Oxygen metabolism after cardiac arrest: Patterns and associations with survival.

Aim: Whether 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. Methods: Adults 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. Results: Sixty 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). Conclusion: Higher 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.

Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb-/- mice.

Myoglobin (Mb) plays an important role at rest and during exercise as a reservoir of oxygen and has been suggested to regulate NO• bioavailability under hypoxic/acidic conditions. However, its ultimate role during exercise is still a subject of debate. We aimed to study the effect of Mb deficiency on maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and exercise performance in myoglobin knockout mice (Mb-/- ) when compared to control mice (Mb+/+ ). Furthermore, we also studied NO• bioavailability, assessed as nitrite (NO2 - ) and nitrate (NO3 - ) in the heart, locomotory muscle and in plasma, at rest and during exercise at exhaustion both in Mb-/- and in Mb+/+ mice. The mice performed maximal running incremental exercise on a treadmill with whole-body gas exchange measurements. The Mb-/- mice had lower body mass, heart and hind limb muscle mass (P < 0.001). Mb-/- mice had significantly reduced maximal running performance (P < 0.001). V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ expressed in ml min-1 in Mb-/ - mice was 37% lower than in Mb+/+ mice (P < 0.001) and 13% lower when expressed in ml min-1  kg body mass-1 (P = 0.001). Additionally, Mb-/- mice had significantly lower plasma, heart and locomotory muscle NO2 - levels at rest. During exercise NO2 - increased significantly in the heart and locomotory muscles of Mb-/- and Mb+/+ mice, whereas no significant changes in NO2 - were found in plasma. Our study showed that, contrary to recent suggestions, Mb deficiency significantly impairs V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance in mice. KEY POINTS: Myoglobin knockout mice (Mb-/- ) possess lower maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and poorer maximal running performance than control mice (Mb+/+ ). Respiratory exchange ratio values at high running velocities in Mb-/- mice are higher than in control mice suggesting a shift in substrate utilization towards glucose metabolism in Mb-/- mice at the same running velocities. Lack of myoglobin lowers basal systemic and muscle NO• bioavailability, but does not affect exercise-induced NO2 - changes in plasma, heart and locomotory muscles. The present study demonstrates that myoglobin is of vital importance for V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance as well as explains why previous studies have failed to prove such a role of myoglobin when using the Mb-/- mouse model.

Effect of exogenous and endogenous ketones on respiratory exchange ratio and glucose metabolism in healthy subjects.

This study examined the effect of exogenous ketone bodies (KB) on oxygen consumption (V̇o2), carbon dioxide production (V̇co2), and glucose metabolism. The data were compared with the effects of endogenous ketonemia during both, a ketogenic diet or fasting. Eight healthy individuals [24.1 ± 2.5 yr, body mass index (BMI) 24.3 ± 3.1 kg/m2] participated in a crossover intervention study and were studied in a whole-room indirect calorimeter (WRIC) to assess macronutrient oxidation following four 24-h interventions: isocaloric controlled mixed diet (ISO), ISO supplemented with ketone salts (38.7 g of ß-hydroxybutyrate/day, EXO), isocaloric ketogenic diet (KETO), and total fasting (FAST). A physical activity level of 1.65 was obtained. In addition to plasma KB, 24-h C-peptide and KB excretion rates in the urine and postprandial glucose and insulin levels were measured. Although 24-h KB excretion increased in response to KETO and FAST, there was a modest increase in response to EXO only (P < 0.05). When compared with ISO, V̇o2 significantly increased in KETO (P < 0.01) and EXO (P < 0.001), whereas there was no difference in FAST. V̇co2 increased in EXO but decreased in KETO (both P < 0.01) and FAST (P < 0.001), resulting in 24-h respiratory exchange ratios (RER) of 0.828 ± 0.024 (ISO) and 0.811 ± 0.024 (EXO) (P < 0.05). In response to EXO there were no differences in basal and postprandial glucose and insulin levels, as well as in insulin sensitivity. When compared with ISO, EXO, and KETO, FAST increased homeostatic model assessment ß-cell function (HOMA-B) (all P < 0.05). In conclusion, at energy balance exogenous ketone salts decreased respiratory exchange ratio without affecting glucose tolerance.NEW & NOTEWORTHY Our findings revealed that during isocaloric nutrition, additional exogenous ketone salts increased V̇o2 and V̇co2 while lowering the respiratory exchange ratio (RER). Ketone salts had no effect on postprandial glucose metabolism.

Activated CTHRC1 promotes glycolysis in endothelial cells: Implications for metabolism and angiogenesis.

CTHRC1 is transiently expressed by activated fibroblasts during tissue repair and in certain cancers, and CTHRC1 derived from osteocytes is detectable in circulation. Because its biological activity is poorly understood, we investigated whether the N terminus of CTHRC1 encodes a propeptide requiring cleavage to become activated. The effects of full-length versus cleaved recombinant CTHRC1 on endothelial cell metabolism and gene expression were examined in vitro. Respirometry was performed on Cthrc1 null and wildtype mice to obtain evidence for biological activity of CTHRC1 in vivo. Cleavage of the propeptide observed in vitro was attenuated in the presence of protease inhibitors, and cleaved CTHRC1 significantly promoted glycolysis whereas full-length CTHRC1 was less effective. The respiratory exchange ratio was significantly higher in wildtype mice compared to Cthrc1 null mice, supporting the findings of CTHRC1 promoting glycolysis in vivo. Key enzymes involved in glycolysis were significantly upregulated in endothelial cells in response to treatment with CTHRC1. In healthy human subjects, 58% of the cohort had detectable levels of circulating full-length CTHRC1, whereas all subjects with undetectable levels of full-length CTHRC1 (with one exception) had measurable levels of truncated CTHRC1 (88 pg/ml to >400 ng/ml). Our findings support a concept where CTHRC1 induction in activated fibroblasts at sites of ischemia such as tissue injury or cancer functions to increase glycolysis for ATP production under hypoxic conditions, thereby promoting cell survival and tissue repair. By promoting glycolysis under normoxic conditions, CTHRC1 may also be a contributor to the Warburg effect characteristically observed in many cancers.

Osmotic and metabolic responses to cold acclimation and acute cold challenge in a freeze avoidant lizard, Podarcis siculus.

Ectotherms survive exposure to subzero temperatures through freeze tolerance or freeze avoidance. Among vertebrate ectotherms, glucose is commonly used as a cryoprotectant in freeze tolerant strategies and as an osmolyte in freeze avoidant strategies, while also functioning as a metabolic substrate. Whereas some lizard species are capable of both freeze tolerance and freeze avoidance, Podarcis siculus is limited to freeze avoidance through supercooling. We hypothesized that, even in a freeze-avoidant species such as P. siculus, plasma glucose would accumulate with cold acclimation and would increase in response to acute exposure to subzero temperatures. To investigate this, we tested whether plasma glucose concentration and osmolality would increase in response to a subzero cold challenge before and after cold acclimation. In addition, we examined the relationship between metabolic rate, cold acclimation, and glucose by measuring metabolic rate during the cold challenge trials. We found that plasma glucose increased during the cold challenge trials, and that the increase was more pronounced after cold acclimation. However, baseline plasma glucose decreased throughout cold acclimation. Interestingly, total plasma osmolality did not change, and the increase in glucose only slightly altered freezing point depression. Metabolic rate during the cold challenge decreased after cold acclimation, and changes in respiratory exchange ratio suggest an increased relative use of carbohydrates. Overall, our findings demonstrate an important role for glucose in the response of P. siculus to an acute cold challenge, thus adding evidence for glucose as an important molecule for overwintering ectotherms that use freeze avoidant strategies.

Low-dose peripheral leptin infusion produces selective activation of ventromedial hypothalamic and hindbrain STAT3.

Previous studies have shown that very low dose, acute, single peripheral leptin injections fully activate arcuate nucleus signal transducer and activator of transcription 3 (STAT3), but ventromedial hypothalamus (VMH) pSTAT3 continues to increase with higher doses of leptin that inhibit food intake. The lowest dose that inhibited intake increased circulating leptin 300-fold whereas food intake is inhibited by chronic peripheral leptin infusions that only double circulating leptin. This study examined whether the pattern of hypothalamic pSTAT3 was the same in leptin-infused rats as in leptin-injected rats. Male Sprague-Dawley rats received intraperitoneal infusions of 0, 5, 10, 20, or 40 µg leptin/day for 9 days. The highest dose of leptin increased serum leptin by 50-100%, inhibited food intake for 5 days, but inhibited weight gain and retroperitoneal fat mass for 9 days. Energy expenditure, respiratory exchange ratio, and brown fat temperature did not change. pSTAT3 was quantified in hypothalamic nuclei and the nucleus of the solitary tract (NTS) when food intake was inhibited and when it had returned to control levels. There was no effect of leptin on pSTAT3 in the medial or lateral arcuate nucleus or in the dorsomedial nucleus of the hypothalamus. VMH pSTAT3 was increased only at day 4 when food intake was inhibited, but NTS pSTAT3 was increased at both 4 and 9 days of infusion. These results suggest that activation of leptin VMH receptors contributes to the suppression of food intake, but that hindbrain receptors contribute to a sustained change in metabolism that maintains a reduced weight and fat mass.NEW & NOTEWORTHY Low-dose, chronic peripheral infusions of leptin produced an initial, transient inhibition of food intake that correlated with signal transducer and activator of transcription 3 (STAT3) activation in the ventromedial hypothalamus (VMH) and nucleus of the solitary tract (NTS). When intake normalized, but weight remained suppressed, the NTS was the only area that remained activated. These data suggest that leptin's primary function is to reduce body fat, that hypophagia is a means of achieving this and that different areas of the brain are responsible for the progressive response.

Respiratory gas kinetics in patients with congestive heart failure during recovery from peak exercise.

BACKGROUND: Cardiopulmonary Exercise Testing (CPX) is essential for the assessment of exercise capacity for patients with Chronic Heart Failure (CHF). Respiratory gas and hemodynamic parameters such as Ventilatory Efficiency (VE/VCO2 slope), peak oxygen uptake (peak VO2), and heart rate recovery are established diagnostic and prognostic markers for clinical populations. Previous studies have suggested the clinical value of metrics related to respiratory gas collected during recovery from peak exercise, particularly recovery time to 50% (T1/2) of peak VO2. The current study explores these metrics in detail during recovery from peak exercise in CHF. METHODS: Patients with CHF who were referred for CPX and healthy individuals without formal diagnoses were assessed for inclusion. All subjects performed CPX on cycle ergometers to volitional exhaustion and were monitored for at least five minutes of recovery. CPX data were analyzed for overshoot of respiratory exchange ratio (RER=VCO2/VO2), ventilatory equivalent for oxygen (VE/VO2), end-tidal partial pressure of oxygen (PETO2), and T1/2 of peak VO2 and VCO2. RESULTS: Thirty-two patients with CHF and 30 controls were included. Peak VO2 differed significantly between patients and controls (13.5 ± 3.8 vs. 32.5 ± 9.8 mL/Kg*min-1, p < 0.001). Mean Left Ventricular Ejection Fraction (LVEF) was 35.9 ± 9.8% for patients with CHF compared to 61.1 ± 8.2% in the control group. The T1/2 of VO2, VCO2 and VE was significantly higher in patients (111.3 ± 51.0, 132.0 ± 38.8 and 155.6 ± 45.5s) than in controls (58.08 ± 13.2, 74.3 ± 21.1, 96.7 ± 36.8s; p < 0.001) while the overshoot of PETO2, VE/VO2 and RER was significantly lower in patients (7.2 ± 3.3, 41.9 ± 29.1 and 25.0 ± 13.6%) than in controls (10.1 ± 4.6, 62.1 ± 17.7 and 38.7 ± 15.1%; all p < 0.01). Most of the recovery metrics were significantly correlated with peak VO2 in CHF patients, but not with LVEF. CONCLUSIONS: Patients with CHF have a significantly blunted recovery from peak exercise. This is reflected in delays of VO2, VCO2, VE, PETO2, RER and VE/VO2, reflecting a greater energy required to return to baseline. Abnormal respiratory gas kinetics in CHF was negatively correlated with peak VO2 but not baseline LVEF.

Indirect Calorimetry to Measure Metabolic Rate and Energy Expenditure in Psychiatric Populations: A Systematic Review.

Psychiatric and metabolic disorders are highly comorbid and the relationship between these disorders is bidirectional. The mechanisms underlying the association between psychiatric and metabolic disorders are presently unclear, which warrants investigation into the dynamics of the interplay between metabolism, substrate utilization, and energy expenditure in psychiatric populations, and how these constructs compare to those in healthy controls. Indirect calorimetry (IC) methods are a reliable, minimally invasive means for assessing metabolic rate and substrate utilization in humans. This review synthesizes the extant literature on the use of IC on resting metabolism in psychiatric populations to investigate the interaction between psychiatric and metabolic functioning. Consistently, resting energy expenditures and/or substrate utilization values were significantly different between psychiatric and healthy populations in the studies contained in this review. Furthermore, resting energy expenditure values were systematically overestimated when derived from predictive equations, compared to when measured by IC, in psychiatric populations. High heterogeneity between study populations (e.g., differing diagnoses and drug regimens) and methodologies (e.g., differing posture, time of day, and fasting status at measurement) impeded the synthesis of results. Standardized IC protocols would benefit this line of research by enabling meta-analyses, revealing trends within and between different psychiatric disorders.

Moderators of peak respiratory exchange ratio during exercise testing in children and adolescents with Fontan physiology.

OBJECTIVES: Many patients with Fontan physiology are unable to achieve the minimum criteria for peak effort during cardiopulmonary exercise testing. The purpose of this study is to determine the influence of physical activity and other clinical predictors related to achieving peak exercise criteria, signified by respiratory exchange ratio ≥ 1.1 in youth with Fontan physiology. METHODS: Secondary analysis of a cross-sectional study of 8-18-year-olds with single ventricle post-Fontan palliation who underwent cardiopulmonary exercise testing (James cycle protocol) and completed a past-year physical activity survey. Bivariate associations were assessed by Wilcoxon rank-sum test and simple regression. Conditional inference forest algorithm was used to classify participants achieving respiratory exchange ratio > 1.1 and to predict peak respiratory exchange ratio. RESULTS: Of the n = 43 participants, 65% were male, mean age was 14.0 ± 2.4 years, and 67.4% (n = 29) achieved respiratory exchange ratio ≥ 1.1. Despite some cardiopulmonary exercise stress test variables achieving statistical significance in bivariate associations with participants achieving respiratory exchange ratio > 1.1, the classification accuracy had area under the precision recall curve of 0.55. All variables together explained 21.4% of the variance in respiratory exchange ratio, with peak oxygen pulse being the most informative. CONCLUSION: Demographic, physical activity, and cardiopulmonary exercise test measures could not classify meeting peak exercise criteria (respiratory exchange ratio ≥ 1.1) at a satisfactory accuracy. Correlations between respiratory exchange ratio and oxygen pulse suggest the augmentation of stroke volume with exercise may affect the Fontan patient's ability to sustain high-intensity exercise.

It is time to abandon single-value oxygen uptake energy equivalents.

Physiologists commonly use single-value energy equivalents (e.g., 20.1 kJ/LO2 and 20.9 kJ/LO2) to convert oxygen uptake (V̇o2) to energy, but doing so ignores how the substrate oxidation ratio (carbohydrate:fat) changes across aerobic intensities. Using either 20.1 kJ/LO2 or 20.9 kJ/LO2 can incur systematic errors of up to 7%. In most circumstances, the best approach for estimating energy expenditure is to measure both V̇o2 and V̇co2 and use accurate, species-appropriate stoichiometry. However, there are circumstances when V̇co2 measurements may be unreliable. In those circumstances, we recommend that the research report or compare only V̇o2.NEW & NOTEWORTHY We quantify that the common practice of using single-value oxygen uptake energy equivalents for exercising subjects can incur systematic errors of up to 7%. We argue that such errors can be greatly reduced if researchers measure both V̇o2 and V̇co2 and adopt appropriate stoichiometry equations.

Notational Analysis and Physiological and Metabolic Responses of Male Junior Badminton Match Play.

We examined the game characteristics of badminton and the physiological and metabolic responses in highly trained male junior players. Players from a Badminton England accredited Performance Centre (n = 10, age: 14.0 ± 1.2 y, height: 1.69 ± 0.06 m, body mass: 59.1 ± 5.0 kg) completed a 20-m shuttle run test (V˙O2max: 64 ± 7 mL·kg-1·min-1) and a simulated ability-matched competitive singles badminton game consisting of two 12-min games with a 2-min break wearing the COSMED K5 metabolic system with notational analysis. In five games, 427 points were contested with a rally time of 5.7 ± 3.7 s, a rest time of 11.2 ± 5.9 s, shots per rally of 5.6 ± 3.6, work density of 0.50 ± 0.21, an effective playing time of 32.3 ± 8.4%, and shots frequency of 1.04 ± 0.29. During badminton play, heart rate was 151 ± 12 b·min-1 (82 ± 10% of maximum heart rate), oxygen uptake was 39.2 ± 3.9 mL·kg-1·min-1 (62 ± 7% of V˙O2max), and energy expenditure was 11.2 ± 1.1 kcal·min-1 with a post-game blood lactate of 3.33 ± 0.83 mmol·L-1. Compared to adult badminton play, the physiological responses of junior badminton are lower and may be due to the shorter rally durations. Male junior badminton players should be exposed to training methodologies which include rally durations in excess of what they encounter during match play so as to develop greater consistency. Our observations on game characteristics and physiological responses during junior badminton can be used to inform training practice.

Is the Verification Phase a Suitable Criterion for the Determination of Maximum Oxygen Uptake in Patients with Heart Failure and Reduced Ejection Fraction? A Validation Study.

The verification phase (VP) has been proposed as an alternative to the traditional criteria used for the determination of the maximum oxygen uptake (VO2 max) in several populations. Nonetheless, its validity in patients with heart failure with reduced ejection fraction (HFrEF) remains unclear. Therefore, the aim of this study was to analyse whether the VP is a safe and suitable method to determine the VO2 max in patients with HFrEF. Adult male and female patients with HFrEF performed a ramp-incremental phase (IP), followed by a submaximal constant VP (i.e., 95% of the maximal workload during the IP) on a cycle ergometer. A 5-min active recovery period (i.e., 10 W) was performed between the two exercise phases. Group (i.e., median values) and individual comparisons were performed. VO2 max was confirmed when there was a difference of ≤ 3% in peak oxygen uptake (VO2 peak) values between the two exercise phases. Twenty-one patients (13 males) were finally included. There were no adverse events during the VP. Group comparisons showed no differences in the absolute and relative VO2 peak values between both exercise phases (p = 0.557 and p = 0.400, respectively). The results did not change when only male or female patients were included. In contrast, individual comparisons showed that the VO2 max was confirmed in 11 patients (52.4%) and not confirmed in 10 (47.6%). The submaximal VP is a safe and suitable method for the determination of the VO2 max in patients with HFrEF. In addition, an individual approach should be used because group comparisons could mask individual differences.

Effects of Coix seed extract, Lactobacillus paracasei K56, and their combination on the glycolipid metabolism in obese mice.

Coix seed extract (CSE) and probiotics have been reported to regulate glycolipid metabolism through different modes of action. We tested the effects of CSE, Lactobacillus paracasei K56, and their combination to determine whether they have synergistic effects on glycolipid metabolism of obese mice. We fed male C57BL/6J mice with high-fat diet for 8 weeks to establish an obesity model. The obesity mice were selected and divided into five groups: the model control group and four intervention groups. After 10 weeks of continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower about 2.31-4.41 g, vs. HFD 42.25 g, p < 0.01), and epididymal (lower about 0.58-0.92 g, vs. HFD 2.50 g, p < 0.01) and perirenal fat content (lower about 0.24-0.42 g, vs. HFD 0.88 g, p < 0.05); decreased fasting blood glucose, total cholesterol, triglycerides, and VLDL; and increased HLDL, respiratory exchange ratio, energy expenditure, and amount of exercise performed. K56 + CSE-combined intervention groups were more effective in lowering blood glucose, IL-1ß, and TNF-α levels than the CSE and K56 alone interventions. The content of fatty acid synthase and SREBP-1c protein in liver tissue was lower. The combination has synergistic effects on weight control, fat reduction, and blood glucose regulation by improving the chronic inflammatory state and reducing the content of lipid synthesis-related enzymes of obese mice, which can hinder chronic disease progression. PRACTICAL APPLICATION: Coix seed extract can be used in obese people to regulate abnormal glucose and lipid metabolism and delay the development of chronic diseases.

Niacin supplementation impairs exercise performance.

Several pre-workout supplements contain niacin, although the exercise performance effects of niacin are poorly understood. The purpose of the present study was to examine the performance effects of niacin versus caffeine as a pre-workout supplement. Twenty-five untrained males were recruited to complete three identical ramped aerobic cycling exercise trials. Participants were administered caffeine (CA) at 5 mg/kg body weight, 1000 mg niacin (NI), or a methylcelluloce placebo (PL) supplement prior to each trial. NI treatment induced significantly higher respiratory exchange ratio (RER) during exercise compared to the CA treatment, but not the PL treatment (PL=0.87±0.08, NI=0.91±0.08, CA=0.87±0.08; p=0.02). Similarly, exercise time to exhaustion (in minutes) was significantly different between the NI treatment and the CA treatment, but not the PL treatment (PL=27.45±4.47, NI=26.30±4.91, CA=28.76±4.86; p<0.01). Habitual caffeine use (p=0.16), habitual aerobic exercise (p=0.60), and habitual resistance exercise (p=0.10) did not significantly affect RER. Similarly, habitual caffeine use (p=0.72), habitual aerobic exercise (p=0.08), and habitual resistance exercise (p=0.39) did not significantly affect total work performed. The elevated RER and decreased time to exhaustion in the NI treatment suggests limited lipid availability during exercise and impaired exercise performance.

Respiratory gas kinetics in patients with congestive heart failure during recovery from peak exercise

Abstract Background Cardiopulmonary Exercise Testing (CPX) is essential for the assessment of exercise capacity for patients with Chronic Heart Failure (CHF). Respiratory gas and hemodynamic parameters such as Ventilatory Efficiency (VE/VCO2 slope), peak oxygen uptake (peak VO2), and heart rate recovery are established diagnostic and prognostic markers for clinical populations. Previous studies have suggested the clinical value of metrics related to respiratory gas collected during recovery from peak exercise, particularly recovery time to 50% (T1/2) of peak VO2. The current study explores these metrics in detail during recovery from peak exercise in CHF. Methods Patients with CHF who were referred for CPX and healthy individuals without formal diagnoses were assessed for inclusion. All subjects performed CPX on cycle ergometers to volitional exhaustion and were monitored for at least five minutes of recovery. CPX data were analyzed for overshoot of respiratory exchange ratio (RER=VCO2/VO2), ventilatory equivalent for oxygen (VE/VO2), end-tidal partial pressure of oxygen (PETO2), and T1/2 of peak VO2 and VCO2. Results Thirty-two patients with CHF and 30 controls were included. Peak VO2 differed significantly between patients and controls (13.5 ± 3.8 vs. 32.5 ± 9.8 mL/Kg*min−1, p < 0.001). Mean Left Ventricular Ejection Fraction (LVEF) was 35.9 ± 9.8% for patients with CHF compared to 61.1 ± 8.2% in the control group. The T1/2 of VO2, VCO2 and VE was significantly higher in patients (111.3 ± 51.0, 132.0 ± 38.8 and 155.6 ± 45.5s) than in controls (58.08 ± 13.2, 74.3 ± 21.1, 96.7 ± 36.8s; p < 0.001) while the overshoot of PETO2, VE/VO2 and RER was significantly lower in patients (7.2 ± 3.3, 41.9 ± 29.1 and 25.0 ± 13.6%) than in controls (10.1 ± 4.6, 62.1 ± 17.7 and 38.7 ± 15.1%; all p < 0.01). Most of the recovery metrics were significantly correlated with peak VO2 in CHF patients, but not with LVEF. Conclusions Patients with CHF have a significantly blunted recovery from peak exercise. This is reflected in delays of VO2, VCO2, VE, PETO2, RER and VE/VO2, reflecting a greater energy required to return to baseline. Abnormal respiratory gas kinetics in CHF was negatively correlated with peak VO2 but not baseline LVEF.

A Cyclist on a Tricyclic: Exercise Intolerance Due to Chronotropic Incompetence.

Depression in athletes is prevalent, and antidepressant treatment may have a cardiovascular impact. We present a case, documented by serial exercise testing, of exertional intolerance due to chronotropic incompetence associated with tricyclic antidepressant use. This case underscores the importance of understanding the mechanism of action and side effects of antidepressants. (Level of Difficulty: Advanced.).

Acute Effects of Whole-Body Electromyostimulation on Energy Expenditure at Resting and during Uphill Walking in Healthy Young Men.

The effects of the different electrical frequencies of whole-body electrical stimulation (WB-EMS) on energy expenditure (EE) and the respiratory exchange ratio (RER) remain poorly understood. This study aimed to determine the effects of different WB-EMS electrical frequencies on EE and the RER during supine resting and uphill walking. A total of 10 healthy and recreationally active men (21.6 ± 3.3 years old) participated in the present study. Participants completed two testing sessions in a randomized order. In each session, a variety of impulse frequencies (1 hertz (Hz), 2 Hz, 4 Hz, 6 Hz, 8 Hz, and 10 Hz) were applied in a randomized order, allowing a 10 min passive recovery between them. Oxygen consumption and carbon dioxide production were measured to calculate EE and the RER. All frequencies increased EE at rest (all p ≤ 0.001), with 4 Hz being the frequency producing the highest increase (Δ = 8.89 ± 1.49 kcal/min), as did 6 Hz (Δ = 8.05 ± 1.52 kcal/min) and 8 Hz (Δ = 7.04 ± 2.16 kcal/min). An increment in the RER at rest was observed with 4 Hz, 6 Hz, 8 Hz and 10 Hz (all p ≤ 0.016), but not with 1 Hz and 2 Hz (p ≥ 0.923). During uphill walking, the frequency that elicited the highest increase in EE was 6 Hz (Δ = 4.87 ± 0.84 kcal/min) compared to the unstimulated condition. None of the impulse frequencies altered the RER during uphill walking. WB-EMS increases EE in healthy young men both during resting and uphill walking.

A Novel Non-invasive Index of Cardiopulmonary Reserve for the Prediction of Failure of Weaning From Mechanical Ventilation.

PURPOSE: To develop an easy-to-implement prediction index of weaning failure for ICU patients. Materials and methods: We developed a prediction index modifying respiratory exchange ratio (RER), Mod-RER, a parameter measured during the cardiopulmonary exercise test (CPET) based on respiratory quotient. The Mod-RER index is the ratio of partial pressure of CO2 in central venous blood over the difference of partial pressure of O2 in arterial and central venous blood (Mod-RER=PcvCO2/PaO2-PcvO2, where PcvCO2 = partial pressure of CO2 in central venous blood, PaO2 = partial pressure of O2 in arterial blood, and PcvO2 = partial pressure of O2 in central venous blood). We prospectively tested its predictive value, compared to other indices of weaning outcome, in an observational study of difficult-to-wean ICU patients. RESULTS: Mod-RER index increased significantly only in failed trials and receiver operating characteristic (ROC) analysis for prediction of outcome based on Mod-RER index change had an area under the curve (AUC) 0.80 (p<0.001). Mod-RER change exhibited the highest sensitivity (84.6%) and specificity (78.1%) among the tested indices, with the optimal cut-off of 19.3%. Comparison of AUCs did not reach statistical significance (p=0.106). CONCLUSIONS: We conclude that Mod-RER index is an accurate, easy-to-use prediction tool of weaning failure, useful in decision making of timely extubation of ICU patients, especially in the demanding era of the coronavirus disease 2019 (COVID-19) pandemic.

A Cardiac Amino-Terminal GRK2 Peptide Inhibits Maladaptive Adipocyte Hypertrophy and Insulin Resistance During Diet-Induced Obesity.

Heart disease remains the leading cause of death, and mortality rates positively correlate with the presence of obesity and diabetes. Despite the correlation between cardiac and metabolic dysregulation, the mechanistic pathway(s) of interorgan crosstalk still remain undefined. This study reveals that cardiac-restricted expression of an amino-terminal peptide of GRK2 (ßARKnt) preserves systemic and cardiac insulin responsiveness, and protects against adipocyte maladaptive hypertrophy in a diet-induced obesity model. These data suggest a cardiac-driven mechanism to ameliorate maladaptive cardiac remodeling and improve systemic metabolic homeostasis that may lead to new treatment modalities for cardioprotection in obesity and obesity-related metabolic syndromes.

Effect of a High Fat Diet vs. High Carbohydrate Diets With Different Glycemic Indices on Metabolic Parameters in Male Endurance Athletes: A Pilot Trial.

Consuming low glycemic carbohydrates leads to an increased muscle fat utilization and preservation of intramuscular glycogen, which is associated with improved flexibility to metabolize either carbohydrates or fats during endurance exercise. The purpose of this trial was to investigate the effect of a 4-week high fat low carbohydrate (HFLC-G: ≥65% high glycemic carbohydrates per day; n = 9) vs. high carbohydrate low glycemic (LGI-G: ≥65% low glycemic carbohydrates daily; n = 10) or high glycemic (HGI-G: ≥65% fat, ≤ 50 g carbohydrates daily; n = 9) diet on fat and carbohydrate metabolism at rest and during exercise in 28 male athletes. Changes in metabolic parameters under resting conditions and during cycle ergometry (submaximal and with incremental workload) from pre- to post-intervention were determined by lactate diagnostics and measurements of the respiratory exchange ratio (RER). Additionally, body composition and perceptual responses to the diets [visual analog scale (VAS)] were measured. A significance level of α = 0.05 was considered. HFLC-G was associated with markedly decreased lactate concentrations during the submaximal (-0.553 ± 0.783 mmol/l, p = 0.067) and incremental cycle test [-5.00 ± 5.71 (mmol/l) × min; p = 0.030] and reduced RER values at rest (-0.058 ± 0.108; p = 0.146) during the submaximal (-0.078 ± 0.046; p = 0.001) and incremental cycle test (-1.64 ± 0.700 RER × minutes; p < 0.001). In the HFLC-G, fat mass (p < 0.001) decreased. In LGI-G lactate, concentrations decreased in the incremental cycle test [-6.56 ± 6.65 (mmol/l) × min; p = 0.012]. In the LGI-G, fat mass (p < 0.01) and VAS values decreased, indicating improved levels of gastrointestinal conditions and perception of effort during training. The main findings in the HGI-G were increased RER (0.047 ± 0.076; p = 0.117) and lactate concentrations (0.170 ± 0.206 mmol/l, p = 0.038) at rest. Although the impact on fat oxidation in the LGI-G was not as pronounced as following the HFLC diet, the adaptations in the LGI-G were consistent with an improved metabolic flexibility and additional benefits regarding exercise performance in male athletes.