Arteriovenous Oxygen Content Difference Research Articles

Abstract 15726: Large-Scale Plasma Proteomics and Mendelian Randomization of Cardiovascular Performance and Peak Arterio-Venous Oxygen Difference Identify Novel Biology Related to VO 2 max

Introduction: VO 2 max is the product of maximal cardiac output (Q) (maximal stroke volume (SVmax) x heart rate) and peak arterio-venous oxygen content difference (a-vO 2 diff). SVmax and peak a-vO 2 diff have important implications across the spectrum of human health and performance. However, the molecular mechanisms underlying SVmax and peak a-vO 2 diff remain largely unknown. We characterize SVmax and peak a-vO 2 diff using large-scale plasma proteomics and genotyping to identify circulating proteins and putative mediators of these traits. Methods: 763 physically inactive adults without overt cardiovascular disease underwent cardiopulmonary exercise testing with rigorous measurements of Q. High-throughput plasma proteomic profiling was performed to identify proteins associated with SVmax, a-vO 2 diff, and VO 2 max. cis-Mendelian Randomization (MR) analysis was conducted to assess causal relationships between protein markers and cardiovascular performance traits. Results: Proteomic profiling revealed associations between SVmax and several adiposity-related proteins, as well as secretory muscle factors (cathepsin B, α-actinin 2, and troponin I) (Figure). Proteins associated with peak a-vO2diff reflected oxygen-carrying capacity, muscle biology, and glucose metabolism (erythropoietin, myoglobin, fructose-1,6-bisphosphatase). Significant overlap was observed between proteins associated with SVmax, a-vO 2 diff, and VO 2 max. Cis-MR identified myocilin (MYOC) and caspase recruitment domain family member 9 (CARD9) as potential mediators of cardiovascular performance and VO 2 max. Conclusions: This study provides novel insights into the molecular influences of cardiovascular performance and VO 2 max. The identified protein markers associated with SVmax and a-vO 2 diff, along with the possible mediators MYOC and CARD9, merit further investigation into their role in endurance exercise capacity and cardiometabolic health.

IMPACT OF PARAVERTEBRAL BLOCKADE ON THE COURSE OF EARLY POSTOPERATIVE PERIOD FOLLOWING SURGICAL INTERVENTION FOR LUNG MALIGNANCIES UNDER INHALED SEVOFLURANE ANESTHESIA

The aim of the study is to investigate the impact of paravertebral blockade on the quality of anti-stress protection of general inhalation anaesthesia based on sevoflurane during operations in patients with lung malignancy. Material and methods. We examined 60 individuals of an average age 55±5.6 years, whose physical status was assessed as class II – III according to the ASA classification. The patients underwent open surgical procedures, including frontal or pneumonectomy, or partial lung resection. The patients were divided into 2 groups depending on the method of anaesthesia: SF group (sevoflurane) (n = 29) received inhaled anaesthesia with sevoflurane; SF+PVB group (n = 31) received the combination of inhaled anaesthesia with PVB. The following indicators were assessed: time of the first administration of the analgesic after surgery, pain intensity by the visual analogue scale (VAS), perfusion systemic pressure (PST), cardiac index (CI), oxygen content in arterial and venous blood, blood lactate levels, indicators of circulatory energy efficiency, cortisol, insulin and HOMA index levels. Indicators were recorded before the surgical operation, at the wake-up stage, on the 1st and 5th days following the operation. Results. In the SF+PVB group, the intensity of pain in the postoperative period was significantly lower than in the SF group. In the SF+PVB group, there was no necessity for administering narcotic analgesics on the first day, while in the SF group, the dose of morphine was 0.27±0.04 mg/kg∙day, the first administration was performed 65.5±10.3 minutes after surgery. CI during surgery and in a day was significantly higher in the SF+PVB group, and the arteriovenous difference in oxygen content was significantly lower. The energy efficiency of blood circulation at the same stages was significantly higher in the SF+PVB group. In the same group, there was a significantly lower concentration of markers of stress responses (cortisol levels and HOMA index). Conclusions. The use of paravertebral blockade under the general anaesthesia based on sevoflurane during operations in patients with lung malignancies contributes to a significant reduction in the pain intensity in the postoperative period; eliminates the need to use narcotic analgesics; provides significantly more stable hemodynamics and significantly more adequate oxygen supply during the operation and in the postoperative period; significantly reduces the intensity of stress reactions as well as significantly improves the energy efficiency of blood circulation.

COURSE OF INHALATION ANAESTHESIA WITH SEVOFLURANE DURING SURGICAL TREATMENT OF PATIENTS WITH MALIGNANT LUNG TUMOURS

Abstract. Aim. Study of the effect of pain intensity on the energy efficiency of blood circulation in patients with lung malignancies after operations under anesthesia using sevoflurane.
 Materials and methods. 29 patients with malignant lung formations have been examined, who underwent open surgical interventions on the volume of lob- or pneumonectomy or resection of part of the lung. The average age of the examined patients was (55±5.6) years, among them men – 17, women – 12. Pain intensity, perfusion systemic pressure, cardiac index, blood flow power, arteriovenous difference in oxygen content, blood lactate concentration, oxygen reserve, circulatory reserve have been determined. These indicators have been determined in four stages: 1) before the operation; 2) awakening; 3) the first day after surgery; 4) the fifth day after surgery.
 Results and their discussion. The intensity of pain determined by the visual analog scale (VAS) was maximum on the 1st day after surgery (4.8±0.8 points), and on the 5th day it returned to the level of the awakening stage. Analgesia was performed with morphine (0.27±0.04 mg/kg on the 1st day) and infusion of infulgan at a dose of 1 g 3 times a day. The circulatory reserve was minimal at the stage of awakening and on the 1st day after surgery (from (381±66) to (390±71) mW/m2), on the 5th day it reached the preoperative level (448±82 mW/m2). Separate indicators of blood circulation do not have a strong dependence on the level of pain that was determined by VAS, but indicators of the energy component of circulation are closely related to the severity of pain.
 Conclusions. The maximum severity of pain in patients with malignant lung formations operated under inhaled anesthesia with sevoflurane is observed on the first day after surgery. Different indicators of hemodynamics and oxygen transport are associated with the intensity of pain measured by VAS with different strengths, which makes it impossible to evaluate the effectiveness of anesthesia. Indicators of circulatory energy efficiency are closely related to the intensity of pain measured using VAS, which proves the value of using monitoring of circulatory energy indicators in assessing the quality of anesthesia.

Simultaneous exercise stress cardiac magnetic resonance and cardiopulmonary exercise testing to elucidate the Fick components of aerobic exercise capacity: a feasibility and reproducibility study and pilot study in hematologic cancer survivors

BackgroundPatients treated for hematologic malignancy often experience reduced exercise capacity and increased fatigue; however whether this reduction is related to cardiac dysfunction or impairment of skeletal muscle oxygen extraction during activity is unknown. Cardiopulmonary exercise testing (CPET) coupled with stress cardiac magnetic resonance (ExeCMR), may provide a noninvasive method to identify the abnormalities of cardiac function or skeletal muscle oxygen extraction. This study was performed to determine the feasibility and reproducibility of a ExeCMR + CPET technique to measure the Fick components of peak oxygen consumption (VO2) and pilot its discriminatory potential in hematologic cancer patients experiencing fatigue.MethodsWe studied 16 individuals undergoing ExeCMR to determine exercise cardiac reserve with simultaneous measures of VO2. The arteriovenous oxygen content difference (a-vO2diff) was calculated as the quotient of VO2/cardiac index (CI). Repeatability in measurements of peak VO2, CI, and a-vO2diff was assessed in seven healthy controls. Finally, we measured the Fick determinants of peak VO2 in hematologic cancer survivors with fatigue (n = 6) and compared them to age/gender-matched healthy controls (n = 6).ResultsStudy procedures were successfully completed without any adverse events in all subjects (N = 16, 100%). The protocol demonstrated good-excellent test-retest reproducibility for peak VO2 (intraclass correlation coefficient [ICC] = 0.992 [95%CI:0.955–0.999]; P < 0.001), peak CI (ICC = 0.970 [95%CI:0.838–0.995]; P < 0.001), and a-vO2diff (ICC = 0.953 [95%CI:0.744–0.992]; P < 0.001). Hematologic cancer survivors with fatigue demonstrated a significantly lower peak VO2 (17.1 [13.5–23.5] vs. 26.0 [19.7–29.5] mL·kg-1·min-1, P = 0.026) and lower peak CI (5.0 [4.7–6.3] vs. 7.4 [7.0-8.8] L·min-1/m2, P = 0.004) without a significant difference in a-vO2diff (14.4 [11.8–16.9] vs. 13.6 [10.9–15.4] mLO2/dL, P = 0.589).ConclusionsNoninvasive measurement of peak VO2 Fick determinants is feasible and reliable with an ExeCMR + CPET protocol in those treated for a hematologic malignancy and may offer insight into the mechanisms of exercise intolerance in those experiencing fatigue.

Predictive value of Pv-aCO2/Ca-vO2 combined blood lactate concentration for primary peritonitis-related septic shock in children

To investigate the prognostic value of the ratio of veno-arterial carbon dioxide partial pressure difference to arterio-venous oxygen content difference (Pv-aCO2/Ca-vO2) in children with primary peritonitis-related septic shock. A retrospective study was conducted. Sixty-three children with primary peritonitis-related septic shock admitted to department of intensive care unit of the Children's Hospital Affiliated to Xi'an Jiaotong University from December 2016 to December 2021 were enrolled. The 28-day all-cause mortality was the primary endpoint event. The children were divided into survival group and death group according to the prognosis. The baseline data, blood gas analysis, blood routine, coagulation, inflammatory status, critical score and other related clinical data of the two groups were statistics. The factors affecting the prognosis were analyzed by binary Logistic regression, and the predictability of risk factors were tested by the receiver operator characteristic curve (ROC curve). The risk factors were stratified according to the cut-off, Kaplan-Meier survival curve analysis compared the prognostic differences between the groups. A total of 63 children were enrolled, including 30 males and 33 females, the average age (5.6±4.0) years old, 16 cases died in 28 days, with mortality was 25.4%. There were no significant differences in gender, age, body weight and pathogen distribution between the two groups. The proportion of mechanical ventilation, surgical intervention, vasoactive drug application, and procalcitonin, C-reactive protein, activated partial thromboplastin time, serum lactate (Lac), Pv-aCO2/Ca-vO2, pediatric sequential organ failure assessment, pediatric risk of mortality III in the death group were higher than those in the survival group. Platelet count, fibrinogen, mean arterial pressure were lower than those in the survival group, and the differences were statistically significant. Binary Logistic regression analysis showed that Lac and Pv-aCO2/Ca-vO2 were independent risk factors affecting the prognosis of children [odds ratio (OR) and 95% confidence interval (95%CI) were 2.01 (1.15-3.21), 2.37 (1.41-3.22), respectively, both P < 0.01]. ROC curve analysis showed that the area under curve (AUC) of Lac, Pv-aCO2/Ca-vO2 and their combination were 0.745, 0.876 and 0.923, the sensitivity were 75%, 85% and 88%, and the specificity were 71%, 87% and 91%, respectively. Risk factors were stratified according to cut-off, and Kaplan-Meier survival curve analysis showed that the 28-day cumulative probability of survival of Lac ≥ 4 mmol/L group was lower than that in Lac < 4 mmol/L group [64.29% (18/28) vs. 82.86% (29/35), P < 0.05]. Pv-aCO2/Ca-vO2 ≥ 1.6 group 28-day cumulative probability of survival was less than Pv-aCO2/Ca-vO2 < 1.6 group [62.07% (18/29) vs. 85.29% (29/34), P < 0.01]. After a hierarchical combination of the two sets of indicator variables, the 28-day cumulative probability of survival of Pv-aCO2/Ca-vO2 ≥ 1.6 and Lac ≥ 4 mmol/L group significantly lower than that of the other three groups (Log-rank test, χ2 = 7.910, P = 0.017). Pv-aCO2/Ca-vO2 combined with Lac has a good predictive value for the prognosis of children with peritonitis-related septic shock.

529 PERSPECTIVES ON CARDIAC OUTPUT EVALUATION IN PULMONARY HYPERTENSION PATIENTS UNDERGOING RIGHT HEART CATHETERIZATION

Abstract Background and aim Right heart catheterization (RHC) is the gold standard for the diagnosing and classifying pulmonary hypertension (PH). Cardiac output (CO) and the derived cardiac index (CI) are cornerstones of the hemodynamic evalution allowing pulmonary vascular resistance (PVR) calculation and risk stratification. According to the current European Guidelines, CO should be assessed by the direct Fick method or thermodilution (TD). The indirect Fick (IF) method based on theorically estimated values for VO2, is deemed acceptable bul lacks reliability. Of note, data from the literature on a direct comparison among these three methods used for CO measurement are poor. The objective of our study is to compare CO evaluation by the DF method (DFCO) with CO assessed by IF (IFCO) and TD (TDCO). Secondly, we aimed at assessing the impact of CO estimation by different methods on PVR measurement and therefore on PH hemodynamic classification. This might translate into relevant diagnostic, prognostic and therapeutic implications. Methods 27 patients underwent RHC. Breath-by breath VO2 was measured through a Rudolph mask connected with a two-way respiratory valve to a metabolic cart and averaged over the course of 12 to 15 minutes. DFCO was calculated using the following formula: VO2 (ml/min)/(arteriovenous oxygen content difference×10). For IFCO, the same formula was used with VO2 computed by the Dehmer and the LaFarge-Miettinen formulas. TDCO was obtained through the injection of 10 ml of cold saline solution (0-4°C), in the right atrium and by measuring the temperature variation in the pulmonary artery. Results RHC revealed PH in 23 patients (85%) Average VO2 by Dehmer formula differed significantly from direct measurement (228.9 ± 27.9 ml/min and 204.4 ± 43.6 ml/min respectively; P = 0.017). By using LaFarge formula, mean estimated VO2 differed from direct measurement without reaching statistical significance (185.3 ± 31.9 ml/min and 204.4 ± 43.6 ml/min respectively, P= 0.072). Average CO values did not differ significantly from each other (DFCO 4.2 ± 1.5 L/min; IFCO 4.7 ± 1.3 L/min; TDCO 4.6 ± 1.2 L/min; P=NS for all pairwise comparisons) and showed significant Pearson's correlation. Out of 27 cases, TDCO differed for more (± 0.5 L/min) than 10% as compared to DFCO in 17 (63%). IFCO differed consistently from DFCO in 12 (44%) and IFCO from TDCO in 17 (63%). Despite discrepancies among different CO measurement methods, Cohen's kappa coefficient showed good agreement between the three methods in high PVR (≥3 WU) estimation (IF vs DF 0.79; TD vs DF 0.83 and IF vs TD 0.92 respectively). Conclusions Our results indicate consistent discrepancies among different approaches for VO2 and CO measurement, however this did not impact over PVR assessment and therefore in PH classification. Probably, this is due to the small sample size and the low number of patients (8 of 27) with values around the pathological cut-off for PVR (3 WU). Further studies are needed to better investigate the magnitude of CO measurement discrepancies among different methods on PVR calculation and hemodynamic classification.

The Clinical Efficacy and Possible Mechanism of Combination Treatment of Cerebral Ischemic Stroke with Ginkgo Biloba Extract and Low-Frequency Repetitive Transcranial Magnetic Stimulation

To study the effect of the combination treatment of ginkgo biloba extract and low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on the oxidative stress and brain neurotransmitters of patients who had cerebral ischemic stroke (CIS). A retrospective analysis was conducted, and 93 CIS patients admitted to the Sichuan Academy of Medical Sciences/Sichuan Provincial People's Hospital from January 2018 to January 2020 were included in the study. They were divided into three groups, the regular treatment group (31 cases), the LF-rTMS group (31 cases), and the combination treatment group (31 cases). Patients in the regular treatment group were given the conventional drug therapy and exercise regimen. The LF-rTMS group received LF-rTMS therapy (for 20-30 min each time, 1 time/d and 5 times/week) in addition to the treatment given to the regular treatment group. The combination treatment group was given ginkgo biloba extract (intravenous drips, once per day) in addition to the treatment given to the LF-rTMS group. The treatment was given continuously for 4 weeks and comparison was made at the end of the 4-week treatment regarding the clinical efficacy, oxidative stress response, cerebral oxygen metabolism, and brain neurotransmitter as shown by the three groups. The treatment efficacy in the combination treatment group (96.77%) was higher than those of the LF-rTMS group (80.65%) and the regular treatment group (54.84%). The LF-rTMS group showed higher treatment efficacy than that of the regular group. The serum superoxide dismutase (SOD) of the combination treatment group was higher than that of the LF-rTMS group and that of the routine group, while the malondialdehyde (MDA) and endothelin-1 (ET-1) of the combination treatment group were lower than those of the LF-rTMS group and the regular treatment group ( P<0.05). The serum SOD of the LF-rTMS group was higher than that of the regular treatment group, while the MDA and ET-1 of the group was lower than those of the regular treatment group ( P<0.05). The arterial oxygen content (CaO 2), arterio-venous oxygen content difference (Ca-vO 2) and cerebral extraction rate of oxygen (CERO 2) in the combination treatment group were lower than those of the LF-rTMS group and the regular treatment group ( P<0.05). The levels of these three indicators of the LF-rTMS group were lower than those of the regular treatment group ( P<0.05). EEG frequencies of gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT) and dopamine (DA) of the combination treatment group were higher than those of the LF-rTMS group and the regular treatment group, while the acetylcholine (Ach) EEG frequency of the combination treatment group was lower than that of the LF-rTMS group and regular treatment group ( P<0.05). The LF-rTMS group showed higher GABA, 5-HT and DA EEG frequencies than those of the regular treatment group, while the Ach EEG frequency of the group was lower than that of the regular treatment group ( P<0.05). All the patients were followed up for 6 months, and recurrence rate was lower in the combination treatment group (3.23%) than that of the LF-rTMS group (19.35%) and the regular treatment group (25.81%) ( P<0.05). The combination treatment of ginkgo biloba extract and LF-rTMS helped to improve the clinical outcome of CIS patients, which may be related to the inhibition of oxidative stress, improvement in cerebral oxygen metabolism, and regulation of brain neurotransmitter.

Utility of venous‐to‐arterial carbon dioxide changes to arteriovenous oxygen content ratios in the prognosis of severe sepsis and septic shock: A systematic review and meta‐analysis

Background:Sepsis patients with insufficient tissue perfusion and hypoxia should be identified and resuscitated immediately. Recently, venous‐to‐arterial carbon dioxide pressure changes and the arteriovenous oxygen content difference ratio (Pcv‐aCO2/Ca‐vO2) as a predictor of tissue perfusion recovery and poor prognosis.Objectives:Pcv‐aCO2/Ca‐vO2 is a substitute for respiratory entropy, the elevation of which indicates a lack of tissue perfusion. Pcv‐aCO2/Ca‐vO2 can be used as an indicator to predict the prognosis of patients with sepsis or septic shock, but its prognostic value has not been fully evaluated. Here, we have performed a meta‐analysis to assess its predictive value for mortality.Methods:Meta‐analysis of Observational Studies in Epidemiology group guidelines were followed for this meta‐analysis. We searched the comprehensive electronic databases of PubMed, EMBASE, Web of Science, and Cochrane libraries from inception to March 2019, using the terms including “venous‐arterial,” “carbon dioxide,” “Shock, Septic,” and related keywords. The Newcastle‐Ottawa scale was used for quality evaluation of the literature. A meta‐analysis was performed using RevMan 5.3 and Stata 14.0 software to evaluate the effects of Pcv‐aCO2/Ca‐vO2 on short‐term mortality, sequential organ failure assessment, and acute physiology and chronic health evaluation scores in patients with sepsis or septic shock.Results:The final analysis included 13 clinical studies involving a total of 940 subjects. The results of the meta‐analysis showed that non‐surviving patients had higher Pcv‐aCO2/Ca‐vO2 than survivors after fluid resuscitation (standardized mean difference = 0.68, 95% confidence interval = 0.24–1.12) and blood samples taken 6 h after resuscitation showed a greater risk of mortality (risk ratio = 1.89, 95% confidence interval = 1.48–2.41) and sequential organ failure assessment scores (mean difference = 1.58, 95% confidence interval = 0.88–2.28, P &lt; 0.01) in patients with high Pcv‐aCO2/Ca‐vO2. These differences were statistically significant.Conclusion:This meta‐analysis indicates that Pcv‐aCO2/Ca‐vO2 has predictive value for mortality in patients with sepsis or septic shock. Further studies are now required to determine the optimal threshold for predicting sepsis mortality.Prospero Registration:The protocol for this systematic review was registered on PROSPERO (CRD 42019128134).

Ratio of venous-to-arterial PCO2 to arteriovenous oxygen content difference during regional ischemic or hypoxic hypoxia

The purpose of the study was to evaluate the behavior of the venous-to-arterial CO2 tension difference (ΔPCO2) over the arterial-to-venous oxygen content difference (ΔO2) ratio (ΔPCO2/ΔO2) and the difference between venous-to-arterial CO2 content calculated with the Douglas’ equation (ΔCCO2D) over ΔO2 ratio (ΔCCO2D/ΔO2) and their abilities to reflect the occurrence of anaerobic metabolism in two experimental models of tissue hypoxia: ischemic hypoxia (IH) and hypoxic hypoxia (HH). We also aimed to assess the influence of metabolic acidosis and Haldane effects on the PCO2/CO2 content relationship. In a vascularly isolated, innervated dog hindlimb perfused with a pump-membrane oxygenator system, the oxygen delivery (DO2) was lowered in a stepwise manner to decrease it beyond critical DO2 (DO2crit) by lowering either arterial PO2 (HH-model) or flow (IH-model). Twelve anesthetized and mechanically ventilated dogs were studied, 6 in each model. Limb DO2, oxygen consumption ({dot{text{V}}text{O}}_{2}), ΔPCO2/ΔO2, and ΔCCO2D/ΔO2 were obtained every 15 min. Beyond DO2crit, {dot{text{V}}text{O}}_{2} decreased, indicating dysoxia. ΔPCO2/ΔO2, and ΔCCO2D/ΔO2 increased significantly only after reaching DO2crit in both models. At DO2crit, ΔPCO2/ΔO2 was significantly higher in the HH-model than in the IH-model (1.82 ± 0.09 vs. 1.39 ± 0.06, p = 0.002). At DO2crit, ΔCCO2D/ΔO2 was not significantly different between the two groups (0.87 ± 0.05 for IH vs. 1.01 ± 0.06 for HH, p = 0.09). Below DO2crit, we observed a discrepancy between the behavior of the two indices. In both models, ΔPCO2/ΔO2 continued to increase significantly (higher in the HH-model), whereas ΔCCO2D/ΔO2 tended to decrease to become not significantly different from its baseline in the IH-model. Metabolic acidosis significantly influenced the PCO2/CO2 content relationship, but not the Haldane effect. ΔPCO2/ΔO2 was able to depict the occurrence of anaerobic metabolism in both tissue hypoxia models. However, at very low DO2 values, ΔPCO2/ΔO2 did not only reflect the ongoing anaerobic metabolism; it was confounded by the effects of metabolic acidosis on the CO2–hemoglobin dissociation curve, and then it should be interpreted with caution.

The impact of vatinoxan on medetomidine–ketamine–midazolam immobilization in Patagonian maras (Dolichotis patagonum)

ObjectiveTo compare cardiovascular and ventilatory effects, immobilization quality and effects on tissue perfusion of a medetomidine–ketamine–midazolam combination with or without vatinoxan (MK-467), a peripherally acting α2-adrenoceptor antagonist. Study designRandomized, blinded, crossover study. AnimalsA group of nine healthy Patagonian maras (Dolichotis patagonum). MethodsMaras were immobilized twice with: 1) medetomidine hydrochloride (0.1 mg kg–1) + ketamine (5 mg kg–1) + midazolam (0.1 mg kg–1) (MKM) + saline or 2) MKM + vatinoxan hydrochloride (0.8 mg kg–1), administered intramuscularly. Drugs were mixed in the same syringe. At 20, 30 and 40 minutes after injection, invasive blood pressure, heart rate, respiration rate, end-tidal CO2, haemoglobin oxygen saturation, and muscle oxygenation were measured, arteriovenous oxygen content difference was calculated. Muscle tone, jaw tone, spontaneous blinking and palpebral reflex were evaluated. Times to initial effect, recumbency, initial arousal and control of the head were recorded. Paired t test, Wilcoxon matched-pairs signed rank test and analysis of variance were used to compare protocols; (p < 0.05). ResultsVatinoxan significantly reduced systolic (p = 0.0002), mean (MAP; p < 0.0001) and diastolic (p < 0.0001) arterial blood pressures between 20 and 40 minutes. MAPs at 30 minutes (mean ± standard deviation) with MKM and MKM + vatinoxan were 105 ± 12 and 71 ± 14 mmHg, respectively. Without vatinoxan, four animals were hypertensive (MAP > 120 mmHg), whereas with vatinoxan, four animals were hypotensive (MAP < 60 mmHg). Muscle and jaw tone were significantly more frequently present with MKM (both p = 0.039). Other measurements did not significantly differ between protocols. Conclusions and clinical relevanceIn Patagonian maras, vatinoxan attenuated the increase in blood pressure induced by medetomidine. Muscle and jaw tone were more frequently present with MKM, indicating that quality of immobilization with vatinoxan was more profound.

Abstract 17257: Stroke Volume Reserve Index in HFrEF: A Non-Invasive Predictor of Early Clinical Outcomes and Marker of Inotropic Reserve

Introduction: We investigated whether stroke volume reserve index (SVRI), a novel non-invasive measure of inotropic reserve at submaximal exercise, would predict 1-year mortality and need for advanced therapies in heart-failure with reduced ejection fraction (HFrEF) patients. Methods: We retrospectively studied a consecutive series of 245 ambulatory patients (57±11 years, 84% men) with HFrEF at a single center who underwent cardiopulmonary exercise testing (CPET) from January 2013 to December 2018. The primary outcome was defined as heart-transplantation, urgent left ventricular assist device (LVAD) implantation or death within 1 year of evaluation. SVRI was estimated at rest and at anaerobic threshold by VO 2 (oxygen consumption)/pulse and previously validated estimates of C[a-v]O 2 (arteriovenous difference in oxygen content). Multivariate regression selected the optimal predictors. Results: Among HFrEF patients studied, 82 (33.5%) deteriorated: 34 required heart-transplantation, 20 required LVADs and 28 died. SVRI of less than 130% was the best predictor of clinical deterioration (OR 3.98, p&lt;0.005), followed by cardiac index of less than 2 L/min/m 2 (OR 3.74, p&lt;0.005), and peak VO 2 below the International Society for Heart and Lung Transplantation (ISHLT) cut-off (OR 3.01, p=0.008). Kaplan-Meier curves showed that 1-year event-free survival was significantly better amongst patients with normal SVRI, compared to patients with impaired inotropic reserve. Notably, HFrEF patients with an abnormal SVRI had a poor 1-year prognosis regardless of their peak VO 2 . Conclusions: SVRI is a non-invasive measurement that provides a measure of inotropic reserve at submaximal exercise, provides valuable prognostic information independent of other known and validated CPET parameters, and may predict deterioration in HFrEF patients more accurately than currently recommended CPET predictors. SVRI and peak VO 2 provide complementary prognostic information.

Impact of Hypothermia on Oxygenation Variables and Metabolism in Survivors of Out-of-Hospital Cardiac Arrest Undergoing Targeted Temperature Management at 33°C Versus 36°C.

Targeted temperature management (TTM) exerts substantial impact on hemodynamic function in out-of-hospital cardiac arrest (OHCA) patients. Whole-body oxygen consumption (VO2) and delivery (DO2) have not previously been investigated in a clinical setting during TTM at different levels of temperature after OHCA. A substudy of 151 patients randomized at a single center in the TTM-trial, where patients were randomly assigned TTM at 33°C (TTM33) or 36°C (TTM36) for 24 hours. We calculated VO2 according to the principle of Fick (VO2 = cardiac output*arteriovenous oxygen content difference). DO2 was calculated as cardiac output*arterial oxygen content. Cardiac output was measured by pulmonary artery catheter with thermodilution. Arteriovenous oxygen content difference was calculated from arterial and mixed venous oxygen saturation and hemoglobin. Oxygen extraction ratio = VO2/DO2. At 24 hours, the VO2 was 169 ± 59 mL O2 per minute in TTM33 and 217 ± 53 mL O2 per minute in TTM36 (p < 0.0001). During 24 hours of TTM, the overall difference was 53 mL O2 minute (95% confidence interval [CI]: 31-74, pgroup < 0.0001). After rewarming at 36 and 48 hours, there was no difference in VO2 between the groups. DO2 was overall 277 mL O2 per minute (95% CI: 175-379, pgroup < 0.0001) higher in the TTM36-group during TTM. Oxygen extraction ratio during TTM was not significantly different between the two groups (2% [95% CI: -0.1 to 5, pgroup = 0.09]). VO2 during the first 36 hours after OHCA correlated significantly with temperature, and VO2 was 19 mL O2 per minute lower per degree reduction in temperature (95% CI: 15-22), p < 0.0001. TTM at 33°C compared to 36°C after OHCA is associated with significantly lower VO2 and DO2, however, oxygen extraction ratio was not significantly different. For each degree lower body temperature, the VO2 fell by 19 mL O2 per minute.

Peripheral Determinants of Oxygen Utilization in Heart Failure With Preserved Ejection Fraction: Central Role of Adiposity

The aim of this study was to determine the arteriovenous oxygen content difference (ΔAVo2) in adult subjects with and without heart failure with preserved ejection fraction (HFpEF) during systemic and forearm exercise. Subjects with HFpEF had reduced ΔAVo2. Forearm diffusional conductance for oxygen, a lumped conductance parameter that incorporates all impediments to the movement of oxygen from red blood cells in skeletal muscle capillaries into the mitochondria within myocytes, was estimated. Forearm diffusional conductance for oxygen was not different among adults with HFpEF, those with hypertension, and healthy control subjects; therefore, diffusional conductance cannot explain the reduced forearm ΔAVo2. Instead, adiposity was strongly associated with ΔAVo2, suggesting an active role for adipose tissue in reducing exercise capacity in patients with HFpEF.

Abstract WP165: Retinal Oxygen Metabolic, Anatomical, and Biochemical Changes in Experimental Carotid Artery Occlusion

Purpose: Retinal ischemia has been implicated in vision-threatening diseases. Permanent bilateral common carotid artery occlusion (BCCAO) studies have reported retinal degeneration and gliosis, as well as cerebral degeneration. We hypothesized that BCCAO-induced long-term (3 to 14 days) impairments to oxygen delivery (DO 2 ), extraction fraction (OEF), and metabolism (MO 2 ) affect cellular morphology and biochemical pathways. Methods: Twenty-one rats underwent BCCAO or sham surgery. Blood flow and vascular oxygen tension imaging was performed in both eyes. Images were analyzed to derive retinal arterial and venous oxygen contents (O 2A , O 2V ), arteriovenous oxygen content difference (O 2AV ), and total retinal blood flow (TRBF). The following equations were used: DO 2 =TRBF*O 2A ; MO 2 =TRBF*O 2AV ; OEF=MO 2 /DO 2 . After imaging, immunohistochemistry and histological assays were performed on retinal sections. Results: Compared to the sham group, DO 2 was reduced in 3-day (β=-622 nLO 2 /min), 7-day (β=-614 nLO 2 /min), and 14-day (β=-605 nLO 2 /min) BCCAO groups. MO 2 was reduced in 3-day (β=-215 nLO 2 /min), 7-day (β=-256 nLO 2 /min), and 14-day (β=-262 nLO 2 /min) BCCAO groups. Compared to the sham group, OEF was increased in 3-day (β=0.405) and 7-day (β=0.209) BCCAO groups. Compared to the sham group, the thickness of the nerve fiber (β=-14.6 μm), inner nuclear (β=-7.21 μm), outer plexiform (β=-6.70 μm), and inner retina (β=-30.7 μm) layers were decreased, while thickness of the outer nuclear layer was increased (β=7.88 μm) in the 14-day BCCAO group. Gliosis was increased in the 14-day BCCAO group compared to all other groups. Compared to the sham group, TUNEL-positive cells in inner and outer nuclear layers were increased in the 3-day BCCAO group. Conclusions: The findings confirm our hypothesis that BCCAO-induced reduction in retinal DO 2 resulted in increased OEF, impairment of MO 2 , and inner retinal cell death after 3 days, whereas increased gliosis and degeneration of inner retinal cells were observed after 14 days. When compared to brain literature, the retina—an extension of the diencephalon-- showed a similar reduction in blood flow and increase in both OEF and cell-death at 3-days following BCCAO.

Dyspnea Postpulmonary Embolism From Physiological Dead Space Proportion and Stroke Volume Defects During Exercise

Many patients with pulmonary embolism (PE) report dyspnea on exertion following long-term treatment. Increased physiological dead space proportion (VD/VT) and decreased cardiac stroke volume reserve may distinguish persistent effects of PE itself from symptoms reflecting comorbid conditions or deconditioning. This retrospective study analyzed a consecutive series of incremental symptom-limited cardiopulmonary exercise tests that had been ordered to evaluate persistent dyspnea on exertion following long-term treatment for acute PE. Physiological VD/VT was determined at anaerobic threshold from exhaled CO2 and transcutaneous Pco2 (validated against Paco2 measurements). Cardiac stroke volume reserve was estimated at rest and at anaerobic threshold by using oxygen consumption/pulse and previously validated estimates of the arteriovenous oxygen content difference. Cardiopulmonary exercise tests were performed on 40 patients with post-PE dyspnea. In 65.0%(95%CI, 50.2-79.8), VD/VT at anaerobic threshold was abnormally elevated, stroke volume reserve was decreased, or both defects occurred. VD/VT at anaerobic threshold was abnormally elevated (≥ 0.27) in 35.0%(95%CI, 20.2-49.8). VD/VT at anaerobic threshold significantly correlated with the extent of unmatched perfusion defects on subsequent ventilation-perfusion scans (P= .0085). In 55.0%(95%CI, 39.6-70.4), stroke volume reserve at anaerobic threshold was abnormally decreased (≤ 128%of the resting value). Both defects were present in 25.0%(95%CI, 11.6-38.4). Increased VD/VT at anaerobic threshold and decreased stroke volume reserve during exercise are common among patients with dyspnea on exertion after long-term treatment of PE. The defects can be disclosed noninvasively by using cardiopulmonary exercise testing.

Influences of acute hypervolemic hemodilution on serum levels of S-100β protein, NSE and POCD in elderly patients with spinal surgery

To explore the influences of acute hypervolemic hemodilution(AHH) on serum levels of S-100β protein, neuron specific enolase(NSE) and postoperative cognitive dysfunction POCD in elderly patients with spinal surgery. A total of 80 cases elderly patients requiring elective spinal operation were divided into AHH group and C group according to random digits table, 40 cases in each group, with ASA grade I-II. The patients in AHH group were infused 6% hydroxyethyl starch 130/0.4 at a rate of 20 ml/min after anesthesia induction, and blood volume increased by about 20%, the patients in C group were not received AHH, anesthesia and surgical methods were the same as those in AHH group. Intraoperative blood volume, allogeneic blood transfusion and urine volume were recorded. Mean arterial pressure(MAP), heart rate(HR), central venous pressure(CVP) at preoperative 1 d, 1 h after the start of surgery, end of operation, 12 h after surgery were observed. Arterial blood oxygen content (CaO₂), venous blood oxygen content (CjvO₂), arteriovenous oxygen content difference (Da-jvO₂), and cerebral oxygen uptake(CERO₂) were measured at 1 d before surgery, 15 min after surgery, 45 min after surgery, end of surgery. Mini-mental state examination(MMSE) score and serum levels of S-100β protein, NSE were measured at 1 d before surgery, 1, 3, 7 d after surgery. POCD rates of two groups were recorded. Intraoperative blood loss and allogeneic blood transfusion in AHH group was significantly lower than those in C group(P<0.05), and the urine volume was significantly higher than that in C group (P<0.05). Compared with preoperative 1 day, MAP was decreased and CVP was increased at end of surgery in AHH group, compared with C group at the same time, MAP was lower and CVP was higher in AHH group, but both were in normal range. Compared with preoperative 1 day and C group, the levels of Da-jvO₂ and CERO₂ in AHH group was decreased at 15, 45 min after the start of the operation and end of surgery(P<0.05). Compared with preoperative 1 day, MMSE scores of two groups at 1 day after surgery was decreased (P<0.05), the levels of S-100β protein and NSE were increased(P<0.05), and restored at 3, 7 days after surgery. There was statistical difference in MMSE scores, the levels of S-100β protein, NSE at 1 day after surgery between two groups (P<0.05). There was no statistical difference in POCD rate between two groups(P>0.05). AHH can significantly reduce intraoperative blood loss and blood transfusion in elderly patients with spinal surgery, and decrease the levels of S-100β protein and NSE, does not increase the risk of the occurrence of POCD.

Prospective, observational study of carbon dioxide gaps and free energy change and their association with fluid therapy following cardiac surgery.

Background Venoarterial carbon dioxide pressure (pv-a CO2 ) and content (Cv-a CO2 ) differences, including the ratio to arteriovenous oxygen content difference (Ca-v O2 ), and free energy changes (-∆∆Ga-v ) may reflect tissue hypoperfusion. The associations with changes in cardiac output (CO) or oxygen consumption (VO2 ) following fluid bolus administration were investigated. Methods Single-centre, observational study of 89 adult post-operative cardiac surgical patients admitted to ICU. The pv-a CO2 , Cv-a CO2 and their ratios to Ca-v O2 as well as the -∆∆Ga-v were determined before and after a 250-500mL fluid bolus using arterial, central venous and mixed venous blood gas analyses. Responses associated with changes ≥ or <15% in CO or oxygen consumption (VO2 ) were compared. Results In 234 boluses, the mixed venous to arterial pv-a CO2 and its ratio to Ca-v O2 were independently associated with an increase in CO; odds ratio 1.3 (95% CI 1.1-1.5) and 1.7 (95% CI 1.5-1.9) respectively, P<.001) and VO2 ; odds ratio 2.1 (95% CI 1.3-3.1), P<.001 for Ca-v O2 . No measures of pv-a CO2 , Cv-a CO2 or related ratios to the Ca-v O2 were associated with an increase in CO ≥15% following a single volume bolus. The mixed venous and central venous Cv-a CO2 to Ca-v O2 ratios were different for the first bolus episode only; mean differences 0.81 (95% CI 0.13-1.5), P=.02 and 0.44 (95% CI 0.06-0.82), P=.02, respectively, for increased VO2 ≥15%. The -∆∆Ga-v did not change. Conclusion The venoarterial carbon dioxide gradients and related calculations to assess the adequacy of tissue perfusion before a fluid bolus were not associated with subsequent increases in CO of oxygen consumption. Editorial Comment In some shock conditions, regional tissue hypoperfusion can be obvious and arterio-venous differences for CO2 or O2 may reflect this. This is not always the case; sometimes there are A-V differences or even a high lactate level without any obvious regional tissue hypoperfusion. Fluid therapy is a cornerstone in shock resuscitation treatment, but determining optimal fluid therapy is challenging, particularly as fluid overload may be detrimental. Fluid challenges are used as an "ex juvantebus" method to dose fluid therapy, but it is not clear if a positive response reflects a state of hypoperfusion or the existence of a cardiac reserve. Still, a better understanding on how to target and guide fluid therapy is welcome, and studies digging into the problem are needed. Here, invasively monitored post-operative cardiac surgery patients are assessed as a model to investigate if carbon dioxide gaps and free energy charge may be useful in detecting possible tissue hypoperfusion.

Discrimination of wet or dried arterial and venous blood for forensic applications via eosin fluorescence lifetime

The arteriovenous oxygen content difference disappears after blood is exposed to air. The blood oxygen level-dependent imaging method is unable to differentiate oxygen-saturated arteriovenous bloods, and no other method exists for determining them. To overcome this limitation, we first proposed that the fluorescence lifetime of eosin added to wet whole blood (WB) can distinguish air-exposed wet arterial blood (AB) from venous blood (VB). We then demonstrated that the urea level in wet WB can be employed as an indicator for further confirmation of wet arteriovenous blood based on the change in the eosin lifetime in the urease-urea reaction. Because arterial clots mostly comprise aggregated platelets in dried blood whereas venous clots contain higher amounts of fibrin. The eosin-stained platelets and fibrin have different eosin lifetimes, and this difference between platelets and fibrin during clotting when the blood dries explains why the eosin lifetime can be used to differentiate air-exposed wet and dried blood. Moreover, we found that the eosin short lifetime (τ1), mean lifetime (τm), and lifetime-based scatter parameters can be applied to discriminate dried AB and VB clots. Indeed, fluorescence lifetime imaging microscopy (FLIM) could be a potential method to support bloodstain pattern analysis in criminal cases.

Alterations in Retinal Oxygen Delivery, Metabolism, and Extraction Fraction During Bilateral Common Carotid Artery Occlusion in Rats.

PurposeThe purpose of the current study was to investigate alterations in retinal oxygen delivery, metabolism, and extraction fraction and elucidate their relationships in an experimental model of retinal ischemia.MethodsWe subjected 14 rats to permanent bilateral common carotid artery occlusion using clamp or suture ligation, or they underwent sham procedure. Within 30 minutes of the procedure, phosphorescence lifetime imaging was performed to measure retinal vascular oxygen tension and derive arterial and venous oxygen contents, and arteriovenous oxygen content difference. Fluorescent microsphere and red-free retinal imaging were performed to measure total retinal blood flow. Retinal oxygen delivery rate (DO2), oxygen metabolism rate (MO2), and oxygen extraction fraction (OEF) were calculated.ResultsDO2 and MO2 were lower in ligation and clamp groups compared to the sham group, and also lower in the ligation group compared to the clamp group (P ≤ 0.05). OEF was higher in the ligation group compared to clamp and sham groups (P ≤ 0.03). The relationships of MO2 and OEF with DO2 were mathematically modeled by exponential functions. With moderate DO2 reductions, OEF increased while MO2 minimally decreased. Under severe DO2 reductions, OEF reached a maximum value and subsequently MO2 decreased with DO2.ConclusionsThe findings improve knowledge of mechanisms that can maintain MO2 and may clarify the pathophysiology of retinal ischemic injury.

How can CO2-derived indices guide resuscitation in critically ill patients?

Assessing the adequacy of oxygen delivery with oxygen requirements is one of the key-goal of haemodynamic resuscitation. Clinical examination, lactate and central or mixed venous oxygen saturation (SvO2 and ScvO2, respectively) all have their limitations. Many of them may be overcome by the use of the carbon dioxide (CO2)-derived variables. The venoarterial difference in CO2 tension ("ΔPCO2" or "PCO2 gap") is not an indicator of anaerobic metabolism since it is influenced by the oxygen consumption. By contrast, it reliably indicates whether blood flow is sufficient to carry CO2 from the peripheral tissue to the lungs in view of its clearance: it, thus, reflects the adequacy of cardiac output with the metabolic condition. The ratio of the PCO2 gap with the arteriovenous difference of oxygen content (PCO2 gap/Ca-vO2) might be a marker of anaerobiosis. Conversely to SvO2 and ScvO2, it remains interpretable if the oxygen extraction is impaired as it is in case of sepsis. Compared to lactate, it has the main advantage to change without delay and to provide a real-time monitoring of tissue hypoxia.