Immune cell expression patterns of CD39/CD73 ectonucleotidases in rodent models of cardiac arrest and resuscitation.

Background: Cardiac arrest (CA) is a significant public health concern. There is the high imminent mortality and survival in those who are resuscitated is substantively compromised by the post-CA syndrome (PCAS), characterized by multiorgan ischemia-reperfusion injury (IRI). The inflammatory response in PCAS is complex and involves various immune cell types, including lymphocytes and myeloid cells that have been shown to exacerbate organ IRI, such as myocardial infarction. Purinergic signaling, as regulated by CD39 and CD73, has emerged as centrally important in the context of organ-specific IRI. Hence, comprehensive understanding of such purinergic responses may be likewise imperative for improving outcomes in PCAS. Methods: We have investigated alterations of immune cell populations after CA by utilizing rodent models of PCAS. Blood and spleen were collected after CA and resuscitation and underwent flow cytometry analysis to evaluate shifts in CD3+CD4+ helper T cells, CD3+CD8a+ cytotoxic T cells, and CD4/CD8a ratios. We then examined the expression of CD39 and CD73 across diverse cell types, including myeloid cells, T lymphocytes, and B lymphocytes. Results: In both rat and mouse models, there were significant increases in the frequency of CD3+CD4+ T lymphocytes in PCAS (rat, P < 0.01; mouse, P < 0.001), with consequently elevated CD4/CD8a ratios in whole blood (both, P < 0.001). Moreover, CD39 and CD73 expression on blood leukocytes were markedly increased (rat, P < 0.05; mouse, P < 0.01 at 24h). Further analysis in the experimental mouse model revealed that CD11b+ myeloid cells, with significant increase in their population (P < 0.01), had high level of CD39 (88.80 ± 2.05 %) and increased expression of CD73 (P < 0.05). CD19+ B lymphocytes showed slight increases of CD39 (P < 0.05 at 2h) and CD73 (P < 0.05 at 2h), while, CD3+ T lymphocytes had decreased levels of them. These findings suggested a distinct patterns of expression of CD39 and CD73 in these specific immune cell populations after CA. Conclusions: These data have provided comprehensive insights into the immune response after CA, highlighting high-level expressions of CD39 and CD73 in myeloid cells.

Association of tissue oxygen saturation levels with skeletal muscle injury in the critically ill.

This study aimed to investigate the association between the level of tissue oxygen saturation (StO2) and quadriceps/skeletal muscle dysfunction, measured using the Medical Research Council (MRC) scale and ultrasonography, in critically ill patients. Thirty-four patients hospitalized at the Critical Care Medicine Center of Kindai University Hospital, between January 2022 and March 2023, were enrolled in this study. The StO2 of the quadriceps muscle was measured via near-infrared spectroscopy. Muscle atrophy was measured by the thickness, cross-sectional area (CSA), and echo intensity of the rectus femoris (RF). These values were evaluated every alternate day until 13 days after admission or until discharge, whichever occurred first. Muscle weakness was assessed using the sum score of the MRC scale (MRC-SS), with the patient sitting at bedside. The mean age of the patients was 67.3 ± 15.3 years, and 20 (59%) were men. Seven patients (21%) were admitted for trauma, and 27 (79%) were admitted for medical emergencies or others. The mean score for the MRC-SS was 51.0 ± 7.9 points. RF thickness and CSA significantly decreased after day 7 (p < 0.05). There were no significant changes in StO2 levels during hospitalization. However, there were positive correlations between the nadir StO2 during hospitalization and MRC-SS, and changes in RF thickness and CSA at discharge (r = 0.41, p = 0.03; r = 0.37, p = 0.03; and r = 0.35, p = 0.05, respectively). StO2 in the quadriceps muscle may be useful for predicting muscle atrophy and dysfunction in patients with critical illnesses.

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.

Life-Threatening Hematuria as Initial Presentation of a Complicated Transplant Renal Artery Pseudoaneurysm.

In this case report, we describe the clinical course of a complicated transplant renal artery (TRA) pseudoaneurysm, clinically featured by gross and massive hematuria one month after a kidney transplant was performed on a 50 year-old male patient. TRA pseudoaneurysm is a rare but potentially life-threatening complication that may result in bleeding, infection, graft dysfunction/loss, lower limb ischemia/loss, hemorrhagic shock, and death. TRA pseudoaneurysm treatment remains challenging as it needs to be tailored to the patient characteristics including hemodynamic stability, graft function, anatomy, presentation, and pseudoaneurysm features. This publication discusses the clinical scenario of massive gross hematuria that derived from a retroperitoneal hematoma which originated from an actively bleeding TRA pseudoaneurysm. This case highlights the combined approach of endovascular stent placement and subsequent transplant nephrectomy as a last resort in the management of intractable bleeding from a complicated TRA pseudoaneurysm. To the best of our knowledge, this is the first published case report of an actively bleeding TRA anastomotic pseudoaneurysm that caused a massive retroperitoneal bleed that in turn evacuated via the bladder after disrupting the ureter-to-bladder anastomosis. A temporizing hemostatic arterial stent placed percutaneously allowed for a safer and controlled emergency transplant nephrectomy.

COVID-19-Associated Portal Vein Thrombosis Post-Cholecystitis.

This case study describes a 45-year-old Caucasian male with a past medical history of obesity, hypertension, and non-insulin-dependent diabetes mellitus, who in the setting of coronavirus disease 2019 (COVID-19) pneumonia, developed portal vein thrombosis (PVT) presenting as an acute abdomen after hospital discharge from a cholecystitis episode. PVT is a very infrequent thromboembolic condition, classically occurring in patients with systemic conditions such as cirrhosis, malignancy, pancreatitis, diverticulitis, autoimmunity, and thrombophilia. PVT can cause serious complications, such as intestinal infarction, or even death, if not promptly treated. Due to the limited number of reports in the literature describing PVT in the COVID-19 setting, its prevalence, natural history, mechanism, and precise clinical features remain unknown. Therefore, clinical suspicion should be high for PVT, in any COVID-19 patient who presents with abdominal pain or associated signs and symptoms. To the best of our knowledge, this is the first report of COVID-19-associated PVT causing extensive thrombosis in the portal vein and its right branch, occurring in the setting of early-stage cirrhosis after a preceding episode of cholecystitis.

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.

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.

Intracranial Hypertension following Acute Mesenteric Ischemia: A Case Study on the Multiple Compartment Syndrome.

In this case study, we describe a 25-year-old male who was admitted due to a severe traumatic brain injury, requiring invasive intracranial pressure monitoring. At 48 hours posttrauma, he developed intracranial hypertension refractory to medical treatment without tomographic changes in the brain. Subsequently, intra-abdominal hypertension and tomographic signs of abdominal surgical pathology were observed. An exploratory laparotomy was performed with an intraoperative diagnosis of acute mesenteric ischemia. After surgical intervention for the abdominal pathology, intracranial pressure was restored to physiological values with a favorable recovery of the patient. In this report, the relationship between intracranial pressure and intra-abdominal pressure is discussed, highlighting the delicate association between the brain, abdomen, and thorax. Measures should be taken to avoid increases in intra-abdominal pressure in neurocritical patients. When treating intracranial hypertension refractory to conventional measures, abdominal causes and multiple compartment syndrome must be considered. The cranial compartment has physiological interdependence with other body compartments, where one can be modified by variations from another, giving rise to the concept of multiple compartment syndrome. Understanding this relationship is fundamental for a comprehensive approach of the neurocritical patient. To the best of our knowledge, this is the first report of a comatose patient post-traumatic brain injury, who developed medically unresponsive intracranial hypertension secondary to acute mesenteric ischemia, in which surgical resolution of intra-abdominal pathology resulted in intracranial pressure normalization and restitutio ad integrum of neurological status.

Continuously increased generation of ROS in human plasma after cardiac arrest as determined by Amplex Red oxidation.

Oxidative stress is believed to be a major cause of injury after cardiac arrest (CA). While the effects of ROS generated within tissues have been extensively investigated, the potential of plasma-generated ROS in contributing to CA pathology has not been examined. We utilized Amplex Red (AR) to measure the real time-generation of ROS in isolated plasma from human CA patients. We first used post-CA rat plasma to identify interfering factors for AR oxidation, and then applied this knowledge to analyze human plasma samples, accounting for the identified confounders. We found significantly increased AR oxidation rates lasting for 4 h in post-CA rat plasma compared to baseline. AR oxidation was unchanged with removal of horseradish peroxidase or addition of catalase. However, adding carboxylesterase inhibitors significantly decreased AR oxidation in rat plasma, which implicated increased carboxylesterase activity, not ROS leading to increased AR oxidation. AR oxidation rates were also significantly increased in human CA patient plasma compared to control and this increase persisted even with carboxylesterase inhibition, suggesting continuously increased ROS-generation within plasma post-CA in humans. The increased ROS generation may be one major source of injury post-CA that may be mitigated with antioxidative therapeutic strategies that can manage the ROS systemically generated in plasma over time.KEY POLICY HIGHLIGHTSWe examined the potential of plasma as a source of ROS generation post-cardiac arrestRat cardiac arrest was used to guide the application of Amplex Red in human plasmaROS generation in plasma is significantly increased after cardiac arrest in humansScavenging excessive ROS in post-resuscitation plasma may improve outcomes of patients.

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.

Machine learning algorithms for predicting days of high incidence for out-of-hospital cardiac arrest.

Predicting out-of-hospital cardiac arrest (OHCA) events might improve outcomes of OHCA patients. We hypothesized that machine learning algorithms using meteorological information would predict OHCA incidences. We used the Japanese population-based repository database of OHCA and weather information. The Tokyo data (2005-2012) was used as the training cohort and datasets of the top six populated prefectures (2013-2015) as the test. Eight various algorithms were evaluated to predict the high-incidence OHCA days, defined as the daily events exceeding 75% tile of our dataset, using meteorological and chronological values: temperature, humidity, air pressure, months, days, national holidays, the day before the holidays, the day after the holidays, and New Year's holidays. Additionally, we evaluated the contribution of each feature by Shapley Additive exPlanations (SHAP) values. The training cohort included 96,597 OHCA patients. The eXtreme Gradient Boosting (XGBoost) had the highest area under the receiver operating curve (AUROC) of 0.906 (95% confidence interval; 0.868-0.944). In the test cohorts, the XGBoost algorithms also had high AUROC (0.862-0.923). The SHAP values indicated that the "mean temperature on the previous day" impacted the most on the model. Algorithms using machine learning with meteorological and chronological information could predict OHCA events accurately.

Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents.

BACKGROUND: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia-reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. RESULTS: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. CONCLUSIONS: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest.

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.

External Stenting (Exostenting) to Correct Vascular Torsion and Angulation.

Organ transplantation can be associated with vascular torsions and angulations of both recipient and donor vessels. Such kinks and/or torsions of vessels can compromise the vascular integrity, obstruct inflow and/or outflow, and result in loss of the organ and/or body parts. On many occasions, mild angulations and torsions can be successfully addressed by repositioning the organ. In cases where the abnormal findings persist, maneuvers such as placing a fat pad to create a smoother curve, or even opening the peritoneum (in the case of kidney transplants) to allow for a better positioning of the organ, are associated with successful outcomes. When such torsions/angulations persist despite these approaches, further innovative tactics are required. In the current report, we propose a technique that involves longitudinally opening of a synthetic graft that is rigid enough to maintain its shape, such as a ringed polytetrafluoroethylene graft, and placing it as an external stent around the angulated/torsioned vessel. This maneuver will correct the underlying vascular compromise without having to perform any further invasive interventions, such as reimplanting the organ or resecting part of the involved vessel. Although primarily illustrated for application by describing an instance in which exostenting was applied during kidney transplantation, our approach could be applied to any vessel under many circumstances where angulations/twists are encountered. In this report, we describe the use of an external stent, also called exostenting, to correct a severe torsion/angulation of the external iliac artery in a kidney transplant recipient where all other measures were unsuccessful.

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.

Bio-physiological susceptibility of the brain, heart, and lungs to systemic ischemia reperfusion and hyperoxia-induced injury in post-cardiac arrest rats.

Cardiac arrest (CA) patients suffer from systemic ischemia-reperfusion (IR) injury leading to multiple organ failure; however, few studies have focused on tissue-specific pathophysiological responses to IR-induced oxidative stress. Herein, we investigated biological and physiological parameters of the brain and heart, and we particularly focused on the lung dysfunction that has not been well studied to date. We aimed to understand tissue-specific susceptibility to oxidative stress and tested how oxygen concentrations in the post-resuscitation setting would affect outcomes. Rats were resuscitated from 10 min of asphyxia CA. Mechanical ventilation was initiated at the beginning of cardiopulmonary resuscitation. We examined animals with or without CA, and those were further divided into the animals exposed to 100% oxygen (CA_Hypero) or those with 30% oxygen (CA_Normo) for 2 h after resuscitation. Biological and physiological parameters of the brain, heart, and lungs were assessed. The brain and lung functions were decreased after CA and resuscitation indicated by worse modified neurological score as compared to baseline (222 ± 33 vs. 500 ± 0, P < 0.05), and decreased PaO2 (20 min after resuscitation: 113 ± 9 vs. baseline: 128 ± 9 mmHg, P < 0.05) and increased airway pressure (2 h: 10.3 ± 0.3 vs. baseline: 8.1 ± 0.2 mmHg, P < 0.001), whereas the heart function measured by echocardiography did not show significant differences compared before and after CA (ejection fraction, 24 h: 77.9 ± 3.3% vs. baseline: 82.2 ± 1.9%, P = 0.2886; fractional shortening, 24 h: 42.9 ± 3.1% vs. baseline: 45.7 ± 1.9%, P = 0.4658). Likewise, increases of superoxide production in the brain and lungs were remarkable, while those in the heart were moderate. mRNA gene expression analysis revealed that CA_Hypero group had increases in Il1b as compared to CA_Normo group significantly in the brain (P < 0.01) and lungs (P < 0.001) but not the heart (P = 0.4848). Similarly, hyperoxia-induced increases in other inflammatory and apoptotic mRNA gene expression were observed in the brain, whereas no differences were found in the heart. Upon systemic IR injury initiated by asphyxia CA, hyperoxia-induced injury exacerbated inflammation/apoptosis signals in the brain and lungs but might not affect the heart. Hyperoxia following asphyxia CA is more damaging to the brain and lungs but not the heart.

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.

An Automation System Equivalent to the Douglas Bag Technique Enables Continuous and Repeat Metabolic Measurements in Patients Undergoing Mechanical Ventilation.

PURPOSE: To develop a system that is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (V̇o2), carbon dioxide generation (V̇co2), and respiratory quotient (RQ) and to validate its use in clinical settings. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Healthy volunteers and patients 18 years or older who received mechanical ventilation were enrolled. FINDINGS: Data from 3 healthy volunteers and 7 patients were analyzed in this study. The interrater reliability between the automation device and DB methods were 0.999, 0.993, and 0.993 for V̇o2, V̇co2, and RQ, respectively. In healthy volunteers, mean (SD) V̇o2, V̇co2, and RQ measured by DB were 411 (100) mL/min, 288 (79) mL/min, and 0.70 (0.03) at high fraction of inspired oxygen (Fio2) and 323 (46) mL/min, 280 (45) mL/min, and 0.85 (0.05) at normal Fio2, respectively. V̇o2 was significantly higher (P < 0.05) and RQ was lower (P < 0.01) in the high Fio2 group as compared to those in the normal Fio2 group. Values measured by the automation system were 227 (31) mL/min, 141 (18) mL/min, and 0.62 (0.04) at high Fio2 and 209 (25) mL/min, 147 (18) mL/min, and 0.70 (0.06) at normal Fio2, respectively. RQ was significantly lower (P < 0.05) in the high Fio2 group as compared to the normal Fio2 group. We also successfully performed continuous and repeat measurements by using the device. The longest measurement reached 12 hours 15 minutes, including 50 cycles of repeat measurements that are equivalent to the DB technique as described above. IMPLICATIONS: We developed an automation system that enables repeat measurements of V̇o2, V̇co2, and RQ, and the accuracy was equivalent to the DB technique. High Fio2 may decrease RQ because of an increase in V̇o2.