to be an easily translatable intervention for improving survival and preventing brain damage after CA.

The role of pyruvate-induced enhancement of oxygen metabolism in extracellular purinergic signaling in the post-cardiac arrest rat model.

Purine nucleotide adenosine triphosphate (ATP) is a source of intracellular energy maintained by mitochondrial oxidative phosphorylation. However, when released from ischemic cells into the extracellular space, they act as death-signaling molecules (eATP). Despite there being potential benefit in using pyruvate to enhance mitochondria by inducing a highly oxidative metabolic state, its association with eATP levels is still poorly understood. Therefore, while we hypothesized that pyruvate could beneficially increase intracellular ATP with the enhancement of mitochondrial function after cardiac arrest (CA), our main focus was whether a proportion of the raised intracellular ATP would detrimentally leak out into the extracellular space. As indicated by the increased levels in systemic oxygen consumption, intravenous administrations of bolus (500 mg/kg) and continuous infusion (1000 mg/kg/h) of pyruvate successfully increased oxygen metabolism in post 10-min CA rats. Plasma ATP levels increased significantly from 67 ± 11 nM before CA to 227 ± 103 nM 2 h after the resuscitation; however, pyruvate administration did not affect post-CA ATP levels. Notably, pyruvate improved post-CA cardiac contraction and acidemia (low pH). We also found that pyruvate increased systemic CO2 production post-CA. These data support that pyruvate has therapeutic potential for improving CA outcomes by enhancing oxygen and energy metabolism in the brain and heart and attenuating intracellular hydrogen ion disorders, but does not exacerbate the death-signaling of eATP in the blood.

The association between specific narrative elements and patient perspectives on acute pain treatment.

BACKGROUND: Narratives are effective tools for communicating with patients about opioid prescribing for acute pain and improving patient satisfaction with pain management. It remains unclear, however, whether specific narrative elements may be particularly effective at influencing patient perspectives. METHODS: This study was a secondary analysis of data collected for Life STORRIED, a multicenter RCT. Participants included 433 patients between 18 and 70 years-old presenting to the emergency department (ED) with renal colic or musculoskeletal back pain. Participants were instructed to view one or more narrative videos during their ED visit in which a patient storyteller discussed their experiences with opioids. We examined associations between exposure to individual narrative features and patients' 1) preference for opioids, 2) recall of opioid-related risks and 3) perspectives about the care they received. RESULTS: Participants were more likely to watch videos featuring storytellers who shared their race or gender. We found that participants who watched videos that contained specific narrative elements, for example mention of prescribed opioids, were more likely to recall having received information about pain treatment options on the day after discharge (86.3% versus 72.9%, p = 0.02). Participants who watched a video that discussed family history of addiction reported more participation in their treatment decision than those who did not (7.6 versus 6.8 on a ten-point scale, p = 0.04). CONCLUSIONS: Participants preferentially view narratives featuring storytellers who share their race or gender. Narrative elements were not meaningfully associated with patient-centered outcomes. These findings have implications for the design of narrative communication tools.

Continuous and repeat metabolic measurements compared between post-cardiothoracic surgery and critical care patients.

OBJECTIVE: Using a system, which accuracy is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), we aimed to continuously measure these metabolic indicators and compare the values between post-cardiothoracic surgery and critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older patients who underwent mechanical ventilation were enrolled. RESULTS: We included 4 post-surgery and 6 critical care patients. Of those, 3 critical care patients died. The longest measurement reached to 12 h and 15 min and 50 cycles of repeat measurements were performed. VO2 of the post-surgery patients were 234 ± 14, 262 ± 27, 212 ± 16, and 192 ± 20 mL/min, and those of critical care patients were 122 ± 20, 189 ± 9, 191 ± 7, 191 ± 24, 212 ± 12, and 135 ± 21 mL/min, respectively. The value of VO2 was more variable in the post-surgery patients and the range of each patient was 44, 126, 71, and 67, respectively. SOFA scores were higher in non-survivors and there were negative correlations of RQ with SOFA. CONCLUSIONS: We developed an accurate system that enables continuous and repeat measurements of VO2, VCO2, and RQ. Critical care patients may have less activity in metabolism represented by less variable values of VO2 and VCO2 over time as compared to those of post-cardiothoracic surgery patients. Additionally, an alteration of these values may mean a systemic distinction of the metabolism of critically ill patients.

Insufficient Oxygen Supplementation During Cardiopulmonary Resuscitation Leads to Unfavorable Biological Response While Hyperoxygenation Contributes to Metabolic Compensation.

Sudden cardiac arrest (CA) is the third leading cause of death. Immediate reoxygenation with high concentrations of supplemental oxygen (O2) during cardiopulmonary resuscitation (CPR) is recommended according to the current guidelines for adult CA. However, a point in controversy exists because of the known harm of prolonged exposure to 100% O2. Therefore, there have been much debate on an optimal use of supplemental O2, yet little is known about the duration and dosage of O2 administration. To test whether supplying a high concentration of O2 during CPR and post resuscitation is beneficial or harmful, rats subjected to 10-minute asphyxia CA were administered either 100% O2 (n = 8) or 30% O2 (n = 8) for 2 hours after CPR. Two hours after initiating CPR, the brain, lung, and heart tissues were collected to compare mRNA gene expression levels of inflammatory cytokines, apoptotic and oxidative stress-related markers. The 100% O2 group had significantly shorter time to return of spontaneous circulation (ROSC) than the 30% O2 group (62.9 ± 2.2 and 77.5 ± 5.9 seconds, respectively, P < 0.05). Arterial blood gas analysis revealed that the 100% O2 group had significantly higher PaCO2 (49.4 ± 4.9 mmHg and 43.0 ± 3.0 mmHg, P < 0.01), TCO2 (29.8 ± 2.7 and 26.6 ± 1.1 mmol/L, P < 0.05), HCO3- (28.1 ± 2.4 and 25.4 ± 1.2 mmol/L, P < 0.05), and BE (2.6 ± 2.3 and 0.1 ± 1.4 mmol/L, P < 0.05) at 2 hours after initiating CPR, but no changes in pH (7.37 ± 0.03 and 7.38 ± 0.03, ns). Inflammation- (Il6, Tnf) and apoptosis- (Casp3) related mRNA gene expression levels were significantly low in the 100% O2 group in the brain, however, oxidative stress moderator Hmox1 increased in the 100% O2 group. Likewise, mRNA gene expression of Icam1, Casp9, Bcl2, and Bax were low in the 100% O2 group in the lung. Contrarily, mRNA gene expression of Il1b and Icam1 were low in the 30% O2 group in the heart. Supplying 30% O2 during and after CPR significantly delayed the time to ROSC and increased inflammation-/apoptosis- related gene expression in the brain and lung, indicating that insufficient O2 was associated with unfavorable biological responses post CA, while prolonged exposure to high-concentration O2 should be still cautious in general.

Neurological Improvement via Lysophosphatidic Acid Administration in a Rodent Model of Cardiac Arrest-Induced Brain Injury.

Lysophosphatidic acid (LPA) serves as a fundamental constituent of phospholipids. While prior studies have shown detrimental effects of LPA in a range of pathological conditions, including brain ischemia, no studies have explored the impact of LPA in the context of cardiac arrest (CA). The aim of this study is to evaluate the effects of the intravenous administration of an LPA species containing oleic acid, LPA (18:1) on the neurological function of rats (male, Sprague Dawley) following 8 min of asphyxial CA. Baseline characteristics, including body weight, surgical procedure time, and vital signs before cardiac arrest, were similar between LPA (18:1)-treated (n = 10) and vehicle-treated (n = 10) groups. There was no statistically significant difference in 24 h survival between the two groups. However, LPA (18:1)-treated rats exhibited significantly improved neurological function at 24 h examination (LPA (18:1), 85.4% ± 3.1 vs. vehicle, 74.0% ± 3.3, p = 0.045). This difference was most apparent in the retention of coordination ability in the LPA (18:1) group (LPA (18:1), 71.9% ± 7.4 vs. vehicle, 25.0% ± 9.1, p < 0.001). Overall, LPA (18:1) administration in post-cardiac arrest rats significantly improved neurological function, especially coordination ability at 24 h after cardiac arrest. LPA (18:1) has the potential to serve as a novel therapeutic in cardiac arrest.

Cardiopulmonary resuscitation in special circumstances.

Cardiopulmonary resuscitation prioritises treatment for cardiac arrests from a primary cardiac cause, which make up the majority of treated cardiac arrests. Early chest compressions and, when indicated, a defibrillation shock from a bystander give the best chance of survival with a good neurological status. Cardiac arrest can also be caused by special circumstances, such as asphyxia, trauma, pulmonary embolism, accidental hypothermia, anaphylaxis, or COVID-19, and during pregnancy or perioperatively. Cardiac arrests in these circumstances represent an increasing proportion of all treated cardiac arrests, often have a preventable cause, and require additional interventions to correct a reversible cause during resuscitation. The evidence for treating these conditions is mostly of low or very low certainty and further studies are needed. Irrespective of the cause, treatments for cardiac arrest are time sensitive and most effective when given early-every minute counts.

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

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.

Diagnostic value of transpulmonary thermodilution measurements for acute respiratory distress syndrome in a pig model of septic shock.

BACKGROUND: No direct approach assessing pulmonary vascular permeability exists in the current therapeutic strategy for patients with acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution measures hemodynamic parameters such as pulmonary vascular permeability index and extravascular lung water, enabling clinicians to assess ARDS severity. The aim of this study is to explore a precise transpulmonary thermodilution-based criteria for quantifying the severity of lung injury using a clinically relevant septic-ARDS pig model. METHODS: Thirteen female pigs (weight: 31 ± 2 kg) were intubated, mechanically ventilated under anesthesia, and either assigned to septic shock-induced ARDS or control group. To confirm the development of ARDS, we performed computed tomography (CT) imaging in randomly selected animals. The pulmonary vascular permeability index, extravascular lung water, and other hemodynamic parameters were consecutively measured during the development of septic lung injury. Lung status was categorized as normal (partial pressure of oxygen/fraction of inspired oxygen ≥ 400), or injured at different degrees: pre-ARDS (300-400), mild-to-moderate ARDS (100-300), or severe ARDS (< 100). We also measured serum inflammatory cytokines and high mobility group box 1 levels during the experiment to explore the relationship of the pulmonary vascular permeability index with these inflammatory markers. RESULTS: Using CT image, we verified that animals subjected to ARDS presented an extent of consolidation in bilateral gravitationally dependent gradient that expands over time, with diffuse ground-glass opacification. Further, the post-mortem histopathological analysis for lung tissue identified the key features of diffuse alveolar damage in all animals subjected to ARDS. Both pulmonary vascular permeability index and extravascular lung water increased significantly, according to disease severity. Receiver operating characteristic analysis demonstrated that a cut-off value of 3.9 for the permeability index provided optimal sensitivity and specificity for predicting severe ARDS (area under the curve: 0.99, 95% confidence interval, 0.98-1.00; sensitivity = 100%, and specificity = 92.5%). The pulmonary vascular permeability index was superior in its diagnostic value than extravascular lung water. Furthermore, the pulmonary vascular permeability index was significantly associated with multiple parameters reflecting clinicopathological changes in animals with ARDS. CONCLUSION: The pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.

Oxyhaemoglobin Level Measured Using Near-Infrared Spectrometer Is Associated with Brain Mitochondrial Dysfunction After Cardiac Arrest in Rats.

Cerebral blood oxygenation (CBO), measured using near-infrared spectroscopy (NIRS), can play an important role in post-cardiac arrest (CA) care as this emerging technology allows for noninvasive real-time monitoring of the dynamic changes of tissue oxygenation. We recently reported that oxyhaemoglobin (oxy-Hb), measured using NIRS, may be used to evaluate the quality of chest compressions by monitoring the brain tissue oxygenation, which is a critical component for successful resuscitation. Mitochondria are the key to understanding the pathophysiology of post-CA oxygen metabolism. In this study, we focused on mitochondrial dysfunction, aiming to explore its association with CBO parameters such as oxy-Hb and deoxyhaemoglobin (deoxy-Hb) or tissue oxygenation index (TOI). Male Sprague-Dawley rats were used in the study. We applied NIRS between the nasion and the upper cervical spine. Following 10 min of CA, the rats underwent cardiopulmonary resuscitation (CPR) with a bolus injection of 20 µg/kg epinephrine. At 10 and 20 min after CPR, brain, and kidney tissues were collected. We isolated mitochondria from these tissues and evaluated the association between CBO and mitochondrial oxygen consumption ratios. There were no significant differences in the mitochondrial yields (10 vs. 20 min after resuscitation: brain, 1.33 ± 0.68 vs. 1.30 ± 0.75 mg/g; kidney, 19.5 ± 3.2 vs. 16.9 ± 5.3 mg/g, respectively). State 3 mitochondrial oxygen consumption rates, known as ADP-stimulated respiration, demonstrated a significant difference at 10 vs. 20 min after CPR (brain, 170 ± 26 vs. 115 ± 17 nmol/min/mg protein; kidney, 170 ± 20 vs. 130 ± 16 nmol/min/mg protein, respectively), whereas there was no significant difference in ADP non-dependent state 4 oxygen consumption rates (brain, 34.0 ± 6.7 vs. 31.8 ± 10 nmol/min/mg protein; kidney, 29.8 ± 4.8 vs. 21.0 ± 2.6 nmol/min/mg protein, respectively). Consequently, the respiratory control ratio (RCR = state 3/state 4) showed a significant difference over time, but this was only noted in the brain (brain, 5.0 ± 0.29 vs. 3.8 ± 0.64; kidney, 5.8 ± 0.53 vs. 6.2 ± 0.25 nmol/min/mg protein, respectively). The oxy-Hb levels had a dynamic change after resuscitation, and they had a significant association with the RCR of the brain mitochondria (r = 0.8311, p = 0.0102), whereas deoxy-Hb and TOI did not (r = -0.1252, p = 0.7677; r = 0.4186, p = 0.302, respectively). The RCRs of the kidney mitochondria did not have a significant association with CBO (oxy-Hb, r = -0.1087, p = 0.7977; deoxy-Hb, r = 0.1565, p = 0.7113; TOI, r = -0.1687, p = 0.6896, respectively). The brain mitochondrial respiratory dysfunction occurred over time, and it was seen at the time points between 10 and 20 min after CPR. The oxy-Hb level was associated with brain mitochondrial dysfunction during the early post-resuscitation period.