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Our prior study reveals that the distension-contraction profiles using high-resolution manometry impedance recordings can distinguish patients with dysphagia symptom but normal esophageal function testing ("functional dysphagia") from control subjects. The aim of this study was to determine the diagnostic value of the recording protocol used in our prior studies (10-mL swallows with subjects in the Trendelenburg position) against the standard clinical protocol (5-mL swallows with subjects in the supine position). We used advanced machine learning techniques and robust metrics for classification purposes. Studies were performed on 30 healthy subjects and 30 patients with functional dysphagia. A custom-built software was used to extract the relevant distension-contraction features of esophageal peristalsis. Ensemble methods, i.e., gradient boost, support vector machines (SVMs), and logit boost, were used as the primary machine learning algorithms. Although the individual contraction features were marginally different between the two groups, the distension features of peristalsis were significantly different. The receiver operating characteristic (ROC) curve values for the standard recording protocol and the distension features ranged from 0.74 to 0.82; they were significantly better for the protocol used in our prior studies, ranging from 0.81 to 0.91. The ROC curve values using three machine learning algorithms were far superior for the distension than the contraction features of esophageal peristalsis, revealing a value of 0.95 for the SVM algorithm. Current patient classification for esophageal motility disorders, based on the contraction phase of peristalsis, ignores a large number of patients who have an abnormality in the distension phase of peristalsis. Distension-contraction plots should be the standard for assessing esophageal peristalsis in clinical practice. NEW & NOTEWORTHY: Our findings underscore the superiority of distension features over contraction metrics in diagnosing esophageal dysfunctions. By leveraging state-of-the-art machine learning techniques, our study highlights the diagnostic potential of distension-contraction plots of peristalsis. Implementation of these plots could significantly enhance the accuracy of identifying patients with esophageal motor disorders, advocating for their adoption as the standard in clinical practice. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to clarify the impact of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. Nine older females (mean ± SD, 70 ± 6 yr) and 11 younger females (20 ± 1 yr) completed the study. A passive leg raising (PLR) test was performed wherein the participants were positioned supine (baseline, 0°), and their lower limbs were passively lifted at 10°, 20°, 30°, and 40° (3 min at each angle). Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. The central venous pressure was estimated based on peripheral venous pressure (eCVP), which was monitored using a cannula in the right large antecubital vein. Baseline MSNA was higher in older females than in younger females. MSNA burst frequency (BF) decreased during the PLR test in both older and younger females, but the magnitude of the decrease in MSNA BF was smaller in older females than in younger females (older, −3.5 ± 1.5 vs. younger, −6.3 ± 1.5 bursts/min at 40° from baseline, P = 0.014). The eCVP increased during the PLR in both groups, and there was no difference in the changes in eCVP between the two groups (older, +1.07 ± 0.37 vs. younger, +1.12 ± 0.33 mmHg at 40° from baseline, P = 0.941). These results suggest that inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age in females. NEW & NOTEWORTHY: There were no available data concerning the effect of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. The magnitude of the decrease in muscle sympathetic nerve activity during passive leg raising (10°–40°) was smaller in older females than in young females. In females, inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age. [ABSTRACT FROM AUTHOR]

Although perceptual thresholds have been widely studied, vestibuloocular reflex (VOR) thresholds have received less attention, so the relationship between VOR and perceptual thresholds remains unclear. We compared the frequency dependence of human VOR thresholds to human perceptual thresholds for yaw head rotation in both upright ("yaw rotation") and supine ("yaw tilt") positions, using the same human subjects and motion device. VOR thresholds were generally a little smaller than perceptual thresholds. We also found that horizontal VOR thresholds for both yaw rotation about an Earth-vertical axis and yaw tilt (yaw rotation about an Earth-horizontal axis) were relatively constant across four frequencies (0.2, 0.5, 1, and 2 Hz), with little difference between yaw rotation and yaw tilt VOR thresholds. For yaw tilt stimuli, perceptual thresholds were slightly lower at the lowest frequency and nearly constant at all other (higher) frequencies. However, for yaw rotation, perceptual thresholds increased significantly at the lowest frequency (0.2 Hz). We conclude 1) that VOR thresholds were relatively constant across frequency for both yaw rotation and yaw tilt, 2) that the known contributions of velocity storage to the VOR likely yielded these VOR thresholds that were similar for yaw rotation and yaw tilt for all frequencies tested, and 3) that the integration of otolith and horizontal canal signals during yaw tilt when supine contributes to stable perceptual thresholds, especially relative to the low-frequency perceptual thresholds recorded during yaw rotation. NEW & NOTEWORTHY: We describe for the first time that human VOR thresholds differ from human forced-choice perceptual thresholds, with the difference especially evident at frequencies below 0.5 Hz. We also report that VOR thresholds are relatively constant across frequency for both yaw rotation and yaw tilt. These findings are consistent with the idea that high-pass filtering in cortical pathways impacts cognitive decision-making. [ABSTRACT FROM AUTHOR]

Although measuring right ventricular (RV) function during exercise is more informative than assessing it at rest, the relationship between RV reserve function, exercise capacity, and health-related quality of life (HRQoL) in patients with left ventricular assist devices (LVAD) remains unresolved. We aimed to investigate whether RV reserve assessed by the change in RV stroke work index (RVSWI) during exercise is correlated with exercise capacity and HRQoL in patients with LVAD. We prospectively assessed 24 consecutive patients with LVAD who underwent invasive right heart catheterization in the supine position. Exercise capacity and HRQoL were assessed using the 6-min walk distance (6 MWD) and peak oxygen consumption (VO2) in cardiopulmonary exercise testing, and the EuroQol visual analog scale (EQ-VAS), respectively. The patients were divided into two groups according to the median DRVSWI (change from rest to peak exercise). Patients with lower DRVSWI had significantly lower changes in cardiac index and absolute value of RV dP/dt than those with higher ΔRVSWI. The ΔRVSWI was positively correlated with 6 MWD (r = 0.59, P = 0.003) and peak VO2 (r = 0.56, P = 0.006). In addition, ΔRVSWI was positively correlated with the EQ-VAS (r = 0.44, P = 0.030). In contrast, there was no significant correlation between RVSWI at rest and 6 MWD (r = -0.34, P = 0.88), peak VO2 (r = 0.074, P = 0.74), or EQ-VAS (r = 0.127, P = 0.56). Our findings suggest that the assessment of RV reserve function is useful for risk stratification in patients with LVAD. [ABSTRACT FROM AUTHOR]

Altered gravity affects hemodynamics and blood flow in the neck. At least one incidence of jugular venous thrombosis has been reported in an astronaut on the International Space Station. This investigation explores the impact of changes in the direction of the gravitational vector on the characteristics of the neck arteries and veins. Twelve subjects underwent graded tilt from 45° head-up to 45° head-down in 15° increments in both supine and prone positions. At each angle, the cross-sectional area of the left and right common carotid arteries (ACCA) and internal jugular veins (AIJV) were measured by ultrasound. Internal jugular venous pressure (IJVP) was also measured by compression sonography. Gravitational dose-response curves were generated from experimental data. ACCA did not show any gravitational dependence. Conversely, both AIJV and IJVP increased in a nonlinear fashion with head-down tilt. AIJV was significantly larger on the right side than the left side at all tilt angles. In addition, IJVP was significantly elevated in the prone position compared with the supine position, most likely because of raised intrathoracic pressure while prone. Dose-response curves were compared with existing experimental data from parabolic flight and spaceflight studies, showing good agreement on an acute timescale. The quantification of jugular hemodynamics as a function of changes in the gravitational vector presented here provides a terrestrial model to reference spaceflight-induced changes, contributes to the assessment of the pathogenesis of spaceflight venous thromboembolism events, and informs the development of countermeasures. [ABSTRACT FROM AUTHOR]

The muscle mechanoreflex has been considered to make a small contribution to the cardiovascular response to exercise in healthy humans because no pressor response has been observed during stimulation of mechanosensitive receptors, such as static passive stretching, during many human studies. There is room for rethinking this consideration since the pressor response to upper limb exercise is greater than that to lower limb exercise. We examined whether static passive stretching of the forearm muscles causes a muscle mechanoreflex-induced pressor response in humans. Eighteen healthy men were recruited for this study. After a 15-min rest period in the supine position with a neutral (0°) wrist joint angle, all participants completed static passive stretching of the forearm for 60 s at four different intensities: minimal painful passive stretching (PPS), moderate-intensity passive stretching (MPS), low-intensity passive stretching (LPS), and no load (NL). During the procedure, beat-to-beat arterial blood pressure was measured using finger photoplethysmography. The force generated between the passively stretched hand and the experimenter's hands was recorded using a force transducer. Mean arterial pressure (MAP) during PPS and MPS significantly increased from baseline during the last 40 s (P < 0.05). MAP was significantly greater at 50 s and 60 s, depending on the intensity. MPS induced a greater peak response in MAP than lower intensities (P < 0.05). None of the subjects reported pain during the MPS and LPS trials. Static passive stimulation of the forearm is an effective method of isolating the muscle mechanoareflex-induced pressor response in humans. [ABSTRACT FROM AUTHOR]

The muscle mechanoreflex has been considered to make a small contribution to the cardiovascular response to exercise in healthy humans because no pressor response has been observed during stimulation of mechanosensitive receptors, such as static passive stretching, during many human studies. There is room for rethinking this consideration since the pressor response to upper limb exercise is greater than that to lower limb exercise. We examined whether static passive stretching of the forearm muscles causes a muscle mechanoreflex-induced pressor response in humans. Eighteen healthy men were recruited for this study. After a 15-min rest period in the supine position with a neutral (0°) wrist joint angle, all participants completed static passive stretching of the forearm for 60 s at four different intensities: minimal painful passive stretching (PPS), moderate-intensity passive stretching (MPS), low-intensity passive stretching (LPS), and no load (NL). During the procedure, beat-to-beat arterial blood pressure was measured using finger photoplethysmography. The force generated between the passively stretched hand and the experimenter's hands was recorded using a force transducer. Mean arterial pressure (MAP) during PPS and MPS significantly increased from baseline during the last 40 s (P < 0.05). MAP was significantly greater at 50 s and 60 s, depending on the intensity. MPS induced a greater peak response in MAP than lower intensities (P < 0.05). None of the subjects reported pain during the MPS and LPS trials. Static passive stimulation of the forearm is an effective method of isolating the muscle mechanoareflex-induced pressor response in humans. [ABSTRACT FROM AUTHOR]

In this crossover study, we investigated the influence of inorganic nitrate (NO-3 ) supplementation on venous volume and compliance in the resting forearm and calf. Twenty healthy young adults were assigned to receive an NO-3 -rich beverage [beetroot juice (BRJ): 140 mL; ~8 mmol NO-3 ] or an NO-3 -depleted control beverage [prune juice (CON): 166 mL; < 0.01 mmol NO-3 ). Two hours after consuming the allocated beverage, each participant rested in the supine position for 20 min. Cuffs were then placed around the right upper arm and right thigh, inflated to 60 mmHg for 8 min, and then decreased to 0 mmHg at a rate of 1 mmHg/s. During inflation and deflation of cuff pressure, changes in venous volume in the forearm and calf were measured by venous occlusion plethysmography. Venous compliance was calculated as the numerical derivative of the cuff pressure-venous volume curve in the limbs. The plasma NO-3 concentration was elevated by intake of BRJ (before, 15.5 ± 5.8 mM; after, 572.0 ± 116.1 mM, P < 0.05) but not by CON (before, 14.8 ± 7.2 mM; after, 15.3 ± 7.4 mM, P > 0.05). On the other hand, there was no significant difference in venous volume or compliance in the forearm or calf between BRJ and CON. These findings suggest that although acute inorganic NO-3 supplementation may enhance the activity of nitric oxide (NO) via nitrite → NO pathway, it does not influence venous volume or compliance in the limbs in healthy young adults. [ABSTRACT FROM AUTHOR]

Changes in the gravitational vector by postural changes or weightlessness induce fluid shifts, impacting ocular hemodynamics and regional pressures. This investigation explores the impact of changes in the direction of the gravitational vector on intraocular pressure (IOP), mean arterial pressure at eye level (MAPeye), and ocular perfusion pressure (OPP), which is critical for ocular health. Thirteen subjects underwent 360( of tilt (including both prone and supine positions) at 15° increments. At each angle, steady-state IOP and MAPeye were measured, and OPP calculated as MAPeye – IOP. Experimental data were also compared to a six-compartment lumped-parameter model of the eye. Mean IOP, MAPeye, and OPP significantly increased from 0° supine to 90° head-down tilt (HDT) by 20.7 ± 1.7 mmHg (P < 0.001), 38.5 ± 4.1 mmHg (P < 0.001), and 17.4 ± 3.2 mmHg (P < 0.001), respectively. Head-up tilt (HUT) significantly decreased OPP by 16.5 ± 2.5 mmHg (P < 0.001). IOP was significantly higher in prone versus supine position for much of the tilt range. Our study indicates that OPP is highly gravitationally dependent. Specifically, data show that MAPeye is more gravitationally dependent than IOP, thus causing OPP to increase during HDT and to decrease during HUT. In addition, IOP was elevated in prone position compared with supine position due to the additional hydrostatic column between the base of the rostral globe to the mid-coronal plane, supporting the notion that hydrostatic forces play an important role in ocular hemodynamics. Changes in OPP as a function of changes in gravitational stress and/or weightlessness may play a role in the pathogenesis of spaceflight-associated neuro-ocular syndrome. [ABSTRACT FROM AUTHOR]

We hypothesized that during rapid uptilting at rest, due to vagal withdrawal, arterial baroreflex sensitivity (BRS) may decrease promptly and precede the operating point (OP) resetting, whereas different kinetics are expected during exercise steady state, due to lower vagal activity than at rest. To test this, eleven subjects were rapidly (<2 s) tilted from supine (S) to upright (U) and vice versa every 3 min, at rest and during steady-state 50 W pedaling. Mean arterial pressure (MAP) was measured by finger cuff (Portapres) and R-to-R interval (RRi) by electrocardiography. BRS was computed with the sequence method both during steady and unsteady states. At rest, BRS was 35.1 ms·mmHg-1 (SD = 17.1) in S and 16.7 ms·mmHg-1 (SD = 6.4) in U (P < 0.01), RRi was 901 ms (SD = 118) in S and 749 ms (SD = 98) in U (P < 0.01), and MAP was 76 mmHg (SD = 11) in S and 83 mmHg (SD = 8) in U (P < 0.01). During uptilt, BRS decreased promptly [first BRS sequence was 19.7 ms·mmHg-1 (SD = 5.0)] and was followed by an OP resetting (MAP increase without changes in RRi). At exercise, BRS and OP did not differ between supine and upright positions [BRS was 7.7 ms·mmHg-1 (SD = 3.0) and 7.7 ms·mmHg-1 (SD = 3.5), MAP was 85 mmHg (SD = 13) and 88 mmHg (SD = 10), and RRi was 622 ms (SD = 61) and 600 ms (SD = 70), respectively]. The results support the tested hypothesis. The prompt BRS decrease during uptilt at rest may be ascribed to a vagal withdrawal, similarly to what occurs at exercise onset. The OP resetting may be due to a slower control mechanism, possibly an increase in sympathetic activity. [ABSTRACT FROM AUTHOR]

Clinical use of heated, high-flow nasal cannula (HFNC) for noninvasive respiratory support is increasing and may have a therapeutic role in stabilizing the upper airway in obstructive sleep apnea (OSA). However, physiological mechanisms by which HFNC therapy may improve upper airway function and effects of different temperature modes are unclear. Accordingly, this study aimed to determine effects of incremental flows and temperature modes (heated and nonheated) of HFNC on upper airway muscle activity (genioglossus), pharyngeal airway pressure, breathing parameters, and perceived comfort. Six participants (2 females, aged 35 ± 14 yr) were studied during wakefulness in the supine position and received HFNC at variable flows (0-60 L/min) during heated (37°C) and nonheated (21°C) modes. Breathing parameters via calibrated Respitrace inductance bands (chest and abdomen), upper airway pressures via airway transducers, and genioglossus muscle activity via intramuscular bipolar fine wire electrodes were measured. Comfort levels during HFNC were quantified using a visual analog scale. Increasing HFNC flows did not increase genioglossus muscle activation despite increased negative epiglottic pressure swings (P = 0.009). HFNC provided -7 cmH2O positive airway pressure at 60 L/min in nonheated and heated modes. In addition, increasing the magnitude of HFNC flow reduced breathing frequency (P = 0.045), increased expiratory time (P = 0.040), increased peak inspiratory flow (P = 0.002), and increased discomfort (P = 0.004). Greater discomfort occurred at higher flows in the nonheated versus the heated mode (P = 0.034). These findings provide novel insight into key physiological changes that occur with HFNC for respiratory support and indicate that the primary mechanism for improved upper airway stability is positive airway pressure, not increased pharyngeal muscle activity. [ABSTRACT FROM AUTHOR]

Postexercise reduction in blood pressure, termed postexercise hypotension (PEH), is relevant for both acute and chronic health reasons and potentially for peripheral cardiovascular adaptations. We investigated the interactive effects of exercise intensity and recovery postures (seated, supine, and standing) on PEH. Thirteen normotensive men underwent a V̇o 2max test on a cycle ergometer and five exhaustive constant load trials to determine critical power (CP) and the gas exchange threshold (GET). Subsequently, work-matched exercise trials were performed at two discrete exercise intensities (10% > CP and 10% < GET), with 1 h of recovery in each of the three postures. For both exercise intensities, standing posture resulted in a more substantial PEH (all P < 0.01). For both standing and seated recovery postures, the higher exercise intensity led to larger reductions in systolic [standing: -33 (11) vs. -21 (8) mmHg; seated: -34 (32) vs. -17 (37) mmHg, P < 0.01], diastolic [standing: -18 (7) vs. -8 (5) mmHg; seated: -10 (10) vs. -1 (4) mmHg, P < 0.01], and mean arterial pressures [-13 (8) vs. -2 (4) mmHg, P < 0.01], whereas in the supine recovery posture, the reduction in diastolic [-9 (9) vs. -4 (3) mmHg, P = 0.08) and mean arterial pressures [-7 (5) vs. -3 (4) mmHg, P = 0.06] was not consistently affected by prior exercise intensity. PEH is more pronounced during recovery from exercise performed above CP versus below GET. However, the effect of exercise intensity on PEH is largely abolished when recovery is performed in the supine posture. NEW & NOTEWORTHY The magnitude of postexercise hypotension is greater following the intensity above the critical power in a standing position.

The article presents the discussion on central venous pressure (CVP) falling below supine levels upon entering weightlessness. Topics include pressure drop in the thorax being transmitted to the intrathoracic vasculature creating a drop in CVP; and esophageal pressure being commonly used as a surrogate for intrathoracic pressure and measured using a balloon in the lower one-third of the esophagus, just posterior to the heart.

Regional viscoelastic properties of thoracic tissues in acute respiratory distress syndrome (ARDS) and their change with position and positive end-expiratory pressure (PEEP) are unknown. In an experimental porcine ARDS, dorsal and ventral lung (R2,L and E2,L) and chest wall (R2,cw and E2,cw) viscoelastic resistive (R) and elastic (E) parameters were measured at 20, 15, 10, and 5 cmH2O PEEP in supine and prone position. E2 and R2 were obtained by fitting the decay of pressure after end-inspiratory occlusion to the equation: Pviscmax (t) =R2 e-t/t2, where t is the length of occlusion and s2 time constant. E2 was equal to R2/s2. R2,cw and E2,cw were measured from esophageal, dorsal, and ventral pleural pressures. Global R2,L and E2,L were obtained from the global transpulmonary pressure (airway pressure-esophageal pressure), and regional R2,L and E2,L from the dorsal and ventral airway pressure-pleural pressure difference. Lung ventilation was measured by electrical impedance tomography (EIT). Global R2, cw and E2,cw did not change with PEEP or position. Global R2,L [median(Q1-Q3)] was 37.1 (11.0-65.1), 5.1 (4.3-5.5), 12.1 (8.4-19.5), and 41.0 (26.6-53.5) cmH2O/L/s in supine, and 15.3 (9.1-41.9), 7.9 (5.7-11.0), 8.0 (5.1-12.1), and 12.9 (6.4-19.4) cmH2O/L in prone from 20 to 5 cmH2O PEEP (P = 0.06 for PEEP and P = 0.06 for position). Dorsal R2,L significantly and positively correlated with the amount of collapse measured with EIT. Global and regional lung and chest wall viscoelastic parameters can be described by a simple rheological model. Regional E2 and R2 were uninfluenced by PEEP and position except for PEEP on dorsal E2,L and position on dorsal E2,cw. [ABSTRACT FROM AUTHOR]

Earlier reports suggest that limb venous distension evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) (i.e., venous distension reflex). Our recent report also shows that suction of arterially occluded limb evokes venous distension reflex. We postulate that the venous distension reflex contributes to autonomic responses to orthostatic stress. In this study, we hypothesized that orthostatic tolerance would be linked to the MSNA response seen with lower limb suction. Fifteen healthy subjects were tested in the supine position. Negative pressure (-100 mmHg) was applied on an arterially occluded lower limb for 2 min. MSNA from the peroneal nerve in the limb not exposed to suction, ECG, and BP (Finometer) was recorded throughout the study. Limb occlusion without suction was used as a control trial. In a separate visit, the individual's orthostatic tolerance was assessed using a graded lower body negative pressure (LBNP) tolerance test. Mean arterial BP and MSNA (18.6 ± 1.9 to 23.6 ± 2.0 bursts/min) significantly (both P < 0.05) increased during limb suction. Orthostatic tolerance index positively correlated (R = 0.636, P = 0.011) with the MSNA response seen with suction during occlusion. Since the venous distension reflex strength correlates with the level of orthostatic tolerance, we speculate that lower-limb venous distension reflex engagement increases the sympathetic responses during orthostatic challenge and serves to maintain BP with postural stress. [ABSTRACT FROM AUTHOR]

Patients with mild chronic obstructive pulmonary disease (COPD) demonstrate resting pulmonary vascular dysfunction as well as a blunted pulmonary diffusing capacity (DLCO) and pulmonary capillary blood volume (VC) response to exercise. The transition from the upright to supine position increases central blood volume and perfusion pressure, which may overcome microvascular dysfunction in an otherwise intact alveolar-capillary interface. The present study examined whether the supine position normalized DLCO and VC responses to exercise in mild COPD. Sixteen mild COPD participants and 13 age-, gender-, and height-matched controls completed DLCO maneuvers at rest and during exercise in the upright and supine position. The multiple FIO2 -DLCO method was used to determine DLCO, VC, and membrane diffusion capacity (DM). All three variables were adjusted for alveolar volume (DLCOAdj, VCAdj, and DMAdj). The supine position reduced alveolar volume similarly in both groups, but oxygen consumption and cardiac output were unaffected. DLCOAdj, DMAdj, and VCAdj were all lower in COPD. These same variables all increased with upright and supine exercise in both groups. DLCOAdj was unaffected by the supine position. VCAdj increased in the supine position similarly in both groups. DMAdj was reduced in the supine position in both groups. While the supine position increased exercise VCAdj in COPD, the increase was of similar magnitude to healthy controls; therefore, exercise VC remained blunted in COPD. The persistent reduction in exercise DLCO and VC when supine suggests that pulmonary vascular destruction is a contributing factor to the blunted DLCO and VC response to exercise in mild COPD. NEW & NOTEWORTHY Patients with mild chronic obstructive pulmonary disease demonstrate a combination of reversible pulmonary microvascular dysfunction and irreversible pulmonary microvascular destruction. [ABSTRACT FROM AUTHOR]

Esophageal pressure has been suggested as adequate surrogate of the pleural pressure. We investigate after lung surgery the determinants of the esophageal and intrathoracic pressures and their differences. The esophageal pressure (through esophageal balloon) and the intrathoracic/pleural pressure (through the chest tube on the surgery side) were measured after surgery in 28 patients immediately after lobectomy or wedge resection. Measurements were made in the nondependent lateral position (without or with ventilation of the operated lung) and in the supine position. In the lateral position with the nondependent lung, collapsed or ventilated, the differences between esophageal and pleural pressure amounted to 4.4 ± 1.6 and 5.1 ± 1.7 cmH2O. In the supine position, the difference amounted to 7.3 ± 2.8 cmH2O. In the supine position, the estimated compressive forces on the mediastinum were 10.5 ± 3.1 cmH2O and on the iso-gravitational pleural plane 3.2 ± 1.8 cmH2O. A simple model describing the roles of chest, lung, and pneumothorax volume matching on the pleural pressure genesis was developed; modeled pleural pressure = 1.0057 × measured pleural pressure + 0.6592 (r² = 0.8). Whatever the position and the ventilator settings, the esophageal pressure changed in a 1:1 ratio with the changes in pleural pressure. Consequently, chest wall elastance (Ecw) measured by intrathoracic (Ecw = ΔPpl/tidal volume) or esophageal pressure (Ecw = ΔPes/tidal volume) was identical in all the positions we tested. We conclude that esophageal and pleural pressures may be largely different depending on body position (gravitational forces) and lung-chest wall volume matching. Their changes, however, are identical. [ABSTRACT FROM AUTHOR]

Chronic effects of inspiratory muscle training (IMT) on autonomic function and baroreflex regulation are poorly studied. This study aims at evaluating chronic effects of different IMT intensities on cardiovascular control in amateur cyclists. A longitudinal, randomized, controlled blind study was performed on 30 recreational male cyclists undergoing IMT for 11 wk. Participants were randomly allocated into sham-trained group (SHAM, n = 9), trained group at 60% of the maximal inspiratory pressure (MIP60, n = 10), and trained group at critical inspiratory pressure (CIP, n = 11). Electrocardiogram, finger arterial pressure, and respiratory movements were recorded before (PRE) and after (POST) training at rest in supine position (REST) and during active standing (STAND). From the beat-to-beat series of heart period (HP) and systolic arterial pressure (SAP), we computed time domain markers, frequency domain indexes in the low frequency (0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) bands, an entropy-based complexity index (CI), and baroreflex markers estimated from spontaneous HP-SAP sequences. Compared with SHAM, the positive effect of MIP60 over the HP series led to the HF power increase during REST (PRE: 521.2 ± 447.5 ms²; POST: 1,161 ± 878.9 ms²) and the CI rise during STAND (PRE: 0.82 ± 0.18; POST: 0.97 ± 0.13). Conversely, the negative effect of CIP took the form of the decreased HP mean during STAND (PRE: 791 ± 71 ms; POST: 737 ± 95 ms). No effect of IMT was visible over SAP and baroreflex markers. These findings suggest that moderate-intensity IMT might be beneficial when the goal is to limit cardiac sympathetic hyperactivity at REST and/or in response to STAND. [ABSTRACT FROM AUTHOR]

In heart period (HP) variability (HPV) recordings the percentage of negative HP variations tends to be greater than that of positive ones and this pattern is referred to as HPV asymmetry (HPVA). HPVA has been studied in several experimental conditions in healthy and pathological populations, but its origin is unclear. The baroreflex (BR) exhibits an asymmetric behavior as well given that it reacts more importantly to positive than negative arterial pressure (AP) variations. We tested the hypothesis that the BR asymmetry (BRA) is a HPVA determinant over spontaneous fluctuations of HP and systolic AP (SAP). We studied 100 healthy subjects (age from 21 to 70 yr, 54 men) comprising 20 subjects in each age decade. Electrocardiogram and noninvasive AP were recorded for 15 min at rest in supine position (REST) and during active standing (STAND). The HPVA was evaluated via Porta's index and Guzik's index, while the BRA was assessed as the difference, and normalized difference, between BR sensitivities computed over positive and negative SAP variations via the sequence method applied to HP and SAP variability. HPVA significantly increased during STAND and decreased progressively with age. BRA was not significantly detected both at REST and during STAND. However, we found a significant positive association between BRA and HPVA markers during STAND persisting even within the age groups. This study supports the use of HPVA indexes as descriptors of BRA and identified a challenge soliciting the BR response like STAND to maximize the association between HPVA and BRA markers. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that acute changes in arterial blood pressure (BP) when astronauts moved between supine and standing posture before and after spaceflight can be tracked by beat-to-beat changes in pulse arrival time (PAT). Nine male crewmembers (45 ± 7 yr of age; mean mission length: 165 ± 13 days) participated in a standardized supine-to-sit-to-stand test (5 min-30 s-3 min) before flight and 1 day following return to Earth with continuous monitoring of ECG and finger arterial BP. PAT was determined from the R-wave of the ECG to the foot of the BP waveform. On average, modest cardiovascular deconditioning was detected by ??10 beats/min increase in heart rate in supine and standing posture after spaceflight (P < 0.05). When looking across the full data collection period, the r² values between inverse of PAT (1/PAT) and systolic (SBP) and diastolic BP (DBP) varied considerably between individuals (SBP preflight 0.142 ± 0.186, postflight 0.262 ± 0.243). Individual variability was consistent during periods of transition (SBP preflight 0.284 ± 0.324, postflight 0.297 ± 0.269); however, when SBP dropped >20 mmHg, r² was significant in 5 of 5 preflight tests and 5 of 7 postflight tests. The standard error of the estimate based on a simple linear model during both pre- and postflight testing was 9-11 mmHg for SBP and 6-7 mmHg for DBP. Overall, the results support the hypothesis that PAT tracked dynamic changes in BP. PAT as a noninvasive, nonintrusive surrogate for changes in BP could be developed as an indicator of risk for syncope on return from space- flight or other Earth-based applications. NEW & NOTEWORTHY Astronauts returning to Earth's gravity are at increased risk of low blood pressure on standing. Arterial pulse arrival time tracked the decrease in arterial blood pressure on moving from supine to upright posture. Nonintrusive technology providing indicators sensitive to acute changes in blood pressure could act as an early warning system to identify risk for hypotension that place astronauts, or people on Earth, at risk of impaired cognitive performance, fainting, and falls. [ABSTRACT FROM AUTHOR]

Prolonged sitting has been shown to promote endothelial dysfunction in the lower legs. Furthermore, it has been reported that simple sitting-interruption strategies, including calf raises, prevent leg endothelial dysfunction. However, it is unclear whether prolonged sitting affects central cardiovascular health, or whether simple sitting-interruption strategies prevent impaired central cardiovascular health. This study sought to answer two questions: in young, healthy adults 1) does prolonged sitting (3 h) lead to increased aortic stiffness, and 2) do intermittent calf raise exercises to prevent pooling prevent aortic stiffening. Twenty young, healthy participants (21.7 ± 2.5 yr, 70% female, 25.5 ± 6.1 kg/m2) were randomized to 3 h of sitting with (CALF) or without (CON) 10 calf raises every 10 min. Aortic stiffening [carotid-femoral pulse wave velocity (PWV)] was measured in the supine position pre- and post-sitting. Venous pooling during sitting was estimated with total hemoglobin (tHB) concentration using near-infrared spectroscopy. There were no condition - time interactions. Following 3 h of sitting, PWV significantly increased (0.30 ± 0.46 m/s, P < 0.001). There was no condition effect for PWV (P = 0.694), indicating the intermittent calf rises did not preserve central cardiovascular health. tHb was not significantly affected by sitting (P = 0.446) but was 1.9 μM higher for CON versus CALF (P = 0.106). Sitting increases aortic stiffness in young, healthy individuals, a process that may be influenced by lower extremity blood pooling. Calf raises, which have been reported to preserve vascular function in the legs, do not appear to provide sufficient stimulus for maintaining central cardiovascular health. NEW & NOTEWORTHY Although simple strategies, such as fidgeting or calf raises, are sufficient for preserving vascular function in the legs, data from the current study indicate that such strategies are not sufficient for maintaining central cardiovascular health, which is linked to cardiovascular disease. [ABSTRACT FROM AUTHOR]

The extrinsic tongue muscles are activated in coordination with pharyngeal muscles to dilate the airways as needed during breathing. The genioglossus (GG) activity is known to be modulated by several reflexes evoked via the mechanoreceptors of the upper airways. The primary objective of this paper was to investigate the effectiveness of activating these reflex pathways using mechanical stimulation of the mandible or the submandibular muscles. In eight healthy subjects, 3-s long, 5-mm vertical mechanical vibrations were delivered at 8 and 12 Hz to the lower jaw in a seated position, while the GG EMG was recorded using a custom-made sublingual electrode, along with the activity of the masseter (MS) and mylohyoid (MH). All three muscle activities were significantly higher during stimulation compared with the baseline (P < 0.02), and the increase was larger at 12 Hz versus 8 Hz (P < 0.02). All three muscle responses had components that synchronized with the mechanical stimuli, but those of MS were much more strongly phase-locked to the vibrational cycle. In 10 healthy subjects, we also applied mechanical vibrations to the submandibular muscles at three different stimulation intensities, while subjects were lying in a supine position. The GG activity increased significantly above the baseline (P = 0.026) in 9 out of 10 subjects, and the elevated activity persisted after termination of the stimulus for a few seconds. The results demonstrate that GG muscle responses can be evoked with mechanical vibrations applied to the lower jaw or the submandibular muscles in healthy subjects during wakefulness. [ABSTRACT FROM AUTHOR]

The location of lung regions with compromised ventilation (often called ventilation defects) during a bronchoconstriction event may be influenced by posture. We aimed to determine the effect of prone versus supine posture on the spatial pattern of methacholine-induced bronchoconstriction in six healthy adults (ages 21-41, 3 women) using specific ventilation imaging. Three postural conditions were chosen to assign the effect of posture to the drug administration and/or imaging phase of the experiment: supine methacholine administration followed by supine imaging, prone methacholine administration followed by supine imaging, and prone methacholine administration followed by prone imaging. The two conditions in which imaging was performed supine had similar spatial patterns of bronchoconstriction despite a change in posture during methacholine administration; the odds ratio for recurrent constriction was mean (SD) = 7.4 (3.9). Conversely, dissimilar spatial patterns of bronchoconstriction emerged when posture during imaging was changed; the odds ratio for recurrent constriction between the prone methacholine/supine imaging condition and the prone methacholine/prone imaging condition was 1.2 (0.9). Logistic regression showed that height above the dependent lung border was a significant negative predictor of constriction in the two supine imaging conditions (P < 0.001 for each) but not in the prone imaging condition (P = 0.20). These results show that the spatial pattern of methacholine bronchoconstriction is recurrent in the supine posture, regardless of whether methacholine is given prone or supine but that prone posture during imaging eliminates that recurrent pattern and reduces its dependence on gravitational height. [ABSTRACT FROM AUTHOR]

Small-amplitude, higher frequency oscillations of the body or limb are typically observed when humans attempt to maintain the position of a body or limb in space. Recent investigations have suggested that these involuntary movements of the body during stance could be used as an exploratory means of acquiring sensory information. In the present study, we wanted to determine whether a similar phenomenon would be observed in an upper limb postural task that does not involve whole body postural control. Participants were placed in a supine position with the arm pointing vertically and were asked to maintain the position of the limb in space with and without visual feedback. The wrist was attached to an apparatus that allowed the experimenter to stabilize or “lock” movements of the arm without the participants’ awareness. When participants were “locked,” the forces recorded predicted greater accelerations than those observed when the arm was freely moving with and without visual feedback. From unlocked to locked, angular accelerations increased in the eyes-closed condition and when participants were provided visual feedback of arm angular displacements. Irrespective of their origin, small displacements of the limb may be used as an exploratory means of acquiring sensory information from the surrounding environment. [ABSTRACT FROM AUTHOR]

Moderate-intensity aerobic exercise increases cerebral blood velocity (CBv) primarily due to hyperpnea-induced vasodilation; however, the integrative control of cerebral blood flow (CBF) allows other factors to contribute to the vasodilation. Although lower body negative pressure (LBNP) can reduce CBv, the exact LBNP intensity required to blunt the aforementioned exercise-induced CBv response is unknown. This could hold utility for concussion recovery, allowing individuals to exercise at higher intensities without symptom exacerbation. Thirty-two healthy adults (age: 20-33 yr; 19 females/13 males) completed a stepwise maximal exercise test during a first visit to determine each participant's wattage associated with their exercise-induced maximal CBv increase. During the second visit, following supine rest, participants completed moderate-intensity exercise at their determined threshold, while progressive LBNP was applied at 0, -20, -40, -60, -70, -80, and ∼88 Torr. Bilateral middle cerebral artery blood velocities (MCAvs), mean arterial pressure (MAP), heart rate, respiratory rate, and end-tidal carbon dioxide levels were measured continuously. Two-way analysis of variance with effect sizes compared between sexes and stages. Compared with resting supine baseline, averaged MCAv was elevated during 0 and -20 Torr LBNP ( q value > 7.73; P < 0.001); however, no differences were noted between baseline and -40 to -70 Torr ( q value < |4.24|; P > 0.262). Differences were present between females and males for absolute MCAv measures ( q value > 11.2; P < 0.001), but not when normalized to baseline ( q value < 0.03; P > 0.951). Supine cycling-elicited increases in MCAv are able to be blunted during the application of LBNP ranging from -40 to -70 Torr. The blunted CBv response demonstrates the potential benefit of allowing individuals to aerobically train (moderate-intensity supine cycling with LBNP) without exacerbating symptoms during the concussion recovery phase. NEW & NOTEWORTHY The current investigation demonstrated that moderate-intensity supine cycling-induced increases in cerebral blood velocities were balanced by the lower body negative pressure-induced decreases in cerebral blood velocity. Although performed in a healthy population, the results may lend themselves to a potential treatment option for individuals recovering from concussion or experience persistent concussion symptoms.

Intraocular pressure (IOP) initially increases when an individual enters microgravity compared with baseline values when an individual is in a seated position. This has been attributed to a headward fluid shift that increases venous pressures in the head. The change in IOP exceeds changes measured immediately after moving from seated to supine postures on Earth, when a similar fluid shift is produced. Furthermore, central venous and cerebrospinal fluid pressures are at or below supine position levels when measured initially upon entering microgravity, unlike when moving from seated to supine postures on Earth, when these pressures increase. To investigate the effects of altering gravitational forces on the eye, we made ocular measurements on 24 subjects (13 men, 11 women) in the seated, supine, and prone positions in the laboratory, and upon entering microgravity during parabolic flight. IOP in microgravity (16.3 ± 2.7 mmHg) was significantly elevated above values in the seated (11.5 ± 2.0 mmHg) and supine (13.7 ± 3.0 mmHg) positions, and was significantly less than pressure in the prone position (20.3 ± 2.6 mmHg). In all measurements, P < 0.001. Choroidal area was significantly increased in subjects in a microgravity environment (P < 0.007) compared with values from subjects in seated (increase of 0.09 ± 0.1 mm2) and supine (increase of 0.06 ± 0.09 mm2) positions. IOP results are consistent with the hypothesis that hydrostatic gradients affect IOP, and may explain how IOP can increase beyond supine values in microgravity when central venous and intracranial pressure do not. Understanding gravitational effects on the eye may help develop hypotheses for how microgravityinduced visual changes develop. [ABSTRACT FROM AUTHOR]

The cerebral pressure-flow relationship can be quantified as a high-pass filter, where slow oscillations are buffered (<0.20 Hz) and faster oscillations are passed through relatively unimpeded. During moderate intensity exercise, previous studies have reported paradoxical transfer function analysis (TFA) findings (altered phase or intact gain). This study aimed to determine whether these previous findings accurately represent this relationship. Both younger (20-30 yr; n = 10) and older (62-72 yr; n = 9) adults were examined. To enhance the signal-to-noise ratio, large oscillations in blood pressure (via oscillatory lower body negative pressure; OLBNP) were induced during steady-state moderate intensity supine exercise (~45-50% of heart rate reserve). Beat-to-beat blood pressure, cerebral blood velocity, and end-tidal PCO2 were monitored. Very low frequency (0.02-0.07 Hz) and low frequency (0.07-0.20 Hz) range spontaneous data were quantified. Driven OLBNP point estimates were sampled at 0.05 and 0.10 Hz. The OLBNP maneuvers augmented coherence to >0.97 at 0.05 Hz and >0.98 at 0.10 Hz in both age groups. The OLBNP protocol conclusively revealed the cerebrovascular system functions as a high-pass filter during exercise throughout aging. It was also discovered that the older adults had elevations (+71%) in normalized gain (+0.46 ± 0.36%/%: 0.05 Hz) and reductions (-34%) in phase (-0.24 ± 0.22 radian: 0.10 Hz). There were also age-related phase differences between resting and exercise conditions. It is speculated that these age-related changes in the TFA metrics are mediated by alterations in vasoactive factors, sympathetic tone, or the mechanical buffering of the compliance vessels. [ABSTRACT FROM AUTHOR]

Morning blood pressure (BP) surge is considered to be an independent risk factor for cardiovascular diseases. We tested the hypothesis that increased large-artery stiffness and impaired sympathetic baroreflex sensitivity (BRS) contribute to augmented morning surge in elderly hypertensive subjects. Morning surge was assessed as morning systolic BP averaged for 2 h just after waking up minus minimal sleeping systolic BP by using ambulatory BP monitoring (ABPM) in 40 untreated hypertensive [68 ± 1 (SE) yr] and 30 normotensive (68 ± 1 yr) subjects. Beat-by-beat finger BP and muscle sympathetic nerve activity (MSNA) were recorded in the supine position and at 60° upright tilt. We assessed arterial stiffness with carotid-to-femoral pulse wave velocity (cfPWV) and sympathetic BRS during spontaneous breathing. Awake and asleep ABPM-BPs and morning surge were higher in hypertensive than normotensive subjects (all P < 0.001). cfPWV was higher (P = 0.002) and sympathetic BRS was lower (P = 0.096) in hypertensive than normotensive subjects. Hypertensive subjects with morning surge ≥35 mmHg (median value) had higher cfPWV (11.9 ± 0.5 vs. 9.9 ± 0.4 m/s, P = 0.002) and lower sympathetic BRS (supine: -2.71 ± 0.25 vs. -3.73 ± 0.29, P = 0.011; upright: -2.62 ± 0.22 vs. -3.51 ± 0.35 bursts·100 beats-1·mmHg-1, P = 0.052) than those with morning surge <35 mmHg. MSNA indices were similar between groups (all P 0.05), while upright total peripheral resistance was higher in hypertensive subjects with greater morning surge than those with lesser morning surge (P = 0.050). Morning surge was correlated positively with cfPWV (r = 0.59, P < 0.001) and negatively with sympathetic BRS (r = 0.51, P < 0.001) in hypertensive subjects only. Thus, morning BP surge is associated with arterial stiffness and sympathetic BRS, as well as vasoreactivity during orthostasis in hypertensive seniors. [ABSTRACT FROM AUTHOR]

Mental stress consistently induces a pressor response that is often accompanied by a paradoxical increase of muscle sympathetic nerve activity (MSNA). The purpose of the present study was to evaluate sympathetic baroreflex sensitivity (BRS) by examining the relations between spontaneous fluctuations of diastolic arterial pressure (DAP) and MSNA. We hypothesized that sympathetic BRS would be attenuated during mental stress. DAP and MSNA were recorded during 5 min of supine baseline, 5 min of mental stress, and 5 min of recovery in 32 young healthy adults. Burst incidence and area were determined for each cardiac cycle and placed into 3-mmHg DAP bins; the slopes between DAP and MSNA provided an index of sympathetic BRS. Correlations between DAP and MSNA were strong (>0.5) during baseline in 31 of 32 subjects, but we evaluated the change in slope only for those subjects maintaining a strong correlation during mental stress (16 subjects). During baseline, the relation between DAP and MSNA was negative when expressed as either burst incidence [slope = -1.95 ± 0.18 bursts·(100 beats)-1·mmHg-1; r = -0.86 ± 0.03] or total MSNA [slope = -438 ± 91 units·(beat)-1 mmHg-1; r = -0.76 ± 0.06]. During mental stress, the slope between burst incidence and DAP was significantly reduced [slope = -1.14 ± 0.12 bursts·(100 beats)-1·mmHg-1; r = -0.72 ± 0.03; P < 0.01], indicating attenuation of sympathetic BRS. A more detailed analysis revealed an attenuation of sympathetic BRS during the first 2 min of mental stress (P < 0.01) but no change during the final 3 min of mental stress (P = 0.25). The present study demonstrates that acute mental stress attenuates sympathetic BRS, which may partially contribute to sympathoexcitation during the mental stress-pressor response. However, this attenuation appears to be isolated to the onset of mental stress. Moreover, variable MSNA responses to mental stress do not appear to be directly related to sympathetic BRS. [ABSTRACT FROM AUTHOR]

Using small animal PET with 68Ga-mdiolabeled human albumin microspheres (Ga-68-microspheres), we investigated the effect of posture on regional puLmonary blood flow (PBF) in normal rats. This in vivo method is noninvasive and quantitative, and it allows for repeated longitudinal measurements. The purpose of the experiment was to quantify spatial differences in PBF in small animals in different postures. Two studies were performed in anesthetized, spontaneously breathing Wistar rats. Study 1 was designed to determine PBF in the prone and supine positions. Ga-68-microspheres were given to five prone and eight supine animals. We found that PBF increased in dorsal regions of supine animals (0.75) more than in prone animals (0.70; P = 0.037), according to a steeper vertical gradient of flow in supine than in prone animals. No differences in spatial heterogeneity were detected. Study 2 was designed to determine the effects of tissue distribution on PBF measurements. Because microspheres remained fixed in the lung, PET was performed on animals in the position in which they received Ga-68-microsphere injections and thereafter in the opposite posture. The distribution of PBF showed a preference for dorsal regions in both positions, but the distribution was dependent on the position during administration of the microspheres. We conclude that PET using Ga-68-microspheres can detect and quantify regional PBF in animals as small as the rat. PBF distributions differed between the prone and supine postures and were influenced by the distribution of lung tissue within the thorax. [ABSTRACT FROM AUTHOR]

We manipulated the baseline metabolic rate and body position to explore the effect of the interaction between recruitment of discrete sections of the muscle fiber pool and muscle O2 delivery on pulmonary O2 uptake (VO2) kinetics during cycle exercise. We hypothesized that phase II VO2 kinetics (τp) in the transition from moderateto severe-intensity exercise would be significantly slower in the supine than upright position because of a compromise to muscle perfusion and that a priming bout of severe-intensity exercise would return τp during supine exercise to τp during upright exercise. Eight male subjects [35 ± 13 (SD) yr] completed a series of "step" transitions to severe-intensity cycle exercise from an "unloaded" (20-W) baseline and a baseline of moderate-intensity exercise in the supine and upright body positions. τp was not significantly different between supine and upright exercise during transitions from a 20-W baseline to moderateor severe-intensity exercise but was significantly greater during moderateto severe-intensity exercise in the supine position (54 ± 19 vs. 38 ± 10 s, P < 0.05). Priming significantly reduced τp during moderateto severe-intensity supine exercise (34 ± 9 s), returning it to a value that was not significantly different from τp in the upright position. This effect occurred in the absence of changes in estimated muscle fractional O2 extraction (from the near-infrared spectroscopyderived deoxygenated Hb concentration signal), such that the priminginduced facilitation of muscle blood flow matched increased O2 utilization in the recruited fibers, resulting in a speeding of VO2 kinetics. These findings suggest that, during supine cycling, priming speeds VO2 kinetics by providing an increased driving pressure for O2 diffusion in the higher-order (i.e., type II) fibers, which would be recruited in the transition from moderate-to-severe-intensity exercise and are known to be especially sensitive to limitations in O2 supply. [ABSTRACT FROM AUTHOR]

The venoarteriolar response (VAR) increases vascular resistance upon increases in venous transmural pressure in cutaneous, subcutaneous, and muscle vascular beds. During orthostasis, it has been proposed that up to 45% of the increase in systemic vascular tone is due to VAR-related local mechanism(s). The objective of this project was to test the hypothesis that heat stress attenuates VAR-mediated cutaneous and whole leg vasoconstriction. During normothermic conditions, measurements of cutaneous blood flow (laser-Doppler flowmetry) and femoral artery blood flow (Doppler ultrasound) were obtained from both legs during supine and leg-dependent conditions. These measurements were repeated following a whole body heat stress (increase in internal temperature of 1.4 ± 0.2°C). Before leg dependency, cutaneous (CVC) and femoral vascular conductances (FVC) were significantly elevated in both legs during heat stress relative to normothermia (P < 0.001). During leg dependency the absolute decrease in CVC was attenuated during heat stress (P < 0.01) while the absolute decrease in FVC was unaffected (P = 0.90). When CVC and FVC data were analyzed as a relative change from their respective baseline values, heat stress significantly attenuated the magnitude of vasoconstriction due to leg dependency in the cutaneous and femoral circulations (P < 0.001 for both variables). These data suggest that an attenuated local vasoconstriction, evoked via the venoarteriolar response, may contribute to reduced blood pressure control and thus reduced orthostatic tolerance that occurs in heat-stressed individuals. [ABSTRACT FROM AUTHOR]

The explanation for prone and supine differences in tissue density and pleural pressure gradients in the healthy lung has been inferred from several studies as compression of dependent tissue by the heart in the supine posture; however, this hypothesis has not been directly confirmed. Differences could also arise from change in shape of the chest wall and diaphragm, and because of shape with respect to gravity. The contribution of this third mechanism is explored here. Tissue density and static elastic recoil were estimated in the supine and prone left human lung at functional residual capacity using a finite-element analysis. Supine model geometries were derived from multidetector row computed tomography imaging of two subjects: one normal (subject 1), and one with small airway disease (subject 2). For each subject, the prone model was the supine lung shape with gravity reversed; therefore, the prone model was isolated from the influence of displacement of the diaphragm, chest wall, or heart. Model estimates were validated against multidetector row computed tomography measurement of regional density for each subject supine and an independent study of the prone and supine lung. The magnitude of the gradient in density supine (-4.33%/cm for subject 1, and -4.96%/cm for subject 2) was nearly twice as large as for the prone lung (-2.72%/cm for subject 1, and -2.51%/cm for subject 2), consistent with measurements in dogs. The corresponding pleural pressure gradients were 0.54 cmH2O/cm (subject 1) and 0.56 cmH2O/cm (subject 2) for supine, and 0.29 cmH2O/cm (subject 1) and 0.27 cmH2O/cm (subject 2) for prone. A smaller prone gradient was predicted without shape change of the "container" or support of the heart by the lung. The influence of the heart was to constrain the shape in which the lung deformed. [ABSTRACT FROM AUTHOR]