Key Points
Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth.
Gravity has a profound effect on ...fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure.
This being said, intracranial pressure is not reduced to the levels observed in the 90 deg seated upright posture on Earth. Thus, over 24 h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts.
Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure (ICP). This syndrome is considered the most mission‐critical medical problem identified in the past decade of manned spaceflight. We recruited five men and three women who had an Ommaya reservoir inserted for the delivery of prophylactic CNS chemotherapy, but were free of their malignant disease for at least 1 year. ICP was assessed by placing a fluid‐filled 25 gauge butterfly needle into the Ommaya reservoir. Subjects were studied in the upright and supine position, during acute zero gravity (parabolic flight) and prolonged simulated microgravity (6 deg head‐down tilt bedrest). ICP was lower when seated in the 90 deg upright posture compared to lying supine (seated, 4 ± 1 vs. supine, 15 ± 2 mmHg). Whilst lying in the supine posture, central venous pressure (supine, 7 ± 3 vs. microgravity, 4 ± 2 mmHg) and ICP (supine, 17 ± 2 vs. microgravity, 13 ± 2 mmHg) were reduced in acute zero gravity, although not to the levels observed in the 90 deg seated upright posture on Earth. Prolonged periods of simulated microgravity did not cause progressive elevations in ICP (supine, 15 ± 2 vs. 24 h head‐down tilt, 15 ± 4 mmHg). Complete removal of gravity does not pathologically elevate ICP but does prevent the normal lowering of ICP when upright. These findings suggest the human brain is protected by the daily circadian cycles in regional ICPs, without which pathology may occur.
Key Points
Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth.
Gravity has a profound effect on fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure.
This being said, intracranial pressure is not reduced to the levels observed in the 90 deg seated upright posture on Earth. Thus, over 24 h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts.
Abstract The primary chronic symptom in patients with clinically stable heart failure (HF) is reduced exercise tolerance, measured as decreased peak aerobic power (peak oxygen consumption V o2 ), and ...is associated with reduced quality of life and survival. Exercise-based cardiac rehabilitation (EBCR) is a safe and effective intervention to improve peak V o2 , muscle strength, physical functional performance, and quality of life and is associated with a reduction in overall and HF-specific hospitalization in clinically stable patients with HF. Despite these salient benefits, fewer than one-tenth of eligible patients with HF are referred for EBCR after hospitalization. In this review, selection for and timing of EBCR for patients with HF, as well as exercise prescription guidelines with special emphasis on the optimal exercise training intensity to improve peak Vo2 , are discussed.
Key points
During long‐term missions, some astronauts experience structural and functional changes of the eyes and brain which resemble signs/symptoms experienced by patients with intracranial ...hypertension.
Weightlessness prevents the normal cerebral volume and pressure ‘unloading’ associated with upright postures on Earth, which may be part of the cerebral and ocular pathophysiology.
By placing the lower body in a negative pressure device (LBNP) that pulls fluid away from cranial compartments, we simulated effects of gravity and significantly lowered pressure within the brain parenchyma and ventricle compartments.
Application of incremental LBNP demonstrated a non‐linear dose–response curve, suggesting 20 mmHg LBNP as the optimal level for reducing pressure in the brain without impairing cerebral perfusion pressure.
This non‐invasive method of reducing pressure in the brain holds potential as a countermeasure in space as well as having treatment potential for patients on Earth with traumatic brain injury or other pathology leading to intracranial hypertension.
Patients with elevated intracranial pressure (ICP) exhibit neuro‐ocular symptoms including headache, papilloedema and loss of vision. Some of these symptoms are also present in astronauts during and after prolonged space‐flight where lack of gravitational stress prevents daily lowering of ICP associated with upright posture. Lower body negative pressure (LBNP) simulates the effects of gravity by displacing fluid caudally and we hypothesized that LBNP would lower ICP without compromising cerebral perfusion. Ten cerebrally intact volunteers were included: six ambulatory neurosurgical patients with parenchymal ICP‐sensors and four former cancer patients with Ommaya‐reservoirs to the frontal horn of a lateral ventricle. We applied LBNP while recording ICP and blood pressure while supine, and during simulated intracranial hypertension by 15° head‐down tilt. LBNP from 0 to 50 mmHg at increments of 10 mmHg lowered ICP in a non‐linear dose‐dependent fashion; when supine (n = 10), ICP was decreased from 15 ± 2 mmHg to 14 ± 4, 12 ± 5, 11 ± 4, 10 ± 3 and 9 ± 4 mmHg, respectively (P < 0.0001). Cerebral perfusion pressure (CPP), calculated as mean arterial blood pressure at midbrain level minus ICP, was unchanged (from 70 ± 12 mmHg to 67 ± 9, 69 ± 10, 70 ± 12, 72 ± 13 and 74 ± 15 mmHg; P = 0.02). A 15° head‐down tilt (n = 6) increased ICP to 26 ± 4 mmHg, while application of LBNP lowered ICP (to 21 ± 4, 20 ± 4, 18 ± 4, 17 ± 4 and 17 ± 4 mmHg; P < 0.0001) and increased CPP (P < 0.01). An LBNP of 20 mmHg may be the optimal level to lower ICP without impairing CPP to counteract spaceflight‐associated neuro‐ocular syndrome in astronauts. Furthermore, LBNP holds clinical potential as a safe, non‐invasive method for lowering ICP and improving CPP for patients with pathologically elevated ICP on Earth.
Key points
During long‐term missions, some astronauts experience structural and functional changes of the eyes and brain which resemble signs/symptoms experienced by patients with intracranial hypertension.
Weightlessness prevents the normal cerebral volume and pressure ‘unloading’ associated with upright postures on Earth, which may be part of the cerebral and ocular pathophysiology.
By placing the lower body in a negative pressure device (LBNP) that pulls fluid away from cranial compartments, we simulated effects of gravity and significantly lowered pressure within the brain parenchyma and ventricle compartments.
Application of incremental LBNP demonstrated a non‐linear dose–response curve, suggesting 20 mmHg LBNP as the optimal level for reducing pressure in the brain without impairing cerebral perfusion pressure.
This non‐invasive method of reducing pressure in the brain holds potential as a countermeasure in space as well as having treatment potential for patients on Earth with traumatic brain injury or other pathology leading to intracranial hypertension.
Key points
The beneficial effects of sustained or lifelong (>25 years) endurance exercise on cardiovascular structure and exercise function have been largely established in men.
The current findings ...indicate that committed (≥4 weekly exercise sessions) lifelong exercise results in substantial benefits in exercise capacity (V̇O2max), cardiovascular function at submaximal and maximal exercise, left ventricular mass and compliance, and blood volume compared to similarly aged or even younger (middle‐age) untrained women.
Endurance exercise training should be considered a key strategy to prevent cardiovascular disease with ageing in women as well as men.
This study was a retrospective, cross‐sectional analysis of exercise performance and left ventricular (LV) morphology in 70 women to examine whether women who have performed regular, lifelong endurance exercise acquire the same beneficial adaptations in cardiovascular structure and function and exercise performance that have been reported previously in men. Three groups of women were examined: (1) 35 older (>60 years) untrained women (older untrained, OU), (2) 13 older women who had consistently performed four or more endurance exercise sessions weekly for at least 25 years (older trained, OT), and (3) 22 middle‐aged (range 35–59 years) untrained women (middle‐aged untrained, MU) as a reference control for the appropriate age‐related changes. Oxygen uptake (V̇O2) and cardiovascular function (cardiac output (Q̇); stroke volume (SV) acetylene rebreathing) were examined at rest, steady‐state submaximal exercise and maximal exercise (maximal oxygen uptake, V̇O2max). Blood volume (CO rebreathing) and LV mass (cardiac magnetic resonance imaging), plus invasive measures of static and dynamic chamber compliance were also examined. V̇O2max (p < 0.001) and maximal exercise Q̇ and SV were larger in older trained women compared to the two untrained groups (∼17% and ∼27% for Q̇ and SV, respectively, versus MU; ∼40% and ∼38% versus OU, all p < 0.001). Blood volume (mL kg−1) and LV mass index (g m−2) were larger in OT versus OU (∼11% and ∼16%, respectively, both P ≤ 0.015) Static LV chamber compliance was greater in OT compared to both untrained groups (median (25–75%): MU: 0.065 (0.049–0.080); OU: 0.085 (0.061–0.138); OT: 0.047 (0.031–0.054), P ≤ 0.053). Collectively, these findings indicate that lifetime endurance exercise appears to be extremely effective at preserving or even enhancing cardiovascular structure and function with advanced age in women.
Key points
The beneficial effects of sustained or lifelong (>25 years) endurance exercise on cardiovascular structure and exercise function have been largely established in men.
The current findings indicate that committed (≥4 weekly exercise sessions) lifelong exercise results in substantial benefits in exercise capacity (V̇O2max), cardiovascular function at submaximal and maximal exercise, left ventricular mass and compliance, and blood volume compared to similarly aged or even younger (middle‐age) untrained women.
Endurance exercise training should be considered a key strategy to prevent cardiovascular disease with ageing in women as well as men.
Patients with heart failure with preserved ejection fraction (HFpEF) have similar degrees of exercise intolerance and dyspnea as patients with heart failure with reduced EF (HFrEF). The underlying ...pathophysiology leading to impaired exertional ability in the HFpEF syndrome is not completely understood, and a growing body of evidence suggests "peripheral," i.e., noncardiac, factors may play an important role. Changes in skeletal muscle function (decreased muscle mass, capillary density, mitochondrial volume, and phosphorylative capacity) are common findings in HFrEF. While cardiac failure and decreased cardiac reserve account for a large proportion of the decline in oxygen consumption in HFrEF, impaired oxygen diffusion and decreased skeletal muscle oxidative capacity can also hinder aerobic performance, functional capacity and oxygen consumption (V̇o2) kinetics. The impact of skeletal muscle dysfunction and abnormal oxidative capacity may be even more pronounced in HFpEF, a disease predominantly affecting the elderly and women, two demographic groups with a high prevalence of sarcopenia. In this review, we 1) describe the basic concepts of skeletal muscle oxygen kinetics and 2) evaluate evidence suggesting limitations in aerobic performance and functional capacity in HFpEF subjects may, in part, be due to alterations in skeletal muscle oxygen delivery and utilization. Improving oxygen kinetics with specific training regimens may improve exercise efficiency and reduce the tremendous burden imposed by skeletal muscle upon the cardiovascular system.
Mechanisms of Left Atrial Enlargement in Obesity Aiad, Norman N.; Hearon, Christopher; Hieda, Michinari ...
The American journal of cardiology,
08/2019, Letnik:
124, Številka:
3
Journal Article
Recenzirano
Left atrial (LA) enlargement is common in obesity. We sought to determine the influence of ventricular (LV) remodeling on LA size in obesity. We studied 50 otherwise healthy obese subjects (body mass ...index 37.2 ± 4.6 kg/m2, 50 ± 6 years) and 58 age and gender-matched nonobese controls (body mass index 26.2 ± 2.9 kg/m2, 52 ± 5 years). Diastolic function, relative wall thickness (RWT), and LV mass were assessed using echocardiography. LA and LV volume was measured by 3D-echocardiography. Primary outcome was the ratio of LA volume indexed to LV volume in obese and control subjects. Obese subjects had substantially larger LA volumes compared with control subjects (61.0 ± 16.9 vs 38.9 ± 9.2 ml, p < 0.0001). When scaled to body size or lean mass, differences in LA size persisted. However, when indexed to LV end-diastolic volume, LA volumes between control and obese subjects were comparable (obese vs controls: 0.44 ± 0.15 vs 0.42 ± 0.10, p = 0.46). A small subset of obese subjects (26%) had LA volume markedly out of proportion to LV volume (LA/LV volume ratio ≥0.5) and displayed concentric LV remodeling with larger RWT and LV mass compared with obese subjects with LA/LV <0.5 (RWT: 0.46 ± 0.09 vs 0.36 ± 0.06, p < 0.0001; LV mass: 79 ± 18 vs 62 ± 13 g/m2 p < 0.01). In conclusion, LA enlargement in patients with obesity generally occurs commensurate with LV enlargement and parallels eccentric LV remodeling. LA enlargement out of proportion to LV size is associated with increased RWT and mass. This unique signature may identify obese subjects with pathologic LA remodeling.
A trial fibrillation (AF), the most common human cardiac arrhythmia, is associated with abnormal intracellular Ca2+ handling. Diastolic Ca2+ release from the sarcoplasmic reticulum via "leaky" ...ryanodine receptors (RyR2s) is hypothesized to contribute to arrhythmogenesis in AF, but the molecular mechanisms are incompletely understood. Here, we have shown that mice with a genetic gain-of-function defect in Ryr2 (which we termed Ryr2R176Q/+ mice) did not exhibit spontaneous AF but that rapid atrial pacing unmasked an increased vulnerability to AF in these mice compared with wild-type mice. Rapid atrial pacing resulted in increased Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of RyR2, while both pharmacologic and genetic inhibition of CaMKII prevented AF inducibility in Ryr2R176Q/+ mice. This result suggests that AF requires both an arrhythmogenic substrate (e.g., RyR2 mutation) and enhanced CaMKII activity. Increased CaMKII phosphorylation of RyR2 was observed in atrial biopsies from mice with atrial enlargement and spontaneous AF, goats with lone AF, and patients with chronic AF. Genetic inhibition of CaMKII phosphorylation of RyR2 in Ryr2S2814A knockin mice reduced AF inducibility in a vagotonic AF model. Together, these findings suggest that increased RyR2-dependent Ca2+ leakage due to enhanced CaMKII activity is an important downstream effect of CaMKII in individuals susceptible to AF induction.
Compared with younger adults, passive heating induced increases in cardiac output are attenuated by ∼50% in older adults. This attenuated response may be associated with older individuals' inability ...to maintain stroke volume through ionotropic mechanisms and/or through altered chronotropic mechanisms. The purpose of this study was to identify the interactive effect of age and hyperthermia on cardiac responsiveness to dobutamine-induced cardiac stimulation. Eleven young (26 ± 4 yr) and 8 older (68 ± 5 yr) participants underwent a normothermic and a hyperthermic (baseline core temperature +1.2°C) trial on the same day. In both thermal conditions, after baseline measurements, intravenous dobutamine was administered for 12 min at 5 µg/kg/min, followed by 12 min at 15 µg/kg/min. Primary measurements included echocardiography-based assessments of cardiac function, gastrointestinal and skin temperatures, heart rate, and mean arterial pressure. Heart rate responses to dobutamine were similar between groups in both thermal conditions (
> 0.05). The peak systolic mitral annular velocity (S'), i.e., an index of left ventricular longitudinal systolic function, was similar between groups for both thermal conditions at baseline. While normothermic, the increase in S' between groups was similar with dobutamine administration. However, while hyperthermic, the increase in S' was attenuated in the older participants with dobutamine (
< 0.001). Healthy, older individuals show attenuated inotropic, but maintained chronotropic responsiveness to dobutamine administration during hyperthermia. These data suggest that older individuals have a reduced capacity to increase cardiomyocyte contractility, estimated by changes in S', via β1-adrenergic mechanisms while hyperthermic.
BACKGROUND:Moderate intensity exercise is associated with a decreased incidence of atrial fibrillation. However, extensive training in competitive athletes is associated with an increased atrial ...fibrillation risk. We evaluated the effects of 24 months of high intensity exercise training on left atrial (LA) mechanical and electric remodeling in sedentary, healthy middle-aged adults.
METHODS:Sixty-one participants (53±5 years) were randomized to 10 months of exercise training followed by 14 months of maintenance exercise or stretching/balance control. Fourteen Masters athletes were added for comparison. Left ventricular (LV) and LA volumes underwent 3D echocardiographic assessment, and signal-averaged electrocardiographs for filtered P-wave duration and atrial late potentials were completed at 0, 10, and 24 months. Extended ambulatory monitoring was performed at 0 and 24 months. Within and between group differences from baseline were compared using mixed-effects model repeated-measures analysis.
RESULTS:Fifty-three participants completed the study (25 control, 28 exercise) with 88±11% adherence to assigned exercise sessions. In the exercise group, both LA and LV end diastolic volumes increased proportionately (19% and 17%, respectively) after 10 months of training (peak training load). However, only LA volumes continued to increase with an additional 14 months of exercise training (LA volumes 55%; LV end diastolic volumes 15% at 24 months versus baseline; P<0.0001 for all). The LA:LV end diastolic volumes ratio did not change from baseline to 10 months, but increased 31% from baseline in the Ex group (P<0.0001) at 24 months, without a change in controls. There were no between group differences in the LA ejection fraction, filtered P-wave duration, atrial late potentials, and premature atrial contraction burden at 24 months and no atrial fibrillation was detected. Compared with Masters athletes, the exercise group demonstrated lower absolute LA and LV volumes, but had a similar LA:LV ratio after 24 months of training.
CONCLUSIONS:Twenty-four months of high intensity exercise training resulted in LA greater than LV mechanical remodeling with no observed electric remodeling. Together, these data suggest different thresholds for electrophysiological and mechanical changes may exist in response to exercise training, and provide evidence supporting a potential mechanism by which high intensity exercise training leads to atrial fibrillation.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT02039154.
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