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.

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.

Postcoiling syndrome including headache and fever after endovascular cerebral aneurysmal coil embolization: A narrative review.

Endovascular cerebral aneurysmal coil embolization is becoming more popular than direct aneurysmal neck clipping due to its noninferiority in long-term outcomes and being less invasive. Neuroradiologists often find postoperative symptoms such as headache and fever after unruptured aneurysmal coil embolization, however, they have not paid much attention because symptoms almost always resolve spontaneously within a few days. Since the concept of this syndrome has not been standardized, we named it postcoiling syndrome (PCS). In this short review, we reviewed the criteria, risk factors, mechanisms, significance, and treatment of PCS based on a few pieces of literature. Almost all literature has regarded that some kind of bioactive reaction might be involved in PCS. Preliminary data showed the possibility of inhibition of PCS by histamine-2 receptor antagonists. PCS also might have the potential of more predictive maker than previously reported risk factors for recurrence after aneurysm coil embolization. Further investigation is needed in the future, including the accumulation of cases, unification of concepts, and mid-to-long-term follow-up.

Inverted gull-wing hinge decompressive craniotomy for infantile acute subdural hematoma: A case report.

Infantile severe acute subdural hematomas (ASDHs) usually require a decompressive craniotomy. However, these infantile patients often suffer surgical site infection and aseptic bone-flap resorption after external decompression. In this report, we showed a case of a simplified hinge decompressive craniotomy in an infant with severe ASDH. A 2-month-old girl suffered from status epilepticus, impaired consciousness, multiple rib fractures, bilateral fundus hemorrhage, and a right ASDH. We performed a simplified hinge decompressive craniotomy, making a vascularized bone flap with a hinge using the partial temporal bone and temporal muscle and not fixing the bone flap like an inverted gull wing. Cranioplasty was performed 4 weeks after the decompression craniotomy with replaced resorbable substitute dura. Six months after the transfer, her development was generally in line with her age. The decompressive craniotomy with an inverted gull-wing hinge has shown a good outcome.

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.

A Case of Intracranial Vertebral Artery Stenosis Treated with Percutaneous Transluminal Angioplasty and Stenting Guided by Brain Oximetry.

Surgical treatment should be considered for patients with severe vertebrobasilar artery (VBA) stenosis or progressive symptoms, but there is currently no clear treatment algorithm. We report a case of symptomatic intracranial vertebral artery stenosis with repeated cerebral infarction treated by percutaneous transluminal angioplasty (PTA) and stenting and monitoring of oxygen saturation by a brain oximeter. The patient was a 76-year-old man referred to our hospital due to infarction in the right cerebellum. Angiography showed 60% stenosis in the right vertebral artery and 90% stenosis in the left vertebral artery with progressive stenosis in the left. The patient was treated with intravenous and oral triple antiplatelet therapy but had dizziness again with new cerebral infarctions in the left cerebellum and right pontine. We shaved the patient's hair up to the superior nuchal line and placed left and right oximeter probes on each cerebellar hemisphere (2 cm lateral and 2 cm caudal from the external occipital protuberance). Under evaluation of blood flow in the posterior circulation with INVOS Cerebral/Somatic Oximeter, PTA and stent placement were performed for left vertebral artery stenosis. Postoperatively, the dizziness disappeared, and the patient was discharged on his own with good outcome. He has not had a recurrent stroke in over 6 years. Although medical treatment is generally considered the first choice for VBA stenosis, recurrent cerebral infarction occurs at a high rate in symptomatic lesions, and the prognosis is poor. In addition, the perioperative complication rate is not low, and there is no established method for evaluating perfusion of posterior circulation. The brain oximeter is already known to be useful in carotid artery (CA) revascularisation. In this report, we were able to perform a minimally invasive evaluation of blood flow in the posterior circulation using the brain oximeter which might be useful for surgical revascularisation not only in CA but also in VBA.

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.

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.

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

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

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

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

Near-Infrared Spectroscopy Might Help Prevent Onset of Cerebral Hyperperfusion Syndrome.

Cerebral hyperperfusion syndrome (CHS) is a rare but fatal perioperative complication after surgical correction of carotid stenosis. Despite numerous treatment options for preventing CHS, it does occur in some patients. We developed the outlet gate technique (OGT), in which the embolic balloon was deflated gradually in accordance with the ratio of oxygen saturation measured by a brain oximeter of the ipsilateral brain region to that in the contralateral region. Between June 2017 and May 2018, 39 patients with carotid stenosis underwent endovascular carotid revascularization procedures; of these, 20 underwent the procedure with the OGT. CBO was measured five times in those 20 patients: before the procedure, with the embolic protection device (EPD) on, with the EPD off, during the procedure, and after the procedure. Preventive treatment options were used more frequently in these patients, and although their surgical status seemed more complicated, perioperative complications were not increased. There were almost significant differences between CBO values except between those during and after the procedure with the OGT. This showed that the OGT allowed for stabilization of the CBO and thus has the potential to prevent CHS.

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

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

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

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

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

Clinical investigators have focused on the real-time evaluation of cerebral blood oxygenation (CBO) by near-infrared spectroscopy (NIRS) during cardiopulmonary resuscitation (CPR). A previous study showed that an abrupt increase of oxy-hemoglobin (Hb) level and tissue oxygenation index (TOI) was associated with the timing of return of spontaneous circulation (ROSC). However, it is not clear how TOI alters before and after CPR including a period of cardiac arrest (CA). Therefore, this study aimed to assess CBO with asphyxia CA and its association with CPR to ROSC in rats. Male Sprague-Dawley rats were used. We attached NIRS (NIRO-200NX, Hamamatsu Photonics, Japan) from the nasion to the upper cervical spine in rats. A ten-minute asphyxia was given to induce CA. After CA, mechanical ventilation was restarted, and manual CPR was performed. We examined the mean arterial pressure (MAP), end-tidal carbon dioxide (ETCO2), and Oxy/Deoxy-Hb and TOI. Out of 14 rats, 11 obtained sustained ROSC. After the induction of asphyxia, a rapid drop of TOI was observed, followed by a subsequent increase of Oxy-Hb, Deoxy-Hb, and TOI with CPR. Recent CPR guidelines suggest the use of ETCO2 during CPR since its abrupt increase is a reasonable indicator of ROSC. In this study, abrupt increases in MAP, ETCO2, and TOI were observed at the time of ROSC. TOI can be an alternative to ETCO2 for identifying ROSC after CA, and it also has the capability of monitoring CBO during and after CPR.

Methodological Issue of Mitochondrial Isolation in Acute-Injury Rat Model: Asphyxia Cardiac Arrest and Resuscitation.

Background: Identification of the mechanisms underlying mitochondrial dysfunction is key to understanding the pathophysiology of acute injuries such as cardiac arrest (CA); however, effective methods for measurement of mitochondrial function associated with mitochondrial isolation have been debated for a long time. This study aimed to evaluate the dysregulation of mitochondrial respiratory function after CA while testing the sampling bias that might be induced by the mitochondrial isolation method. Materials and Methods: Adult rats were subjected to 10-min asphyxia-induced CA. 30 min after resuscitation, the brain and kidney mitochondria from animals in sham and CA groups were isolated (n = 8, each). The mitochondrial quantity, expressed as protein concentration (isolation yields), was determined, and the oxygen consumption rates were measured. ADP-dependent (state-3) and ADP-limited (state-4) respiration activities were compared between the groups. Mitochondrial quantity was evaluated based on citrate synthase (CS) activity and cytochrome c concentration, measured independent of the isolation yields. Results: The state-3 respiration activity and isolation yield in the CA group were significantly lower than those in the sham group (brain, p < 0.01; kidney, p < 0.001). The CS activity was significantly lower in the CA group as compared to that in the sham group (brain, p < 0.01; kidney, p < 0.01). Cytochrome c levels in the CA group showed a similar trend (brain, p = 0.08; kidney, p = 0.25). Conclusions: CA decreased mitochondrial respiration activity and the quantity of mitochondria isolated from the tissues. Owing to the nature of fragmented or damaged mitochondrial membranes caused by acute injury, there is a potential loss of disrupted mitochondria. Thus, it is plausible that the mitochondrial function in the acute-injury model may be underestimated as this loss is not considered.

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

Background Cardiac arrest (CA) can induce oxidative stress after resuscitation, which causes cellular and organ damage. We hypothesized that post-resuscitation normoxic therapy would protect organs against oxidative stress and improve oxygen metabolism and survival. We tested the oxygen-sensitive reactive oxygen species from mitochondria to determine the association with hyperoxia-induced oxidative stress. Methods and Results Sprague-Dawley rats were subjected to 10-minute asphyxia-induced CA with a fraction of inspired O2 of 0.3 or 1.0 (normoxia versus hyperoxia, respectively) after resuscitation. The survival rate at 48 hours was higher in the normoxia group than in the hyperoxia group (77% versus 28%, P<0.01), and normoxia gave a lower neurological deficit score (359±140 versus 452±85, P<0.05) and wet to dry weight ratio (4.6±0.4 versus 5.6±0.5, P<0.01). Oxidative stress was correlated with increased oxygen levels: normoxia resulted in a significant decrease in oxidative stress across multiple organs and lower oxygen consumption resulting in normalized respiratory quotient (0.81±0.05 versus 0.58±0.03, P<0.01). After CA, mitochondrial reactive oxygen species increased by ≈2-fold under hyperoxia. Heme oxygenase expression was also oxygen-sensitive, but it was paradoxically low in the lung after CA. In contrast, the HMGB-1 (high mobility group box-1) protein was not oxygen-sensitive and was induced by CA. Conclusions Post-resuscitation normoxic therapy attenuated the oxidative stress in multiple organs and improved post-CA organ injury, oxygen metabolism, and survival. Additionally, post-CA hyperoxia increased the mitochondrial reactive oxygen species and activated the antioxidation system.

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

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