Journal of applied physiology最新文献

Impaired cerebrovascular control in patients with heart failure with reduced ejection fraction (HFrEF) has been attributed to cardiac impairment and exaggerated sympathetic-mediated cerebral vasoconstriction. The goal of this study was to examine the effect of muscle metaboreflex activation (MMA) on cerebrovascular hemodynamics in patients with HFrEF under conditions of preserved cardiac output. It was hypothesized that reductions in the index of cerebral blood flow and cerebrovascular conductance (CVCi) during MMA would be exaggerated in HFrEF and independent of reduced cardiac output. Middle cerebral blood velocity (MCA_Vmean; transcranial Doppler), blood pressure, cardiac output (Finometer) and end-tidal CO₂ were examined at rest, during isomteric handgrip, and during muscle MMA (post-exercise circulatory occlusion) in 18 patients with HFrEF and 21 healthy, sex- and age-matched controls. To minimize differences in β-adrenergic control, patients with HFrEF withdrew from β-blockade medications prior to the study. Cardiac index and blood pressure were not significantly different between groups under any condition. The MCA_Vmean was lower at rest and during exercise in HFrEF. The CVCi (MCA_Vmean/mean arterial pressure) and MCA_Vmean decreased during MMA in the control group. In contrast, the CVCi remained unchanged and MCA_Vmean increased during MMA in the HFrEF group. Despite similar systemic hemodynamics, patients with HFrEF display lower MCA_Vmean at rest and an increase in MCA_Vmean during MMA. These novel findings implicate aspects other than reduced cardiac output or exaggerated sympathetic constriction as underlying causes of altered cerebrovascular regulation in HFrEF.

The biomechanics underlying bouncing exercises are characterized by the spring-like behavior of the human leg. This study investigated a specific form of hopping-performed with an extended knee and minimal ground contact duration-to examine how muscle dynamics contribute to leg stiffness adjustment. This constrained hopping pattern allows us to isolate the role of ankle joint, especially plantarflexor muscle-tendon complex (MTC). To quantitatively analyze changes in the MTC of the medial gastrocnemius muscle (MG), we utilized an MTC model comprising an active spring and a passive spring connected in series, representing a contractile component (CC) and series elastic component (SEC), respectively. We hypothesized that an increase in CC stiffness would coincide with the increase in leg stiffness, thereby enabling hopping at higher frequencies. Joints and MG fascicle dynamics were collected across different hop frequencies. The results showed that the stiffness of the MTC increased with hop frequency and exhibited a strong correlation with the leg stiffness. In addition, with increasing frequency, the fascicle contractions shifted from isometric to concentric. Consequently, a negative CC stiffness was observed, thereby increasing the overall MTC stiffness. Although this result appears to diverge from our initial hypothesis, the effect of negative CC stiffness on MTC stiffness can be understood, from the perspective of two springs in series, as an extension of the very high stiffness effect. This quantitative understanding of the dynamic interaction between the fascicle and tendon provides deeper insight into the adjustment mechanisms underlying bouncing gaits.

The lack of direct measures of brain blood pressure (BBP) has severely restricted understanding of cerebral pressure-flow relationships and their control. We sought to evaluate the feasibility of directly measuring BBP and its pulsatility between the aorta and middle cerebral artery (MCA) during elective endovascular surgical procedures. We report five case studies (four female, 61 ± 13 yr; means ± SD) of patients undergoing cerebrovascular interventional procedures for aneurysm and stenoses, using direct BBP measures with the COMET 2 pressure guidewire system (Boston Scientific). Patients were supine, intubated, and under anesthesia. The sensor wire was inserted via the femoral artery, measuring, as feasible, blood pressure (BP) in the aorta to MCA vascular segments, referenced to the radial artery BP waveform (arterial catheter). Mean arterial pressure varied between the radial (80 ± 18 mmHg), internal carotid artery (ICA; 70 ± 25 mmHg), and MCA (62 ± 29 mmHg), and marked interindividual heterogeneity was observed. Pulse pressure was higher in the radial artery (68 ± 23 mmHg) compared with the intracranial ICA (ICAi; 43 ± 29 mmHg) and MCA (M1; 25 ± 12 mmHg) segments. Direct measures of BBP in humans are feasible in this interventional surgery model. Although limited by the small sample size, the results suggest a heterogenous pattern of change between systemic and brain measures of blood pressure and pulse pressure.NEW & NOTEWORTHY We explored the feasibility of making direct measures of blood pressure in the large arteries at the base of the brain in humans. Measures were made with an optical sensor positioned in the aorta, common carotid, internal carotid artery external to the cranium, internal carotid artery within the cranium, and/or middle cerebral artery (MCA), M1 segment. Measures varied across individuals, as did the pressure gradient from systemic pressures to those in the MCA.

Intrathoracic pressure modulates cardiac loading conditions, which then influence left ventricular (LV) chamber function, and may occur with underlying myocardial mechanical alterations. We investigated the independent effects of inspiratory negative and expiratory positive intrathoracic pressure on septal geometry, LV chamber function, and rotation, twist, and strain indices. After baseline, 20 healthy adults (11M/9F, 23 ± 4 yr) performed resistive breathing to manipulate inspiratory (-30, -20, -10 cmH₂O) or expiratory (+10, +20 cmH₂O) intrathoracic pressure. Echocardiography was used to acquire LV-focused two-dimensional (2-D) images, and mitral Doppler inflow and annular tissue velocity spectra. Images were analyzed for LV chamber volumes, tissue velocities, transmitral filling velocities, and speckle tracking-derived LV longitudinal, radial, and circumferential strain and strain-rate, basal and apical rotation, and twist. Across negative pressure trials, most profoundly at -30 cmH₂O, we observed progressive end-diastolic septal flattening (3.9 ± 0.4 vs. 3.2 ± 0.4 cm, P < 0.05) and decreases in LV end-diastolic volume (103 ± 23 vs. 115 ± 25 mL, P < 0.05) and stroke volume, whereas end-systolic volume was unchanged. However, LV apical and basal rotation, twist (13.3° ± 3.6° vs. 13.9° ± 3.7°, P = 0.890), and circumferential, radial, and longitudinal strain indices were largely unchanged. During positive pressure trials, we observed main effects for septal flattening (P = 0.014) confined to inspiration, and modestly reduced LV end-diastolic volume (P < 0.001), end-systolic volume (P = 0.033), and stroke volume. Again, myocardial mechanics parameters changed little. Collectively, our data suggest that both positive and negative intrathoracic pressures can exacerbate direct ventricular interaction through opposing mechanisms that attenuate LV end-diastolic volume and stroke volume, but without specific changes in myocardial mechanics or mitral inflow.NEW & NOTEWORTHY Incrementally more negative or positive intrathoracic pressures, relative to normal dynamic breathing, progressively attenuate left ventricular end-diastolic volume and stroke volume in healthy younger adults. Incrementally more negative or positive intrathoracic pressures were each associated with progressive septal flattening during inspiration, indicating direct ventricular interaction. However, left ventricular transmitral inflow velocities, and myocardial rotation, twist, and circumferential, longitudinal, and radial strain parameters changed little.

Women living in an impoverished environment after birth have an increased risk of developing postpartum depression (PP-Dep) and hypertension (PP-HTN). The mechanisms underlying these heightened risks are unknown and understudied. To examine the relation between reduced environmental resources, PP-Dep, and PP-HTN, postpartum rodent dams were exposed to the low-resource limited bedding and nesting (LBN) chronic stress model during weaning. Postpartum dams were divided into control (CTL) and experimental (LBN) groups, in which the experimental group experienced LBN. At 6 wks postpartum, blood pressure, sucrose preference tests (a proxy for anhedonia and depression), corticosterone, and markers of neuroinflammation were measured. We hypothesized that postpartum dams exposed to LBN will have increased corticosterone, neuroinflammation, depression-like behaviors, and HTN. Results show that postpartum dams exposed to an impoverished environment exhibit decreased sucrose preference, increased circulating corticosterone, and elevated neuroinflammation (∼150% increased TNF-α and astrocyte activation in the cerebrum). No changes in blood pressure were observed. However, there was a strong correlation between postpartum blood pressure and corticosterone and blood pressure and TNF-α levels. Importantly, this study provides insights into the pathology and development of PP-HTN and PP-Dep in the postpartum period, which will enable the discovery of novel therapeutic approaches.NEW & NOTEWORTHY Postpartum dams exposed to a low-resource environment experience anhedonia, elevated corticosterone, and neuroinflammation. Increases in corticosterone and neuroinflammation may contribute to the development of postpartum depression (PP-Dep) and postpartum hypertension (PP-HTN). Healthcare providers should consider asking questions about the social economic status and accessibility of resources for women after pregnancy. This study advocates for extended postpartum care beyond traditional care and better implementation of assessments for PP-Dep and PP-HTN.

The purpose of this study was to investigate the ability of mechanotherapy to enhance recovery or prevent loss of muscle size with disuse in female rats. Female F344/BN rats were assigned to weight bearing (WB), hindlimb suspended (HS) for 14 days with reambulation for 7 days without mechanotherapy or reambulation (RA) with mechanotherapy (RAM) (study 1), or to WB, HS for 7 days, with HS mechanotherapy (HSM) or without mechanotherapy (study 2) to gastrocnemius muscle. Muscle fiber cross-sectional area (CSA) and fiber type, collagen, satellite cell number, and protein synthesis (k_syn) and degradation (k_deg) were assessed. Study 1: muscle weight, but not CSA, was higher in RAM compared with HS, but CSA was higher in RA compared with HS. Myofibrillar k_syn was higher in RA and RAM compared to WB and HS but not different between RA and RAM. Myofibrillar k_deg was lower with mechanotherapy compared to HS. Study 2: muscle weight, CSA, and myofibrillar k_syn and k_deg were not different with mechanotherapy. Collagen content was lower with mechanotherapy but collagen k_syn was not. Mechanotherapy was not associated with changes in fiber type, satellite cell, or myonuclear number in either study. Compared to males, female rats had less muscle loss with HS, which was associated with less loss of myofibrillar k_syn. Recovery from atrophy was associated with higher k_syn in female and lower k_deg in male rats. Female rat muscles do not exhibit a growth response to mechanotherapy with disuse or reambulation. Furthermore, male and female rats show distinct responses to different mechanical stimuli.NEW & NOTEWORTHY This study investigates the response of female rats to mechanical stimulation in both active and passive forms following and during muscle disuse atrophy. New findings indicate that female rats respond to active loading with enhanced muscle regrowth and protein synthesis, whereas passive loading using mechanotherapy did not affect atrophy or recovery of female muscles. Comparison with published data indicates that there are distinct differences in male and female rats in their response to mechanical stimuli.

Violation of the National Institute of Occupational Safety and Health (NIOSH) heat stress recommendations by exceeding the allowable wet bulb globe temperature (WBGT) for a given work intensity and work-rest ratio augments acute kidney injury (AKI) risk. Here, we tested the hypothesis that exceeding the allowable work intensity at a given WBGT and work-rest ratio would also worsen AKI risk. Twelve healthy adults completed two NIOSH recommendation compliant trials and one noncompliant trial consisting of a 4 h (half workday) exposure. Work-rest ratio was fixed at 30 min of walking and 30 min of rest each hour. Work intensity (metabolic heat production) was prescribed as a function of WBGT-412 ± 51 W [27.3 ± 0.3°C; high-intensity compliant (C_high)], 290 ± 75 W [31.6 ± 0.2°C; low-intensity compliant (C_low)], and 410 ± 61 W [31.7 ± 0.2°C; high-intensity noncompliant (NC_high)]. AKI risk was quantified by the product of urinary insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinase 2 normalized to urine specific gravity ([IGFBP7·TIMP-2]_USG). Peak core temperature was higher in NC_high trial (38.3 ± 0.4°C) compared with the compliant trials (C_high: 38.0 ± 0.3°C; C_low: 37.8 ± 0.4°C; P ≤ 0.0095). [IGFBP7·TIMP-2]_USG increased from pre- to immediately postexposure in all trials (time effect: P = 0.0454) but the peak increase was not different between trials [C_high: 0.89 ± 1.7 (ng/mL)²/1,000; C_low: 0.78 ± 1.7 (ng/mL)²/1,000; NC_high: 1.0 ± 1.4 (ng/mL)²/1,000; P = 0.7811]. Violating the NIOSH recommendations by exceeding either the allowable work intensity (i.e., NC_high vs. C_low) or WBGT (i.e., NC_high vs. C_high) resulted in a modest elevation in peak core temperature but did not modify AKI risk.NEW & NOTEWORTHY We demonstrate that violation of the National Institute for Occupational Safety and Health heat stress recommendations by exceeding allowable work intensity by ∼120 W or environmental limits by ∼4°C wet bulb globe temperature (WBGT) at 30-min work-rest per hour results in a modest elevation in peak core temperature but does not augment acute kidney injury risk compared with scenarios that adhered to the NIOSH recommendations during simulated occupational heat stress.

Hyperpolarized ¹²⁹Xe MRI/MRS enables quantitative mapping of function in lung airspaces, membrane tissue, and red blood cells (RBCs) within the pulmonary capillaries. The RBC signal also exhibits cardiogenic oscillations that are reduced in precapillary pulmonary hypertension (PH). This effect is obscured in patients with concomitant defects in transfer from airspaces to RBCs, which increase RBC oscillation amplitudes. Here, we provide a framework for interpreting RBC oscillations and show their relationship to pulsatile blood flow, capillary blood volume, capillary compliance, and impedance of the capillary and venous circulation. This framework was first applied to characterize RBC oscillations in a cohort of subjects with pulmonary disease but no known PH (n = 129). ¹²⁹Xe MRI of RBC transfer was used to estimate capillary blood volume, and as it decreased, RBC oscillations sharply increased ([Formula: see text] = 0.53), consistent with model predictions. Model-derived fit parameters were then used to estimate the distribution of pulmonary vascular resistance (PVR) across arterial, capillary, and venous circulation and to correct oscillations for RBC transfer defects. Seventy percent of PVR was estimated to arise from pulmonary arteries, 11% from capillaries, and 19% from veins. When tested in a second cohort of subjects who underwent ¹²⁹Xe MRI/MRS and right heart catheterization (n = 40), oscillations corrected for capillary blood volume correlated moderately with PVR (r² = 0.27, P = 0.0014). For every 1.96 Wood units (WU) increase in PVR, corrected oscillations decreased by 1 absolute percentage point. This work demonstrates that, although ¹²⁹Xe-RBC oscillations are only indirectly sensitive to precapillary obstruction, corrected oscillations below 7.5% were 100% specific for elevated PVR.NEW & NOTEWORTHY Cardiogenic oscillations in the ¹²⁹Xe red blood cell (RBC) resonance decrease in precapillary pulmonary hypertension (PH) but are enhanced when capillary blood volume is reduced. To separate these effects, we developed a physiological model that used ¹²⁹Xe gas exchange MRI to estimate blood volume, which was used to correct oscillation amplitude measurements. Corrected amplitudes correlated significantly with pulmonary vascular resistance, highlighting the potential for future noninvasive detection of PH.

Short duration heat acclimation (HA) (≤5 daily heat exposures) elicits incomplete adaptation compared with longer interventions, possibly due to the lower accumulated thermal "dose." It is unknown if matching thermal "dose" over a shorter timescale elicits comparable adaptation to a longer intervention. Using a parallel-groups design, we compared: 1) "condensed" HA (CHA; n = 17 males) consisting of 4 × 75 min·day^-1 heat exposures [target rectal temperature (T_rec) = 38.5 °C] for two consecutive days, with 2) "traditional" HA (THA; n = 15 males) consisting of 1 × 75 min·day^-1 heat exposure (target T_rec = 38.5°C) for eight consecutive days. Physiological responses to exercise heat stress, hypoxia, and normoxic exercise performance were evaluated pre- and postintervention. Thermal (T_rec over final 45 min: CHA = 38.45 ± 0.17°C, THA = 38.53 ± 0.13°C, P = 0.126) and cardiovascular strain were not different during interventions, indicating similar thermal "dose," although CHA had lower sweating rate, higher starting T_rec, and greater inflammation, gastrointestinal permeability, and renal stress (P < 0.05). However, CHA elicited an array of thermophysiological adaptations that did not differ from THA [reduced indices of peak thermal (e.g., Δ peak T_rec CHA = -0.28 ± 0.26°C, THA = -0.36 ± 0.17°C, P = 0.303) and cardiovascular strain, inflammation, and renal stress; blood and plasma volume expansion; improved perceptual indices], although improvements in resting thermal strain (e.g., Δ resting T_rec CHA = -0.14 ± 0.21°C, THA = -0.35 ± 0.29°C, P = 0.027) and sweating rate were less with CHA. Both interventions improved aspects of hypoxic tolerance, but effects on temperate normoxic exercise indices were limited. The diminished thermal strain was well-maintained over a 22-day decay period. In conclusion, CHA could represent a viable acclimation option for time-restricted young healthy males preparing for a hot, and possibly high-altitude, environment.NEW & NOTEWORTHY This study has shown, for the first time, that a novel condensed heat acclimation program can elicit an array of thermophysiological adaptations, many of which do not differ from traditional heat acclimation. These findings suggest that accumulated thermal "dose" is an important factor contributing to the adaptive responses to heat stress and that condensed heat acclimation may represent a viable option for time-restricted individuals (e.g., military personnel, firefighters, and athletes) preparing to enter a hot environment.