Arteriovenous Oxygen Difference Research Articles

Cardiovascular Hemodynamic Response to Peak Exercise in Individuals with Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, progressive neurological condition that results in physical disability brought about, in part, by decreased aerobic capacity. Physical disability and aerobic deconditioning may increase risks of cardiovascular morbidity and mortality. The reduction in aerobic capacity may be associated with low maximal heart rate and/or low cardiac output. Yet it is unclear if the cardiovascular hemodynamic response to peak exercise differs between individuals with and without MS who have similar aerobic capacities. Purpose: To compare the cardiovascular hemodynamic response to peak exercise between individuals with and without MS, with similar aerobic capacities. We hypothesized individuals with similar aerobic capacities would also exhibit similar hemodynamic responses, regardless of disease condition. Methods: Individuals with MS (n=14 (2 males), 38 ± 8 yrs, 24.6 ± 4.5 kg/m 2 ) and without MS (n=14 (1 male), 33 ± 9 yrs, 28.8 ± 13.8 kg/m 2 ) underwent maximal incremental cycle exercise test to assess maximal aerobic capacity (VO 2 peak). Heart rate (HR) was measured continuously via Polar Heart Rate Monitor. Ascending aortic blood flow velocity images (VTI) via continuous wave Doppler echocardiography, and brachial blood pressure (BP) via brachial sphygmomanometry were obtained every other minute of the exercise test. Stroke volume (SV) was calculated from VTI and the area of the aorta, cardiac output (Q) was calculated as SV × HR, and Mean arterial pressure (MAP) was calculated from BP. Maximal arteriovenous oxygen difference (avO2diff) was calculated as VO 2 peak ⁄ Q. Results: There was no significant difference in VO 2 peak between groups (MS: 30.8 ml/kg·min -1 vs CON: 28.2 ml/kg·min -1 , p=0.65). Both groups (MS and CON) had significant time (rest to peak) differences in SV (rest: MS = 74.6 ± 32.5 mL, CON = 65.7 ± 23.1 mL, peak: MS = 114.4 ± 42.4 mL, CON = 84.2 ± 33.3 mL; p<0.001), HR (rest: MS = 65 ± 15 bpm, CON = 61 ± 10 bpm, peak: MS = 167 ± 13 bpm, CON = 175 ± 11 bpm; p<0.001), Q (rest: MS = 4.7 ± 2.2 L/m, CON = 4.0 ± 1.3 L/m, peak: MS = 12.3 ± 5.0 L/min, CON = 12.3 ± 5.1 L/min; p<0.001), and MAP (rest: MS = 84 ± 10 mmHg, CON = 83 ± 13 mmHg, peak: MS = 102 ± 7 mmHg, CON = 104 ± 17 mmHg, p <0.001). There was also a significant group by time interaction in HR (p = 0.04), but no group by time interactions in SV, Q, or MAP. Finally, there was not significant difference in avO 2 diff between groups (MS: 2.3 ± 1.2 mL/100 mL vs CON: 2.7 ± 1.5 mL/100 mL). Conclusion: Our findings suggest that individuals with MS exhibit different cardiac hemodynamics to achieve maximal aerobic capacity than those without MS. Individuals with MS reached maximal Q via a slightly higher, although statistically non-significant, stroke volume but a lower HR. This suggests that people with MS may rely on different mechanisms for achieving VO2peak compared to controls, but future research is needed to elucidate this hemodynamic pattern. Department of Defense office of the Congressionally Directed Medical Research Program on Multiple Sclerosis This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association of complication of type 2 diabetes mellitus with hemodynamics and exercise capacity in patients with heart failure with preserved ejection fraction: a case–control study in individuals aged 65–80 years

BackgroundType 2 diabetes mellitus (T2DM) is a frequently observed complication in patients with heart failure with preserved ejection fraction (HFpEF). Although a characteristic finding in such patients is a decrease in objective exercise capacity represented by peak oxygen uptake (peakVO2), exercise capacity and its predictors in HFpEF with T2DM remain not clearly understood. This case–control study aimed to investigate the association between exercise capacity and hemodynamics indicators and T2DM comorbidity in patients with HFpEF aged 65–80 years.MethodsNinety-nine stable outpatients with HFpEF and 50 age-and-sex-matched controls were enrolled. Patients with HFpEF were classified as HFpEF with T2DM (n = 51, median age, 76 years) or without T2DM (n = 48, median age, 76 years). The peakVO2 and ventilatory equivalent versus carbon dioxide output slope (VE vs VCO2 slope) were measured by cardiopulmonary exercise testing. The peak heart rate (HR) and peak stroke volume index (SI) were measured using impedance cardiography, and the estimated arteriovenous oxygen difference (peak a-vO2 diff) was calculated with Fick's equation. The obtained data were compared among the three groups using analysis of covariance adjusted for the β-blocker medication, presence or absence of sarcopenia, and hemoglobin levels in order to determine the T2DM effects on exercise capacity and hemodynamics in patients with HFpEF.ResultsIn HFpEF with T2DM compared with HFpEF without T2DM and the controls, the prevalence of sarcopenia, chronotropic incompetence, and anemia were significantly higher (p < 0.001). The peakVO2 (Controls 23.5 vs. without T2DM 15.1 vs. with T2DM 11.6 mL/min/kg), peak HR (Controls 164 vs. without T2DM 132 vs. with T2DM 120 bpm/min), peak a-vO2 (Controls 13.1 vs without T2DM 10.6 vs with T2DM 8.9 mL/100 mL), and VE vs VCO2 slope (Controls 33.2 vs without T2DM 35.0 vs with T2DM 38.2) were significantly worsened in patients with HFpEF with T2DM (median, p < 0.001). There was no significant difference in peak SI among the three groups.ConclusionsOur results suggested that comorbid T2DM in patients with HFpEF may reduce exercise capacity, HR response, peripheral oxygen extraction, and ventilation efficiency. These results may help identify cardiovascular phenotypes of HFpEF complicated with T2DM and intervention targets for improving exercise intolerance.

Comparison of Hemodynamic Effects of Dobutamine and Ephedrine Infusions in Isoflurane-Anesthetized Horses.

The objective of this study was to compare the hemodynamic effects of dobutamine and ephedrine during the management of anesthesia-related hypotension in healthy horses. Thirteen horses underwent general anesthesia with isoflurane and were randomly divided into two different groups, one of which received a dobutamine constant rate infusion (CRI) (1 µg/kg bwt/min) and the other received an ephedrine CRI (20 µg/kg bwt/min) when hypotension (<60 mmHg) was identified, following up to 15 min after the blood pressure reached 70 mmHg. All horses were equipped with a pulmonary artery catheter and a peripheral artery catheter, and multiparameter monitoring commenced as soon as they were under mechanical ventilation. Hemodynamic parameters were recorded, while tissue perfusion markers (peripheral oxygen saturation, arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial plasma bicarbonate concentration, arterial oxygen saturation, mixed venous oxygen saturation, mixed venous oxygen content, arterial oxygen content, arteriovenous oxygen difference, oxygen delivery index, oxygen consumption index, and oxygen extraction ratio), serum lactate concentration, and troponin I concentrations were analyzed before the start of infusions (T0), when the blood pressure reached 70 mmHg (T1), and 15 min after T1 (T2). The time to restore the arterial pressure was similar in both groups (p > 0.05); however, the heart rate was higher in the ephedrine group (p = 0.0098), and sinus bradyarrhythmia occurred in the dobutamine group. Furthermore, both experimental protocols increased cardiac output (p = 0.0012), cardiac index (p = 0.0013), systemic vascular resistance (p = 0.008), systemic vascular resistance index (p < 0.001), and ameliorated perfusion markers. In the dobutamine group, the pulmonary artery wedge pressure (p < 0.001) and systolic index (p = 0.003) were elevated, while the arteriovenous oxygen difference was reduced in the ephedrine group (p = 0.02). Troponin I was used as a myocardial injury indicator, and did not differ between moments or between groups (p > 0.05). We concluded that both drugs were effective and safe to treat anesthetic hypotension under the conditions of this study.

Skeletal muscle optoacoustics reveals patterns of circulatory function and oxygen metabolism during exercise

Imaging skeletal muscle function and metabolism, as reported by local hemodynamics and oxygen kinetics, can elucidate muscle performance, severity of an underlying disease or outcome of a treatment. Herein, we used multispectral optoacoustic tomography (MSOT) to image hemodynamics and oxygen kinetics within muscle during exercise. Four healthy volunteers underwent three different hand-grip exercise challenges (60s isometric, 120s intermittent isometric and 60s isotonic). During isometric contraction, MSOT showed a decrease of HbO2, Hb and total blood volume (TBV), followed by a prominent increase after the end of contraction. Corresponding hemodynamic behaviors were recorded during the intermittent isometric and isotonic exercises. A more detailed analysis of MSOT readouts revealed insights into arteriovenous oxygen differences and muscle oxygen consumption during all exercise schemes. These results demonstrate an excellent capability of visualizing both circulatory function and oxygen metabolism within skeletal muscle under exercise, with great potential implications for muscle research, including relevant disease diagnostics.

Reduced cardiovascular reserve capacity in long-term allogeneic stem cell transplant survivors

Premature cardiovascular mortality is increased in long-term allogeneic stem cell transplant (allo-SCT) survivors, but little information exists regarding subclinical cardiovascular dysfunction in this population. We compared peak oxygen uptake ({{dot{mathrm V}}}O2peak), a prognostic cardiovascular marker, and its determinants between long-term allo-SCT survivors and non-cancer controls. Fourteen allo-SCT survivors (mean ± SD, 44 ± 15 years, 50% male, median time since allo-SCT: 6.5 years [range 2–20]) and 14 age- and sex-matched controls (46 ± 13 years, 50% male) underwent cardiopulmonary exercise testing to quantify {{dot{mathrm V}}}O2peak. Resting echocardiography (left-ventricular ejection fraction and strain), exercise cardiac MRI (peak cardiac and stroke volume index [CIpeak, SVIpeak]), biochemistry (hemoglobin, troponin-I, B-natriuretic peptide), dual-energy x-ray absorptiometry (lean [LM] and fat [FM] mass, percent body fat [%BF]) and Fick-principal calculation (arteriovenous oxygen difference) were also performed. Survivors exhibited impaired {{dot{mathrm V}}}O2peak as compared with controls (25.9 ± 5.1 vs. 33.7 ± 6.5 ml kg−1 min−1, p = 0.002), which coincided with reduced CIpeak (6.6 ± 0.8 vs. 8.6 ± 1.9 L min−1 m−2; p = 0.001) secondary to reduced SVIpeak (48 ± 4 vs. 61 ± 8 ml m−2; p < 0.001) rather than chronotropic impairment, and higher %BF (difference, 7.9%, p = 0.007) due to greater FM (5.8 kg; p = 0.069) and lower LM (4.3 kg, p = 0.25). All other measures were similar between groups. Despite comparable resting cardiac function and biomarker profiles, survivors exhibited reduced {{dot{mathrm V}}}O2peak and exercise cardiac function and increased %BF relative to controls. These results highlight potential therapeutic avenues and the utility of exercise-based cardiovascular assessment in unmasking cardiovascular dysfunction in allo-SCT survivors.

Sex differences in heart failure patients assessed by combined echocardiographic and cardiopulmonary exercise testing.

We aimed to test the differences in peak VO2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET). Patients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HFpEF), HF with mildly reduced or reduced ejection fraction (HFmrEF/HFrEF), and patients without HF (control). These groups were further stratified by sex. One hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HFpEF showed attenuated increases in end diastolic volume index (P = 0.040 for sex × time interaction), significantly elevated E/e' (P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio (P = 0.040 for sex × time interaction), and lesser increases in A-VO2 difference (P = 0.003 for sex × time interaction), comparing to males with HFpEF. Females diagnosed with HFmrEF/HFrEF showed diminished increases in end diastolic volume index (P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HFmrEF/HFrEF. This resulted in reduced increases in peak stroke volume index (P = 0.010 for sex × time interaction) and cardiac output (P = 0.050 for sex × time interaction). Combined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HFpEF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HFmrEF/HFrEF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics.

Physiological Variables that Contribute to Aerobic Fitness in Boys during Early Adolescence in the Context of Basketball Training and the Maturity Level.

The aim of this study was to assess physiological variables that contribute to aerobic fitness in respect to basketball training and the maturity level in adolescent boys. Our subjects were 28 basketball-trained and 22 control-group boys (average age: 11.83 ± 0.43 years). An incremental treadmill running test to exhaustion was performed twice with a 1-year interval between the sessions to determine the following peak aerobic fitness variables: oxygen uptake, stroke volume, cardiac output, minute ventilation, and others. Maturity offset was used to evaluate the maturity level. The basketball-trained group exhibited a higher peak ratio-scaled oxygen uptake (1st session: 50.55 ± 6.21 and 46.57 ± 5.68 ml/kg/min in basketball and control-group boys, respectively, p = 0.024; 2nd session: 54.50 ± 6.50 and 45.33 ± 5.99 ml/kg/min, respectively, p < 0.001) during both testing sessions. During the 2nd session, the basketball-trained group also showed a significantly higher peak arteriovenous oxygen difference (basketball-trained boys: 14.02 ± 2.17 ml/100 ml; control-group boys: 12.52 ± 2.49 ml/100 ml; p = 0.027) and peak minute ventilation (basketball-trained boys: 96.08 ± 21.71 l/min; control-group boys: 83.14 ± 17.85 l/min; p = 0.028). The maturity level among the basketball-trained boys was correlated with peak variables: oxygen uptake, stroke volume, cardiac output, and minute ventilation, but not with the ratio-scaled oxygen uptake. In conclusion, basketball training at a young age among boys improved aerobic fitness compared with sedentary boys. More mature basketball players were not superior to their less mature peers regarding aerobic fitness after adjusting for body dimensions.

Flexible, Implantable, Pulse Oximetry Sensors: Toward Long-Term Monitoring of Blood Oxygen Saturations

Pulse oximetry is the most widespread method of monitoring heart rate and blood oxygen levels in both clinical and non-clinical settings. Current devices are ridged, bulky, and suitable only for short-term use. While the next generation of devices are moving toward wearable technologies, this focus on being unobtrusive is insufficient. To enable continuous high quality long-term monitoring, implanted devices are required. These will eliminate interference from light and sensitivity to skin pigmentation, allow enhanced performance during movement, and have no concerns around percussive damage. Here, an inexpensive, ultra-flexible pulse oximetry probe is demonstrated. The hybrid devices are fabricated on 5 µm Parylene C using laser ablation to define the circuit, and integrate small, rigid optoelectronic components. These are demonstrated in vivo on anesthetized pigs. Both transmission mode, and the novel reflection mode, are shown to be effective geometries for this. The heart rate measured by these devices shows < 2% variance from concurrent peripheral pulse oximetry measurements, along with an average variance of around 2.5% attributed predominantly to differences between central and peripheral oxygen saturations. In addition, it is shown that when implemented directly on the femoral artery, these devices record a more acute response to the variation in oxygen intake compared to the peripheral measurements. Finally, the same devices are shown to have the potential for use in monitoring venous oxygen content. This could open up the possibility of continuous monitoring of arteriovenous oxygen difference. These devices are straightforward to produce, biocompatible, and can be easily implanted during cardiovascular surgery, offering a route toward long-term implantation for continuous patient monitoring.

The Effects of Body Composition, Physical Fitness on Time of Useful Consciousness in Hypobaric Hypoxia.

Several previous studies have reported that hypoxia accidents of fighter pilots are rarer than gravity-induced loss of consciousness and spatial disorientation; however, the risk is greater. Therefore, this study aimed to investigate the relationship between physical fitness and body composition on time of useful consciousness (TUC) in hypobaric hypoxia. Body composition and physical fitness testing on human participants were performed; subsequently, they were exposed to hypobaric hypoxia at a simulated altitude of 25,000 ft. Cognitive testing of the participants was accomplished by having them perform arithmetic task tables until they stopped writing for a period exceeding 5 seconds, at which point, they were placed on 100% oxygen. TUC was measured from the time the participants removed their oxygen masks to the time when the oxygen masks were placed back on them. Pearson's correlation was used to determine the relationship between TUC and other variables, and multiple regression was performed to determine the independent variables that best explain the TUC. TUC was positively correlated with the maximum oxygen uptake, stroke volume, arteriovenous oxygen difference, and endurance (sit-up and push-up). The maximum heart rate on the ground, high altitude, body fat mass, and percent body fat were negatively correlated with TUC. A regression analysis showed that 84.5% of the TUC can be explained by body composition and physical fitness. Our results revealed that increased cardiorespiratory fitness and decreased body fat mass could significantly impact the TUC. Therefore, for Air Force pilots who are frequently at high altitudes and at risk for exposure to hypoxia, aerobic exercise is significant to hypoxia tolerance.

Rapid cardiovascular aging following allogeneic hematopoietic cell transplantation for hematological malignancy.

Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential cure for high-risk hematological malignancy; however, long-term survivors experience increased cardiovascular morbidity and mortality. It is unclear how allo-HCT impacts cardiovascular function in the short-term. Thus, this 3-month prospective study sought to evaluate the short-term cardiovascular impact of allo-HCT in hematological cancer patients, compared to an age-matched non-cancer control group. Before and ~3-months following allo-HCT, 17 hematological cancer patients (45 ± 18 years) underwent cardiopulmonary exercise testing to quantify peak oxygen uptake (VO2peak)-a measure of integrative cardiovascular function. Then, to determine the degree to which changes in VO2peak are mediated by cardiac vs. non-cardiac factors, participants underwent exercise cardiac MRI (cardiac reserve), resting echocardiography (left-ventricular ejection fraction [LVEF], global longitudinal strain [GLS]), dual-energy x-ray absorptiometry (lean [LM] and fat mass [FM]), blood pressure (BP) assessment, hemoglobin sampling, and arteriovenous oxygen difference (a-vO2diff) estimation via the Fick equation. Twelve controls (43 ± 13 years) underwent identical testing at equivalent baseline and 3-month time intervals. Significant group-by-time interactions were observed for absolute VO2peak (p = 0.006), bodyweight-indexed VO2peak (p = 0.015), LM (p = 0.001) and cardiac reserve (p = 0.019), which were driven by 26, 24, 6, and 26% reductions in the allo-HCT group (all p ≤ 0.001), respectively, as no significant changes were observed in the age-matched control group. No significant group-by-time interactions were observed for LVEF, GLS, FM, hemoglobin, BP or a-vO2diff, though a-vO2diff declined 12% in allo-HCT (p = 0.028). In summary, allo-HCT severely impairs VO2peak, reflecting central and peripheral dysfunction. These results indicate allo-HCT rapidly accelerates cardiovascular aging and reinforces the need for early preventive cardiovascular intervention in this high-risk group.

심혈관계의 운동 생리

One of the essential points of cardiac rehabilitation is to understanding the exercise physiology of exercise-induced metabolic changes through the study of the acute responses and chronic adaptation to exercise. Exercise capacity is expressed as maximal oxygen consumption (VO2max) and its unit is expressed as the amount of oxygen consumed per kilogram of body weight per minute (mL/kg/min). VO2 can be calculated as stroke volume x heart rate x arteriovenous oxygen difference, and in cardiac rehabilitation, the arteriovenous oxygen difference should be maximized. Oxygen consumption during exercise is expressed as a multiple of oxygen consumption during rest. Metabolic equivalent (MET) is the basic metabolic energy consumed during rest, which is 3.5 mL/kg/min. Myocardial oxygen uptake (MVO2) is determined by myocardial wall tension, contractility, and heart rate. It does not increase further when the angina threshold is reached. Aerobic training can lower MVO2 at rest and at submaximal exercise intensity. As a result, when performing the same intensity of activity, MVO2 is lowered and the margin of safety is widened, and preventing from occurring at the same intensity or higher intensity compared to the past. It is very useful to know each individual

Exertional dyspnea responses to the Dyspnea Challenge in heart failure: Comparison to chronic obstructive pulmonary disease

BackgroundIn heart failure (HF), exertional dyspnea is a common symptom, but validated field-based tests for its measurement are limited. The Dyspnea Challenge is a two-minute uphill treadmill walk designed to measure exertional dyspnea in cardiopulmonary disease. ObjectivesThe purpose of this study was to establish the test-retest reliability of the Dyspnea Challenge in HF and to compare the exercise responses to a group with chronic obstructive pulmonary disease (COPD). MethodsThe study was an experimental, single-blind, randomized, multi-site project that recruited individuals with HF (New York Heart Association I-III) and COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV). Participants completed two visits. On the first visit, participants performed two six-minute walk tests (6MWT), followed by two to three Dyspnea Challenges to calculate treadmill speed and gradient. At Visit Two, participants performed two separate Dyspnea Challenges, with one including measures of pulmonary gas exchange and central hemodynamics. ResultsTwenty-one individuals with HF (10 female; 66±11years; ejection fraction:45.3 ± 6.1%; six-minute distance(6MWD) 520 ± 97 m), and 25 COPD (11 female; 68 ± 10 yr; forced expiratory volume in 1 s:47.6 ± 11.5%; 6MWD: 430 ± 101 m). Intraclass correlation coefficients demonstrated excellent test-retest reliability for HF (0.94, P<.01) and COPD (0.95, P<.01). While achieving similar end-exercise exertional dyspnea intensities (P=.60), the HF group walked at a higher average speed (4.2 ± 0.8 vs. 3.5 ± 0.8km·h−1) and gradient (10.3 ± 2.8 vs. 9.6 ± 2.8%) and a greater oxygen uptake (P<.01) and ventilation (P<.01) than those with COPD. While achieving similar cardiac outputs (P=.98), stroke volumes (P=.97), and heart rates (P=.83), those with HF displayed a larger arteriovenous oxygen difference (P<.01), while those with COPD exhibited greater decreases in inspiratory capacity (P=.03), arterial oxygen saturation (P=.02), and breathing reserve (P<.01). ConclusionsThe Dyspnea Challenge is a reliable test-retest measure of exertional dyspnea in HF. Typical to their pathologies, HF seemed limited by an inadequate modulation of cardiac output, while ventilatory constraints hampered those with COPD.

Abstract 10041: Cardiopulmonary Performance Among Heart Failure Patients Before and After Left Ventricular Assist Device Implantation

Introduction: Continuous-flow left ventricular assist devices (CF-LVAD) improve survival and subjective assessments of health-related quality-of-life (HRqOL) when implanted into patients with advanced heart failure with reduced ejection fraction (HFrEF). However, functional capacity remains severely reduced. Hypothesis: LVAD flow during exercise contributes minimally to overall functional capacity. Exercise tolerance depends on intrinsic factors such as cardiac output (Qc) and arteriovenous oxygen difference (avo2 diff ). Methods: Ten patients (9 male, 60±10 years), underwent three invasive cardiopulmonary exercise tests on upright cycle ergometry. Visits were arranged 1) before (median, IQR: 0.3, 0.1-0.05 months) implantation, 2) after (4.2, 3.1-5.3 months) implantation with CF-LVAD speed held constant, and 3) with increases in pump speed during exercise (2.3, 1.9-3.0 months) after Visit 2. Submaximal functional capacity was measured by six-minute hall walk (6MHW). Fick Qc was measured via pulmonary artery catheter and gas exchange parameters determined by indirect calorimetry. Subjective assessments of HRqOL were obtained prior to and following implantation. Results: Following implantation, HRqOL and 6MHW improved. The avo2 diff and Qc predicted Watts achieved during exercise testing pre-implantation. The avo2diff, but not LVAD flow or Qc, predicted Watts achieved on multivariable analysis with both fixed and variable pumps speeds ( Table 1 ). Conclusions: Submaximal exercise performance and subjective HFrEF severity improved post implantation. The primary determinant of workload achieved during exercise testing, regardless of whether participants exercised at a fixed pump speed or with increases in pump speed, was the (A-V)O2 difference. LVAD flow contributes minimally to functional capacity.

Right Ventricular Dysfunction During Endurance Exercise as Determined by Pressure-Volume Analysis

A 37-year-old athlete completed invasive endurance (90 km) bicycle exercise testing for right ventricular pressure-volume analysis. Increased right ventricular afterload caused declines in ventricular-arterial coupling and cardiac output, causing increased arteriovenous oxygen difference to maintain oxygen uptake. These findings demonstrate effects of changes in right ventricular performance on exercise capacity. (Level of Difficulty: Intermediate.)

Hemodynamic and Echocardiographic Predictors of Mortality in Pediatric Patients on Venoarterial Extracorporeal Membrane Oxygenation: A Multicenter Investigation

Venoarterial extracorporeal membrane oxygenation (ECMO) supports patients with advanced cardiac dysfunction; however, mortality occurs in a significant subset of patients. The authors performed a multicenter, prospective study to determine hemodynamic and echocardiographic predictors of mortality in children placed on ECMO for cardiac support. Over 8years, six heart centers prospectively assessed echocardiographic and hemodynamic variables on full and minimum ECMO flow. Sixty-three patients were enrolled, ranging in age from 1day to 16years. Hemodynamic measurements included heart rate, vasoactive inotropic score, arteriovenous oxygen difference, pulse pressure, and lactate. Echocardiographic variables included shortening fraction, ejection fraction (EF), right ventricular fractional area change, outflow tract Doppler-derived stroke distance (velocity-time integral [VTI]), and degree of atrioventricular valve regurgitation. Patients were stratified into two groups: those who were able to wean within 48hours of assessment and survived without ventricular assist devices or orthotopic heart transplantation (successful wean group) and those with unsuccessful weaning. For each patient, variables were compared between full and minimum ECMO flow for each group. Thirty-eight patients (60%) formed the unsuccessful group (two with ventricular assist devices, four with orthotopic heart transplantation, 24 deaths), and 25 constituted the successful wean group. At minimum flow, higher EF (53±16% vs 40±20%, P=.0094), less mitral regurgitation (0.8±0.9 vs 1.4±0.9, P=.0329), and lower central venous pressure (12.0±3.9 vs 14.7±5.4mm Hg), along with higher VTI (9.0±2.9 vs 6.8±3.7cm, P=.0154), correlated successful weaning. A longer duration of ECMO (8 vs 5days, P<.0002) was associated with unsuccessful weaning. Multivariate logistic regression predicted minimum-flow EF and VTI to independently predict successful weaning with cutoff values by receiver operating characteristic analysis of EF > 41% (area under the curve, 0.712; P=.0005) and VTI > 7.9cm (area under the curve, 0.729; P=.0010). Diminished VTI or EF during ECMO weaning predicts the need for orthotopic heart transplantation or ventricular assist device support or death in children on ECMO for cardiac dysfunction. Increased postwean central venous pressure or mitral regurgitation along with a prolonged ECMO course also predicted these adverse outcomes. These measurements should be used to help discriminate which patients will require alternative methods of circulatory support for survival.

Non-invasive cardiac output monitoring with electrical velocimetry after cardiac surgery in infants.

Low cardiac output following cardiac surgery is a major determinant of outcome that may be improved by early detection, yet there are no widely accepted methods for its measurement in young children. We evaluated the feasibility of the routine use of electrical velocimetry, a non-invasive technique providing continuous measurement of cardiac output, in infants in the early postoperative period. With ethical approval and parental consent, infants undergoing cardiac surgery were recruited. The ICON electrical velocimetry monitor was attached on admission to the intensive care unit (ICU) and remained for up to 24h. A total of 15 infants were recruited, median age 3months (interquartile range (IQR) 0.5-7.5) and weight 4.8kg (IQR 3.9-7.1), undergoing various operations. Cardiac index had a weak correlation with arterial lactate (r=-0.24, p=0.02) and no correlation with blood pressure, central venous pressure or arteriovenous oxygen difference. Data were recorded for a median of 19h (range 5-24), with lead detachment or movement artefact the most common causes of data loss. There was marked minute-to-minute variability, with 25% of consecutive measurements having >5% variability. Cardiac index measured by electrical velocimetry in infants in the early postoperative period is impaired by frequent data loss and marked intrapatient variability. Our feasibility study suggests that it is unsuitable for use as a routine monitoring tool in the setting of postsurgical ICU care.

Ventilatory efficiency is superior to peak oxygen uptake for prediction of lung resection cardiovascular complications.

Ventilatory efficiency (VE/VCO2 slope) has been shown superior to peak oxygen consumption (VO2) for prediction of post-operative pulmonary complications in patients undergoing thoracotomy. VE/VCO2 slope is determined by ventilatory drive and ventilation/perfusion mismatch whereas VO2 is related to cardiac output and arteriovenous oxygen difference. We hypothesized pre-operative VO2 predicts post-operative cardiovascular complications in patients undergoing lung resection. Lung resection candidates from a published study were evaluated by post-hoc analysis. All of the patients underwent preoperative cardiopulmonary exercise testing. Post-operative cardiovascular complications were assessed during the first 30 post-operative days or hospital stay. One-way analysis of variance or the Kruskal-Wallis test, and multivariate logistic regression were used for statistical analysis and data summarized as median (IQR). Of 353 subjects, 30 (9%) developed pulmonary complications only (excluded from further analysis), while 78 subjects (22%) developed cardiovascular complications and were divided into two groups for analysis: cardiovascular only (n = 49) and cardiovascular with pulmonary complications (n = 29). Compared to patients without complications (n = 245), peak VO2 was significantly lower in the cardiovascular with pulmonary complications group [19.9 ml/kg/min (16.5-25) vs. 16.3 ml/kg/min (15-20.3); P<0.01] but not in the cardiovascular only complications group [19.9 ml/kg/min (16.5-25) vs 19.0 ml/kg/min (16-23.1); P = 0.18]. In contrast, VE/VCO2 slope was significantly higher in both cardiovascular only [29 (25-33) vs. 31 (27-37); P = 0.05] and cardiovascular with pulmonary complication groups [29 (25-33) vs. 37 (34-42); P<0.01)]. Logistic regression analysis showed VE/VCO2 slope [OR = 1.06; 95%CI (1.01-1.11); P = 0.01; AUC = 0.74], but not peak VO2 to be independently associated with post-operative cardiovascular complications. VE/VCO2 slope is superior to peak VO2 for prediction of post-operative cardiovascular complications in lung resection candidates.

Limits to submaximal and maximal exercise in patients with hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HCM) often have reduced exercise capacity, and it is unclear whether cardiovascular regulation during exercise is intact in these patients. We aimed to determine the relationship between cardiac output (Q̇c) and oxygen uptake (V̇o2), and stroke volume (SV) reserve in HCM compared with healthy participants and participants with left ventricular hypertrophy (LVH) but not HCM. Sixteen patients with HCM (48 ± 7 yr, 44% female), 16 participants with LVH (49 ± 5 yr, 44% female), and 61 healthy controls (CON: 52 ± 5 yr, 52% female) completed submaximal steady-state treadmill exercise followed by a maximal exercise test. V̇o2, Q̇c, SV, and arteriovenous oxygen difference were measured during rest and exercise, and Q̇c/V̇o2 slopes were constructed, The Q̇c/V̇o2 slope was blunted in HCM compared with CON and LVH [HCM 4.9 ± 0.7 vs. CON 5.5 ± 1.0 (P = 0.027) vs. LVH 6.0 ± 1.0 AU (P = 0.002)] and participants with HCM had a lower SV reserve (HCM 53 ± 33%, controls 83 ± 33%, LVH 82 ± 22%; HCM vs. controls P = 0.002; HCM vs. LVH P = 0.015). Despite a blunted Q̇c/V̇o2 slope, 75% of patients with HCM achieved ≥80% predicted V̇o2max by augmenting a-vo2 difference at maximal exercise (16.0 ± 0.8 mL/100 mL vs. 13.8 ± 2.7 mL/100 mL, P = 0.021). Patients with HCM do not appropriately match Q̇c to metabolic demand, primarily due to inadequate stroke volume augmentation. Despite this central limitation, many patients achieve normal exercise capacities by significantly increasing peripheral oxygen extraction.NEW & NOTEWORTHY Through state-of-the-art hemodynamic and oxygen uptake methodologies, this study found the cardiac output response to increasing metabolic demand is blunted among patients with hypertrophic cardiomyopathy (HCM), primarily due to a reduced stroke volume reserve. Many patients with HCM augment their peripheral oxygen extraction during maximal exercise to achieve normal exercise capacity and overcome ineffective matching of cardiac output. Peripheral adaptations that compensate for cardiac limitations may contribute to the heterogeneity of functional limitations observed within this patient population.

Influence of the Digestive Tract on Enzyme Activity

Enzyme activity at the digestive tract level was experimentally studied on rabbits and mini-pigs. The enzyme activity in the blood flow supplied to and from the rabbit stomach and intestines was assessed. In rabbits, the arteriovenous oxygen difference revealed a decrease in the lactate dehydrogenase and amylase activity under an increase in the alkaline phosphatase activity. A regular dependence in the dynamics of gamma-glutamyl transferase activity in the intestinal mucosa and chyme fractions was established. It was found that gamma-glutamyl transferase activity decreases in the distal direction in the mucosa of the small intestine wall. Its maximum activity was determined in the soluble fraction of the small intestine chyme, with a characteristic decrease in the distal direction. Due to the hydration of the cavitary mucus glycoproteins in the chyme and the existence of the latter in the form of an enteroplasm, the enzyme is assumed to localize in the enteric medium between the soluble and dense endogenous fraction with the purpose of displaying the maximum transport activity. A conclusion was made about the plasma-forming role of the digestive tract in terms of blood enzyme activity.

Calculation of hemodynamics by the Fick method in pulmonary hypertension associated with congenital heart defects

In December, 2021 at the IXth All-Russian Congress «Pulmonary Hypertension – 2021» the first Eurasian guidelines for the diagnosis and treatment of pulmonary hypertension associated with congenital heart disease (CHD) in adults were approved. In this review, the expert group presents the basic principles of calculating hemodynamics according to Fick for the systemic and pulmonary circulation. The method is indispensable for congenital heart defects. Theoretical and practical aspects of calculating hemodynamics with arteriovenous, venoarterial and bidirectional shunting are considered. The calculation of the cardiac index of each of the circles of blood circulation is performed on the basis of oxygen consumption, the oxygen capacity of the blood and the oxygen arteriovenous difference of each of the circles of blood circulation. Formulas are given for calculating the cardiac index of the systemic and pulmonary circulation, the cardiac index of effective blood flow, arteriovenous and venoarterial shunt, pulmonary and peripheral vascular resistance, as well as the classical table and the LaFarge and Miettinen formula for the calculated oxygen consumption depending on gender, age and heart rate. The review is illustrated with three clinical examples. Calculation of hemodynamics according to Fick should be started after getting acquainted with the anatomy and clinic of congenital heart disease: diagnosis, typical hemodynamic disorders, number and possible direction of shunts, saturation by pulse oximeter on the arms and legs; a purely mechanistic approach that does not take into account the clinical picture can reduce the information content and reliability of the method. The Fick method is somewhat limited by the impossibility of catheterization of the left atrium with an intact interatrial septum. Inaccuracies that are possible when assessing absolute indicators by the indirect Fick method are leveled when calculating their relative values, and the values are identical in reliability to the direct method. The Fick method, due to the obviously high error, is not advisable to use if there is another source of pulmonary blood flow besides the pulmonary artery system, as well as with a low arteriovenous difference in circulatory circles.