Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction: The CAMEO-DAPA Trial.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors reduce risk of hospitalization for heart failure in patients who have heart failure with preserved ejection fraction (HFpEF), but the hemodynamic mechanisms underlying these benefits remain unclear. This study sought to determine whether treatment with dapagliflozin affects pulmonary capillary wedge pressure (PCWP) at rest and during exercise in patients with HFpEF. METHODS: This was a single-center, double-blinded, randomized, placebo-controlled trial testing the effects of 10 mg of dapagliflozin once daily in patients with HFpEF. Patients with New York Heart Association class II or III heart failure, ejection fraction ≥50%, and elevated PCWP during exercise were recruited. Cardiac hemodynamics were measured at rest and during exercise using high-fidelity micromanometers at baseline and after 24 weeks of treatment. The primary end point was a change from baseline in rest and peak exercise PCWPs that incorporated both measurements, and was compared using a mixed-model likelihood ratio test. Key secondary end points included body weight and directly measured blood and plasma volumes. Expired gas analysis was performed evaluate oxygen transport in tandem with arterial lactate sampling. RESULTS: Among 38 patients completing baseline assessments (median age 68 years; 66% women; 71% obese), 37 completed the trial. Treatment with dapagliflozin resulted in reduction in the primary end point of change in PCWP at rest and during exercise at 24 weeks relative to treatment with placebo (likelihood ratio test for overall changes in PCWP; P<0.001), with lower PCWP at rest (estimated treatment difference [ETD], -3.5 mm Hg [95% CI, -6.6 to -0.4]; P=0.029) and maximal exercise (ETD, -5.7 mm Hg [95% CI, -10.8 to -0.7]; P=0.027). Body weight was reduced with dapagliflozin (ETD, -3.5 kg [95% CI, -5.9 to -1.1]; P=0.006), as was plasma volume (ETD, -285 mL [95% CI, -510 to -60]; P=0.014), but there was no significant effect on red blood cell volume. There were no differences in oxygen consumption at 20-W or peak exercise, but dapagliflozin decreased arterial lactate at 20 W (-0.70 ± 0.77 versus 0.37 ± 1.29 mM; P=0.006). CONCLUSIONS: In patients with HFpEF, treatment with dapagliflozin reduces resting and exercise PCWP, along with the favorable effects on plasma volume and body weight. These findings provide new insight into the hemodynamic mechanisms of benefit with sodium-glucose cotransporter-2 inhibitors in HFpEF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04730947.

Effect of Dexmedetomidine on Intestinal Barrier in Patients Undergoing Gastrointestinal Surgery-A Single-Center Randomized Clinical Trial.

INTRODUCTION: Gastrointestinal failure results in death in critically ill patients. This study aimed to explore the effect of dexmedetomidine (DEX) on intestinal barrier function and its mechanism in critically ill patients undergoing gastrointestinal surgery. METHODS: Patients undergoing gastrointestinal surgery were randomized into the DEX group (n = 21) or midazolam (MID) group (n = 21). Sufentanil was used for analgesia in both groups. In the DEX group, DEX was loaded (1 µg/kg) before sedation and infused (0.7 µg/kg/h) during sedation. In the MID group, MID was loaded (0.05 mg/kg) before sedation and infused (0.1 mg/kg/h) during sedation. The mean arterial pressure , heart rate , borborygmus resumption time , first defecation time, length of intensive care unit stay, and length of hospital stay were observed. The diamine oxidase (DAO), D-lactate , TNF-α, IL-6, and α7nAChR levels in plasma or hemocytes were detected before the start of sedation (0 h) and after sedation (24 h). RESULTS: No significant differences in age, sex, body mass index, Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were noted (P > 0.05). The mean arterial pressure between 0 h and 24 h showed no significant difference between the groups (P > 0.05), but the heart rate was significantly lower in the DEX group (P = 0.042). The borborygmus resumption time was significantly earlier in the DEX group (P = 0.034). The lengths of intensive care unit stay (P = 0.016) and hospital stay (P = 0.031) were significantly shorter in the DEX group. The TNF-α level in the DEX group was lower at 24 h than 0 h. The D-lactate level was significantly lower in the DEX group than the MID group at 24 h (P = 0.016). The expression of α7nAChR in the DEX group was significantly higher at 24 h than 0 h (P < 0.05). CONCLUSIONS: DEX maintained intestinal barrier integrity in patients undergoing gastrointestinal surgery through the cholinergic anti-inflammatory pathway.

Assessing predictors of futility in patients receiving massive transfusions.

BACKGROUND: Massive transfusions are associated with a high mortality rate, but there is little evidence indicating when such efforts are futile. The purpose of this study was to identify clinical variables that could be used as futility indicators in massively transfused patients. METHODS: We retrospectively analyzed 138 adult surgical patients at our institution receiving a massive transfusion (2016-2019). Peak lactate and nadir pH within 24 h of massive transfusion initiation, along with other clinical variables, were assessed as predictors of the primary outcome, in-hospital mortality. RESULTS: The overall rate of in-hospital mortality among our patient population was 52.9% (n = 73). Increasing lactate and decreasing pH were associated with greater mortality among massively transfused patients. Mortality rates were ~2-fold higher for patients in the highest lactate category (≥10.0 mmol/L: 25 of 37; 67.6%) compared to the lowest category (0.0-4.9 mmol/L: 17 of 48; 35.4%) (p = .005), and ~2.5-fold higher for patients in the lowest pH category (<7.00: 8 of 9; 88.9%) compared to the highest category (≥7.40: 8 of 23; 34.7%) (p = .016). Increasing age was also associated with higher mortality (≥65 years: 24 of 33; 72.7%) when compared to younger patients (18-64 years: 49 of 105; 46.7%) (p = .010). CONCLUSIONS: Peak lactate ≥10.0 mmol/L, nadir pH <7.00, and age ≥65 years were significantly associated with higher rates of in-hospital mortality among massively transfused patients. Incorporating these clinical parameters into a futility index for massive transfusions will be useful in situations where blood products are scarce and/or mortality may be unavoidable.

Compensatory reserve detects subclinical shock with more expeditious prediction for need of life-saving interventions compared to systolic blood pressure and blood lactate.

INTRODUCTION: We conducted a prospective observational study on 205 trauma patients at a level I trauma facility to test the hypothesis that a compensatory reserve measurement (CRM) would identify higher risk for progression to shock and/or need a life-saving interventions (LSIs) earlier than systolic blood pressure (SBP) and blood lactate (LAC). METHODS: A composite outcome metric included blood transfusion, procedural LSI, and mortality. Discrete measures assessed as abnormal (ab) were SBP <90 mmHg, CRM <60%, and LAC >2.0. A graded categorization of shock was defined as: no shock (normal [n] SBP [n-SBP], n-CRM, n-LAC); sub-clinical shock (ab-CRM, n-SBP, n-LAC); occult shock (n-SBP, ab-CRM, ab-LAC); or overt shock (ab-SBP, ab-CRM, ab-LAC). RESULTS: Three patients displayed overt shock, 53 displayed sub-clinical shock, and 149 displayed no shock. After incorporating lactate into the analysis, 86 patients demonstrated no shock, 25 were classified as sub-clinical shock, 91 were classified as occult shock, and 3 were characterized as overt shock. Each shock subcategory revealed a graded increase requiring LSI and transfusion. Initial CRM was associated with progression to shock (odds ratio = 0.97; p < .001) at an earlier time than SBP or LAC. CONCLUSIONS: Initial CRM uncovers a clinically relevant subset of patients who are not detected by SBP and LAC. Our results suggest CRM could be used to more expeditiously identify injured patients likely to deteriorate to shock, with requirements for blood transfusion or procedural LSI.

Investigating oxythiamine levels in children undergoing kidney transplantation and the risk of immediate post-operative metabolic and hemodynamic decompensation.

BACKGROUND: Oxythiamine is a uremic toxin that acts as an antimetabolite to thiamine and has been associated with cases of Shoshin beriberi syndrome in adults. We sought to identify whether surgical stress and ischemia/reperfusion injury may precipitate functional thiamine deficiency in children peritransplant. METHODS: We retrospectively analyzed a cohort of pediatric kidney transplant recipients. Oxythiamine levels were measured in pre-transplant serum samples by mass spectrometry and tested for association with severity of lactic acidosis in the first 24 h post-transplant. Secondary outcomes included association with hyperglycemia and indicators of dialysis adequacy (DA). RESULTS: Forty-seven patients were included in the analysis. Median oxythiamine levels differed by modality, measuring 0.67 nM (IQR 0.31, 0.74), 0.34 nM (IQR 0.28, 0.56), and 0.25 nM (IQR 0.17, 0.38) for peritoneal dialysis (PD), hemodialysis (HD), and no dialysis, respectively (p = 0.05). Oxythiamine was associated with 24-h lactate levels (r = 0.38, p = 0.02) and negatively associated with DA (r = - 0.44, p = 0.02). Median oxythiamine levels were higher in patients with poor DA (0.92 nM (IQR 0.51, 1.01) vs. 0.40 nM (IQR 0.24, 0.51), p < 0.01). Sensitivity analysis showed absence of residual association of oxythiamine with 24-h lactate or dialysis modality, but remained significant for DA (p = 0.03). One patient manifested Shoshin beriberi syndrome (oxythiamine 2.03 nM). CONCLUSIONS: Oxythiamine levels are associated with DA at transplant. Patients on PD with no residual kidney function and low DA manifest the highest oxythiamine levels and may be at an increased risk for developing acute Shoshin beriberi syndrome in the early post-transplant period.

Outcomes of left ventricular unloading with a transseptal cannula during extracorporeal membrane oxygenation in adults.

We evaluated the benefit of left ventricular (LV) unloading using a percutaneous transseptal left atrial (LA) drain catheter via femoral vein incorporated into the ECMO venous circuit. This single-center retrospective observational study analyzed clinical outcomes of the LA venting group (N = 62) who underwent percutaneous transseptal LA drain placement comparing with the conventionally treated control group (N = 62) with an arterial pulse pressure below 10 mm Hg for at least 24 hours from December 2012 to August 2018. The ECMO weaning rate (61.3% vs. 38.7%, P = .012) and cardiac transplantation rate (29.0% vs. 11.3%, P = .014) were higher in the LA venting group than in the control group. Inhospital mortality was not significantly different (56.5% vs. 69.4%, P = .191). Pulmonary congestion mostly improved after LA decompression (61.3%, P = .003). A serum lactate level at 24 hours after LA venting of more than 2.2 mmol/L was associated with poor outcomes. LA venting via transseptal cannula reduced pulmonary venous congestion and achieved higher rates of successful ECMO weaning and cardiac transplantation. Placement of a transseptal venous drain cannula should be considered in patients with uncontrolled pulmonary edema secondary to severe LV loading undergoing VA-ECMO.

Prognostic utility of lactate concentrations and kinetics to predict adverse events associated with acute drug overdose.

OBJECTIVE: Clinical research on drug intoxication is necessary for appropriate action in emergency departments (EDs). However, currently, there are no evident biomarkers for predicting adverse events (AEs) in patients with drug intoxication. We aimed to evaluate the prognostic value of serum lactate concentrations and lactate kinetics for AEs such as cardiogenic or respiratory failure in patients admitted to the ED with acute drug overdose. METHODS: We conducted a single-center retrospective study by reviewing the prospective suicide registry of patients visiting the ED. The primary outcome was composite AEs at any point during the ED visit or hospital stay. RESULTS: A total of 566 patients with acute drug overdose were enrolled in this study. Of these, 62 patients had AEs, whereas 363 patients did not, yielding an AE rate of 14.6%. The median 0 h lactate concentrations in the AE and non-AE groups were 2.7 [2.1-5.1] mmol/L and 2.1 [1.4-2.9] mmol/L, respectively (p < 0.001). The median 6 h lactate concentrations in the AE and non-AE groups were 2.0 [1.5-3.9] mmol/L and 1.3 [0.9-2.2] mmol/L, respectively (p < 0.001). The area under the curve of lactate at 0 h for predicting AEs was 0.705 (95% CI: 0.659-0.748). The optimal lactate cutoff point was 4.2 mmol/L (37.1% sensitivity, 92.8% specificity). Multivariable analysis using a stepwise backward method showed that the 0 h lactate concentration was associated with AEs in acute drug intoxication after adjusting for confounders (adjusted OR of 0 h lactate, 1.47; 95% CI, 1.23-1.77). However, the 6 h lactate concentrations, lactate clearance, and delta lactate levels did not predict the outcomes. CONCLUSION: Lactate concentrations and kinetics in patients admitted to the ED with an acute drug overdose exhibited limited prognostic utility in predicting AEs and should be interpreted with caution when considered for clinical decision-making.

Serum total carbon dioxide as a prognostic factor for 28-day mortality in patients with sepsis.

OBJECTIVE: Metabolic acidosis is commonly associated with the disease severity in patients with sepsis or septic shock. This study was performed to investigate the association between serum total carbon dioxide (TCO2) concentration and 28-day mortality in patients with sepsis. METHODS: This study was a multicenter retrospective cohort study of patients with sepsis or septic shock. The relationships between serum TCO2 and 28-day mortality, bicarbonate, pH, lactate, and anion gap were determined with cubic spline curves. The patients were divided into four groups according to their serum TCO2 concentration: Group I (TCO2 > 20 mmol/l), Group II (15 < TCO2 ≤ 20 mg/dl), Group III (10 < TCO2 ≤ 15 mmol/l), and Group IV (TCO2 ≤ 10 mmol/l). RESULTS: A total of 3168 patients were included in the analysis, and the overall mortality rate was 24.1%. Serum TCO2 concentrations below 20 mmol/l showed an almost linear correlation with mortality as well as with lactate, bicarbonate, and pH. The 28-day mortality rates of Group I, II, III, and IV were 18.3%, 23.6%, 32.6%, and 50.0%, respectively (p < .001). In Multivariable Cox proportional hazard regression analysis, the groups with lower serum TCO2 concentrations had a higher risk of 28-day mortality compared with Group I: Group II (Hazard ratio (HR), 1.35; 95% confidence interval (CI), 1.11-1.64), Group III (HR, 1.74; 95% CI, 1.37-2.21), and Group IV (HR, 2.72; 95% CI, 2.03-3.64). CONCLUSIONS: Serum TCO2 concentrations of 20 mmol/l or less were associated with 28-day mortality in patients with sepsis.

Multicenter retrospective analysis of the risk factors for delayed neurological sequelae after acute carbon monoxide poisoning.

OBJECTIVE: Delayed neurological sequelae (DNS) is a devastating consequence following acute carbon monoxide (CO) poisoning. This study aims at exploring the independent predictors of DNS in patients with CO exposure. METHODS: Data of patients with diagnosis of CO poisoning was retrospectively collected and reviewed in 5 regional medical facilities. Patients were classified into the DNS group and non-DNS group according to clinical findings during a follow-up period of 6 months. Demographic characteristics, co-morbidities, clinical manifestations, and treatment strategies were compared to identify possible correlative factors. Multivariate analysis was performed to determine the independent predictors of DNS. RESULTS: We screened 1129 patients and enrolled 326 cases (158 males, average age 44.56 ± 16.08 years) in the analysis. Thirty-seven (11.35%) developed DNS at a median interval of 33 days. Uni-variable analysis identified older age, higher body mass index, hypertension, loss of consciousness, longer CO exposure, lower Glasgow Coma Scale (GCS) on-site/at emergency room, and elevation of lactate as relevant factors for DNS; while multivariable logistic regression revealed that older age (OR = 1.11; p < 0.001), longer duration of CO exposure (OR = 1.54; p = 0.023), GCS on-site (OR = 2.06; p < 0.001), and GCS at emergency room (OR = 1.33; p = 0.048) were independent predictors for DNS. CONCLUSIONS: Our multicenter study demonstrated older age, longer duration of CO exposure, and GCS score were independent predictors of DNS in COP patients. GCS scored on-site might be a more sensitive and specific parameter compared with GCS evaluated at the emergency room. Further prospective studies in a larger patient cohort are warranted to draw a comprehensive conclusion.

Target blood pressure management during cardiopulmonary bypass improves lactate levels after cardiac surgery: a randomized controlled trial.

BACKGROUND: Hyperlactatemia is associated with a poor prognosis in cardiac surgery patients. This study explored the impact of target blood pressure management during cardiopulmonary bypass (CPB) on blood lactate levels after cardiac surgery. METHODS: Adult patients undergoing cardiac valve surgery between 20/1/2020 and 30/6/2020 at Shanghai Chest Hospital were enrolled. The patients were randomized into a low mean arterial pressure (L-MAP) group (target MAP between 50 and 60 mmHg) or a high mean arterial pressure (H-MAP) group (target MAP between 70 and 80 mmHg), n = 20 for each. Norepinephrine was titrated only during CPB to maintain MAP at the target level. Blood lactate levels in the two groups were detected before the operation (T0), at the end of CPB (T1), at the end of the operation (T2), 1 h after the operation (T3), 6 h after the operation (T4) and 24 h after the operation (T5). The primary outcome was the blood lactate level at the end of the operation (T2). The secondary outcomes included the blood lactate level at T1, T3, T4, and T5 and the dose of epinephrine and dopamine within 24 h after the operation, time to extubation, length of stay in the ICU, incidence of readmission within 30 days, and mortality within 1 year. RESULTS: Forty patents were enrolled and analyzed in the study. The lactate level in the H-MAP group was significantly lower than that in the L-MAP group at the end of the operation (3.1 [IQR 2.1, 5.0] vs. 2.1 [IQR 1.7, 2.9], P = 0.008) and at the end of CPB and 1 hour after surgery. The dose of epinephrine within 24 h after the operation, time to extubation and length of stay in the ICU in the L-MAP group were significantly higher than those in the H-MAP group. CONCLUSIONS: Maintaining a relatively higher MAP during CPB deceased the blood lactate level at the end of surgery, reduced epinephrine consumption, and shortened the time to extubation and length of stay in the ICU after surgery. TRIAL REGISTRATION: This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 8/1/2020 with the registration number ChiCTR2000028941 . It was conducted from 20/1/2020 to 30/6/2020 as a single, blinded trial in Shanghai Chest Hospital.

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

PURPOSE: To 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. METHODS: Fifteen 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 ([Formula: see text]), 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. RESULTS: There 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. CONCLUSIONS: Roller 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.

Physiological responses to maximal 4 s sprint interval cycling using inertial loading: the influence of inter-sprint recovery duration.

PURPOSE: Interval exercise allows very high-power outputs to be maintained, a key for stimulating training adaptations. The main purpose of this study was to develop a sprint interval protocol that stimulated both anaerobic and aerobic systems while maximizing power output and minimizing fatigue. The secondary goal was to investigate the influence of inter-sprint recovery duration. METHODS: Sixteen (8 females) participants (age: 23.5 ± 3.4 years, peak oxygen consumption (VO2peak): 45.6 ± 9.2 ml kg-1 min-1) took part in this study. The exercise protocol involved 30 bouts of 4 s maximal cycling sprints using an 'Inertial Load Ergometer'. Recovery durations between sprints of 15, 30 and 45 s were studied in three trials. RESULTS: Peak power output (PPO) was maintained while taking 45 and 30 s of recovery, although it was 9% higher (p < 0.05) during 45 vs. 30 s. PPO with 15 s recovery declined 18% (p < 0.05) and then stabilized as did oxygen consumption (72±2% VO2peak) at a level that might reflect the peak rate of ATP-PC resynthesis from oxidative metabolism. The 15-, 30-, and 45 s trials elicited 72, 56, and 49% VO2peak and 86, 80, and 75% of maximal heart rate (all p<0.001). Perceived exertion increased with shorter recovery periods but remained at 12.6-14.7 and never became 'very hard'. CONCLUSION: The present study describes the use of an inertial-load ergometer to accommodate repeated 4 s maximal cycling sprints that elicit 72% VO2peak when the recovery period is 15 s. However, a recovery duration of 15 s was insufficient for the maintenance of power generation. TRIAL REGISTRATION NUMBER AND DATE: NCT04448925, 26 Jun 2020; retrospectively registered to clinicaltrials.gov.

Physiological responses and cycle characteristics during double-poling versus diagonal-stride roller-skiing in junior cross-country skiers.

PURPOSE: This study aimed to compare physiological factors and cycle characteristics during cross-country (XC) roller-skiing at matched inclines and speeds using the double-poling (DP) and diagonal-stride (DS) sub-techniques in junior female and male XC skiers. METHODS: Twenty-three well-trained junior XC skiers (11 women, 12 men; age 18.2 ± 1.2 yr.) completed two treadmill roller-skiing tests in a randomized order using either DP or DS. The exercise protocols were identical and included a 5 min warm-up, 4 × 5 min submaximal stages, and an incremental test to exhaustion, all performed at a 5° incline. RESULTS: No significant three-way interactions were observed between sex, submaximal exercise intensity, and sub-technique. For the pooled sample, higher values were observed for DP versus DS during submaximal exercise for the mean oxygen uptake kinetics response time (33%), energy cost (18%), heart rate (HR) (9%), blood lactate concentration (5.1 versus 2.1 mmol·L-1), rating of perceived exertion (12%), and cycle rate (25%), while cycle length was lower (19%) (all P < 0.001). During the time-to-exhaustion (TTE) test, peak oxygen uptake ([Formula: see text]O2peak), peak HR, and peak oxygen pulse were 8%, 2%, and 6% lower, respectively, for DP than DS, with a 29% shorter TTE during DP (pooled data, all P < 0.001). CONCLUSION: In well-trained junior XC skiers, DP was found to exert a greater physiological load than DS during uphill XC roller-skiing at submaximal intensities. During the TTE test, both female and male athletes were able to ski for longer and reached markedly higher [Formula: see text]O2peak values when using DS compared to DP.

Degradation of energy cost with fatigue induced by trail running: effect of distance.

PURPOSE: The effect of trail running competitions on cost of running (Cr) remains unclear and no study has directly examined the effect of distances in similar conditions on Cr. Accordingly, the aims of this study were to (i) assess the effect of trail running races of 40-170 km on Cr and (ii) to assess whether the incline at which Cr is measured influences changes in Cr. METHODS: Twenty trail runners completed races of < 100 km (SHORT) and 26 trail runners completed races of > 100 km (LONG) on similar courses and environmental conditions. Oxygen uptake, respiratory exchange ratio, ventilation, and blood lactate were measured before and after the events on a treadmill with 0% (FLAT) and 15% incline (UH) and Cr was calculated. RESULTS: Cr increased significantly after SHORT but not LONG races. There was no clear relationship between changes in Cr and changes in ventilation or blood lactate. There was a significant correlation (r = 0.75, p < 0.01) between changes in FLAT and UH Cr, and the change in Cr was not affected by the incline at which Cr was measured. CONCLUSION: The distance of the trail running race, but not the slope at which it is measured, influence the changes in Cr with fatigue. The mechanism by which Cr increases only in SHORT is not related to increased cost of breathing.

Ramp vs. step tests: valid alternatives to determine the maximal lactate steady-state intensity?

PURPOSE: The aims of this study were (1) to investigate if the respiratory compensation point (RCP) as derived from ramp incremental (RI) exercise could accurately predict the power output (PO) at the maximal lactate steady state (MLSS), and (2) to compare its accuracy with the second lactate threshold (LT2) obtained from step incremental (SI) exercise. METHODS: Nineteen participants performed a RI test (30 W·min-1) to determine RCP, a SI test (30 or 40 W·3 min-1) to determine LT2, and two or more constant work rate (CWR) tests to determine MLSS. For each participant, the [Formula: see text]O2/PO relationship for RI and CWR exercise was established. The ramp-identified PO at RCP was corrected by accounting for the gap between these relationships using the individually determined [Formula: see text] O2/PO regression above GET (RCPcorr-1) or using a fixed regression slope (RCPcorr-2). LT2 was determined using four methods: Dmax, modified Dmax (ModDmax), 4-mM threshold (LT4mM) and an expert-determined LT2 (LT2-expert). RESULTS: RCPcorr-1 (235 ± 69 W), RCPcorr-2 (228 ± 58 W) and LT2-expert (227 ± 61 W) were not different from MLSS (225 ± 60 W). Dmax (203 ± 53 W) underestimated MLSS, while RCP (280 ± 60 W), ModDmax (235 ± 67 W) and LT4mM (234 ± 68 W) overestimated MLSS. The [Formula: see text]O2 at RCP (3.13 ± 0.79L·min-1) and LT2-expert (2.99 ± 0.19L·min-1) did not differ from MLSS (3.05 ± 0.72 L·min-1). CONCLUSION: This study demonstrated that RCP as derived from RI exercise and LT2 as derived from SI exercise can be equally accurate to determine the PO associated with MLSS. Although these results confirmed the suitability of RI and SI tests for this purpose, they also highlighted the importance of an appropriate threshold method selection and the eye of the expert.

Influence of the MCT1-T1470A polymorphism (rs1049434) on repeated sprint ability and blood lactate accumulation in elite football players: a pilot study.

PURPOSE: The aim of this study is to investigate the influence of the MCT1 T1470A polymorphism (rs1049434) on repeated sprint ability (RSA) and lactate accumulation after RSA testing. METHODS: Twenty-six elite Italian male football players (age: 17.7 ± 0.78 years; height: 179.2 ± 7.40 cm; weight: 72.1 ± 5.38 kg) performed RSA testing (6 × 30-m sprints with an active recovery between sprints), and lactate measurements were obtained at 1, 3, 5, 7, and 10 min post-exercise. Genotyping for the MCT1 T1470A polymorphism was performed using PCR. RESULTS: Genotype distributions were in Hardy-Weinberg equilibrium, being 42% wildtype (A/A), 46% heterozygotes (T/A), and 12% mutated homozygotes (T/T). Significant differences between genotypic groups were found in the two final sprint times of the RSA test. Under a dominant model, carriers of the major A-allele (Glu-490) in the dominant model showed a significantly lower sprint time compared to footballers with the T/T (Asp/Asp) genotype (5th Sprint time: A/A + T/A = 4.60 s vs TT = 4.97 s, 95% CI 0.07-0.67, p = 0.022; 6th Sprint: A/A + T/A = 4.56 s vs T/T = 4.87 s, 95% CI 0.05-0.57, p = 0.033). CONCLUSIONS: The T1470A (Glu490Asp) polymorphism of MCT1 was associated with RSA. Our findings suggest that the presence of the major A-allele (Glu-490) is favourable for RSA in football players.

Wearing compression tights post-exercise enhances recovery hemodynamics and subsequent cycling performance.

PURPOSE: To investigate sports compression garment (CG)-induced recovery hemodynamics and their potential impact on subsequent cycling performance. METHODS: In a randomized crossover design, 13 physically active men (20.9 ± 1.4 years; 65.9 ± 7.8 kg; 173.3 ± 4.8 cm; peak power output 254.2 ± 27.2 W) underwent 2 experimental trials. During each experimental trial, the subjects performed 20-min fatiguing preload cycling followed by 60-min passive recovery wearing either a sports CG (28.6 ± 9.4 mmHg) or gymnastic pants (CON). A 5-min all-out cycling performance test was subsequently conducted and power output and cadence were recorded. Cardiac output (CO) and stroke volume (SV) were measured using Doppler ultrasound (USCOM®). Heart rate (HR), blood lactate [BLa-], ratings of perceived exertion (RPE), leg muscle soreness (LMS), mean arterial pressure (MAP) and systemic vascular resistance (SVR) were monitored at 5, 15, 30, 45, 60 min during passive recovery. RESULTS: During the subsequent 5-min all-out cycling performance test, power output (215.2 ± 24.0 vs. 210.8 ± 21.5 W, CG vs. CON) and cadence (72.5 ± 3.8 vs. 71.2 ± 4.8 rpm, CG vs. CON) were higher in CG than CON (P < 0.05). SV was higher at 15, 30 and 45 min (P < 0.05), CO was higher at 5 and 45 min (P < 0.05), HR was lower at 15 and 30 min (P < 0.05) and [BLa-] was lower at 5 and 15 min (P < 0.05) during passive recovery, while LMS was lower at all time-points (P < 0.05) compared with CON. CONCLUSION: Sports CG improves subsequent cycling performance by enhancing hemodynamic responses and attenuating perceived muscle soreness during passive recovery in physically active men.

Post-exercise cardiac autonomic and cardiovascular responses to heart rate-matched and work rate-matched hypoxic exercise.

PURPOSE: This study investigated the effect of performing hypoxic exercise at the same heart rate (HR) or work rate (WR) as normoxic exercise on post-exercise autonomic and cardiovascular responses. METHODS: Thirteen men performed three interval-type exercise sessions (5 × 5-min; 1-min recovery): normoxic exercise at 80% of the WR at the first ventilatory threshold (N), hypoxic exercise (FiO2 = 14.2%) at the same WR as N (H-WR) and hypoxic exercise at the same HR as N (H-HR). Autonomic and cardiovascular assessments were conducted before and after exercise, both at rest and during active squat-stand manoeuvres (SS). RESULTS: Compared to N, H-WR elicited a higher HR response (≈ 83% vs ≈ 75%HRmax, p < 0.001) and H-HR a reduced exercise WR (- 21.1 ± 9.3%, p < 0.001). Cardiac parasympathetic indices were reduced 15 min after exercise and recovered within 60 min in N and H-HR, but not after H-WR (p < 0.05). H-WR altered cardiac baroreflex sensitivity (cBRS) both at rest and during SS (specifically in the control of blood pressure fall during standing phases) in the first 60 min after the exercise bout (p < 0.05). Post-exercise hypotension (PEH) did not occur in H-HR (p > 0.05) but lasted longer in H-WR than in N (p < 0.05). CONCLUSIONS: Moderate HR-matched hypoxic exercise mimicked post-exercise autonomic responses of normoxic exercise without resulting in significant PEH. This may relate to the reduced WR and the limited associated mechanical/metabolic strain. Conversely, WR-matched hypoxic exercise impacted upon post-exercise autonomic and cardiovascular responses, delaying cardiac autonomic recovery, temporarily decreasing cBRS and evoking prolonged PEH.

Decreased exercise capacity in young athletes using self-adapted mouthguards.

PURPOSE: There is evidence of both the preventive effects and poor acceptance of mouthguards. There are various effects on performance depending on the type of mouthguard model. Hemodynamic responses to wearing a mouthguard have not been described. The aim of this study was to investigate the effects of self-adapted mouthguards with breathing channels (SAMGvent). METHODS: In this randomized crossover study, 17 healthy, active subjects (age 25.12 ± 2.19 years) underwent body plethysmography and performed two incremental exertion tests wearing a (SAMGvent) and not wearing (CON) a mouthguard. Blood lactate, spirometrics, and thoracic impedance were measured during these maximum exercise tests. RESULTS: The mean values using a SAMGvent revealed significantly greater airway resistance compared to CON (0.53 ± 0.16 kPa·L-1 vs. 0.35 ± 0.10 kPa·L-1, respectively; p = < 0.01). At maximum load, ventilation with SAMGvent was less than CON (118.4 ± 28.17 L min-1 vs. 128.2 ± 32.16 L min-1, respectively; p = < 0.01). At submaximal loads, blood lactate responses with SAMGvent were higher than CON (8.68 ± 2.20 mmol·L-1 vs. 7.89 ± 1.65 mmol·L-1, respectively; p < 0.01). Maximum performance with a SAMGvent was 265.9 ± 59.9 W, and without a mouthguard was 272.9 ± 60.8 W (p < 0.01). Maximum stroke volume was higher using a SAMGvent than without using a mouthguard (138.4 ± 29.9 mL vs. 130.2 ± 21.2 mL, respectively; p < 0.01). CONCLUSION: Use of a self-adapted mouthguard led to increased metabolic effort and a significant reduction in ventilation parameters. Unchanged oxygen uptake may be the result of cardiopulmonary compensation and increased breathing efforts, which slightly affects performance. These results and the obvious preventive effects of mouthguards support their use in sports.

Augmented muscle glycogen utilization following a single session of sprint training in hypoxia.

PURPOSE: This study determined the effect of a single session of sprint interval training in hypoxia on muscle glycogen content among athletes. METHODS: Ten male college track and field sprinters (mean ± standard error of the mean: age, 21.1 ± 0.2 years; height, 177 ± 2 cm; body weight, 67 ± 2 kg) performed two exercise trials under either hypoxia [HYPO; fraction of inspired oxygen (FiO2), 14.5%] or normoxia (NOR: FiO2, 20.9%). The exercise consisted of 3 × 30 s maximal cycle sprints with 8-min rest periods between sets. Before and immediately after the exercise, the muscle glycogen content was measured using carbon magnetic resonance spectroscopy in vastus lateralis and vastus intermedius muscles. Moreover, power output, blood lactate concentrations, metabolic responses (respiratory oxygen uptake and carbon dioxide output), and muscle oxygenation were evaluated. RESULTS: Exercise significantly decreased muscle glycogen content in both trials (interaction, P = 0.03; main effect for time, P < 0.01). Relative changes in muscle glycogen content following exercise were significantly higher in the HYPO trial (- 43.5 ± 0.4%) than in the NOR trial (- 34.0 ± 0.3%; P < 0.01). The mean power output did not significantly differ between the two trials (P = 0.80). The blood lactate concentration after exercise was not significantly different between trials (P = 0.31). CONCLUSION: A single session of sprint interval training (3 × 30 s sprints) in hypoxia caused a greater decrease in muscle glycogen content compared with the same exercise under normoxia without interfering with the power output.