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This study aimed to characterize peak exercise cardiac function and thigh muscle fatty infiltration and their relationships with VO2peak among anthracycline-treated breast cancer survivors (BCS). BCS who received anthracycline chemotherapy ~ 1 year earlier (n = 16) and matched controls (matched-CON, n = 16) were enrolled. Resting and peak exercise cardiac function, myocardial T1 mapping (marker of fibrosis), and thigh muscle fat infiltration were assessed by magnetic resonance imaging, and VO2peak by cycle test. Compared to matched-CON, BCS had lower peak SV (64 ± 9 vs 57 ± 10 mL/m2, p = 0.038), GLS (− 30.4 ± 2.2 vs − 28.0 ± 2.5%, p = 0.008), and arteriovenous oxygen difference (16.4 ± 3.6 vs 15.2 ± 3.9 mL/100 mL, p = 0.054). Mediation analysis showed: (1) greater myocardial T1 time (fibrosis) is inversely related to cardiac output and end-systolic volume exercise reserve; (2) greater thigh muscle fatty infiltration is inversely related to arteriovenous oxygen difference; both of which negatively influence VO2peak. Peak SV (R2 = 65%) and thigh muscle fat fraction (R2 = 68%) were similarly strong independent predictors of VO2peak in BCS and matched-CON combined. Post-anthracyclines, myocardial fibrosis is associated with impaired cardiac reserve, and thigh muscle fatty infiltration is associated with impaired oxygen extraction, which both contribute to VO2peak.

Purpose This study aimed to review traditional and new perspectives in the interpretation of the development of youth cardiorespiratory fitness (CRF). Methods We analyzed data from (i) the literature which for 80 yr has been traditionally based on interpretations of peak oxygen uptake (V˙O2) in ratio with body mass (BM) and (ii) recent multilevel allometric models founded on 994 (475 from girls) determinations of 10- to 16-yr-olds’ peak V˙O2 with measures of age, maturity status, and morphological covariates (BM and fat-free mass), and from 10 to 13 yr, 110 peak V˙O2 determinations of maximum cardiovascular covariates (stroke volume, cardiac output, and arteriovenous oxygen difference). Results The application of ratio scaling of physiological variables requires satisfying specific statistical assumptions that are seldom met. In direct conflict with the ratio-scaled data interpretation of CRF, multilevel allometric modeling shows that with BM controlled, peak V˙O2 increases with age but the effect is smaller in girls than boys. Maturity status exerts a positive effect on peak V˙O2, in addition to those of age and BM. Changes in maximum cardiovascular covariates contribute to explaining the development of CRF, but fat-free mass (as a surrogate for active muscle mass) is the most powerful single influence. With age, maturity status, morphological covariates, and maximum cardiovascular covariates controlled, there remains an unexplained ~4% to ~9% sex difference in peak V˙O2. Conclusions The traditional interpretation of peak V˙O2 in ratio with BM is fallacious and leads to spurious correlations with other health-related variables. Studies of the development of CRF require analyses of sex-specific, concurrent changes in age- and maturation-driven morphological and maximum cardiovascular covariates. Multilevel allometric modeling provides a rigorous, flexible, and sensitive method of data analysis.

Background Maximum oxygen uptake is an established measurement of diagnosing chronic heart failure and underlies various central and peripheral factors. However, central and peripheral factors are little investigated, because they are usually measured invasively. The aim of this study was to compare non-invasively measured central and peripheral factors of oxygen uptake between patients with chronic heart failure and healthy controls. Methods Ten male patients with heart failure with reduced ejection fraction (62 ± 4 years; body mass index: 27.7 ± 1.8 kg/m2; ejection fraction: 30 ± 4%) and ten male healthy controls (59 ± 3 years; body mass index: 27.7 ± 1.3 kg/m2) were tested for blood pressure, heart rate, stroke volume, cardiac output, and cardiac power output (central factors) as well as muscle oxygen saturation of the vastus lateralis and biceps brachii muscle (peripheral factors) during an incremental cycling test. Stroke volume and muscle oxygen saturation were non-invasively measured by a bioreactance analysis and near-infrared spectroscopy, respectively. Additionally, a maximum isometric strength test of the knee extensors was conducted. Magnitude-based inferences were computed for statistical analyses. Results Patients had a likely to most likely lower oxygen uptake, mean arterial pressure, and heart rate at maximum load as well as very likely lower isometric peak torque. Contrary, patients had a possibly to likely higher stroke volume and muscle oxygen saturation of the vastus lateralis muscle at maximum load. Differences in cardiac output, cardiac power output, and muscle oxygen saturation of the biceps brachii muscle at maximum load were unclear. Conclusions Non-invasively measured central and peripheral factors of oxygen uptake differ between patients with chronic heart failure and healthy controls. Therefore, it is promising to measure both types of factors in patients with chronic heart failure to optimize the diagnosis and therapy.

When exercising with a small muscle mass, the mass-specific O2 delivery exceeds the muscle oxidative capacity resulting in a lower O2 extraction compared with whole-body exercise. We elevated the muscle oxidative capacity and tested its impact on O2 extraction during small muscle mass exercise. Nine individuals conducted six weeks of one-legged knee extension (1L-KE) endurance training. After training, the trained leg (TL) displayed 45% higher citrate synthase and COX-IV protein content in vastus lateralis and 15%-22% higher pulmonary oxygen uptake ( V˙O2peak ) and peak power output ( W˙peak ) during 1L-KE than the control leg (CON; all P

OBJECTIVES RBC transfusions can increase oxygen availability to the tissues, but studies have provided conflicting results. The objectives of this study were, therefore, to evaluate, using systematic review and meta-analysis, the effects of transfusion on hemodynamic/oxygenation variables in patients without acute bleeding. DATA SOURCES PubMed, Scopus, Cochrane Database of Systematic Reviews, and Embase from inception until June 30, 2019. STUDY SELECTION All articles that reported values of prespecified hemodynamic or oxygenation variables before and after RBC transfusion. DATA EXTRACTION Publication year, number of patients, number of transfusions and the type of population studied, hemodynamic and oxygenation data (heart rate, cardiac index, mixed venous oxygen saturation or central venous oxygen saturation, oxygen delivery index, oxygen consumption index, oxygen extraction ratio, arteriovenous oxygen difference and arterial blood lactate) before and after transfusion. We performed a meta-analysis for each variable for which there were sufficient data to estimate mean differences. We also performed subgroup analyses comparing septic with nonseptic patients. DATA SYNTHESIS We retrieved 6,420 studies; 33 met the inclusion criteria, 14 of which were in patients with sepsis. In the meta-analysis, the estimated mean differences and 95% CIs comparing the periods before and after transfusion were -0.0 L/min/m (-0.1 to 0.1 L/min/m) (p = 0.86) for cardiac index; -1.8 beats/min (-3.7 to 0.1 beats/min) (p = 0.06) for heart rate; 96.8 mL/min/m (71.1-122.5 mL/min/m) (p < 0.01) for oxygen delivery index; 2.9% (2.2-3.5%) (p < 0.01) for mixed venous oxygen saturation or central venous oxygen saturation; -3.7% (-4.4% to -3.0%) (p < 0.01) for oxygen extraction ratio; and 4.9 mL/min/m (0.9-9.0 mL/min/m) (p = 0.02) for oxygen consumption index. The estimated mean difference for oxygen consumption index in the patients with sepsis was 8.4 mL/min/m (2.3-14.5 mL/min/m; p = 0.01). CONCLUSIONS Transfusion was not associated with a decrease in mean cardiac output or mean heart rate. The increase in mean oxygen delivery following transfusion was associated with an increase in mean oxygen consumption after transfusion, especially in patients with sepsis.

Objectives The aim of this study was to evaluate the association between age and invasive cardiovascular hemodynamics during upright exercise among healthy adults. Background The marked age-related decline in maximal exercise oxygen uptake (peak VO2) may contribute to the high burden of heart failure among older individuals and their greater severity of exertional symptoms. However, the mechanisms underlying this decline are not well understood. Methods A total of 104 healthy community-dwelling volunteers age 20 to 76 years well screened for cardiovascular disease underwent exhaustive upright exercise with brachial and pulmonary artery catheters; radionuclide ventriculography; and expired gas analysis for the measurement of peak VO2, cardiac output, left ventricular stroke volume, end-diastolic volume, end-systolic volume, ejection fraction, pulmonary capillary wedge pressure, and arteriovenous oxygen difference. Results Over a 5.5-decade age range, there was a 40% decline in peak VO2 due primarily to reduced peak exercise cardiac output; peak arteriovenous oxygen difference was unaffected by age. The lower age-related exercise cardiac output was related to lower peak exercise heart rate and stroke volume. Aging was also associated with lower peak exercise ejection fraction, indicating reduced inotropic reserve. Peak exercise end-diastolic volume was lower with aging despite similar left ventricular filling pressure, suggesting age-related reduced diastolic compliance limiting the use of the Frank-Starling mechanism to compensate for reduced chronotropic and inotropic reserves. These age relationships were unaffected by sex. Conclusions The age-related decline in exercise capacity among healthy persons is due predominantly to cardiac mechanisms, including reduced chronotropic and inotropic reserve and possibly reduced Frank-Starling reserve. Peak exercise left ventricular filling pressure and arteriovenous oxygen difference are unchanged with healthy aging.

Cardiac rehabilitation (CR) is indicated in all patients after acute myocardial infarction (AMI) to improve prognosis and exercise capacity (EC). Previous studies reported that up to a third of patients did not improve their EC after CR (non-responders). Our aim was to assess the cardiac and peripheral mechanisms of EC improvement after CR using combined exercise echocardiography and cardiopulmonary exercise testing (CPET-SE). The responders included patients with an improved EC assessed as a rise in peak oxygen uptake (VO2) ≥ 1 mL/kg/min. Peripheral oxygen extraction was calculated as arteriovenous oxygen difference (A-VO2Diff). Out of 41 patients (67% male, mean age 57.5 ± 10 years) after AMI with left ventricular ejection fraction (LVEF) ≥ 40%, 73% improved their EC. In responders, peak VO2 improved by 27% from 17.9 ± 5.2 mL/kg/min to 22.7 ± 5.1 mL/kg/min, p &lt, 0.001, while non-responders had a non-significant 5% decrease in peak VO2. In the responder group, the peak exercise heart rate, early diastolic myocardial velocity at peak exercise, LVEF at rest and at peak exercise, and A-VO2Diff at peak exercise increased, the minute ventilation to carbon dioxide production slope decreased, but the stroke volume and cardiac index were unchanged after CR. Non-responders had no changes in assessed parameters. EC improvement after CR of patients with preserved LVEF after AMI is associated with an increased heart rate response and better peripheral oxygen extraction during exercise.

Summary Aims Aims were to assess: (1) the relationships between oxygen pulse and areteriovenous oxygen difference; and (2) the reproducibility of cardiac output and stroke volume values during submaximal and maximal exercises. Methods Twelve healthy male participated in the study. They were tested on five occasions, separated by periods of 3 days. After tests familiarization, they performed a duplicate progressive maximal exercise on a cycle ergometer to measure maximal oxygen uptake, maximal aerobic power, maximal cardiac output, maximal Stroke Volume and maximal Heart rate. At the fourth and fifth visits, subjects performed two graded submaximal physical exercises. Values collected during duplicated submaximal and maximal exercises were used for the assessment of the reliability of cardiovascular measurements. Results We found no significant differences between cardiac output and stroke volume values in both first and second trial. All coefficients of variation were under 10% and intra class correlation coefficients values were high than 0.90 during submaximal and maximal exercises. The linear regression analyses indicated high r-squared between oxygen pulse and areteriovenous oxygen difference until 50% of maximal aerobic power. However, at 60% and 100% of maximal aerobic power, this relationship was not found. We found significant increases of stroke volume (P Conclusion Using the impedance device, cardiac output and stroke volume values were reproducible during submaximal and maximal exercises. Oxygen pulse could be a predictor of arteriovenous oxygen difference during submaximal exercise (until 50% of the maximal aerobic power) in healthy subjects.

INTRODUCTION Pediatric heart transplant (HTx) recipients have reduced exercise capacity typically two-thirds of predicted values, the mechanisms of which are not fully understood. We sought to assess the cardiorespiratory responses to progressive exercise in HTx relative to controls matched for age, sex, body size, and work rate. METHODS Fourteen HTx recipients and matched controls underwent exercise stress echocardiography on a semisupine cycle ergometer. Hemodynamics, left ventricular (LV) dimensions, and volumes were obtained and indexed to body surface area. Oxygen consumption (V˙O2) was measured, and arteriovenous oxygen difference was estimated using the Fick Principle. RESULTS At rest, LV mass index (P = 0.03) and volumes (P < 0.001) were significantly smaller in HTx, whereas wall thickness (P < 0.01) and LV mass-to-volume ratio (P = 0.01) were greater. Differences in LV dimensions and stroke volume persisted throughout exercise, but the pattern of response was similar between groups as HR increased. As exercise progressed, heart rate and cardiac index increased to a lesser extent in HTx. Despite this, V˙O2 was similar (P = 0.82) at equivalent work rates as HTx had a greater change in arteriovenous oxygen difference (P < 0.01). CONCLUSIONS When matched for work rate, HTx had similar metabolic responses to controls despite having smaller LV chambers and an attenuated increase in hemodynamic responses. These findings suggest that HTx may increase peripheral O2 extraction as a compensatory mechanism in response to reduced cardiovascular function.

Elevated arterial–central venous carbon dioxide partial pressure difference (AVCO2) may be an important marker to predict tissue and organ hypoperfusion in adults. We analyzed the hemodynamic data of infants with congenital heart disease who underwent corrective repair with cardiopulmonary bypass (CPB) to identify whether AVCO2 has clinical significance in early postoperative tissue hypoperfusion, occurrence of complications, and clinical outcomes. Infants with clinical conditions of hypoperfusion, without volume responsiveness and with ineffective initial treatment, within 3 h of cardiac surgery were enrolled in this study. A pulse contour cardiac output catheter was used to monitor the cardiac index (CI). Eight measurements of arterial blood gas and central venous blood gas were taken within 42 h after surgery. Clinical data of all patients were recorded. A total of 69 children were enrolled in this study. Arteriovenous oxygen difference, AVCO2, lactic acid level, and vasoactive inotropic score in the hypoperfusion group (oxygen supply/oxygen consumption ratio [DO2/VO2] of ≤ 2) were significantly higher than those in the non-hypoperfusion group (DO2/VO2 > 2), while the CI in the hypoperfusion group was significantly lower than that in the non-hypoperfusion group. The cutoff value of AVCO2 to predict DO2/VO2 ≤ 2 was 12.3 within 42 h of surgery with area under the curve of 0.84. High AVCO2 is more likely to be associated with some complications and prolonged mechanical ventilation and length of stay in the intensive care unit. Elevated AVCO2 within 42 h of CPB in infants is associated with tissue and organ hypoperfusion and incidence of complications. Persistent or repeated increase in AVCO2 indicates poor prognosis.

Epicardial adipose tissue may affect hemodynamics and cardiorespiratory fitness as it is a metabolically active visceral adipose tissue and a source of inflammatory bioactive substances that can substantially modulate cardiovascular morphology and function. However, the associations between epicardial adipose tissue and hemodynamics and cardiorespiratory fitness remain unclear. This cross-sectional study aimed to examine the association between epicardial adipose tissue volume and hemodynamics, and cardiorespiratory fitness among Japanese individuals of various ages and of both sexes. Epicardial adipose tissue volume was measured in 120 participants (age, 21–85 years) by cardiac magnetic resonance imaging. To evaluate cardiorespiratory fitness, peak oxygen uptake was measured by cardiopulmonary exercise testing. Peak cardiac output and arteriovenous oxygen difference were calculated by impedance cardiography. The epicardial adipose tissue volume was significantly increased in middle-aged and older women. The epicardial adipose tissue volume was significantly and negatively correlated to peak cardiac output and peak oxygen uptake, regardless of age and sex; furthermore, epicardial adipose tissue showed a strong negative correlation with peak heart rate. Epicardial adipose tissue and peak cardiac output were significantly associated (β = -0.359, 95% confidence interval, -0.119 to -0.049, p < 0.001), even after multivariate adjustment (R2 = 0.778). However, in the multiple regression analysis with peak oxygen uptake as a dependent variable, the epicardial adipose tissue volume was not an independent predictor. These data suggest that increased epicardial adipose tissue volume may be correlated with decreased peak oxygen uptake, which might have mediated the abnormal hemodynamics among Japanese people of various ages and of both sexes. Interventions targeting epicardial adipose tissue could potentially improve hemodynamics and cardiorespiratory fitness.

Exercise intolerance after acute myocardial infarction (AMI) is a predictor of worse prognosis, but its causes are complex and poorly studied. This study assessed the determinants of exercise intolerance using combined stress echocardiography and cardiopulmonary exercise testing (CPET-SE) in patients treated for AMI. We prospectively enrolled patients with left ventricular ejection fraction (LV EF) ≥40% for more than 4 weeks after the first AMI. Stroke volume, heart rate, and arteriovenous oxygen difference (A-VO2Diff) were assessed during symptom-limited CPET-SE. Patients were divided into four groups according to the percentage of predicted oxygen uptake (VO2) (Group 1, 2 was 19.5 ± 5.4 mL/kg/min. A better exercise capacity was related to a higher percent predicted heart rate (Group 2 vs. Group 4, p 2Diff (Group 1 vs. Group 3, p 2 and percent predicted VO2 had a significant positive correlation with percent predicted heart rate at peak exercise (r = 0.28, p = 0.01 and r = 0.46, p < 0.001) and peak A-VO2Diff (r = 0.68, p p = 0.001) but not with peak stroke volume. Exercise capacity in patients treated for AMI with LV EF ≥40% is related to heart rate response during exercise and peak peripheral oxygen extraction. CPET-SE enables non-invasive assessment of the mechanisms of exercise intolerance.

Background. Achieving hemodynamic stabilization does not prevent progressive tissue hypoperfusion and organ dysfunction during resuscitation of septic shock patients. Many indicators have been proposed to judge the optimization of oxygen delivery to meet tissue oxygen consumption. Methods. A prospective observational study was conducted to evaluate and validate combining CO2 gap and oxygen-derived variables with lactate clearance during early hours of resuscitation of adults presenting with septic shock. Results. Our study included 456 adults with a mean age of 63.2 ± 6.9 years, with 71.9% being males. Respiratory and urinary infections were the origin of about 75% of sepsis. Mortality occurred in 164 (35.9%) patients. The APACHE II score was 18.2 ± 3.7 versus 34.3 ± 6.8 ( p < 0.001 ), the initial SOFA score was 5.8 ± 3.1 versus 7.3 ± 1.4 ( p = 0.001 ), while the SOFA score after 48 hours was 4.2 ± 1.8 versus 9.4 ± 3.1 ( p < 0.001 ) in the survivors and nonsurvivors, respectively. Hospital mortality was independently predicted by hyperlactatemia (OR: 2.47; 95% CI: 1.63–6.82, p = 0.004 ), PvaCO2 gap (OR: 2.62; 95% CI: 1.28–6.74, p = 0.026 ), PvaCO2/CavO2 ratio (OR: 2.16; 95% CI: 1.49–5.74, p = 0.006 ), and increased SOFA score after 48 hours of admission (OR: 1.86; 95% CI: 1.36–8.13, p = 0.02 ). A blood lactate cutoff of 40 mg/dl at the 6th hour of resuscitation (T6) had a 92.7% sensitivity and 75.3% specificity for predicting hospital mortality (AUROC = 0.902) with 81.6% accuracy. Combining the lactate cutoff of 40 mg/dl and PvaCO2/CavO2 ratio cutoff of 1.4 increased the specificity to 93.2% with a sensitivity of 75.6% in predicting mortality and with 86.8% accuracy. Combining the lactate cutoff of 40 mg/dl and PvaCO2 gap of 6 mmHg increased the sensitivity to 93% and increased the specificity to 98% in predicting mortality with 91% accuracy. Conclusion. Combining the carbon dioxide gap and arteriovenous oxygen difference with lactate clearance during early hours of resuscitation of septic shock patients helps to predict hospital mortality more accurately.

Background: The functional limitation of patients with COPD results from a respiratory impairment and a reduction in peripheral muscle extraction. Inasmuch as the circulatory system is not a limiting factor, it can serve a useful adaptive role to optimise oxygen transport. Objective: To assess the extent to which compensatory cardiocirculatory adjustments are present when there is reduced oxygen transfer. Methods: Using a subset (N=115) from the Canadian longitudinal COPD cohort study (CanCOLD), we compared results from continuous measurements of ventilation,VO2 and bioimpedance (Physio-Flow®) cardiac output (CO) during peak incremental cycling. Arteriovenous oxygen difference was computed using Fick equation (Da-vO2 = VO2 / CO). Subjects were grouped for disease severity : Gr. A: At Risk,ever smokers (N=51) Gr. B: GOLD1 (N=33) Gr.C:GOLD2 (N=31). There were no group differences in age, body mass index or sex ratio. Results: The figure below shows that the CO vs Da-vO2 relationship with increasing VO2 is not different between groups A and B but the relationship is shifted up and leftward in group C indicating a compensatory increase in CO for VO2 over approximately 1000ml. Conclusion: Severity of COPD, even moderate, negatively impacts peripheral O2 extraction. An elevation in CO is then observed which serves as partial compensation to optimize the O2 transport function.

BackgroundExercise capacity (EC) after acute myocardial infarction (AMI) influences prognosis, but the causes of its reduction are complex and not sufficiently studied.MethodsWe prospectively enrolled consecutive patients who underwent percutaneous coronary intervention for their first AMI with left ventricular ejection fraction (LV EF) >40% at least 4 weeks after AMI. We performed combined stress echocardiography and cardiopulmonary exercise testing (CPET-SE) using a semi-supine cycle ergometer to determine predictors of EC (peak oxygen uptake [VO2]).ResultsAmong 81 patients (70% male, mean age 58 ± 11 years), 40% had AMI with ST-segment elevation, and 60% non ST-segment elevation, LV EF was 57 ± 7%; wall motion score index, 1.18 (IQR 1.06 – 1.31); peak VO2, 19.5 ± 5.4 mL/kg/min. Multivariate analysis revealed that parameters at peak exercise: heart rate (β = 0.17, p < 0.001), stroke volume (β = 0.09, p < 0.001), and arteriovenous oxygen difference (A-VO2Diff, β = 93.51, p < 0.001) were independently positively correlated with peak VO2, with A-VO2Diff being its strongest contributor.ConclusionsIn patients treated for AMI with normal/mildly reduced LV EF, EC is associated with peak peripheral oxygen extraction as well as peak heart rate and peak stroke volume. CPET-SE is a useful tool to evaluate decreased fitness in this group.

Introduction:For CHD patients undergoing corrective surgery utilising cardiopulmonary bypass, post-operative inhaled nitric oxide has been administered to alleviate pulmonary hypertension. We performed a systematic review and meta-analyses to determine the effect of inhaled nitric oxide on haemodynamics, gas exchange, and hospitalisation characteristics in children immediately after cardiopulmonary bypass.Materials and methods:A systematic review of the literature was performed to identify full-text manuscripts in English. PubMed, EMBASE, and the Cochrane databases were queried. Once manuscripts were identified for inclusion, a list of all the endpoints in each manuscript was created. Endpoints with data present from two or more studies were then kept for pooled analyses. All endpoints included were continuous variables and so mean and standard deviation were utilised as the effect data for comparison.Results:A total of eight studies were deemed appropriate for inclusion. There were significant differences with decreases in mean pulmonary artery pressure of −6.82 mmHg, left atrial pressure of −1.16 mmHg, arteriovenous oxygen difference of −1.63, arterial carbon dioxide concentration of −2.41 mmHg, mechanical ventilation duration of −8.56 hours, and length of cardiac ICU stay duration of −0.91 days. All significant variables achieved p < 0.001.Conclusion:Inhaled nitric oxide in children immediately after cardiopulmonary bypass decreases mean pulmonary artery pressure significantly and decreases the arterial carbon dioxide concentration significantly without significantly altering other haemodynamic parameters. This results in a statistically shorter duration of mechanical ventilation and cardiac ICU length of stay without altering overall hospital length of stay.

Adolf Fick was a German physiologist, born in Kassel in 1829, who studied medicine at the University of Marburg and graduated in 1851. He worked first in Zurich and then in Wurzburg. Most of his studies were based on physics and mathematics, and deep analysis, and only later were proven by experiments. Fick's name in physics is associated to the laws of diffusion of solutions, and in medicine to the principle of cardiac output calculation. In 1855, he proposed Fick's laws on gas diffusion. In 1870, he devised Fick's principle, which allows the measurement of cardiac output and calculations of intracardiac shunts from the arteriovenous oxygen difference. The method was later generalized to the Fick principle, according to which the flow of an indicator taken up or released by an organ corresponds to the difference between the indicator flows in the inflow and outflow tracts. Fick invented several devices most of them aimed to improve precision in his physiologic experiments. In 1868, he invented the plethysmograph, for recording the speed of blood in the human artery. In 1888, the tonometer for measuring from outside the hydrostatic pressure inside the eyeball. After 3 decades as Professor in Wurzburg, he retired. Fick died at Blankenberge, Belgium in 1901 age 71 years old.

We analysed the importance of systemic and peripheral arteriovenous O2 difference ( a - v ¯ O 2 difference and a-vf O2 difference, respectively) and O2 extraction fraction for maximal oxygen uptake ( V ˙ O 2max ). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion versus perfusion limitations vary with V ˙ O 2max . Articles (n = 17) publishing individual data (n = 154) on V ˙ O 2max , maximal cardiac output ( Q ˙ max ; indicator-dilution or the Fick method), a - v ¯ O 2 difference (catheters or the Fick equation) and systemic O2 extraction fraction were identified. For the peripheral responses, group-mean data (articles: n = 27; subjects: n = 234) on leg blood flow (LBF; thermodilution), a-vf O2 difference and O2 extraction fraction (arterial and femoral venous catheters) were obtained. Q ˙ max and two-LBF increased linearly by 4.9-6.0 L · min-1 per 1 L · min-1 increase in V ˙ O 2max (R2 = .73 and R2 = .67, respectively; both P a - v ¯ O 2 difference increased from 118-168 mL · L-1 from a V ˙ O 2max of 2-4.5 L · min-1 followed by a reduction (second-order polynomial: R2 = .27). After accounting for a hypoxemia-induced decrease in arterial O2 content with increasing V ˙ O 2max (R2 = .17; P V ˙ O 2max : 4.5 L · min-1 ) with no further change (exponential decay model: R2 = .42). Likewise, leg O2 extraction fraction increased with V ˙ O 2max to approach a maximal value of ~90-95% (R2 = .83). Muscle O2 diffusing capacity and the equilibration index Y increased linearly with V ˙ O 2max (R2 = .77 and R2 = .31, respectively; both P V ˙ O 2max , enhanced O2 extraction fraction (≥90%) contributes to the remarkably high V ˙ O 2max in endurance-trained individuals.

Background Physiological adaptations of stroke patients after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) remain unclear. Objective This study determined the HIIT and MICT effects on aerobic capacity, cerebral oxygenation, peak cardiac output (CO), and serum brain-derived neurotrophic factor (BDNF) in stroke patients. Methods We included 23 stroke patients with age about 55 years and stroke duration > 24 months; participants completed 36 sessions of exercise training for 30 min; 13 were randomly assigned to perform MICT at 60% of peak oxygen consumption (VO2peak) and 10 to perform HIIT at alternating 80% (3 min) and 40% (3 min) VO2peak. Before and after interventions, we evaluated VO2peak, peak CO, arteriovenous oxygen difference (AV O2diff), bilateral frontal cortex oxygenation (relative changes of oxyhemoglobin Δ[O2Hb], deoxyhemoglobin Δ[HHb], and total hemoglobin Δ[THb] levels), serum brain-derived neurotrophic factor (BDNF) level, and fluorescent cell staining for neuron morphology and percentage of cell-bearing neurites (% neurites). Results HIIT induced significant increases in VO2peak (P = 0.008), CO (P = 0.038), Δ[HHb] (P = 0.046), Δ[THb] (P = 0.046), and serum BDNF level (P = 0.012). The improvement in VO2peak was significantly greater with HIIT than MICT (20.7% vs. 9.8%, P = 0.031), as was AV O2diff (P = 0.041), Δ[HHb] (P = 0.027), and serum BDNF level (P Conclusion As compared with MICT, HIIT-improved aerobic capacity by increasing systemic tissue O2 extraction in stroke patients. Increased cerebral O2 utilization in the involved hemisphere was also identified after HIIT. These physiological adaptations may be associated with increased serum BDNF level. In vitro dendritic growth in neurons treated with serum from HIIT participants may imply significant effects on neuron activities as compared with MICT. ClinicalTrials.gov identifier NCT04135391 .

Following implantation of a left ventricular assist device (LVAD), acceptable functional performance is now being achieved; however, peak VO2 and peak work load (watts) remain considerably limited. Maximum physical capacity is essentially dependent on generated cardiac output (CO) and arteriovenous oxygen difference (avDO2 ). We investigated the changes in CO and avDO2 during exercise in LVAD patients with an HVAD pump (HeartWare Inc., Framingham, MA, USA). Approximately 6 weeks after implantation, 20 patients (100% male, 60.8 ± 7.3 years old, BMI 25.7 ± 3.3) underwent a six-minute walk test (6MWT), a cardiopulmonary exercise test (CPET), and noninvasive hemodynamic measurement. The mean six-minute walking distance (6MWD) was 403 m (68% of predicted), and mean peak VO2 was 10.9 mL/kg/min (39% of predicted). Mean total CO improved from 3.8 L at rest to 7.0 L at maximum exercise. The mean avDO2 increased from 7.4 mL/dL (44% of oxygen content) at rest to 13.2 mL/dL (75% of oxygen content) at maximum exercise. There was a significant increase in both total CO (P

Objectives The aim of this study was to compare the relative impairment in different exercise hemodynamic reserve parameters in patients with heart failure with preserved ejection fraction (HFpEF) and control patients using a study-level meta-analysis. Background A cardinal manifestation of chronic HFpEF is severely decreased exercise capacity. Developing effective therapies for exercise intolerance in HFpEF requires optimal understanding of the factors underlying exercise intolerance. Methods Data were included from 17 unique cohorts that measured peak oxygen uptake and hemodynamic or echocardiographic parameters during exercise in patients with HFpEF and control subjects in this meta-analysis. Standardized mean differences (SMDs) in the exercise reserve (exercise − resting) measures of hemodynamic or echocardiographic parameters between the HFpEF and control groups were pooled in a random-effects meta-analysis. Results The pooled analysis included 910 patients with HFpEF and 476 control subjects. In pooled analysis, patients with HFpEF had significantly lower peak oxygen uptake (SMD: −2.13; 95% confidence interval [CI]: −2.68 to −1.57). Among hemodynamic exercise reserve parameters, the largest impairment was observed in chronotropic response reserve (change in heart rate from rest to peak exercise; SMD: −1.87; 95% CI: −2.44 to −1.29), followed by exaggerated increase in pulmonary capillary wedge pressure with exercise (SMD: 1.78; 95% CI: 1.46 to 2.09). Significant abnormalities were also observed in the arteriovenous oxygen difference reserve and stroke volume reserve between the HFpEF and control groups. Conclusions The most consistent and severe hemodynamic reserve abnormalities observed in patients with HFpEF were impairment in chronotropic reserve and exaggerated increase in pulmonary capillary wedge pressure with exercise. These may be important targets for therapeutic strategies to improve exercise tolerance in patients with HFpEF.

Background A reduced cardiac output (CO) response during exercise is a major limiting factor in heart failure (HF). Oxygen consumption (VO 2 ) is directly proportional to CO. Peripheral mechanisms via arteriovenous oxygen difference (Δ(a-v)O 2 ) play a pivotal role in chronic HF. We hypothesized a weak correlation between peak VO 2 and peak CO with a greater Δ(a-v)O 2 variability in most severe HF. Methods We analyzed 278 HF patients (NYHA II–III) who performed maximal cardiopulmonary exercise test with non-invasive CO measurement by inert gas rebreathing. Results Median peakVO 2 , CO and Δ(a-v)O 2 were 0.96 (0.78–1.28) L/min, 6.3 (5.1–8.0) L/min and 16.0 (14.2–18.0) mL/100 mL respectively, with a linear relationship between VO 2 and CO: CO = 5.3 × VO 2 + 1.13 (r 2 = 0.705, p 2 2 0.80 (0.67–0.94) L/min, peakCO 5.6 (4.7–6.5) L/min, peakΔ(a-v)O 2 14.8 (12.9–17.1) mL/100 mL. Group 2 (89 patients) peakVO 2 ≥ 50– 2 1.02 (0.84–1.29) L/min, peakCO 6.4 (5.1–8.0) L/min, peakΔ(a-v)O 2 16.7 (15.0–18.5) mL/100 mL. Group 3 (88 patients) peakVO 2 ≥ 65% pred: peakVO 2 1.28 (0.93–1.66) L/min, peakCO 8.0 (6.2–9.7) L/min, peakΔ(a-v)O 2 16.8 (14.6–18.3) mL/100 mL. A peakVO 2 and peakCO linear relationship was observed in Group 1 (r 2 = 0.381, p 2 = 0.756, p 2 = 0.744, p Conclusions With worsening HF we observed a progressive reduction of peak CO and peak VO 2 . However in most compromised patients also peripheral mechanisms play a role as indicated by reduced Δ(a-v)O 2 .

Objective Pharmacologically induced electroencephalogram (EEG) silence increases tolerance of ischemic period by reducing cerebral metabolism. We hypothesized that sevoflurane, a cerebral vasodilator, will maintain cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) better than propofol, a cerebral vasoconstrictor, during EEG silence. To validate this, we compared the effect of sevoflurane and propofol on CBF and CMRO2 during surgical plane of anasthesia (SP) and burst suppression on EEG (BS). Methods We conducted a prospective, double-blinded trial where patients undergoing neurosurgery were randomized to receive propofol or sevoflurane. Mean velocity (MV) and pulsatility index (PI) of bilateral middle cerebral arteries (MCA) were measured as surrogate of CBF. Jugular venous oxygen saturation (SjvO2) and arteriovenous oxygen difference (AjvDO2) were obtained to assess CMRO2. The values were compared between groups using Student t test and within the group with analysis of variance at SP and BS. Results BS decreased MV and increased PI in propofol group (P Conclusions In our study, sevoflurane had a safer profile on cerebral oxygenation during BS while not altering the CBF, suggesting increased availability of oxygen. Propofol, on the other hand, produced cerebral vasoconstriction with BS. The effect of propofol on oxygenation was unpredictable, with low SjvO2 and high AjvDO2 even at surgical plane of anesthesia.

In the course of time implantation of left ventricular assist devices (LVAD) has become an alternative to heart transplantation due to the enormous technical developments and miniaturization of these systems. Following implantation most patients show a significant improvement in their clinical condition and exercise capacity as measured by the New York Heart Association (NYHA) classification; nevertheless, exercise tolerance remains clearly limited even after LVAD implantation. The complex physiological and hemodynamic changes in LVAD patients both at rest and during exercise are ultimately not completely understood. The aim of this article is to describe the current state of scientific knowledge with respect to the physical capacity of patients with terminal heart failure after LVAD implantation at rest and during exercise. The influence of increasing the pump speed and continuous physical exercise training on the physical capacity in the long-term course is reviewed. The significance of new diagnostic tools, such as the non-invasive inert gas rebreathing method for measurement of cardiac output and arteriovenous oxygen difference (AVDO2) in assessment of the performance of LVAD patients is discussed.

PURPOSE Continuous peripheral pulse oximetry for monitoring adequacy of oxygenation is probably the most important technological advance for patients' monitoring and safety in the last decades. Pulse oximetry has the disadvantage of measuring the peripheral circulation, and the only mean to measure oxygen content of the central circulation is by invasive technology. Determination of blood oxyhaemoglobin saturation in the retinal vessels of the eye can be achieved noninvasively through spectrophotometric retinal oximetry which provides access to the central nervous system circulation. The aim of the thesis was to determine whether retinal oximetry technique can be applied for estimation of the central nervous system circulation which until now has only been possible invasively. This was achieved by measuring oxyhaemoglobin saturation in three adult subject study groups: in people with central retinal vein occlusion (CRVO) to observe local tissue hypoxia, in patients with severe chronic obstructive pulmonary disease (COPD) on long-term oxygen therapy to observe systemic hypoxaemia and in healthy subjects during hyperoxic breathing to observe systemic hyperoxemia. In addition, the fourth study that is mentioned was performed to test whether retinal oximetry is feasible for neonates. METHODS Retinal oximetry in central retinal vein occlusion: Sixteen subjects with central retinal vein occlusion participated in the study. The oxyhaemoglobin saturation of the central retinal vein occlusion affected eye was compared with the fellow unaffected eye. Retinal oximetry in healthy people under hyperoxia: Thirty healthy subjects participated in the study, and the oxyhaemoglobin saturation of retinal arterioles and venules was compared between normoxic and hyperoxic breathing. Retinal oximetry in severe chronic obstructive pulmonary disease: Eleven patients with severe chronic obstructive pulmonary disease participated in the study. Retinal oximetry measurements were made with and without their daily supplemental oxygen therapy. Retinal arteriolar oxyhaemoglobin saturation when inspiring ambient air was compared with blood samples from the radial artery and finger pulse oximetry and healthy controls. The healthy control group was assembled from our database for comparison of oxyhaemoglobin saturation of retinal arterioles and venules during the ambient air breathing. The retinal oximeter is based on a conventional fundus camera and a specialized software. A beam splitter coupled with two high-resolution digital cameras allows for simultaneous acquisition of retinal images at separative wavelengths for calculation of oxyhaemoglobin saturation. In addition, retinal images of 28 full-term healthy neonates were obtained with scanning laser ophthalmoscope combined with modified Oxymap analysis software for calculation of the optical density ratio and vessel diameter RESULTS: Retinal oximetry in central retinal vein occlusion: Mean retinal venous oxyhaemoglobin saturation was 31 ± 12% in CRVO eyes and 52 ± 11% in unaffected fellow eyes (mean ± SD, n = 14, p

Assessment of forearm oxygen uptake (O2) during handgrip exercise is a keenly investigated concept for observing small muscle mass metabolism. Although a combination of Doppler ultrasound measurements of brachial artery blood flow () and blood gas drawn from a deep forearm vein has been utilized to calculate forearm O2 for more than two decades, the applicability of this experimental design may benefit from a thorough evaluation of its reliability during graded exercise. Therefore, we evaluated the reliability of this technique during incremental handgrip exercise in ten healthy young (24±3(SD) years.) males. O2 and work rate (WR) exhibited a linear relationship (1.0W: 43.8±10.1mL·min−1; 1.5W: 53.8±14.1mL·min−1; 2.0W: 63.4±16.3mL·min−1; 2.5W: 72.2±17.6mL·min−1; 3.0W: 79.2±18.6mL·min−1; r=0.65, P&nbsp

Light-emitting diodes (LEDs) might have a beneficial impact on cytochrome-c oxidase enzyme activity. Thus, it was hypothesized that photobiomodulation by light-emitting diode therapy (LEDT) could influence aerobic metabolism dynamics. Possible LEDT-mediated aerobic improvements were investigated mainly by a precise characterization of the pulmonary O2 uptake dynamics during moderate exercise transitions. Eight healthy young adults were enrolled in this randomized, double-blind, placebo-controlled, crossover study. A multi-diode array of LEDs was used for muscular pre-conditioning 30 min and 6 h before exercise testing. Pulmonary O2 uptake, carbon dioxide output, cardiac output, heart rate, stroke volume, and total arteriovenous oxygen difference dynamics were evaluated by frequency domain analysis. Comparisons revealed no statistical (p > 0.05) differences between LEDT and placebo, suggesting no significant changes in aerobic system dynamics. These results challenge earlier publications that reported changes in pulmonary O2 uptake during incremental exercise until exhaustion after LEDT. Perhaps, increments in peak pulmonary O2 uptake after LEDT may be a consequence of higher exercise tolerance caused by non-aerobic-related factors as opposed to an improved aerobic response.

Habitual aerobic exercise attenuates elevated vasoconstriction during acute exercise (functional sympatholysis) in older men; however, this effect remains unknown in postmenopausal women (PMW). This study tested the hypothesis that PMW who participate in habitual aerobic exercise demonstrate a greater functional sympatholysis compared with their untrained counterparts. Nineteen PMW (untrained n = 9 vs. trained n = 10) performed 5 min of steady-state (SS) forearm exercise at relative [10% and 20% of maximum voluntary contraction (MVC)] and absolute (5 kg) contraction intensities. Lower-body negative pressure (LBNP) was used to increase sympathetic vasoconstriction during rest and forearm exercise. Brachial artery diameter and blood velocities (via Doppler ultrasound) determined forearm blood flow (FBF; ml/min). Forearm muscle oxygen consumption ([Formula: see text]; ml/min) and arteriovenous oxygen difference (a-vO2diff) were estimated during SS-exercise and SS-exercise with LBNP. Forearm vascular conductance (FVC; ml·min−1·100 mmHg−1) was calculated from FBF and mean arterial pressure (MAP; mmHg). Vasoconstrictor responsiveness was determined as the %change in FVC during LBNP. The reduction in FVC (% change FVC) during LBNP was lower in trained compared with untrained PMW at 10% MVC (−7.3 ± 1.2% vs. −13.0 ± 1.1%; P < 0.05), 20% MVC (−4.4 ± 0.8% vs. −8.6 ± 1.4%; P < 0.05), and 5 kg (−5.3 ± 0.8% vs. −8.9 ± 1.4%; P < 0.05) conditions, whereas there were no differences at rest (−32.7 ± 4.4% vs. −33.7 ± 4.0%). Peripheral (FVC, FBF, and [Formula: see text]) and the magnitude change in systemic hemodynamics (heart rate and MAP) did not differ between groups during exercise. Collectively, the findings present the first evidence suggesting that PMW who participate in aerobic exercise demonstrate a greater functional sympatholysis compared with untrained PMW during mild to moderate forearm exercise. NEW & NOTEWORTHY Habitual aerobic exercise attenuates the elevated sympathetic nervous system-induced vasoconstriction during an acute bout of exercise (improved functional sympatholysis) in aging men; however, this effect remains unknown in postmenopausal women (PMW). The novel findings of this study suggest that habitual aerobic exercise results in an enhanced functional sympatholysis in PMW. Conversely, habitual aerobic exercise does not alter blood flow and oxygen utilization during acute forearm exercise compared with PMW who do not habitually exercise.