Higher Respiratory Exchange Ratio Research Articles

Oxygen metabolism after cardiac arrest: Patterns and associations with survival

AimWhether changes in oxygen metabolism, as measured by oxygen consumption (VO2), carbon dioxide production (VCO2) and the respiratory exchange ratio (RER), are associated with survival after cardiac arrest is poorly understood. In this prospective observational study, we investigated the association between VO2, VCO2, and RER in the initial 12 and 24 h after return of spontaneous circulation (ROSC) and survival to hospital discharge. MethodsAdults with ROSC after cardiac arrest, admitted to the intensive care unit, requiring mechanical ventilation and treated with targeted temperature management were included. VO2 and VCO2 were measured continuously for 24 h after ROSC, using a noninvasive anesthesia monitor. Area under the curve for VO2, VCO2 & RER was calculated using all available values over 12 and 24 h after ROSC. Using logistic regression, we evaluated the relationship between these metabolic variables and survival to hospital discharge. Analyses were adjusted for temperature, vasopressors, and neuromuscular blockade. ResultsSixty four patients were included. Mean age was 64 ± 16 years, and 59% were women. There was no significant association between the area under the curve of VO2 or VCO2 and survival. A higher RER in the initial 12 h was associated with better survival (aOR = 3.97, 95% CI [1.01,15.6], p = 0.048). Survival was lower in those with median RER < 0.7 in the initial 12 h compared with those with a median RER ≥ 0.7 (25% vs 67%, p = 0.011). ConclusionHigher RER in the initial 12 h was associated with survival after cardiac arrest. The etiology of unusually low RERs in this patient population remains unclear.

331-OR: Fasting Metabolic Flexibility in Prediabetes

Metabolic flexibility cannot be easily clinically assessed, but the respiratory exchange ratio (RER) measured via indirect calorimetry can indicate substrate utilization. When indirect calorimetry is performed to measure resting metabolic rate, a normal RER should reflect a lipolytic metabolism (close to 0.7). We aimed to describe fasting glucose metabolism in relation to RER in patients seeking a nutritional intervention. In 10175 patients (7,222 (71%) females, median (quartiles) age of 46 (36, 55) years, and BMI of 28.3 (25.0, 32.3) kg/m2) a greater RER was associated with higher fasting values of glucose, insulin and higher insulin resistance (HOMA-IR), controlling for sex, age, and BMI (differences going from a RER of 0.7 to 1 RER for glucose 1.7 (95% CI 0.66, 2.8; p=0.002), for insulin 1.9 (95% CI 1.3, 2.6; p=&amp;lt;0.001), and for HOMA-IR 0.49 (95% CI 0.32, 0.66; p=&amp;lt;0.001)). As an higher RER relates to an altered glucose metabolism, within the whole sample we selected patients with prediabetes with 1 year follow-up. We matched 86 patients having either a RER indicating a lipolytic metabolism (&amp;lt;0.775) or glycolytic metabolism (&amp;gt;0.925). Patients were matched for sex, age, BMI, waist circumference, and arm muscle area. The high RER group had a lower probability of normalizing fasting glucose level within 1 year (log(OR) -0.89 (95% CI -1.8, -0.03; p=0.046)), with higher fasting glucose levels at followup (5.4 (95% CI 0.98, 9.9; p=0.017)). Moreover, while losing similar weight than the low RER group (-0.55 (95% CI -3.7, 2.6; p=0.7)), they lost a lower amount of fat mass (1.2 (95% CI 0.02, 2.4; p=0.047)). Our results suggest than an higher RER relates to a dysfunctional glycolytic metabolism at rest. We also show that prediabetic patients with higher RER are more likely to not respond to a lifestyle intervention, warranting a more intensive treatment for this subgroup. This lower probability of success doesn’t seem related to a lower adherence to the proscription, as weight loss was similar across RER categories, but to a lower weight loss quality. Disclosure A.Foppiani: None. R.De amicis: None. A.Leone: None. S.Bertoli: None. A.Battezzati: None. Funding Italian National Recovery and Resilience Plan Mission 4 Component 2 Investment 1.3 - Call for Proposals (341) of 15 March 2022 of Italian Ministry of University and Research funded by the European Union - NextGenerationEU (PE00000003) Concession Decree (1550) of 11 October 2022 adopted by the Italian Ministry of University and Research (CUP D93C22000890001)

The efficacy of high- and low-load resistance training in patients with coronary artery disease: a follow-up of a randomised controlled trial

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Slovenian Research Agency. Background Perseverance of beneficial effects of exercise training in cardiac rehabilitation remains understudied. Maximal aerobic capacity (VO2 max) and quality life were mostly maintained at 1 year follow-up after aerobic training (AT) or after a combination of AT and mostly low-load (LL) resistance training (RT), while the effects of high-load (HL) RT remain unknown in patients with coronary artery disease (CAD). Purpose This study investigated the effects of combination of AT with HL-RT or LL-RT in comparison to AT alone on maximal aerobic capacity, physical activity, and quality of life in patients with CAD at 1-year follow-up after cardiac rehabilitation. Methods We initially enrolled 79 patients with CAD to combined AT and HL-RT, combined AT and LL-RT or AT alone, and 59 patients completed the study. The assessments at 1-year follow-up were completed by 53 patients, with [mean (SD) or median (interquartile range)] age = 61 (8) years, height = 172.1 (8.4) cm, weight = 83.93 (14.03) kg and left ventricular ejection fraction = 50 (45,60) %. During the study, all patients performed the same interval aerobic cycling (40 min/session, intervals of 3-5 min of work-load cycling separated by 2 min of unloaded cycling, intensity progressed from 50% to 80% of maximal workload achieved at baseline cardiopulmonary exercise test). In HL-RT-group, the training load progressively increased from 70% of 1-RM (6–11 reps/set) to 80% of 1-RM (6–8 reps/set), while in LL-RT group the training load progressively increased from 35% of 1-RM (12–22 reps/set) to 40% of 1-RM (12–16 reps/set) in the first seven weeks of the intervention. Similar progression of RT was used after 1-RM re-evaluation following 7 weeks of training. After cardiac rehabilitation, patients were given written brochure with included advice on home-based physical activity with emphasis on aerobic and resistance exercises. Maximal aerobic performance, objectively measured physical activity and quality of life were measured after 1-year. Results At 1-year follow-up majority of the patients increased VO2max (62%). Patients increased VO2max (+0.08 l/min, p = 0.022) and had higher respiratory exchange ratio (+0.06, p &amp;lt; 0.001), regardless of the randomisation. There was no significant effect of time x group interaction on the outcomes. VO2max was increased in AT (+0.13 l/min, p = 0.026) and LL-RT (+0.12 l/min, p = 0.031) groups, while respiratory exchange ratio was greater in LL-RT (+0.6, p = 0.004) and HL-RT (+0.7, p = 0.003) groups at follow-up. Post-training physical activity and quality of life were high but remained unchanged after 1 year. Conclusions The combination of AT and HL-RT or LL-RT was not superior to AT alone in changes of maximal aerobic performance, physical activity and quality of life in patients with coronary artery disease at 1-year follow-up.

Gut microbial metabolite delta - valerobetaine (VB) influences energy metabolism by altering fat utilization and satiety-related hormones in mice

There is mounting evidence that the gut microbiota exerts profound influences on systemic homeostasis and metabolism, including effects on host energy metabolism, fatty acid oxidation, and obesity. However, we know little about how the microbiota mechanistically influences these aspects of host biology. Previously, we used mass spectrometry-based metabolomics platforms to demonstrate remarkable differences in the metabolite composition in the hepatic mitochondria of germ-free (GF) and conventional mice and identified Δ-valerobetaine (VB) as a key discriminative molecule. VB was undetectable in GF mice but present in conventional mice. We showed that VB is produced by specific bacterial species and inhibited mitochondrial fatty acid oxidation by suppression of the carnitine shuttle. VB administration to GF and conventional mice increased visceral fat mass and exacerbated hepatic steatosis with a Western-style diet but not a chow control diet and can thus function as a microbiota-derived obesogen. Here we show that VB impacts the physiological aspects of energy metabolism. VB reduces the Oxygen consumption rate (OCR) in HEPG2 cells and alters mitochondria-related protein markers (PGC1α, AMPKα, TFAM) suggesting changes in VB can alter the function of mitochondria. To evaluate whole animal consequences, we utilized the CLAMS-HC metabolic cage system to measure the respiratory exchange ratio (RER) in conventional mice. We found that western diet-fed animals treated with VB (IP 50mg/kg) for a week significantly increased RER compared to control groups on the same diet, whereas there was no impact of VB on regular chow diet-fed animals. Higher RER indicates the usage of glucose rather than the usage of fat, thus shifting the resources to produce energy and enhancing the accumulation/retention of adipose tissue. We also found a significant increase in food intake among VB-treated animals regardless of diet. We further investigated the impact of VB on energy-regulating hormones from serum and found a significant alteration in leptin and ghrelin levels. These data suggest VB alters energy utilization in a diet-dependent fashion possibly through regulating energy satiety hormones. Manipulation of VB levels by changing the intake of dietary precursors, or with VB-producing bacterial taxa, may provide therapeutic approaches to disorders of energy/lipid metabolism. This project has been funded by U.S. NIH R01 AI64462. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evaluation of respiratory exchange ratio (RER) for predicting postoperative outcomes in elderly patients undergoing oncological resection for gastrointestinal malignancies - A prospective cohort study.

Predicting complications after major oncosurgery is particularly daunting in the elderly subcategory of patients owing to factors like preexisting age-related immune cellular senescence and a significant imbalance of oxygen delivery (DO2) and consumption (VO2) characteristic of major oncological surgeries. The respiratory exchange ratio (RER) indicates DO2-VO2 balance and onset of anaerobic metabolism. We evaluated the ability of RER in predicting the occurrence of postoperative complications following geriatric oncosurgery. In the study, we enrolled 96 patients aged 65 years and above undergoing definitive surgery for gastrointestinal malignancy. The RER was calculated at predefined time points by a non-volumetric method from the respiratory parameters as RER = (end-tidal fractional carbon dioxide [FetCO2] - fraction of inspired carbon dioxide [FiCO2]/fraction of inspired oxygen [FiO2] - end-tidal fractional oxygen [FetO2]). Other indices of tissue perfusion, like central venous oxygen saturation and lactate levels, were also recorded. The patients were followed up for postsurgical complications. The predictive value of RER and other perfusion parameters was assessed and compared by appropriate statistical methods. The patients who sustained major complications had a higher RER than the patients who did not sustain complications (1.47 ± 0.99 vs. 0.90 ± 0.31, P = 0.001). An intraoperative cutoff value of RER ≥0.89 was found to best predict postoperative complications at a specificity and sensitivity rate of 81.2% and 76%, respectively. End-operative partial pressure of carbon dioxide (pCO2) gap of >5.2 mm and elevated arterial lactate could also predict postsurgical complications in this age group. The RER can serve as a noninvasive, real-time and sensitive indicator of tissue hypoperfusion and postoperative complications in geriatric gastrointestinal oncosurgery.

Long-term dietary DHA intervention prevents telomere attrition and lipid disturbance in telomerase-deficient male mice.

Previous evidence indicated anti-ageing potential of docosahexaenoic acid (DHA), but the underlying mechanism remains unclear. We investigated protective effect of DHA on telomere attrition and lipid disturbance in male mice with premature ageing caused by telomerase deficiency. Wild-type (WT) and fourth-generation telomerase-deficient (G4 Terc-/-, Terc knockout, KO) male mice (C57BL/6, 2months old) were fed control diet (WT-C and KO-C groups) or DHA-enriched diet containing 0.80% DHA by weight (WT-DHA and KO-DHA groups) for 10months. The ageing phenotypes and metabolic level [carbon dioxide emission, oxygen consumption, and respiratory exchange ratio (RER)] were assessed at the end of the experiment. Telomere length in various tissues and the hepatic gene and protein expression for regulating lipid synthesis and lipolysis were measured. Data were tested using one- or two-factor ANOVA. In KO male mice, DHA prevented weight loss, corrected high RER, and reduced fat loss. Telomere shortening was reduced by 22.3%, 25.5%, and 13.5% in heart, liver, and testes of the KO-DHA group compared with those in the KO-C group. The KO-DHA group exhibited higher gene transcription involved in glycerol-3-phosphate pathway [glycerol-3-phosphate acyltransferase (Gpat)], lower gene expression of β-oxidation [carnitine palmitoyltransferase 1a (Cpt1a)], and upregulation of proteins in lipid synthesis [mammalian target of rapamycin complex 1 (mTORC1) and sterol responsive element binding protein 1 (SREBP1)] in liver than the KO-C group. Long-term DHA intervention attenuates telomere attrition and promotes lipid synthesis via the tuberous sclerosis complex 2 (TSC2)-mTORC1-SREBP1 pathway in KO male mice.

Effects of Low/Medium-Intensity Exercise on Fat Metabolism after a 6-h Fast

The effects of fasting and different exercise intensities on lipid metabolism were investigated in 12 male students aged 19.9 ± 1.4 years, with maximal oxygen consumption (VO2max) of 50.33 ± 4.0 mL/kg/min, using a counterbalanced design. Each participant ran on a treadmill at 45% and 65% VO2max continuously for 20 min, followed by running at 85% VO2max for 20 min (or until exhaustion) under a fed or fasted state (6 h). The respiratory exchange ratio (RER), blood glucose (BGLU), blood lactate (BLA), and blood triglyceride (TG) were analyzed during exercise. The results showed that the intensity of exercise did not significantly affect the BGLU and TG in the fed state. The levels of both RER and BLA increased as the intensity of exercise increased from low to high (45, 65, and 85% VO2max), and more energy was converted from fat into glucose at a high intensity of exercise. In the fasted state of 6 h, the BGLU level increased parallel to the intensity of exercise. The RER was close to 1.0 at a high intensity of exercise, indicating that more energy was converted from glycogen. At the intensities of 45 and 65% VO2max, the RER and concentration of TG were both lower in the fasted than in the fed state, showing that a higher percentage of energy comes from fat than in the fed state at 45 and 65% VO2max. When running at 85% VO2max, the BGLU concentration was higher in the fasted than in the fed state, indicating that the liver tissues release more BGLU for energy in the fasted state. Therefore, in the fasted state, running at 45% and 65% of VO2max significantly affects lipid metabolism. On the contrary, the higher RER and BGLU concentrations when running at 85% VO2max revealed no significant difference between the two probes. This study suggests that medium- and low-intensity exercise (45 and 65% VO2max) in the fasted state enhances lipid metabolism.

Middle-Aged Lpaatδ-Deficient Mice Have Altered Metabolic Measures.

Lysophosphatidic acid acyltransferases/acylglycerophosphate acyltransferases (LPAATs/AGPATs) are a group of homologous enzymes that catalyze the formation of phosphatidic acid (PA) from lysophosphatidic acid. We have previously reported that LPAATδ/AGPAT4 localizes to mitochondria, suggesting a potential role in energy metabolism. However, in prior studies of young Lpaatδ-deficient mice (age 9-12 weeks old), we found no differences in body weights, food intakes, activity levels, respiratory gas exchange, or energy expenditure compared to their wildtype (Wt) littermates. To test whether Lpaatδ-/- mice may develop differences in metabolic measures with advancing age, we recorded body weights and food intakes, and used metabolic chambers to assess ambulatory and locomotor activity levels, oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), and total energy expenditure (heat). Fourteen-month-old Lpaatδ-/- mice had significantly lower mean body weights compared to Wt littermate controls (44.6 ± 1.08 g vs. 53.5 ± 0.42 g, respectively), but no significant differences in food intake or activity levels. This phenotypic difference was accompanied by significantly elevated 24 h daily, and 12 h light and dark photoperiod average VO2 (~20% higher) and VCO2 (~30% higher) measures, as well as higher RER and total energy expenditure (heat) values compared to Wt control littermates. Thus, an age-related metabolic phenotype is evident in Lpaatδ-/- mice. Future studies should examine the role of the lipid-modifying enzyme LPAATδ across the lifespan for greater insight into its role in normal and pathophysiology.

Cardiopulmonary Exercise Testing Characterizes Silent Cardiovascular Abnormalities in Asymptomatic Pediatric Cancer Survivors.

Late-onset cardiovascular complications are serious concerns for pediatric cancer survivors (PCS) including those who are asymptomatic. We investigated whether cardiopulmonary exercise testing (CPET) can delineate the underlying pathophysiology of preclinical cardiovascular abnormalities in PCS. We examined CPET data via cycle ergometer in asymptomatic PCS with normal echocardiogram and age-matched controls. Peak and submaximal parameters were analyzed. Fifty-three PCS and 60 controls were studied. Peak oxygen consumption (VO2), peak work rate (WR), and ventilatory anaerobic threshold (VAT) were significantly lower in PCS than controls (1.86 ± 0.53 vs. 2.23 ± 0.61 L/min, 125 ± 45 vs. 154 ± 46W, and 1.20 ± 0.35 vs. 1.42 ± 0.43 L/min, respectively; all p < 0.01), whereas peak heart rate (HR) and ventilatory efficiency (a slope of minute ventilation over CO2 production or ∆VE/∆VCO2) were comparable. Peak respiratory exchange ratio (RER) was significantly higher in PCS (p = 0.0006). Stroke volume (SV) reserve was decreased in PCS, indicated by simultaneous higher dependency on HR (higher ∆HR/∆WR) and lower peak oxygen pulse (OP). Twelve PCS with high peak RER (≥ 1.3) revealed lower pVO2 and VAT than the rest of PCS despite higher ventilatory efficiency (lower ∆VE/∆VCO2), suggesting fundamental deficiency in oxygen utilization in some PCS. Poor exercise performance in PCS may be mainly attributed to limited stroke volume reserve, but the underlying pathophysiology is multifactorial. Combined assessment of peak and submaximal CPET parameters provided critical information in delineating underlying exercise physiology of PCS.

Physiological responses during a single rebirthing (Breath work) session

Objective: The present report aimed to look at the physiological responses during a typical single Rebirthing session. Material and Methods: Ten healthy young women participated in the study. Their mean age, weight, and height were 37±2.7 years, 54.1±6.4 kg, and 161.2±4.9 cm, respectively. The Rebirthing sessions took place at the Israeli Rebirthing Center in Tel-Aviv. The treatments were carried out by a qualified Rebirthing therapist that has experienced thousands of rebirthing sessions during the last 15 years. Sessions were performed in a dark, quiet room and executed in a one-to-one set-up with the same trained therapist. After around 40-50 minutes, the session approached its end. Metabolic, cardiovascular, pulmonary, and gas-exchange variables were measured breath-by-breath using a commercial portable metabolic system. All data were transmitted wirelessly to an adjacent room in the clinic and continuously monitored by the study's chief researcher. Results: The primary study findings demonstrated that a typical Rebirthing session involving long (45-50 minutes) voluntary hyperventilation generated VO2, RER, HR, and O2 pulse matching well with the physiological demands of the procedure (breath work). At the same time, the ventilatory-related responses exhibited, as expected, exaggerated outcomes, illustrated by the high session's peak and average values of the depth (tidal volume), breathing frequency, and minute ventilation. Gas-exchange attributes showed extremely shallow end-tidal CO2 levels, high end-tidal O2, high respiratory exchange ratio, and very high levels of O2 and CO2 ventilatory equivalents. No significant grievances regarding participants' physical and mental/emotional feelings were reported in the present study. Conclusions: The present study could not solve the apparent divergence between the observed (acute) physiological responses (mainly severe Hypocapnia) and the subjective participants' pleasant emotional state, and in many cases, spiritually uplifting, at the end of each treatment session.

The Modern Double-Poling Technique Is Not More Energy Efficient Than the Old-Fashioned Double-Poling Technique at a Submaximal Work Intensity.

The purpose of the study was to investigate whether there are energy-efficiency differences between the execution of the old-fashioned double-poling technique (DPOLD) and the modern double-poling technique (DPMOD) at a submaximal work intensity among elite male cross-country skiers. Fifteen elite male cross-country skiers completed two 4-min tests at a constant mechanical work rate (MWR) using the DPMOD and DPOLD. During the last minute of each test, the mean oxygen uptake (VO2) and respiratory exchange ratio (RER) were analyzed, from which the metabolic rate (MR) and gross efficiency (GE) were calculated. In addition, the difference between pretest and posttest blood-lactate concentrations (BLadiff) was determined. For each technique, skiers' joint angles (i.e., heel, ankle, knee, hip, shoulder, and elbow) were analyzed at the highest and lowest positions during the double-poling cycle. Paired-samples t-tests were used to investigate differences between DPMOD and DPOLD outcomes. There were no significant differences in either VO2mean, MR, GE, or BLadiff (all P > 0.05) between the DPMOD and DPOLD tests. DPMOD execution was associated with a higher RER (P < 0.05). Significant technique-specific differences were found in either the highest and/or the lowest position for all six analyzed joint angles (all P < 0.001). Hence, despite decades of double-poling technique development, which is reflected in the significant biomechanical differences between DPOLD and DPMOD execution, at submaximal work intensity, the modern technique is not more energy efficient than the old-fashioned technique.

Methods to match high-intensity interval exercise intensity in hypoxia and normoxia – A pilot study

Background/ObjectivesThe aim of this study was to compare high-intensity interval exercise (HIIE) sessions prescribed on the basis of a maximal value (peak power output, PPO) and a submaximal value (lactate threshold, LT) derived from graded exercise tests (GXTs) in normoxia and hypoxia. MethodsA total of ten males (aged 18–37) volunteered to participate in this study. The experimental protocol consisted of a familiarization procedure, two GXTs under normoxia (FiO2 = 0.209) and two GXTs under normobaric hypoxia (FiO2 = 0.140), and three HIIE sessions performed in a random order. The HIIE sessions included one at hypoxia (HY) and two at normoxia (one matched for the absolute intensity in hypoxia, designated as NA, and one matched for the relative intensity in hypoxia, designated as NR). ResultsThe data demonstrated that there was significant lower peak oxygen uptake (V̇O2peak), peak heart rate (HRpeak), PPO, and LT derived from GXTs in hypoxia, with higher respiratory exchange ratio (RER), when compared to those from GXTs performed in normoxia (p < 0.001). Among the three HIIE sessions, the NA session resulted in lower percentage of HRpeak (85.0 ± 7.5% vs 94.4 ± 5.0%; p = 0.002) and V̇O2peak (74.1 ± 9.1% vs 88.7 ± 7.7%; p = 0.005), when compared to the NR session. HIIE sessions in HY and NR resulted in similar percentage of HRpeak and V̇O2peak, as well as similar rating of perceived exertion and RER. The blood lactate level increased immediately after all the three HIIE sessions (p < 0.001), while higher blood lactate concentrations were observed immediately after the HY (p = 0.0003) and NR (p = 0.014) sessions when compared with NA. ConclusionCombining of PPO and LT derived from GXTs can be used to prescribe exercise intensity of HIIE in hypoxia.

Effect of sub-technique transitions on energy expenditure and physiological load in the classical-style technique among elite male cross-country skiers

PurposeTo investigate whether sub-technique transitions in the classical-style technique are associated with increased energy expenditure and/or metabolic stress among elite male cross-country skiers.MethodsFifteen elite male skiers completed three 10-min treadmill roller-skiing tests, each of which consisted of 5 min using the diagonal-stride technique (DS) and 5 min using the double-poling technique (DP), combined in three various modes all ensuring comparable mechanical workload, at an inclination of 2.5° and a speed of 13 km/h. In the first and third tests, the participants used 5 min continuous DS followed by 5 min continuous DP, or vice versa (no transition (NT) test), whereas in the second test, they made transitions between DS and DP every 6 s (repeated transition (RT) test). The last 3 min of each 5-min stage was used to calculate the mean values of oxygen uptake ({dot{text{V}}text{O}}_{{2}}), respiratory exchange ratio (RER), metabolic rate (MR), mechanical work rate (MWR), and gross efficiency (GE). In addition, the pre–post-difference in blood lactate concentration (Ladiff) was determined for each test. Paired-samples t tests were used to investigate differences between tests.ResultsThere were no significant differences between NT and RT tests regarding V̇O2, MR, MWR, or GE. Conversely, significant differences were found in RER and Ladiff, where the NT test was associated with higher RER and Ladiff values.ConclusionsRoller skiing with repeated sub-technique transitions is not associated with an additional aerobic energy contribution; instead, the anaerobic energy contribution was lower compared to that under continuous use of DS and DP.

Individualized hemodynamic optimization guided by indirect measurement of the respiratory exchange ratio in major surgery: study protocol for a randomized controlled trial (the OPHIQUE study)

BackgroundObservational studies have suggested that a high respiratory exchange ratio (RER) is associated with the occurrence of postoperative complications. The study’s primary objective is to demonstrate that the incidence of postoperative complications is lower in an interventional group (patients monitored using a hemodynamic algorithm that incorporates the RER) than in a control group (treated according to standard practice).MethodsWe shall perform a prospective, multicenter, randomized, open-label, superiority trial of consecutive patients undergoing major noncardiac surgery (i.e., abdominal, vascular, and orthopedic surgery). The control group will be treated according to the current guidelines on standard hemodynamic care. The interventional group will be treated according to an algorithm based on the RER. The primary outcome will be the occurrence of at least one complication in the 7 days following surgery. The secondary outcomes will be the length of hospital stay, the total number of complications per patient, the 30-day mortality, the total intraoperative volume of fluids administered, and the Sequential [sepsis-related] Organ Failure Assessment (SOFA) score and laboratory data measured on postoperative days 1, 2, and 7. A total of 350 patients will be included.DiscussionIn the operating theater, the RER is potentially a continuously available, easy-to-read, indirect marker of tissue hypoperfusion and postoperative complications. If the RER does predict the occurrence of tissue hypoperfusion, it will help the physician to provide personalized hemodynamic management and limit the side effects associated with excessive hemodynamic optimization (volume overload, vasoconstriction, etc.).Trial registrationClinicalTrials.gov NCT03852147. Registered on February 25, 2019

Abstract P247: Gut Microbiota From A Rat Model Of Metabolic Syndrome Lowers Fitness Of High Exercise Capacity Rats (HCR/ Tol ) By Impairing Energy Homeostasis And Increasing Blood Pressure

Introduction: Low exercise capacity is a strong predictor of cardiovascular disease and overall mortality. Previously we have shown that rats artificially selected for low intrinsic exercise capacity (LCR) have reduced longevity and develop features consistent with metabolic syndrome (MetS) compared to high intrinsic exercise capacity rats (HCR). Current knowledge suggests that gut microbiota is an important contributor for host fitness. Thus, we hypothesized that transferring gut microbiota from LCR rats into inbred high capacity runner (HCR /Tol ) rats would increase risk factors for MetS, including high blood pressure (BP), gain in body weight (BW), and altered resting energy metabolism. Methods: Gut microbiota was depleted in male HCR/ Tol rats (4 mo.) by an antibiotic cocktail given orally (50mg/kg of BW/day) for 5 days, followed by weekly fecal microbiota transfer (FMT) from male LCR or HCR rats (13 mo.) to generate HCR/ Tol -LCR FMT (n = 5) or HCR/ Tol -HCR FMT (n = 6) groups. BW was measured every 4 weeks. At week 11, whole body metabolism was measured by indirect calorimetry (Oxymax, Columbus Instruments). Respiratory Exchange Ratio (RER), Energy Expenditure (EE), glucose and fat oxidation were calculated from oxygen consumption and carbon dioxide release (VO 2 and VCO 2 ). At week 12, BP was measured by tail-cuff method (Kent Scientific) and treadmill exercise test was done at week 13. Results: Compared to HCR/ Tol -HCR FMT , HCR/ Tol -LCR FMT showed a significant gain in BW (7.2% vs 1.9%, P&lt;0.05), elevated systolic BP (147 vs 120 mmHg, P&lt;0.0001), diastolic BP (112 vs 91 mmHg, P&lt;0.01), and mean BP (123 vs 100 mmHg, P&lt;0.001). BP changes in HCR/ Tol -LCR FMT associated with 1) increased VO 2 (355 vs 320 ml/hr, P&lt;0.05), 2) elevated VCO 2 (350 vs 298 ml/hr, P&lt;0.01), 3) increased EE (1.8 vs 1.6 kcal/hr, P&lt;0.01), 4) higher RER (0.96 vs 0.91, P&lt;0.001), 5) higher glucose oxidation (1.36 vs 1.12 g/kg/hr, P&lt;0.001) and 6) reduced fatty acid oxidation (0.09 vs 0.15 g/kg/hr, P&lt;0.01) and a 23% lower exercise capacity. Conclusions: Gut microbiota from LCR rats strongly associated with poor health outcomes, notably elevated BP and impaired energy metabolism. These findings suggest that altered energy homeostasis by microbiota is mechanistically linked to host BP regulation within MetS.

Regenerative Changes in Resting Energy Balance Demonstrating Metabolic Efficiency and Body Composition Normalization

Resting metabolism plays a critical role in healthy weight management. Metabolic adaptations in response to lifestyle cues induce acclimatization of factors involved in resting state energy homeostasis. PURPOSE: To determine the effects of dietary modification and exercise intensity on resting energy metabolism and body composition in sedentary female cohort. METHODS: Subjects (n=46) with >25% fat mass participated in 10-weeks of 200 kcal·24 h-1 caloric deficit, adherence to whole-foods, plant-based diet, and randomization into three exercise groups. Exercise intensity levels were set by respiratory exchange ratio (RER) ranges determined through submaximal VO2-uptake treadmill test; Low: RER=0.75 (n=16), Moderate: RER=0.85 (n=16), High RER=0.95 (n=14). Resting metabolic rate (RMR) variables—respiratory quotient (RQ), VO2, VCO2, resting energy expenditure (REE), and macronutrient substrate oxidation rates (KCHO, KFAT)—were measured using indirect calorimetry at pre and post treatment stages with whole-body air displacement plethysmography to obtain body composition profiles. One-way ANOVA was performed to evaluate mean changes in resting energy metabolism and body composition. RESULTS: Significant differences in RQ and VCO2 were noted between groups (F 1,46=7.88, p=.001; F 1,46=3.51, p=.039, respectively). Significant differences in KCHO and KFAT substrate oxidation rates were noted between groups likewise (F 1,46=5.74, p=.006; F 1,46=5.05, p=.011, respectively). Changes in total body mass showed significant differences (F 1,46=6.39, p=.004). The most positive improvements in metabolic efficiency variables were appreciated in the low and moderate intensity groups in post hoc analysis. CONCLUSION: The combination of modest caloric adjustment, adherence to plant-based diet, and participating in a low or moderate intensity exercise program confers positive changes in metabolic status and corrective energy homeostasis that promotes effective body composition normalization.

Chronic social stress in mice alters energy status including higher glucose need but lower brain utilization

Chronic stress leads to changes in energy status and is a major risk factor for depression, with common symptoms of reductions in body weight and effortful motivation for reward. Indeed, stress-induced disturbed energy status could be a major aetio-pathogenic factor for depression. Improved understanding of these putative inter-relationships requires animal model studies of effects of stress on both peripheral and central energy-status measures and determinants. Here we conducted a study in mice fed on a standard low-fat diet and exposed to either 15-day chronic social stress (CSS) or control handling (CON). Relative to CON mice, CSS mice had attenuated body weight maintenance/gain despite consuming the same amount of food and expending the same amount of energy at any given body weight. The low weight of CSS mice was associated with less white and brown adipose tissues, and with a high respiratory exchange ratio consistent with increased dependence on glucose as energy substrate. Basal plasma insulin was low in CSS mice and exogenous glucose challenge resulted in a relatively prolonged elevation of blood glucose. With regard to hunger and satiety hormones, respectively, CSS mice had higher levels of acylated ghrelin in plasma and of ghrelin receptor gene expression in ventromedial hypothalamus and lower levels of plasma leptin, relative to CON mice. However, whilst CSS mice displayed this constellation of peripheral changes consistent with increases in energy need and glucose utilization relative to CON mice, they also displayed attenuated uptake of [18F]FDG in brain tissue specifically. Reduced brain glucose utilization in CSS mice could contribute to the reduced effortful motivation for reward in the form of sweet-tasting food that we have reported previously for CSS mice. It will now be important to utilize this model to further understanding of the mechanisms via which chronic stress can increase energy need but decrease brain glucose utilization and how this relates to regional and cellular changes in neural circuits for reward processing relevant to depression.

Maximal oxygen uptake and concentric isokinetic muscle strength in pubertal football trained and untrained boys of the same biological age

The purpose of the present study was to examine the effects of long term (prolonged) football training on maximal oxygen uptake (VO2) and isokinetic muscle strength in young football players and untrained boys of the same biological age. Twenty football competitive boys (mean age 14 ± 0 yrs; height 165.5 ± 8.5 cm; weight 59.9 ± 9.5 kg; years of training 7 ± 3) and eighteen untrained school boys (mean age 14 ± 0; height 168.22 ± 10.46 cm; weight 59.3 ± 9.9 kg) of the same biological age volunteered to participate in the study. Sexual maturation classified according to Tanner’s stage 3. The football players participated both in their school’s physical education program and in their football team training program while the untrained group participated only in their school’s physical education program (2–3 times per week for 40 min). All subjects were tested for maximal oxygen uptake (VO2) and respiratory exchange ratio (RER) on the treadmill using an open circuit spirometry. The isokinetic peak torque values of quadriceps (Q) and hamstrings (H) as well as the H : Q strength ratios were recorded. Hcon : Qcon was calculated as the ratio of the peak concentric torque of H to the peak concentric torque of the Q. Results showed that the trained group had significantly lower heart rate in rest (p < 0.001), higher RER (p < 0.001), maximal blood lactate (BLmax) (p < 0.001) and higher VO2 max in both relative and absolute values (p < 0.001) compared to the untrained group. At angular velocities of 60 ° s−1 and 180 ° s−1 the relative peak torque of Q and H were significantly higher (Q = p < 0.01; H = p < 0.01). However, the absolute values of Q and H as well as the H : Q ratios at all angular velocities did not differ significantly between the two groups. The results suggest that systematic football training (intensity and duration) has a positive effect in metabolic capacity, cardiorespiratory system and neuromuscular function.

Lipolysis defect in white adipose tissue and rapid weight regain.

Weight regain after weight loss is a well-described phenomenon in both humans and animal models of obesity. Reduced energy expenditure and increased caloric intake are considered the main drivers of weight regain. We hypothesized that adipose tissue with obesity memory (OM) has a tissue-autonomous lipolytic defect, allowing for increased efficiency of lipid storage. We utilized a mouse model of diet-induced obesity, which was subjected to 60% caloric restriction to achieve lean body weight, followed by a short period of high-fat diet (HFD) rechallenge. Age-matched lean mice fed HFD for the first time were used as the control group. Upon rechallenge with HFD, mice with OM had higher respiratory exchange ratios than lean mice with no OM despite comparable body weight, suggesting higher utilization of glucose over fatty acid oxidation. White adipose tissue explants with OM had comparable lipolytic response after caloric restriction; however, reduced functional lipolytic response to norepinephrine was noted as early as 5 days after rechallenge with HFD and was accompanied by reduction in hormone-sensitive lipase serine phosphorylation. The relative lipolytic defect was associated with increased expression of inflammatory genes and a decrease in adrenergic receptor genes, most notably Adrb3. Taken together, white adipose tissue of lean mice with OM shows increased sensitization to HFD compared with white adipose tissue with no OM, rendering it resistant to catecholamine-induced lipolysis. This relative lipolytic defect is tissue-autonomous and could play a role in the rapid weight regain observed after weight loss.

Impact of High Respiratory Exchange Ratio During Submaximal Exercise on Adverse Clinical Outcome in Heart Failure

Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown. Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I-III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2 had an inverse correlation with RER at AT workload (r=-0.256), but not at rest (r=-0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER (<0.97) groups. Patients with high RER at AT workload were characterized by older age, lower body mass index, anemia, and advanced NYHA class. After propensity score matching, peak V̇O2 tended to be lower in the high-RER than in the low-RER group (14.9±4.5 vs. 16.1±5.0 mL/kg/min, P=0.06). On Kaplan-Meier analysis, HF patients with a high RER at AT workload had significantly worse clinical outcomes, including all-cause mortality and rate of readmission due to HF worsening over 3 years (29% vs. 15%, P=0.01). High RER during submaximal exercise, particularly at AT workload, is associated with poor clinical outcome in HF patients.