Clinical impact of perioperative atrial fibrillation on long-term recurrence of malignancy.

Perioperative complications have been reported to be associated with a lower incidence of cancer-free survival. Perioperative atrial fibrillation (POAF) is one of occasionally observed complications in patients with malignancies who undergo noncardiac surgeries. However, the long-term clinical impact of POAF on those with malignancies have remained unknown. This was a prospective, single-center, observational study. Patients who underwent noncardiac surgeries for definitive malignancies between 2014 and 2017 were included. The primary and secondary endpoints were 3-year recurrence of malignancies and cancer death, respectively. The present study included consecutive 752 patients (mean age, 68 ± 11 years; males, 62%), and POAF was observed in 77 patients. The follow-up duration was 1037 (interquartile range, 699-1408) days. The 3-year recurrence of malignancies was observed in 239 (32%) patients (POAF, 32 [42%]; non-POAF, 207 [31%]) and 3-year mortality was 130 patients (17%). Cardiac, noncardiac, and cancer deaths were observed in 4 (0.5%), 126 (17%), and 111 (15%) patients, respectively. Multivariate Cox regression analysis demonstrated that POAF was associated with 3-year recurrence of malignancies (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.15-2.52). Landmark analysis demonstrated that POAF tended to be correlated with the incidence of 3-year cancer death (HR, 1.79; 95% CI, 0.96-3.31). In conclusion, POAF is associated with the subsequent recurrence of malignancies. The association of arrhythmia with cancer death may be revealed under longer follow-up durations.Clinical Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018270 . UMIN ID: UMIN000016146.

Validity of transcranial Doppler ultrasonography-determined dynamic cerebral autoregulation estimated using transfer function analysis.

Transcranial Doppler ultrasonography (TCD) is used widely to evaluate dynamic cerebral autoregulation (dCA). However, the validity of TCD-determined dCA remains unknown because TCD is only capable of measuring blood velocity and thus only provides an index as opposed to true blood flow. To test the validity of TCD-determined dCA, in nine healthy subjects, dCA was evaluated by transfer function analysis (TFA) using cerebral blood flow (CBF) or TCD-measured cerebral blood velocity during a perturbation that induces reductions in TCD-determined dCA, lower body negative pressure (LBNP) at two different stages: LBNP - 15 mmHg and - 50 mmHg. Internal carotid artery blood flow (ICA Q) was assessed as an index of CBF using duplex Doppler ultrasound. The TFA low frequency (LF) normalized gain (ngain) calculated using ICA Q increased during LBNP at - 50 mmHg (LBNP50) from rest (P = 0.005) and LBNP at - 15 mmHg (LBNP15) (P = 0.015), indicating an impaired dCA. These responses were the same as those obtained using TCD-measured cerebral blood velocity (from rest and LBNP15; P = 0.001 and P = 0.015). In addition, the ICA Q-determined TFA LF ngain from rest to LBNP50 was significantly correlated with TCD-determined TFA LF ngain (r = 0.460, P = 0.016) despite a low intraclass correlation coefficient. Moreover, in the Bland-Altman analysis, the difference in the TFA LF ngains determined by blood flow and velocity was within the margin of error, indicating that the two measurement methods can be interpreted as equivalent. These findings suggest that TCD-determined dCA can be representative of actual dCA evaluated with CBF.

Pivotal Role of Heart for Orthostasis: Left Ventricular Untwisting Mechanics and Physical Fitness.

Augmentation of left ventricular (LV) untwisting due to central hypovolemia is likely to be a compensatory mechanism for maintaining stroke volume, which is reduced by a decrease in cardiac filling during orthostatic stress. Orthostatic intolerance observed in both high and low fitness levels may be explained by the impaired response of LV untwisting due to central hypovolemia.

Menstrual cycle effects on sympathetic neural burst amplitude distribution during orthostasis in young women.

PURPOSE: Fluctuations in ovarian hormones during the menstrual cycle impact muscle sympathetic nerve activity burst frequency and burst incidence at rest. The purpose of this study was to investigate menstrual cycle effects on sympathetic neural burst amplitude distribution during an orthostatic challenge in young women. METHODS: This study included 11 healthy women (33 ± 10 years [mean ± standard deviation]). Muscle sympathetic nerve activity was measured in the supine position as baseline measurement and during 5 min of 60° upright tilting, during the early follicular phase (low estrogen and progesterone) and mid-luteal phase (high estrogen and progesterone) of the menstrual cycle. Relative burst amplitude distribution of muscle sympathetic nerve activity was characterized by the mean, median, skewness, and kurtosis. RESULTS: From the supine to upright position, mean and median values of relative burst amplitude increased (both P < 0.05), regardless of phases of the menstrual cycle (P = 0.5 and P = 0.7, respectively). In comparison, during the early follicular phase, skewness and kurtosis remained unchanged (P = 0.6 and P = 0.3, respectively) and kurtosis decreased (1.25 ± 1.11 supine vs. - 0.03 ± 0.73 upright; P = 0.02); there was no change in skewness during the mid-luteal phase (P = 0.4). CONCLUSIONS: In response to orthostasis, while the symmetry and tailedness/peakness of burst amplitude distribution do not change during the early follicular phase, the distribution during the mid-luteal phase becomes flatter with a lower but broader peak. The latter result suggests that the firing probability of large axon action potentials in response to orthostatic challenge is higher when estrogen and progesterone levels are elevated. The role of changes in sympathetic neural burst amplitude distribution in orthostatic tolerance remains to be determined.

Broader adaptive range of sympathetic burst size in response to blood pressure change in older women with greater arterial stiffness.

KEY POINTS: In this study, we focused on muscle sympathetic nerve activity (MSNA) burst size and occurrence separately as subcomponents of the sympathetic baroreflex in older adults, and we found that the distribution (variation) of burst size against burst occurrence was greater in women than men. Older women had greater carotid artery stiffness compared with older men, while blood pressure (BP) distribution (variation) was comparable between sexes. Sympathetic baroreflex sensitivity assessed with burst incidence was less sensitive as the carotid artery became stiffer in older men and women, while that assessed with burst area was more sensitive as the carotid artery became stiffer in older women but not in older men. These results help us understand the mechanisms underlying the compensation for the impaired response of MSNA burst occurrence in older women with greater carotid artery stiffness to regulate BP similar to that in older men. ABSTRACT: There are sex differences in arterial stiffness and neural control of blood pressure (BP) among older adults. We examined whether the sympathetic response to BP is greater in older women than men in burst size but not burst occurrence. Burst occurrence and size were assessed with burst interval and area of muscle sympathetic nerve activity, respectively, and the distributions of these indices were evaluated by range during supine rest in 61 healthy older subjects (30 men (69 ± 6 years) and 31 women (68 ± 6 years); means ± SD). Also, we analysed sympathetic baroreflex sensitivity (BRS) with burst occurrence and area simultaneously. Carotid ß-stiffness was measured with B-mode ultrasonic image and carotid BP. The range of burst interval was smaller in older women than men (P = 0.002), while there was no difference in the range of burst area. Carotid ß-stiffness was greater in older women than men (6.7 ± 2.7 vs. 5.1 ± 2.7, P = 0.027). Sympathetic BRS assessed with burst incidence was lower in older women than men (-2.3 ± 1.4 vs. -3.3 ± 1.4 bursts·100 beats-1  mmHg-1 , P = 0.007), while this sex difference was observed when assessed with burst area after adjusting for carotid ß-stiffness (-116.1 ± 135.0 vs. -185.9 ± 148.2 a.u. burst-1  mmHg-1 , P = 0.040), but not before. Sympathetic BRS assessed with burst area was negatively (more sensitive) correlated with carotid ß-stiffness in older women (r = -0.53, P = 0.002) but not men. These data suggest that the response of burst size within each burst is augmented for the baroreflex BP control despite the impaired response of burst occurrence in older women with greater carotid stiffness.

The effect of lifelong endurance exercise on cardiovascular structure and exercise function 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. ABSTRACT: 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.

Impact of Prolonged Spaceflight on Orthostatic Tolerance During Ambulation and Blood Pressure Profiles in Astronauts.

BACKGROUND: Astronauts returning to earth usually demonstrate reduced orthostatic tolerance when assessed on a tilt table or quiet standing, but no studies have evaluated postflight orthostatic tolerance during activities of daily living, when it is most clinically relevant. Ambulatory blood pressure (BP) variability also is associated with orthostatic intolerance in certain patient populations and can capture clinically significant orthostatic hypotension during activities of daily living, especially when measured on a beat-to-beat basis. We evaluated the impact of prolonged spaceflight on orthostatic tolerance and BP profiles in astronauts. METHODS: Ambulatory beat-to-beat BP was recorded using a portable device for multiple 24-hour time periods before, during, and after 6 months of spaceflight in 12 astronauts (4 women; age 48±5 [mean±SD] years). BP variability in the time domain was calculated as the SD. Systolic BP distribution during activities of daily living was characterized by skewness and kurtosis. RESULTS: In contrast with results from previous studies that used tilt tables or stand tests, no astronaut experienced orthostatic intolerance/hypotension during activities of daily living before or after spaceflight. Also, 24-hour systolic BP decreased in space (120±10 mm Hg before spaceflight versus 106±9 mm Hg during spaceflight; P<0.01), but it returned to normal upon landing (122±13 mm Hg). Diastolic BP was unchanged during and after spaceflight. Systolic and diastolic BP variability remained the same before, during, and after spaceflight (both P>0.05). The skewness of systolic BP increased in space (0.74±0.51 versus 1.43±1.00; P=0.001), indicating that signal fluctuations became asymmetrical; however, it returned to preflight levels after landing (0.51±0.42). The kurtosis increased in space (5.01±7.67 versus 11.10±11.79; P=0.010), suggesting that fluctuations concentrated around the mean with a narrow distribution; however, it also returned to preflight levels (2.21±2.56) after return to earth. CONCLUSIONS: Given current countermeasures including in-flight exercise training and volume resuscitation on return, no astronauts experienced orthostatic hypotension or intolerance during routine (for landing day) activities in the initial 24 hours after landing following 6 months in space. Prolonged exposure to spaceflight had little impact on systolic BP variability and its distribution, although the latter showed a transient change in space (accompanied by mild relative hypotension), all of which returned to preflight values after return to earth.

Dynamic characteristics of cerebrovascular reactivity or ventilatory response to change in carbon dioxide.

NEW FINDINGS: What is the central question of this study? What are the dynamic characteristics of cerebrovascular carbon dioxide reactivity and the central respiratory chemoreflex? What is the main finding and its importance? The transfer function gain from the end-tidal partial pressure of carbon dioxide to cerebral blood flow or ventilation decreased in the high frequency range at rest and during exercise. These findings indicate that the dynamic characteristics of both systems were not constant in all frequency ranges, and this trend was not modified by exercise. ABSTRACT: The purpose of this study was to examine the dynamic characteristics of cerebrovascular reactivity and ventilatory response to change in arterial CO2 in all frequency ranges at rest using frequency domain analysis, and also to examine whether this is modified by dynamic exercise as with the traditionally determined cerebrovascular CO2 reactivity. In nine healthy young subjects, at rest and during exercise (cycling exercise at constant predetermined work rate corresponding to a V̇O2 level of 0.90 l min-1 ), the dynamic characteristics of cerebrovascular CO2 reactivity and the central respiratory chemoreflex were assessed by transfer function analysis using a binary white-noise sequence (0-7% inspired CO2 fraction) from the end-tidal partial pressure of CO2 ( PETCO2 ) to the mean middle cerebral artery mean blood velocity (MCA Vm ) or minute ventilation ( V̇E ), respectively. In the high frequency range, both transfer function gains decreased but, interestingly, the cut-off frequency in the transfer function gain from PETCO2 to MCA Vm response was higher than that from PETCO2 to V̇E response at rest (0.024 vs. 0.015 Hz) and during exercise (0.030 vs. 0.011 Hz), indicating that cerebrovascular CO2 reactivity or central respiratory chemoreflex was not constant in all frequency ranges, and this trend was not modified by exercise. These findings suggest that dynamic characteristics of the cerebrovascular CO2 reactivity or central chemoreflex need to be assessed to identify the whole system because the traditional method cannot identify the property of time response of these systems.

Impact of Lifelong Exercise Training Dose on Ventricular-Arterial Coupling.

BACKGROUND: The dynamic Starling mechanism, as assessed by beat-by-beat changes in stroke volume and left ventricular end-diastolic pressure, reflects ventricular-arterial coupling. It deteriorates with age, and is preserved in highly trained masters athletes. Currently, it remains unclear how much exercise over a lifetime is necessary to preserve efficient ventricular-arterial coupling. The purpose of this study was to assess the dose-dependent relationship between lifelong exercise training and the dynamic Starling mechanism in healthy seniors. METHODS: One hundred two seniors were recruited and stratified into 4 groups based on 25 years of exercise training history: sedentary subjects (n=27, <2 sessions/week), casual exercisers (n=25, 2-3 sessions/week), committed exercisers (n=25, 4-5 sessions/week), and competitive Masters Athletes (n=25, 6-7 sessions/week). The dynamic Starling mechanism was estimated by transfer function gain between beat-by-beat changes in diastolic pulmonary artery pressure, a surrogate for left ventricular end-diastolic pressure, and stroke volume index. RESULTS: The transfer function gain of pulmonary artery pressure-stroke volume index was markedly enhanced in committed and competitive exercisers compared with more sedentary seniors and correlated with higher peak oxygen uptake (Vo2) and lower left ventricular stiffness. The power spectral density of pulmonary artery pressure was greater in sedentary adults than in committed and competitive exercisers, whereas the power spectral density of stroke volume index was greater in competitive exercisers than in the other groups. CONCLUSIONS: There is a graded, dose-dependent improvement in ventricular-arterial coupling with increasing amounts of lifelong regular exercise in healthy older individuals. Our data suggest that the optimal dose of lifelong endurance exercise to preserve ventricular-arterial coupling with age appears to be at least 4 to 5 sessions per week.

Does respiratory drive modify the cerebral vascular response to changes in end-tidal carbon dioxide?

NEW FINDINGS: What is the central question of this study? There is an interaction between the regulatory systems of respiration and cerebral blood flow, because the mediator (CO2 ) is the same for both physiological systems. We examined whether the traditional method for determining cerebrovascular reactivity to CO2 is modified by changes in respiration. What is the main finding and its importance? Cerebrovascular reactivity was modified by voluntary changes in respiration during hypercapnia. This finding suggests that an alteration in the respiratory system may result in under- or overestimation of cerebrovascular reactivity determined by traditional methods in healthy adults. ABSTRACT: The cerebral vasculature is sensitive to changes in the arterial partial pressure of CO2 . This physiological mechanism has been well established as a cerebrovascular reactivity to CO2 (CVR). However, arterial CO2 may not be an independent variable in the traditional method for assessment of CVR, because the cerebral blood flow response is also affected by the activation of respiratory drive or higher centres in the brain. We hypothesized that CVR is modified by changes in respiration. To test our hypothesis, in the present study, 10 young, healthy subjects performed hyper- or hypoventilation to change end-tidal CO2 ( PET,CO2 ) with different concentrations of CO2 in the inhaled gas (0, 2.0 and 3.5%). We measured middle cerebral artery mean blood flow velocity by transcranial Doppler ultrasonography to identify the cerebral blood flow response to change in PET,CO2 during each set of conditions. In each set of conditions, PET,CO2 was significantly altered by changes in ventilation, and middle cerebral artery mean blood flow velocity changed accordingly. However, the relationship between changes in middle cerebral artery mean blood flow velocity and PET,CO2 as a response curve of CVR was reset upwards and downwards by hypo- and hyperventilation, respectively, compared with CVR during normal ventilation. The findings of the present study suggest the possibility that an alteration in respiration might lead to under- or overestimation of CVR determined by the traditional methods.

The effect of lifelong exercise frequency on arterial stiffness.

KEY POINTS: This study examined the effect of different 'doses' of lifelong (>25 years) exercise on arterial stiffening (a hallmark of vascular ageing) in older adults. There are clear dose-dependent effects of lifelong exercise training on human arterial stiffness that vary according to the site and size of the arteries. Similar to what we have observed previously with ventricular stiffening, 4-5 days week-1 of committed exercise over a lifetime are necessary to preserve 'youthful' vascular compliance, especially of the large central arteries. Casual exercise training of two to three times per week may be sufficient for middle-sized arteries like the carotid to minimize arterial stiffening with ageing. However, there is little effect of exercise training on the small-sized peripheral arteries at any dose. ABSTRACT: Central arterial stiffness increases with sedentary ageing. While near-daily, vigorous lifelong (>25 years) endurance exercise training prevents arterial stiffening with ageing, this rigorous routine of exercise training over a lifetime is impractical for most individuals. The aim was to examine whether a less frequent 'dose' of lifelong exercise training (four to five sessions per week for > 30 min) that is consistent with current physical activity recommendations elicits similar benefits on central arterial stiffening with ageing. A cross-sectional examination of 102 seniors (>60 years old) who had a consistent lifelong exercise history was performed. Subjects were stratified into four groups based on exercise frequency as an index of exercise 'dose': sedentary: fewer than two sessions per week; casual exercisers: two to three sessions per week; committed exercisers: four to five sessions per week; and Masters athletes: six to seven sessions per week plus regular competitions. Detailed measurements of arterial stiffness and left ventricular afterload were collected. Biological aortic age and central pulse wave velocity were younger in committed exercisers and Masters athletes compared to sedentary seniors. Total arterial compliance index (TACi) was lower, while carotid ß-stiffness index and effective arterial elastance were higher in sedentary seniors compared to the other groups. There appeared to be a dose-response threshold for carotid ß-stiffness index and TACi. Peripheral arterial stiffness was not significantly different among the groups. These data suggest that four to five weekly exercise sessions over a lifetime is associated with reduced central arterial stiffness in the elderly. A less frequent dose of lifelong exercise (two to three sessions per week) is associated with decreased ventricular afterload and peripheral resistance, while peripheral arterial stiffness is unaffected by any dose of exercise.

Long-term effects of a renin inhibitor versus a thiazide diuretic on arterial stiffness and left ventricular diastolic function in elderly hypertensive patients.

Arterial stiffness and cardiac function are important predictors of cardiovascular events in patients with hypertension, even with adequate blood pressure (BP) control. We evaluated whether a direct renin inhibitor, aliskiren, reduces arterial stiffness and modulates left ventricular function compared with a diuretic, hydrochlorothiazide, in elderly hypertensive patients. Twenty-one hypertensive patients [67 ± 14 (SD) yr] were randomly assigned to receive 6-mo aliskiren (n = 11) or hydrochlorothiazide (n = 10)-based therapy. We assessed ß-stiffness of the local arteries, arterial elastance (Ea), and echocardiographic variables, including early (E) and late (A) mitral inflow velocity, deceleration time of E, early (E') and late (A') diastolic mitral annular velocity, and left ventricular end-systolic elastance (Ees) before and after treatment. BP decreased similarly (P < 0.001) after both therapies. ß-Stiffness of the carotid artery decreased after aliskiren but increased after hydrochlorothiazide treatment (aliskiren: 6.42 ± 2.34 pre vs. 5.07 ± 1.29 post; hydrochlorothiazide: 5.05 ± 1.78 vs. 7.25 ± 2.68, P = 0.001 for interaction). ß-Stiffness of the femoral and radial arteries were not different after either treatment. Different from aliskiren, E decreased (73 ± 16 vs. 67 ± 14 cm/s, P = 0.026), and the deceleration time was prolonged (218 ± 40 vs. 236 ± 35 ms, P = 0.032) after hydrochlorothiazide therapy, whereas the E/A, and E' remained unchanged after both treatments. Ea and Ees decreased after aliskiren therapy (both P < 0.05), whereas the Ea/Ees (ventricular-arterial coupling) was maintained after both treatments. Thus, aliskiren decreased the stiffness of carotid artery and left ventricular end-systolic elastance with maintenance of ventricular-arterial coupling without any effects on diastolic filling, while hydrochlorothiazide increased carotid arterial stiffness and slowed early diastolic filling in elderly hypertensive patients.

Asian women have attenuated sympathetic activation but enhanced renal-adrenal responses during pregnancy compared to Caucasian women.

Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal-adrenal system (e.g. low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. In a prospective study, blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30 deg and 60 deg for 5 min each) in 9 Asians (32 ± 1 years (mean ± SEM)) and 12 Caucasians (29 ± 1 years) during pre-, early (≤8 weeks of gestation) and late (32-36 weeks) pregnancy, and post-partum (6-10 weeks after delivery). Supine MSNA increased with pregnancy in both groups (P < 0.001); it was significantly lower in Asians than Caucasians (14 ± 3 vs. 23 ± 3 bursts min(-1) and 16 ± 5 vs. 30 ± 3 bursts min(-1) in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P < 0.001), but was restored during late pregnancy. HR increased during pregnancy (P < 0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31 ± 6 vs. 49 ± 3 bursts min(-1) at 60 deg tilt; P = 0.003). Upright BP was lower in Asians, even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P < 0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal-adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy.

Morning blood pressure surge is associated with arterial stiffness and sympathetic baroreflex sensitivity in hypertensive seniors.

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.

The effect of exercise training on left ventricular relaxation and diastolic suction at rest and during orthostatic stress after bed rest.

A marked reduction in upright stroke volume (SV) contributes substantially to orthostatic intolerance after exposure to spaceflight or bed rest. It is unclear whether slowed left ventricular (LV) relaxation and diastolic suction contribute to the reduction in SV or whether these changes are influenced by exercise training while in bed. Twenty-seven healthy adults completed 5 weeks of -6 deg head-down bed rest (HDBR). During HDBR, nine subjects were sedentary (NOEX), while 18 performed near-daily rowing ergometry (EX). Left ventricular mass, SV, LV end-diastolic volume (LVEDV), pulmonary capillary wedge pressure and Doppler ultrasound indices of LV function were collected pre- and post-HDBR during supine rest (twice) and during reduced LV loading (lower body negative pressure; LBNP) and increased LV loading (saline infusion). Post-HDBR, LV mass increased in the EX group, but decreased in the NOEX group. The reduction in SV and LVEDV during supine rest and LBNP were greater with NOEX in comparison to EX after HDBR. Peak early mitral annular velocity, isovolumic relaxation time, early propagation velocity, a non-invasive index of early diastolic filling and ventricular diastolic suction, and peak global longitudinal early strain rate were slowed during supine rest after HDBR with NOEX; however, these variables were either unaltered or the reduction was less prominent with EX. Doppler ultrasound measures of early diastolic filling, ventricular relaxation and diastolic suction were not significantly affected during LV unloading by LBNP after HDBR in either group. All Doppler indices were restored to pre-HDBR levels in both groups during saline infusion to normalize LV filling pressure after HDBR. It is concluded that Doppler indices of dynamic LV filling were reduced in both groups after HDBR; however, these effects were more pronounced in the NOEX group. Irrespective of group, post-HDBR Doppler parameters were restored when LV filling pressure was increased to pre-HDBR levels during saline infusion. Therefore, the reduction in upright SV after HDBR is more influenced by changes in LV loading conditions, namely left atrial pressure in the setting of LV remodelling, rather than ventricular relaxation and diastolic suction.

Cardiac Effects of Long-Duration Space Flight.

BACKGROUND: Ventricular mass responds to changes in physical activity and loading, with cardiac hypertrophy after exercise training, and cardiac atrophy after sustained inactivity. Ventricular wall stress (ie, loading) decreases during microgravity. Cardiac atrophy does not plateau during 12 weeks of simulated microgravity but is mitigated by concurrent exercise training. OBJECTIVES: The goal of this study was to determine whether the current exercise countermeasures on the International Space Station (ISS) offset cardiac atrophy during prolonged space flight. METHODS: We measured left ventricular (LV) and right ventricular (RV) mass and volumes (via magnetic resonance imaging) in 13 astronauts (4 females; age 49 ± 4 years), between 75 and 60 days before and 3 days after 155 ± 31 days aboard the ISS. Furthermore, we assessed total cardiac work between 21 and 7 days before space flight and 15 days before the end of the mission. Data were compared via paired-samples t-tests. RESULTS: Total cardiac work was lower during space flight (P = 0.008); however, we observed no meaningful difference in LV mass postflight (pre: 115 ± 30 g vs post: 118 ± 29 g; P = 0.053), with marginally higher LV stroke volume (P = 0.074) and ejection fraction postflight (P = 0.075). RV mass (P = 0.999), RV ejection fraction (P = 0.147), and ventricular end-diastolic (P = 0.934) and end-systolic volumes (P = 0.145) were not different postflight. There were strong positive correlations between the relative change in LV mass with the relative changes in total cardiac output (r = 0.73; P = 0.015) and total cardiac work (r = 0.53; P = 0.112). CONCLUSIONS: The current exercise countermeasures used on the ISS appear effective in offsetting reductions in cardiac mass and volume, despite overall reductions in total cardiac work, during prolonged space flight.

Short-term exercise training improves the cardiovascular response to exercise in the postural orthostatic tachycardia syndrome.

Recent studies have suggested the presence of cardiac atrophy as a key component of the pathogenesis of the postural orthostatic tachycardia syndrome (POTS), similar to physical deconditioning. It has also been shown that exercise intolerance is associated with a reduced stroke volume (SV) in POTS, and that the high heart rate (HR) observed at rest and during exercise in these patients is due to this low SV. We tested the hypotheses that (a) circulatory control during exercise is normal in POTS; and (b) that physical 'reconditioning' with exercise training improves exercise performance in patients with POTS. Nineteen (18 women) POTS patients completed a 3 month training programme. Cardiovascular responses during maximal exercise testing were assessed in the upright position before and after training. Resting left ventricular diastolic function was evaluated by Doppler echocardiography. Results were compared with those of 10 well-matched healthy sedentary controls. A lower SV resulted in a higher HR in POTS at any given oxygen uptake (V(O(2))) during exercise while the cardiac output (Q(c))-V(O(2)) relationship was normal. V(O(2peak)) was lower in POTS than controls (26.1 ± 1.0 (SEM) vs. 36.3 ± 0.9 ml kg-1 min-1; P < 0.001) due to a lower peak SV (65 ± 3 vs. 80 ± 5 ml; P = 0.009). After training in POTS, HR became lower at any given due to increased SV without changes in the ­ relationship. V(O(2peak)) increased by 11% (P < 0.001) due to increased peak SV (P = 0.021) and was proportional to total blood volume. Peak HR was similar, but HR recovery from exercise was faster after training than before training (P = 0.036 for training and 0.009 for interaction). Resting diastolic function was mostly normal in POTS before training, though diastolic suction was impaired (P = 0.023). There were no changes in any Doppler index after training. These results suggest that short-term exercise training improves physical fitness and cardiovascular responses during exercise in patients with POTS.

Effect of ageing on left ventricular compliance and distensibility in healthy sedentary humans.

Healthy, but sedentary ageing leads to marked atrophy and stiffening of the heart, with substantially reduced cardiac compliance; but the time course of when this process occurs during normal ageing is unknown. Seventy healthy sedentary subjects (39 female; 21­77 years) were recruited from the Dallas Heart Study, a population-based, random community sample and enriched by a second random sample from employees of Texas Health Resources. Subjects were highly screened for co-morbidities and stratified into four groups according to age: G(21−34): 21­34 years, G(35−49): 35­49 years, G5(0−64): 50­64 years, G(≥65): ≥65 years. All subjects underwent invasive haemodynamic measurements with right heart catheterization to define Starling and left ventricular (LV) pressure­volume curves. LV end-diastolic volumes (EDV) were measured by echocardiography at baseline, −15 and −30 mmHg lower-body negative pressure, and 15 and 30 ml kg(−1) saline infusion with simultaneous measurements of pulmonary capillary wedge pressure. There were no differences in heart rate or blood pressures among the four groups at baseline. Baseline EDV index was smaller in G(≥65) than other groups. LV diastolic pressure­volume curves confirmed a substantially greater LV compliance in G(21−34) compared with G(50−64) and G(≥65), resulting in greater LV volume changes with preload manipulations. Although LV chamber compliance in G(50−64) and G(≥65) appeared identical, pressure­volume curves were shifted leftward, toward a decreased distensibility, with increasing age. These results suggest that LV stiffening in healthy ageing occurs during the transition between youth and middle-age and becomes manifest between the ages of 50 to 64. Thereafter, this LV stiffening is followed by LV volume contraction and remodelling after the age of 65.

Sympathetic activation during early pregnancy in humans.

Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min(-1), 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min(-1); main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm(-5); P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.(-1) min(-1); P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml(-1), P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml(-1), P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.

Effect of exercise training on biologic vascular age in healthy seniors.

Arteriosclerosis with aging leads to central arterial stiffening in humans, which could be a prime cause for increased cardiac afterload in the elderly. The purpose of the present study was to assess the effects of 1 yr of progressive exercise training on central aortic compliance and left ventricular afterload in sedentary healthy elderly volunteers. Ten healthy sedentary seniors and 11 Masters athletes (>65 yr) were recruited. The sedentary seniors underwent 1 yr of progressive exercise training so that at the end of the year, they were exercising ∼200 min/wk. Central aortic compliance was assessed by the Modelflow aortic age, which reflects the intrinsic structural components of aortic compliance. Cardiac afterload was assessed by effective arterial elastance (Ea) with its contributors of peripheral vascular resistance (PVR) and systemic arterial compliance (SAC). After exercise training, Ea, PVR, and SAC were improved in sedentary seniors and became comparable with those of Masters athletes although the Modelflow aortic age was not changed. Moreover, after exercise training, when stroke volume was restored with lower body negative pressure back to pretraining levels, the exercise training-induced improvements in Ea, PVR, and SAC were eliminated. Aortic stiffening with aging was not improved even after 1 yr of progressive endurance exercise training in the previously sedentary elderly, while left ventricular afterload was reduced. This reduced afterload after exercise training appeared to be attributable to cardiovascular functional modulation to an increase in stroke volume rather than to intrinsic structural changes in the arterial wall.