Stroke Volume Response Research Articles

Abnormal spirometry is a predictor of exercise capacity in patients with tetralogy of Fallot

<p>We investigated the association between cardiac factors, spirometry, and exercise testing in patients with tetralogy of Fallot (TOF). Clinical data from patients with TOF performing a cardiopulmonary exercise test (CPET) was collected retrospectively over a 10-year period. 122 patients with TOF were identified, 52 excluded for incomplete exercise, spirometry, or cardiac data for 70 total patients included in the study. There was a male predominance 39 (56%), a mean age of 25 ± 12 years, with 28 (40%) < 18 years of age. The mean number of cardiac surgeries was 2.1 ± 1.2. Most, 46 (69%) had moderate to severe pulmonary valve insufficiency (PI) and 34 (51%) had moderate to severe right ventricular (RV) dilation. Mean forced vital capacity (FVC) was low at 81.8% predicted, and 32 (46%) with low FVC (< 80% predicted). Overall peak VO<sub>2</sub>/kg was low with a mean of 58.2 ± 13.2 % predicted. Using multiple regression analysis, a higher number of cardiac surgeries was an independent predictor of lower FVC (<em>p</em> = 0.01). Lower FVC was itself an independent predictor of lower peak VO<sub>2</sub>/kg and O<sub>2</sub> pulse (<em>p</em> < 0.05). Moderate or severe RV systolic dysfunction was an independent predictor of stroke volume response (<em>p</em> = 0.03).<strong> </strong>Higher body mass index (BMI) was an independent predictor of all exercise measures being worse (<em>p</em> < 0.05). Low FVC and reduced exercise capacity were common in our population of TOF patients. Low FVC was predictive of low exercise capacity while, of the cardiac measures only RV systolic dysfunction was significant and predictive of stroke volume response. Spirometry may be a valuable screening tool in evaluation of TOF patients.</p>

The effects of respiratory rate and tidal volume on pulse pressure variation in healthy lungs–a generalized additive model approach may help overcome limitations

Pulse pressure variation (PPV) is a well-established method for predicting fluid responsiveness in mechanically ventilated patients. The predictive accuracy is, however, disputed for ventilation with low tidal volume (VT) or low heart-rate-to-respiratory-rate ratio (HR/RR). We investigated the effects of VT and RR on PPV and on PPV’s ability to predict fluid responsiveness. We included patients scheduled for open abdominal surgery. Prior to a 250 ml fluid bolus, we ventilated patients with combinations of VT from 4 to 10 ml kg−1 and RR from 10 to 31 min−1. For each of 10 RR-VT combinations, PPV was derived using both a classic approach and a generalized additive model (GAM) approach. The stroke volume (SV) response to fluid was evaluated using uncalibrated pulse contour analysis. An SV increase > 10% defined fluid responsiveness. Fifty of 52 included patients received a fluid bolus. Ten were fluid responders. For all ventilator settings, fluid responsiveness prediction with PPV was inconclusive with point estimates for the area under the receiver operating characteristics curve between 0.62 and 0.82. Both PPV measures were nearly proportional to VT. Higher RR was associated with lower PPV. Classically derived PPV was affected more by RR than GAM-derived PPV. Correcting PPV for VT could improve PPV’s predictive utility. Low HR/RR has limited effect on GAM-derived PPV, indicating that the low HR/RR limitation is related to how PPV is calculated. We did not demonstrate any benefit of GAM-derived PPV in predicting fluid responsiveness.Trial registration: ClinicalTrials.gov, reg. March 6, 2020, NCT04298931.

Volume responsiveness revisited: an observational multicenter study of continuous versus binary outcomes combining echocardiography and venous return physiology.

Echocardiography can assess cardiac preload when fluid administration is used to treat acute circulatory failure. Changes in stroke volume (SV) are inherently a continuous phenomenon relating to the pressure gradient for venous return (VRdP). However, most clinical studies have applied a binary definition based on a fractional change in SV. This study tested the hypothesis that calculating the analog mean systemic filling pressure (Pmsa) and VRdP would enhance echocardiography to describe SV responses to a preload challenge. We investigated 540 (379 males) patients during a standardized passive leg raising (PLR) maneuver. Patients were further categorized by the presence of impaired right ventricular function (impRV) or increased intra-abdominal hypertension (IAH). Multivariable linear regression identified VRdP (partial r = -0.26, P < 0.001), ventilatory-induced variations in superior vena cava diameter (partial r = 0.43, P < 0.001), and left ventricular outflow tract maximum-Doppler velocity (partial r = 0.13, P < 0.001) as independent variables associated with SV changes. The model explained 38% (P < 0.001) of the SV change in the whole cohort and 64% (P < 0.001) when excluding patients with impRV or IAH. The correlation between Pmsa or VRdP and SV changes lost statistical significance with increasing impRV or IAH. A binary definition of volume responsiveness (>10% increase in SV) generated an area under the curve of 0.79 (P < 0.001) in logistic regression but failed to identify Pmsa or VRdP as independent variables and overlooked the confounding influence of impRV and IAH. In conclusion, venous return physiology may enhance echocardiographic assessments of volume responsiveness, which should be based on continuous changes in stroke volume.NEW & NOTEWORTHY The analog mean systemic filling pressure and the pressure gradient for venous return combined with echocardiography predict continuous changes in stroke volume following a passive leg raising maneuver. The confounding effects of impaired right ventricular function and increased intra-abdominal pressure can be identified. Using a binary cutoff for the fractional change in stroke volume, common in previous clinical research, fails to identify the importance of variables relevant to venous return physiology and confounding conditions.

Cardiovascular responses of exercises performed within the extreme exercise domain.

Stroke volume (SV), heart rate (HR) and arterio-venous O2 difference (a-vO2diff) responses to heavy and severe-intensity exercise have been well documented; however, there is a lack of information on the SV, HR and a v-O2diff responses of work rates within extreme exercise domain. The aim of this study was, therefore, to focus on central and peripheral components of VO2 responses to exercises performed within the heavy, severe and extreme exercise domain. Eight well-trained male cyclists participated in this study. Maximal O2 consumption (VO2max) and corresponding work rate (P@VO2max) were determined by multisession constant work rate exercises. Cardiovascular responses to exercises were evaluated by nitrous-oxide rebreathing method with work rates from 40 % to 160 % of P@VO2max, VO2max corresponded to 324+/-39.4 W; however, maximal SV responses occurred at 205+/-54.3 W (p<0.01). Maximal cardiac output (Q), HR, and a vO2diff responses were revealed by the P@VO2max. VO2 response to exercise significantly decreased from severe-intense exercises to the first work rate of extreme exercise domain due to significant decreases in Q, SV, and HR responses (p<0.05), except a v-O2diff (p>0.05). Moreover, non-significant decreases in Q, SV, and a v-O2diff were evaluated as response to increase in work rate belonging to extreme work rates (p>0.05), except the HR (p<0.05). Work rates within the lower district of the extreme exercise domain have an important potential to improve peripheral component of VO2, while the P@VO2max seems the most appropriate intensity for aerobic endurance development as it maximizes the central component of VO2max.

Prognostic Role of Metabolic Exercise Testing in Heart Failure

Heart failure is a clinical syndrome with significant heterogeneity in presentation and severity. Serial risk-stratification and prognostication can guide management decisions, particularly in advanced heart failure, when progression toward advanced therapies or end-of-life care is warranted. Each currently utilized prognostic marker carries its own set of challenges in acquisition, reproducibility, accuracy, and significance. Left ventricular ejection fraction is foundational for heart failure syndrome classification after clinical diagnosis and remains the primary parameter for inclusion in most clinical trials; however, it does not consistently correlate with symptoms and functional capacity, which are also independently prognostic in this patient population. Utilizing the left ventricular ejection fraction as the sole basis of prognostication provides an incomplete characterization of this condition and is prone to misguide medical decision-making when used in isolation. In this review article, we survey and exposit the important role of metabolic exercise testing across the heart failure spectrum, as a complementary diagnostic and prognostic modality. Metabolic exercise testing, also known as cardiopulmonary exercise testing, provides a comprehensive evaluation of the multisystem (i.e., neurological, respiratory, circulatory, and musculoskeletal) response to exercise performance. These differential responses can help identify the predominant contributors to exercise intolerance and exercise symptoms. Additionally, the aerobic exercise capacity (i.e., oxygen consumption during exercise) is directly correlated with overall life expectancy and prognosis in many disease states. Specifically in heart failure patients, metabolic exercise testing provides an accurate, objective, and reproducible assessment of the overall circulatory sufficiency and circulatory reserve during physical stress, being able to isolate the concurrent chronotropic and stroke volume responses for a reliable depiction of the circulatory flow rate in real time.

Stroke volume response during prolonged exercise depends on left ventricular filling: Evidence from a beta-blockade study.

Prolonged moderate intensity exercise leads to a progressive upward drift in heart rate (HR) that may compromise stroke volume (SV). Alternatively, the HR drift may be related to abated SV due to impaired ventricular function. The aim of this study was to examine the effects of cardiovascular drift on left ventricular volumes and in turn SV. Thirteen healthy young males completed two 60-minute cycling bouts on a semi-recumbent cycle ergometer at 57%VO2max either under placebo condition (CON) or after ingesting a small dose of β1-blockers (BB). Measurements of HR, end-diastolic volume (EDV), and end-systolic volume were obtained by echocardiography and used to calculate SV. Other variables such as ear temperature, skin temperature, blood pressure, and blood volume were measured to assess potential changes in thermoregulatory needs and loading conditions. HR drift was successfully prevented when using BB from min10 to min60 (128±9 to 126±8bpm, p=0.29) but not in CON (134±10 to 148±10bpm, p<0.01). Conversely, during the same time, SV increased by 13% when using BB (103±9 to 116±7mL, p<0.01) while it was unchanged in CON (99±7 to 101±9mL, p=0.37). The SV behavior was mediated by a 4% increase in EDV in the BB condition (164±18 to 170±18mL, p<0.01), while no change was observed in the CON condition (162±18 to 160±18mL, p=0.23). In conclusion, blocking HR drift enhances EDV and SV during prolonged exercise. These findings suggest that SV behavior is tightly related to filling time and loading conditions of the left ventricle.

Plasma Pro-atrial Natriuretic Peptide and Stroke Volume Responsiveness for Detecting Deviations in Central Blood Volume Following Major Abdominal Surgery

Journal of the American College of Surgeons 236(5):p S33, May 2023. | DOI: 10.1097/01.XCS.0000932536.74917.f0

Diverse effects of seven-day dry immersion on hemodynamic responses in head-up tilt and lower body negative pressure tests

Head-up tilt (HUT) and lower body negative pressure (LBNP) tests are commonly used to assess orthostatic tolerance after space flight. Due to the mechanistic difference between the effects of these tests, they can provide different patterning of post-flight alterations, but this has not been proven directly, to our knowledge. Dry immersion (DI) is a ground-based experimental model which reproduces the effects of microgravity on the cardiovascular system. The aim of this work was to compare the effects of 7-day DI on hemodynamic responses to HUT and LBNP in 9 young men. HUT (65°, 3 min) and LBNP (Chibis suit, −35 mm Hg, 3 min) tests were carried out 3 days before DI, on the 7th day of DI and on the 3rd day of recovery. ECG (to calculate heart rate, HR), arterial pressure (AP), and stroke volume (SV) were continuously recorded. The tests were repeated 5 times and the data for all repetitions were averaged. Before DI, HUT and LBNP similarly decreased SV, a measure of orthostatic test. On the 7th day of DI, the decrease of SV as well as the increases of HR and mean AP were observed in supine position. DI similarly increased SV and HR responses in HUT and LBNP tests, but the effect on mean AP response was observed in HUT test and absent in LBNB test. All indicators recovered on post-immersion day 3. Therefore, 7-day DI weakens autonomic AP control only in HUT test, presumably, due to inappropriate increase of lower body vascular resistance.

Right Ventricular Function During Exercise After Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension.

Background Pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension improves resting hemodynamics and right ventricular (RV) function. Because exercise tolerance frequently remains impaired, RV function may not have completely normalized after PEA. Therefore, we performed a detailed invasive hemodynamic study to investigate the effect of PEA on RV function during exercise. Methods and Results In this prospective study, all consenting patients with chronic thromboembolic pulmonary hypertension eligible for surgery and able to perform cycle ergometry underwent cardiac magnetic resonance imaging, a maximal cardiopulmonary exercise test, and a submaximal invasive cardiopulmonary exercise test before and 6 months after PEA. Hemodynamic assessment and analysis of RV pressure curves using the single-beat method was used to determine load-independent RV contractility (end systolic elastance), RV afterload (arterial elastance), RV-arterial coupling (end systolic elastance-arterial elastance), and stroke volume both at rest and during exercise. RV rest-to-exercise responses were compared before and after PEA using 2-way repeated-measures analysis of variance with Bonferroni post hoc correction. A total of 19 patients with chronic thromboembolic pulmonary hypertension completed the entire study protocol. Resting hemodynamics improved significantly after PEA. The RV exertional stroke volume response improved 6 months after PEA (79±32 at rest versus 102±28 mL during exercise; P<0.01). Although RV afterload (arterial elastance) increased during exercise, RV contractility (end systolic elastance) did not change during exercise either before (0.43 [0.32-0.58] mm Hg/mL versus 0.45 [0.22-0.65] mm Hg/mL; P=0.6) or after PEA (0.32 [0.23-0.40] mm Hg/mL versus 0.28 [0.19-0.44] mm Hg/mL; P=0.7). In addition, mean pulmonary artery pressure-cardiac output and end systolic elastance-arterial elastance slopes remained unchanged after PEA. Conclusions The exertional RV stroke volume response improves significantly after PEA for chronic thromboembolic pulmonary hypertension despite a persistently abnormal afterload and absence of an RV contractile reserve. This may suggest that at mildly elevated pulmonary pressures, stroke volume is less dependent on RV contractility and afterload and is primarily determined by venous return and conduit function.

1268: EVALUATING LOAD-DEPENDENT CONTRACTILITY TO PREDICT FLUID RESPONSIVENESS IN CRITICALLY ILL CHILDREN

Introduction: Fluid boluses are commonly administered to critically ill children with hypotension, but response is inconsistent. Inability to predict response to bolus may delay vasoactive infusion, increasing time in shock and leading to fluid overload. Stroke volume (SV) response to bolus varies with both contractility and volume of fluid via the Starling curve relationship. The maximum rate of systolic upstroke of the arterial line waveform (dp/dtmax) is a load-dependent estimate of cardiac contractility associated with SV response to bolus. We hypothesized that as dp/dtmax has previously been associated with SV response, dp/dtmax would also be associated with mean arterial pressure (MAP) response to bolus. Methods: This was a retrospective study of IV fluid boluses >10ml/kg given to children who had arterial waveform data captured in Bedmaster® during pediatric intensive care unit admissions from 3/2013-8/2020. At least 2hrs were required between boluses and every bolus had at least 30sec of adequate pre-bolus arterial waveform data. Dp/dtmax was calculated in 10sec intervals from the first difference of adjacent waveform samples and averaged over the 20min pre-bolus. MAP responsiveness was defined as increase by >10% in MAP from pre-bolus to average 20min post-bolus. Logistic regression was used to assess the relationship between dp/dtmax and MAP response. Results: A total of 890 boluses administered to 539 children had available arterial line waveform data. Of these, 624 boluses in 421 patients met inclusion criteria, and 170 (27%) were responders. Univariate analysis did not show a significant relationship between dp/dtmax and MAP response (OR 1.00, 95% CI 0.99, 1.00). This lack of association persisted despite adding to the model fluid volume, age, or exposure to mechanical ventilation (ORs unchanged for all analyses). Conclusions: Pre-bolus dp/dtmax may not be a predictor of MAP fluid response when used in isolation. Given previous association found between dp/dtmax and SV fluid response, this discrepancy might be due to the effect of systemic vascular resistance (SVR) on MAP in children. Future studies of dp/dtmax in particular—and fluid responsiveness in general—may want to consider the effects of SVR in addition to SV when assessing clinical response to IV fluid bolus.

171 SEX AND PHYSICAL EXERCISE: ONE SIZE DOES NOT FIT ALL

Abstract Differences in regulation and adaptations in response to exercise between men and women Numerous cardiovascular adjustments occur during exercise so that cardiac output (CO) rises linearly as a function of VO2 to meet the increased demands of muscular work. There are several genetic, anatomical and hormone sex-related differences that impact the hemodynamic and structural cardiovascular response to exercise. From a hemodynamic point of view, women have lower CO. Females have lower Stroke Volume (SV) and smaller increase in SV in response to exercise, mainly due to their smaller cardiac size/mass, so the main mechanism to enhance CO in women is the increase of HR. Maximum HR has been shown to be similar between females and males and depends mainly on the age rather than on gender. Furthermore, women have lower maximal oxygen uptake (VO2max) values, mainly due to their lower CO, together with differences in peak Da-vO2. Blood volume, hemoglobin, and hematocrit values are 15– 20% lower in women, and sex-based differences exist in pulmonary structure and respiratory function, resulting in a lower oxygen supply for the same quantity of blood flow than men. Moreover, females have lower systolic and diastolic peak blood pressures as compared to males, as they experience a greater drop in systemic vascular resistance during exercise and have lower CO. This could be the reason of the higher occurrence of post-exercise hypotension in women. From a structural point of view, regular physical training induces cardiac remodeling and structural adaptations to improve SV reserve. Trained women exhibited smaller left ventricular wall thickness, cavity size and mass compared to age and fitness-matched men. Women were reported to maintain a normal left ventricular geometry, with a relatively larger increase of cavity dimensions compared with men, evidently influenced by the type of sport praticated. These sex-related differences in cardiac adaptations may be partially explained by the higher concentrations of endogenous anabolic hormones in males and higher hypertrophic potential of male cardiac tissue compared to women. Heart size accounts for many of the sex-based differences in cardiac functional and structural responses, however, it may not entirely account for sex-related cardiovascular differences as they tend to shrink when parameters are normalized for body surface area and lean body mass, suggesting that other factors, such as different body composition, may play a role and indexed parameters should be analyzed rather than absolute values. The more and more large participation of women in a broad variety of sport, together with the increasing awareness about the existence of relevant sex-related differences in response to training, confirm the need to include sex as a biological variable to consider for optimal tailored exercise intervention. Identifying and understanding sex-specific differences is crucial, both from a clinical point of view, as they could impact exercise rehabilitation and prevention strategies, and from a sport and physiological point of view, both in terms of improving performances and reducing injuries.

Stroke Volume and Arterial Pressure Fluid Responsiveness in Patients With Elevated Stroke Volume Variation Undergoing Major Vascular Surgery: A Prospective Intervention Study

The identification of potential hemodynamic indicators to increase the predictive power of stroke-volume variation (SVV) for mean arterial pressure (MAP) and stroke volume (SV) fluid responsiveness. A prospective intervention study. At a single-center university hospital. Nineteen patients during major vascular surgery with 125 fluid interventions. When SVV ≥13% occurred for >30 seconds, 250 mL of Ringer's lactate were given within 2 minutes. Hemodynamic variables, such as pulse-pressure variation (PPV) and dynamic arterial elastance (Edyn), were measured by pulse power-wave analysis. The outcomes were MAP and SV responsiveness, defined as an increase of at least 10% of MAP and SV within 5 minutes of the fluid intervention. Of the fluid interventions, 48% were MAP-responsive, and 66% were SV-responsive. The addition of PPV and Edyn cut-off values to the SVV cut-off decreased sensitivity from 1-to-0.66 to-0.82, and concomitantly increased specificity from 0-to- 0.65-to-0.93 for the prediction of MAP and SV responsiveness in the authors' study setting. The areas under the receiver operating characteristic curves of PPV and Edyn for the prediction of MAP responsiveness were 0.79 and 0.75, respectively. The areas under the receiver operating characteristic curves for PPV and Edyn to predict SV responsiveness were 0.85 and 0.77, respectively. The PPV and Edyn showed good accuracy for the prediction of MAP and SV responsiveness in patients with elevated SVV during vascular surgery. Either PPV or Edyn may be used in conjunction with SVV to better predict MAP and SV fluid responsiveness in patients undergoing vascular surgery.

Abstract 13669: Ascending Aortic Augmentation Pressure Does Not Decrease During Exercise in HFpEF: Implications for SV Reserve Impairment

Aortic augmentation pressure (aAP; difference between first [aP1] and second [aP2] peaks of the aortic pressure waveform) decreases during exercise in young healthy individuals, lowering mid-late systolic afterload, an important determinant of cardiac work and stroke volume (SV). In patients with heart failure and preserved ejection fraction (HFpEF), SV responses to exercise (i.e. SV reserve) are often abnormal (≤ 50%). A lack of fall in aAP during exercise in HFpEF could contribute to impairments in SV reserve. Therefore, we studied 15 HFpEF patients (age, 71 ± 6 years; 10 women; BMI 39.2 ± 6.2 kg/m 2 ) in the seated upright position. During rest and six-minutes of cycling at 20 Watts, we recorded beat-by-beat radial arterial blood pressure and estimated ascending aortic blood pressure waveforms in real-time via a generalized inverse transfer function (SphygmoCor). SV was calculated from cardiac output (Qc, acetylene rebreathe) and heart rate (ECG), with total peripheral resistance (TPR) calculated as the quotient of radial MAP and Qc. HR (Rest: 75 ± 14 vs 20W: 93 ± 12 bpm, P &lt; 0.0001), SV (Rest: 61 ± 17 vs 20W: 84 ± 19 ml, P = 0.0003) and Qc (Rest: 4.5 ± 1.0 vs 20W: 7.7 ± 1.6 L/min, P &lt; 0.0001) increased from rest to 20 Watts, whilst TPR decreased (Rest: 21.3 ± 4.4 vs 20W: 14.0 ± 3.8 mmHg/L/min, P &lt; 0.0001); SV reserve was 43 ± 33 %. Aortic diastolic pressure did not change (Rest: 70 ± 12 vs 20W: 76 ± 15 mmHg, P = 0.0976), whereas aP1 (Rest: 112 ± 18 vs 20W: 130 ± 20 ml, P = 0.0002) and aP2 (Rest: 123 ± 26 vs 20W: 142 ± 25 ml, P = 0.0021) increased during exercise (Figure). Notably, aAP was not different between rest and exercise (Rest: 11 ± 11 vs 20W12 ± 11 mmHg, P = 0.4969). Therefore, the contribution of aAP to mid-late systolic afterload is unchanged during exercise in HFpEF, unlike in young healthy adults. Unchanged aAP may be a mechanism of high mid-late systolic afterload during exercise in HFpEF, which could contribute to impairments in SV reserve related to reduced ventricular contractile reserve.

Abstract 13676: Sublingual Nitroglycerin Lowers Aortic Augmentation Pressure at Rest and During Exercise in Patients With HFpEF

Infusion or inhalation of organic nitrates lower ascending aortic pressures, and reduce mid-late systolic afterload via a reduction in augmentation pressure (aAP, the difference between the first [aP1] and second [aP2] peaks of the aortic pressure waveform) at rest and during exercise in patients with heart failure and preserved ejection fraction (HFpEF). Sublingual nitroglycerin (NTG) is more accessible for patients as compared to the infusion or inhalation of nitrates. It is unknown whether NTG spray (400μg) elicits these same effects as organic nitrates on aortic hemodynamics at rest and during exercise. Therefore, in 15 patients with HFpEF (age, 71 ± 6 years; 10 women; BMI 39.2 ± 6.2 kg/m 2 ), as part of our ongoing clinical trial, we measured beat-by-beat radial artery blood pressure and estimated aortic pressure in real-time via a generalized inverse transfer function (SphygmoCor). Data were collected in the seated upright position at rest and throughout six-minutes of cycling at 20 Watts during either a placebo or NTG condition (randomized order). Stroke volume (SV) was calculated from cardiac output (Qc, acetylene rebreathe) and heart rate (ECG). NTG lowered stroke volume at rest, but not during exercise (Table); however, SV responses to exercise were similar (Placebo: Δ22 ± 19 vs NTG: Δ25 ± 18 ml, P = 0.1991). Aortic diastolic pressure was not different at rest with NTG compared to placebo (Table). aP1 and aP2 were lower at rest with NTG, with greater reductions in aP2 (Table). NTG lowered aAP during rest (Placebo: 11 ± 11 vs NTG: 0 ± 14 mmHg, P = 0.0002) and exercise (Placebo: 12 ± 11 vs NTG: 4 ± 12 mmHg, P &lt; 0.0001). These results suggest patients with HFpEF do not augment SV responses to exercise despite a lower aAP contribution to (mid-late) systolic afterload with NTG. The inability to take advantage of a lower aAP during exercise may reflect impairments in contractile function and end-systolic reserve.

Enhanced Respiratory Frequency Response to Lower Limb Mechanoreceptors Activation in Patients with Chronic Obstructive Pulmonary Disease.

To investigate the mechanoreflex control of respiration and circulation in patients with chronic obstructive pulmonary disease (COPD). Twenty-eight patients with moderate-to-severe COPD (mean ± SD: 67.0 ± 7.9 yr, 10 women) and 14 age- and sex-matched controls (67.9 ± 2.6 yr, 7 women) participated in the study. Their dominant knee was passively moved to stimulate mechanoreceptors, whereas vastus lateralis surface electrical activity checked active contractions. A differential pressure flowmeter, an electrocardiogram, and a servo-controlled finger photoplethysmograph acquired cardiorespiratory data. To gain insight into the mechanoreflex arc, we further analyzed reduced/oxidized glutathione ratio and mechanoreceptor-related gene expression in a vastus lateralis biopsy of additional nine patients (63.9 ± 8.1 yr, 33% women) and eight controls (62.9 ± 9.1 yr, 38% women). Patients with COPD had a greater peak respiratory frequency response (COPD: Δ = 3.2 ± 2.3 vs Controls: 1.8 ± 1.2 cycles per minute, P = 0.036) and a smaller peak tidal volume response to passive knee movement than controls. Ventilation, heart rate, stroke volume, and cardiac output peak responses, and total peripheral resistance nadir response, were unaltered by COPD. In addition, patients had a diminished glutathione ratio (COPD: 13.3 ± 3.8 vs controls: 20.0 ± 5.5 a.u., P = 0.015) and an augmented brain-derived neurotrophic factor expression (COPD: 2.0 ± 0.7 vs controls: 1.1 ± 0.4 a.u., P = 0.002) than controls. Prostaglandin E receptor 4, cyclooxygenase 2, and Piezo1 expression were similar between groups. Respiratory frequency response to mechanoreceptors activation is increased in patients with COPD. This abnormality is possibly linked to glutathione redox imbalance and augmented brain-derived neurotrophic factor expression within locomotor muscles, which could increase mechanically sensitive afferents' stimulation and sensitivity.

Counter pressure maneuvers for syncope prevention: A semi-systematic review and meta-analysis.

Physical counter pressure maneuvers (CPM) are movements that are recommended to delay or prevent syncope (fainting) by recruiting the skeletal muscle pump to augment cardiovascular control. However, these recommendations are largely based on theoretical benefit, with limited data evaluating the efficacy of CPM to prevent syncope in the real-world setting. We conducted a semi-systematic literature review and meta-analysis to assess CPM efficacy, identify literature gaps, and highlight future research needs. Articles were identified through a literature search (PubMed, April 2022) of peer-reviewed publications evaluating the use of counter pressure or other lower body maneuvers to prevent syncope. Two team members independently screened records for inclusion and extracted data. From 476 unique records identified by the search, 45 met inclusion criteria. Articles considered various syncopal conditions (vasovagal = 12, orthostatic hypotension = 8, postural orthostatic tachycardia syndrome = 1, familial dysautonomia = 2, spinal cord injury = 1, blood donation = 10, healthy controls = 11). Maneuvers assessed included hand gripping, leg fidgeting, stepping, tiptoeing, marching, calf raises, postural sway, tensing (upper, lower, whole body), leg crossing, squatting, “crash” position, and bending foreword. CPM were assessed in laboratory-based studies (N = 28), the community setting (N = 4), both laboratory and community settings (N = 3), and during blood donation (N = 10). CPM improved standing systolic blood pressure (+ 14.8 ± 0.6 mmHg, p < 0.001) and heart rate (+ 1.4 ± 0.5 bpm, p = 0.006), however, responses of total peripheral resistance, stroke volume, or cerebral blood flow were not widely documented. Most patients experienced symptom improvement following CPM use (laboratory: 60 ± 4%, community: 72 ± 9%). The most prominent barrier to employing CPM in daily living was the inability to recognize an impending faint. Patterns of postural sway may also recruit the skeletal muscle pump to enhance cardiovascular control, and its potential as a discrete, proactive CPM needs further evaluation. Physical CPM were successful in improving syncopal symptoms and producing cardiovascular responses that may bolster against syncope; however, practical limitations may restrict applicability for use in daily living.

Mid-regional plasma pro-atrial natriuretic peptide and stroke volume responsiveness for detecting deviations in central blood volume following major abdominal surgery.

BackgroundA reduced central blood volume is reflected by a decrease in mid‐regional plasma pro‐atrial natriuretic peptide (MR‐proANP), a stable precursor of ANP, and a volume deficit may also be assessed by the stroke volume (SV) response to head‐down tilt (HDT). We determined plasma MR‐proANP during major abdominal procedures and evaluated whether the patients were volume responsive by the end of the surgery, taking the fluid balance and the crystalloid/colloid ratio into account.MethodsPatients undergoing pancreatic (n = 25), liver (n = 25), or gastroesophageal (n = 38) surgery were included prospectively. Plasma MR‐proANP was determined before and after surgery, and the fluid response was assessed by the SV response to 10° HDT after the procedure. The fluid strategy was based mainly on lactated Ringer's solution for gastroesophageal procedures, while for pancreas and liver surgery, more human albumin 5% was administered.ResultsPlasma MR‐proANP decreased for patients undergoing gastroesophageal surgery (−9% [95% CI −3.2 to −15.3], p = .004) and 10 patients were fluid responsive by the end of surgery (∆SV > 10% during HDT) with an administered crystalloid/colloid ratio of 3.3 (fluid balance +1389 ± 452 ml). Furthermore, plasma MR‐proANP and fluid balance were correlated (r = .352 [95% CI 0.031–0.674], p < .001). In contrast, plasma MR‐proANP did not change significantly during pancreatic and liver surgery during which the crystalloid/colloid ratio was 1.0 (fluid balance +385 ± 478 ml) and 1.9 (fluid balance +513 ± 381 ml), respectively. For these patients, there was no correlation between plasma MR‐proANP and fluid balance, and no patient was fluid responsive.ConclusionPlasma MR‐proANP was reduced in fluid responsive patients by the end of surgery for the patients for whom the fluid strategy was based on more lactated Ringer's solution than human albumin 5%.

Change in Central Cardiovascular Function in Response to Intense Interval Training: A Systematic Review and Meta-analysis.

High-intensity interval training and sprint interval training significantly increase maximal oxygen uptake (V̇O 2max ), which enhances endurance performance and health status. Whether this response is due to increases in central cardiovascular function (cardiac output (CO) and blood volume) or peripheral factors is unknown. This study aimed to conduct a systematic review and meta-analysis to assess the effects of high-intensity interval training and sprint interval training (referred to as intense interval training) on changes in central cardiovascular function. We performed a systematic search of eight databases for studies denoting increases in V̇O 2max in which CO, stroke volume (SV), blood volume, plasma volume, end-diastolic/systolic volume, or hematocrit were measured. Forty-five studies were included in this analysis, comprising 946 men and women of various health status (age and V̇O 2max , 20-76 yr and 13-61 mL·kg -1 ·min -1 ) who performed 6-96 sessions of interval training. Results showed an increase in V̇O 2max with intense interval training that was classified as a large effect ( d = 0.83). SV ( d = 0.69), and CO ( d = 0.49) had moderate effect sizes in response to intense interval training. Of 27 studies in which CO was measured, 77% exhibited significant increases in resting CO or that obtained during exercise. Similarly, 93% of studies revealed significant increases in SV in response to intense interval training. Effect sizes for these outcomes were larger for clinical versus healthy populations. Plasma volume, blood volume, and hematocrit had small effect sizes after training ( d = 0.06-0.14). Increases in V̇O 2max demonstrated with intense interval training are attendant with increases in central O 2 delivery with little contribution from changes in hematocrit, blood volume, or plasma volume.

To identify normovolemia in humans: The stroke volume response to passive leg raising vs. head-down tilt.

Volume responsiveness can be evaluated by tilting maneuvers such as head‐down tilt (HDT) and passive leg raising (PLR), but the two procedures use different references (HDT the supine position; PLR the semi‐recumbent position). We tested whether the two procedures identify “normovolemia” by evaluating the stroke volume (SV) and cardiac output (CO) responses and whether the peripheral perfusion index (PPI) derived from pulse oximetry provides similar information. In randomized order, 10 healthy men were exposed to both HDT and PLR, and evaluations were made also when the subjects fasted. Central cardiovascular variables were derived by pulse contour analysis and changes in central blood volume assessed by thoracic electrical admittance (TEA). During HDT, SV remained stable (fasted 110 ± 16 vs. 109 ± 16 ml; control 113 ± 16 vs. 111 ± 16 ml, p > 0.05) with no change in CO, TEA, PPI, or SV variation (SVV). In contrast during PLR, SV increased (fasted 108 ± 17 vs. 117 ± 17 ml; control 108 ± 18 vs. 117 ± 18 ml, p < 0.05) followed by an increase in TEA (p < 0.05) and CO increased when subjects fasted (6.7 ± 1.5 vs. 7.1 ± 1.5, p = 0.007) with no change in PPI or SVV. In conclusion, SV has a maximal value for rest in supine men, while PLR restores SV as CBV is reduced in a semi‐recumbent position and the procedure thereby makes healthy volunteers seem fluid responsive.

Cholinergic‐mediated Circulatory Responses at the Onset of Isometric Exercise: Does Sex Matter?

IntroductionWe have shown that handgrip exercise evokes an initial decrease in systemic vascular resistance (SVR), which was abolished by cholinergic blockade (glycopyrrolate) and, thereby, augmented the blood pressure (BP) response. These findings suggest that a cholinergic mechanism is important for the BP and SVR responses at the onset of isometric handgrip exercise in humans. Noteworthy, this previous study included men only, and was not designed to investigate the potential existence of sex‐related differences in immediate BP and circulatory responses evoked at the exercise onset. Given this, the aim of this study was to test the hypothesis that women present an attenuated fall in SVR and increased pressor response compared to men at the onset of isometric handgrip exercise due to a blunted cholinergic vasodilation.MethodsTen healthy men (aged 21 ± 1 year) and 10 women (aged 24 ± 1 year) were recruited. Women were non‐oral contraceptives users and performed experiments in the early follicular phase of the menstrual cycle. Participants performed 20s bout of isometric handgrip exercise at 40% of maximal voluntary contraction. Beat‐to‐beat heart rate (HR) (ECG) and mean BP (finger photopletysmography) were continuously measured. Beat‐to‐beat stroke volume (SV) was obtained with the Modelflow method and matched with HR to estimate cardiac output (CO) and SVR. The exercise responses were expressed as a change from 10s immediately before the onset of voluntary contraction.ResultsThe BP response pattern appeared to be different between men and women at the onset of isometric exercise. While men presented a typical exercise‐evoked biphasic BP response (3s: Δ2 ± 2 mmHg; 10s: Δ1 ± 1 mmHg; 20s: Δ5 ± 3 mmHg), women showed a progressive increase in mean BP (3s: Δ1 ± 1 mmHg; 10s; Δ3 ± 1 mmHg; 20s: Δ6 ± 1 mmHg; P=0.681). Men demonstrated a decrease in SVR at 3s (Δ‐0.9 ± 0.3 mmHg.L‐1.min), 10s (Δ ‐1.6 ± 0.4 mmHg.L‐1.min) and 20s (Δ‐1.9 ± 0.7 mmHg.L‐1.min) following the exercise onset, and these responses tended to be attenuated in women (3s: Δ‐0.3 ± 0.3 mmHg.L‐1.min; 10s: Δ‐1.2 ± 0.4 mmHg.L‐1.min; 20s: Δ‐0.6 ± 0.5 mmHg.L‐1.min; P=0.131). There were no sex differences in HR, SV and CO responses to exercise.ConclusionThese findings suggest a lack of sex differences in immediate BP and circulatory responses at the onset of isometric handgrip exercise, indicative of similar cholinergic‐mediated vasodilation in skeletal muscle between men and women.