Effects of combined histamine H1 and H2 receptor blockade on hemodynamic responses to dynamic exercise in males with high-normal blood pressure.

While postexercise hypotension is associated with histamine H1 and H2 receptor-mediated postexercise vasodilation, effects of histaminergic vasodilation on blood pressure (BP) in response to dynamic exercise are not known. Thus, in 20 recreationally active male participants (10 normotensive and 10 with high-normal BP) we examined the effects of histamine H1 and H2 receptor blockade on cardiac output (CO), mean atrial pressure (MAP), aortic stiffness (AoStiff), and total vascular conductance (TVC) at rest and during progressive cycling exercise. Compared with the normotensive group, MAP, CO, and AoStiff were higher in the high-normal group before and after the blockade at rest, while TVC was similar. At the 40% workload, the blockade significantly increased MAP in both groups, while no difference was found in the TVC. CO was higher in the high-normal group than the normotensive group in both conditions. At the 60% workload, the blockade substantially increased MAP and decreased TVC in the normotensive group, while there were no changes in the high-normal group. A similar CO response pattern was observed at the 60% workload. These findings suggest that the mechanism eliciting an exaggerated BP response to exercise in the high-normal group may be partially due to the inability of histamine receptors. Novelty Males with high-normal BP had an exaggerated BP response to exercise. The overactive BP response is known due to an increase in peripheral vasoconstriction. Increase in peripheral vasoconstriction is partially due to inability of histamine receptors.

Contribution of central and peripheral adaptations to changes in maximal oxygen uptake following 4 weeks of sprint interval training.

The current study examined the contribution of central and peripheral adaptations to changes in maximal oxygen uptake (V̇O2max) following sprint interval training (SIT). Twenty-three males completed 4 weekly SIT sessions (8 × 20-s cycling bouts at ∼170% of work rate at V̇O2max, 10-s recovery) for 4 weeks. Following completion of training, the relationship between changes in V̇O2max and changes in central (cardiac output) and peripheral (arterial-mixed venous oxygen difference (a-vO2diff), muscle capillary density, oxidative capacity, fibre-type distribution) adaptations was determined in all participants using correlation analysis. Participants were then divided into tertiles on the basis of the magnitude of their individual V̇O2max responses, and differences in central and peripheral adaptations were examined in the top (HI; ∼10 mL·kg-1·min-1 increase in V̇O2max, p < 0.05) and bottom (LO; no change in V̇O2max, p > 0.05) tertiles (n = 8 each). Training had no impact on maximal cardiac output, and no differences were observed between the LO group and the HI group (p > 0.05). The a-vO2diff increased in the HI group only (p < 0.05) and correlated significantly (r = 0.71, p < 0.01) with changes in V̇O2max across all participants. Muscle capillary density (p < 0.02) and ß-hydroxyacyl-CoA dehydrogenase maximal activity (p < 0.05) increased in both groups, with no between-group differences (p > 0.05). Citrate synthase maximal activity (p < 0.01) and type IIA fibre composition (p < 0.05) increased in the LO group only. Collectively, although the heterogeneity in the observed V̇O2max response following 4 weeks of SIT appears to be attributable to individual differences in systemic vascular and/or muscular adaptations, the markers examined in the current study were unable to explain the divergent V̇O2max responses in the LO and HI groups.

Hemodynamic and metabolic responses to self-paced and ramp-graded exercise testing protocols.

Recent examinations have shown lower maximal oxygen consumption during traditional ramp (RAMP) compared with self-paced (SPV) graded exercise testing (GXT) attributed to differences in cardiac output. The current study examined the differences in hemodynamic and metabolic responses between RAMP and SPV during treadmill exercise. Sixteen recreationally trained men (aged23.7 ± 3.0 years) completed 2 separate treadmill GXT protocols. SPV consisted of five 2-min stages (10 min total) of increasing speed clamped by the Borg RPE6-20 scale. RAMP increased speed by 0.16 km/h every 15 s until volitional exhaustion. All testing was performed at 3% incline. Oxygen consumption was measured via indirect calorimetry; hemodynamic function was measured via thoracic impedance and blood lactate (BLa-) was measured via portable lactate analyzer. Differences between SPV and RAMP protocols were analyzed as group means by using paired-samples t tests (R Core Team 2017). Maximal values for SPV and RAMP were similar (p > 0.05) for oxygen uptake (47.1 ± 3.4 vs. 47.4 ± 3.4 mL·kg-1·min-1), heart rate (198 ± 5 vs. 200 ± 6 beats·min-1), ventilation (158.8 ± 20.7 vs. 159.3 ± 19.0 L·min-1), cardiac output (26.9 ± 5.5 vs. 27.9 ± 4.2 L·min-1), stroke volume (SV) (145.9 ± 29.2 vs. 149.8 ± 25.3 mL·beat-1), arteriovenous oxygen difference (18.5 ± 3.1 vs. 19.7 ± 3.1 mL·dL-1), ventilatory threshold (VT) (78.2 ± 7.2 vs. 79.0% ± 7.6%), and peak BLa- (11.7 ± 2.3 vs. 11.5 ± 2.4 mmol·L-1), respectively. In conclusion, SPV elicits similar maximal hemodynamic responses in comparison to RAMP; however, SV kinetics exhibited unique characteristics based on protocol. These results support SPV as a feasible GXT protocol to identify useful fitness parameters (maximal oxygen uptake, oxygen uptake kinetics, and VT).

Sex differences in the oxygen delivery, extraction, and uptake during moderate-walking exercise transition.

Previous studies in children and older adults demonstrated faster oxygen uptake (V̇O2) kinetics in males compared with females, but young healthy adults have not been studied. We hypothesized that young men would have faster aerobic system dynamics in response to the onset of exercise than women. Interactions between oxygen supply and utilization were characterized by the dynamics of V̇O2, deoxyhemoglobin (HHb), tissue saturation index (TSI), cardiac output (Q̇), and calculated arteriovenous O2 difference (a-vO2diff) in women and men. Eighteen healthy active young women and men (9 of each sex) with similar aerobic fitness levels volunteered for this study. Participants performed an incremental cardiopulmonary treadmill exercise test and 3 moderate-intensity treadmill exercise tests (at 80% V̇O2 of gas exchange threshold). Data related to the moderate exercise were submitted to exponential data modelling to obtain parameters related to the aerobic system dynamics. The time constants of V̇O2, a-vO2diff, HHb, and TSI (30 ± 6, 29 ± 1, 16 ± 1, and 15 ± 2 s, respectively) in women were statistically (p < 0.05) faster than the time constants in men (42 ± 10, 49 ± 21, 19 ± 3, and 20 ± 4 s, respectively). Although Q̇ dynamics were not statistically different (p = 0.06) between groups, there was a trend to slower Q̇ dynamics in men corresponding with the slower V̇O2 kinetics. These results indicated that the peripheral and pulmonary oxygen extraction dynamics were remarkably faster in women. Thus, contrary to the hypothesis, V̇O2 dynamics measured at the mouth at the onset of submaximal treadmill walking were faster in women compared with men.

Three-dimensional transoesophageal echocardiography for cardiac output in critically ill patients: A pilot study of ultrasound versus the thermodilution method.

BACKGROUND: Three-dimensional transoesophageal echocardiography (3D-TOE) is a new noninvasive tool for quantitative assessment of left ventricular (LV) volumes and ejection fraction. AIM: The objective of this pilot study was to evaluate the feasibility and accuracy of 3D-TOE for the estimation of cardiac output (CO), using transpulmonary thermodilution with the Pulse index Contour Continuous Cardiac Output (PiCCO) system as the reference method, in intensive care unit (ICU) patients. METHODS: Fifteen ICU patients on mechanical ventilation prospectively underwent PiCCO catheter implantation and 3D-TOE. 3D-TOE LV end-diastolic and end-systolic volumes were determined using semi-automated software. CO was calculated as the product of LV stroke volume (end-diastolic volume-end-systolic volume) multiplied by heart rate. CO was also determined invasively by transpulmonary thermodilution as the reference method. RESULTS: Among 30 haemodynamic evaluations, 29 (97%) LV 3D-TOE datasets were suitable for CO calculation. The mean 3D-TOE image acquisition and post-processing times were 46 and 155seconds, respectively. There was a correlation (r=0.78; P<0.0001) between PiCCO and 3D-TOE CO. Compared with PiCCO, the 3D-TOE CO mean bias was 0.38L/min, with limits of agreement of -1.97 to 2.74L/min. CONCLUSIONS: Noninvasive estimation of CO by 3D-TOE is feasible in ICU patients. This new semi-automated modality is an additional promising tool for noninvasive haemodynamic assessment of ICU patients. However, the wide limits of agreement with thermodilution observed in this pilot study require further investigation in larger cohorts of patients.

Nebivolol has a beneficial effect in monocrotaline-induced pulmonary hypertension.

Pulmonary hypertension is a rare disorder that, without treatment, is progressive and fatal within 3-4 years. Current treatment involves a diverse group of drugs that target the pulmonary vascular bed. In addition, strategies that increase nitric oxide (NO) formation have a beneficial effect in rodents and patients. Nebivolol, a selective ß1 adrenergic receptor-blocking agent reported to increase NO production and stimulate ß3 receptors, has vasodilator properties suggesting that it may be beneficial in the treatment of pulmonary hypertension. The present study was undertaken to determine whether nebivolol has a beneficial effect in monocrotaline-induced (60 mg/kg) pulmonary hypertension in the rat. These results show that nebivolol treatment (10 mg/kg, once or twice daily) attenuates pulmonary hypertension, reduces right ventricular hypertrophy, and improves pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension. This study demonstrates the presence of ß3 adrenergic receptor immunoreactivity in pulmonary arteries and airways and that nebivolol has pulmonary vasodilator activity. Studies with ß3 receptor agonists (mirabegron, BRL 37344) and antagonists suggest that ß3 receptor-mediated decreases in systemic arterial pressure occur independent of NO release. Our results suggest that nebivolol, a selective vasodilating ß1 receptor antagonist that stimulates ß3 adrenergic receptors and induces vasodilation by increasing NO production, may be beneficial in treating pulmonary hypertensive disorders.

[Validation during exercise of a new device for cardiac output measurement using pulse wave transit time (comparison EsCCO(®) vs. Physioflow(®))]. / Évaluation à l'effort d'une nouvelle méthode de mesure du débit cardiaque basée sur l'analyse de l'onde de pouls (comparaison EsCCO(®) vs Physioflow(®)).

OBJECTIVES: EsCCO is a novel non-invasive continuous cardiac output monitoring system based on pulse wave transit time already validated at rest. The aim of our study was to compare cardiac output measurements obtained simultaneously by EsCCO(®) (Q˙cOP) and impedance cardiography (Physioflow(®) ; Q˙cIMP), in healthy subjects. PATIENTS AND METHODS: Eight healthy subjects (age: 31±9 years, weight: 76±10kg, height: 179±5cm) realized two exercise tests: an incremental ergocycle test performed until exertion (Pmax=269±48W) and a constant load exercise (P=163±27W). Comparison between measurements (Q˙cOP versus Q˙cIMP) obtained during the first test allowed to evaluate the accuracy of the device. Reliability was determined on three repeated measures during the second test, realized at ventilatory threshold. RESULTS: Correlation coefficient between both methods is 0.88 (P<0.01). Mean difference is 0.04±1.49L/min (95 % limits of agreement: +2.94 to -3.00L/min) and only 3/74 measures are not included between the limits of agreement. At high intensity and for cardiac output over than 15 L/min, Q˙cOP signal is lost in almost half the time. Concerning reliability, reproducibility coefficient is 0.87 (P<0.05), only 1.8 % of this variability is due to the method. CONCLUSION: EsCCO(®) measurements are accurate, reliable and allow a good estimation of cardiac output on healthy subjects. The signal lost observed for high cardiac output levels (>15L/min) can limit its utilization during very high intensity exercise.

Differential acute effects of carbohydrate- and protein-rich drinks compared with water on cardiac output during rest and exercise in healthy young men.

The acute effects of drinks rich in protein (PRO) versus carbohydrate (CHO) on cardiovascular hemodynamics and reactivity are uncertain. A randomized crossover design was used to compare 400-mL isoenergetic (1.1 MJ) drinks containing whey protein (PRO; 44 g) or carbohydrate (CHO; 57 g) versus 400 mL of water in 14 healthy men. The primary and secondary outcomes were changes in cardiac output, blood pressure, systemic vascular resistance (SVR) and digital volume pulse measured prior to and 30 min following consumption at rest, during 12 min of multi-stage bicycle ergometry, and 15 min postexercise. The mean change (95% confidence interval (CI)) in resting cardiac output at 30 min was greater for CHO than for PRO or water: 0.7 (0.4 to 1.0), 0.1 (-0.2 to 0.40), and 0.0 (-0.3 to 0.3) L/min (P < 0.001), respectively; the higher cardiac output following CHO was accompanied by an increase in stroke volume and a lower SVR. The mean increments (95% CI) in cardiac output during exercise were CHO 4.7 (4.4 to 5.0), PRO 4.9 (4.6 to 5.2), and water 4.6 (4.3 to 4.9) L/min with the difference between PRO versus water being significant (P < 0.025). There were no other statistically significant differences. In summary, a CHO-rich drink increased cardiac output and lowered SVR in the resting state compared with a PRO-rich drink or water but the effect size of changes in these variables did not differ during or after exercise between CHO and PRO. Neither protein nor carbohydrate affected blood pressure reactivity to exercise.

Ischemic preconditioning does not improve peak exercise capacity at sea level or simulated high altitude in trained male cyclists.

Ischemic preconditioning (IPC) may improve blood flow and oxygen delivery to tissues, including skeletal muscle, and has the potential to improve intense aerobic exercise performance, especially that which results in arterial hypoxemia. The aim of the study was to determine the effects of IPC of the legs on peak exercise capacity (W(peak)), submaximal and peak cardiovascular hemodynamics, and peripheral capillary oxygen saturation (SpO2) in trained males at sea level (SL) and simulated high altitude (HA; 13.3% FIO2, ∼ 3650 m). Fifteen highly trained male cyclists and triathletes completed 2 W(peak) tests (SL and HA) and 4 experimental exercise trials (10 min at 55% altitude-specific W(peak) then increasing by 30 W every 2 min until exhaustion) with and without IPC. HA resulted in significant arterial hypoxemia during exercise compared with SL (73% ± 6% vs. 93% ± 4% SpO2, p < 0.001) that was associated with 21% lower W(peak) values. IPC did not significantly improve W(peak) at SL or HA. Additionally, IPC failed to improve cardiovascular hemodynamics or SpO2 during submaximal exercise or at W(peak). In conclusion, IPC performed 45 min prior to exercise does not improve W(peak) or systemic oxygen delivery during submaximal or peak exercise at SL or HA. Future studies must examine the influence of IPC on local factors, such as working limb blood flow, oxygen delivery, and arteriovenous oxygen difference as well as whether the effectiveness of IPC is altered by the volume of muscle made ischemic, the timing prior to exercise, and high altitude acclimatization.

Stroke volume optimization after anaesthetic induction: An open randomized controlled trial comparing 0.9% NaCl versus 6% hydroxyethyl starch 130/0.4.

OBJECTIVE: Postinduction hypotension during general anaesthesia could be corrected by a rapid cardiac preload optimization by fluid infusion. The type of fluid to be used in this context remains debated. The aim of our study was to compare the amount of fluid challenges required to optimize stroke volume after induction of anaesthesia with colloid (HES) or crystalloid (0.9% NaCl). DESIGN: Open randomized prospective parallel-group study. PATIENTS AND METHODS: Fifty-six adult patients scheduled to undergo orthopaedic surgery under general anaesthesia were randomly assigned to receive, either 0.9% NaCl (n=28), or HES (n=28). Cardiac preload optimization directed by oesophageal Doppler was performed after induction with fluid challenges of 250ml of solution until stroke volume (SV) no longer increased by 10%. Primary endpoint was: number of fluid challenges required to achieve SV optimization. Secondary endpoints were: number of patients responding to the first fluid challenge, proportion of patients requiring ephedrine and the ephedrine dose required to restore arterial pressure. RESULTS: Percentages of responders were 61% and 63% in the 0.9% NaCl and HES groups, respectively. Number of fluid challenges necessary for SV optimization was not significantly different between 0.9% NaCl group and HES group (2 [1-2] versus 2 [1-2], P=0.33). Number of patients needing ephedrine, and well as the associated ephedrine dose, did not differ significantly. CONCLUSIONS: Our study suggests that after induction, crystalloid and colloid expand the intravascular volume with equivalent efficacy immediately after administration and correct in a similar way the postinduction hypotension.