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.

Relationship between arterial stiffness and cognitive function in outpatients with dementia and mild cognitive impairment compared with community residents without dementia.

BACKGROUND: It is unclear whether the dementia patients with Alzheimer's disease (AD) and vascular dementia (VaD) and mixed dementia (MIX, including AD and VaD) would have more developed arterial stiffness as compared with local residents without dementia. The aim of this study was to assess arterial stiffness and cognitive function in different types of dementia patients [AD, VaD, MIX and mild cognitive impairment (MCI)] and community residents without dementia. METHODS: This was a single-center, cross-sectional observational study. We studied a cohort of 600 elderly outpatients with a complaint of memory loss, who were divided into four groups (AD, VaD, MIX and MCI). In addition, they were compared with 55 age-matched local residents without dementia (Controls). We assessed arterial stiffness by brachial-ankle pulse wave velocity (baPWV) and the global cognitive function by the Mini-Mental State Examination (MMSE). RESULTS: The baPWV was higher in AD, VaD and MIX than in MCI and in Controls (P < 0.05). The baPWV was higher in MCI than in Controls (P = 0.021), while MMSE were compatible between them (P = 0.119). The higher baPWV predicted the presence of AD, VaD, MIX and MCI with the odds ratio of 6.46, 8.74, 6.16 and 6.19, respectively. In contrast, there were no difference in baPWV among three different types of dementia (P = 0.191). The linear relationship between baPWV and MMSE was observed in the elderly with MMSE ≥ 23 (R = 0.452, P = 0.033), while it was not in dementia patients (MMSE < 23). CONCLUSIONS: The findings suggest that MCI and dementia patients have stiffer arteries as compared with age-matched local residents, although global cognitive function may be comparable between MCI and the local residents.

Does Cardiac Function Affect Cerebral Blood Flow Regulation?

Many previous studies indicate that heart failure (HF) increases the risk of cognitive dysfunction and stroke, showing the logic that several physiological factors associated with cardiac dysfunctions affect homeostasis in the cerebral circulation. In the chronic process of HF patients, it is suggested that reduced cerebral blood flow (CBF) and abnormal auto-regulation might result in impaired perfusion, metabolic insufficiency, and regional or global structural deteriorations in the brain. However, the mechanism underlying HF-induced brain disease remains unclear. Cardiac dysfunction in patients with HF or HF-induced several physiological abnormalities may cause brain dysfunction. Possible physiological factors should be considered for future studies to prevent brain disease as well as cardiovascular dysfunction in patients with HF.

Influence of head-up tile and lower body negative pressure on the internal jugular vein.

Head-up tilt (HUT)-induced gravitational stress causes collapse of the internal jugular vein (IJV) by decreasing central blood volume and through mass-effect from the surrounding tissues. Besides HUT, lower body negative pressure (LBNP) is used to stimulate orthostatic stress as an experimental model. Compared to HUT, LBNP has less of a gravitational effect because of the supine position; therefore, we hypothesized that LBNP causes less of a decrease in the cross-sectional area of the IJV compared to HUT. We tested the hypothesis by measuring the cross-sectional area of the IJV using B-mode ultrasonography while inducing orthostatic stress at levels of -40 mmHg LBNP and 60° HUT. The cross-sectional area of IJV decreased from the resting baseline during both LBNP and HUT trials, but the LBNP-induced decrease in the cross-sectional area of IJV was smaller than that of HUT (right, -45% ± 49% vs. -78% ± 27%, p = 0.008; left, -49% ± 27% vs. -78% ± 20%, p = 0.004). Since changes in venous outflow may affect cerebral arterial circulation, the findings of the present study suggest that orthostatic stress induced by different techniques modulates cerebral blood flow regulation through its effect on venous outflow.

Clinical impact of noncontrast percutaneous coronary intervention in patients with acute coronary syndrome.

PURPOSE: Contrast-induced acute kidney injury (CI-AKI) is one of the common serious complications of percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). This study aimed to assess the significance of noncontrast strategy in the setting of ACS. METHODS: CI-AKI was defined as an increase in serum creatinine of ?0.5 mg/dL or ?1.25 times from the baseline. One-year worsening renal function (WRF) was defined as an increase of ?0.3mg/dL in serum creatinine from the baseline after PCI. RESULTS: Of 250 ACS patients, 81 were treated with noncontrast PCI. The average doses of contrast medium in the noncontrast and conventional groups were 17 (9?22) ml and 150 (120?200) ml, respectively. CI-AKI was observed in 4 patients (5%) in the noncontrast group and 29 patients (17%) in the conventional group. Noncontrast PCI was associated with a lower incidence of CI-AKI (adjusted odds ratio, 0.26;95% confidence interval [CI], 0.08?0.82). The bootstrap method and inverse probability weighting led to similar results. CI-AKI was associated with a higher incidence of 1-year WRF (adjusted hazard ratio, 2.30;95% CI, 1.12?4.69), while noncontrast PCI was not. CONCLUSIONS: Noncontrast PCI was associated with the lower incidence of CI-AKI in ACS patients. J. Med. Invest. 69 : 57-64, February, 2022.

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.

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.

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.

Effects on physical performance of high protein intake for critically ill adult patients admitted to the intensive care unit: A retrospective propensity-matched analysis.

OBJECTIVES: This study aimed to examine the effects of protein intake on physical performance in critically ill adult patients admitted to the intensive care unit (ICU). METHODS: This was a retrospective cohort study of adult patients mechanically ventilated over 48 h in the ICU who were classified into two groups based on the amount of protein intake: >1.0 g/kg/d (high-protein group) or <1.0 g/kg/d (low-protein group). After adjustment for possible confounding factors with propensity score matching, we compared muscle strength at the time of ICU discharge and the rate of recovery to independent walking between the two groups. RESULTS: One-to-one propensity score matching created 20 pairs. The high-protein group had significantly higher muscle strength than the low-protein group at the time of discharge from the ICU. In addition, the rate of recovery to independent walking before hospital discharge was higher in the high-protein group than the low-protein group (16 of 20 patients [80%] vs. 8 of 20 patients [40%]; P = 0.032). CONCLUSIONS: Our findings indicate that a sufficient amount of protein intake may lead to a higher rate of recovery to independent walking before discharge from the hospital in critically ill patients admitted to the ICU. This finding is likely related to preserved muscle strength at the time of ICU discharge.

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.

Clinical impact of red blood cell transfusion on adverse clinical events in acute heart failure patients with anemia.

BACKGROUND: Anemia has been recognized as an important comorbidity in patients with acute heart failure (AHF) and is associated with adverse clinical events. However, the clinical impact of red blood cell (RBC) transfusion in such patients is unclear. METHOD: This study was a retrospective single-center registry including AHF patients admitted to Kyorin University Hospital between 2007 and 2014. Anemia was defined as a hemoglobin level < 130 g/L in males or < 120 g/L in females. Those with major bleeding with a fall in hemoglobin concentration of >20 g/L were excluded. AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were evaluated. RESULTS: Of 501 AHF patients, 38 were excluded owing to major bleeding; finally, 463 (age, 77 ± 11 years; males, 58%) were evaluated. RBC transfusion during hospitalization was performed in 112 patients (24%). Hemoglobin level on admission was 105 ± 16 g/L (transfusion, 89 ± 17 g/L; no transfusion, 110 ± 12 g/L; p < 0.001). AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were observed in 46 (10%), 16 (3%), and 121 (26%) patients, respectively. Univariate Cox regression analysis demonstrated that RBC transfusion was not associated with AHF readmission at 3 months (hazard ratio: 0.80; 95% confidence interval: 0.39-1.66) The association did not differ at any hemoglobin concentration or left ventricular ejection fraction value. Multivariate Cox regression analysis revealed similar results. Furthermore, RBC transfusion was not correlated with in-hospital and 2-year all-cause mortality. CONCLUSIONS: RBC transfusion was not associated with AHF readmission or all-cause mortality.

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.

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.

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.

Plasma matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs and aging and lifelong exercise adaptations in ventricular and arterial stiffness.

The age-associated increase in cardiac and central arterial stiffness is attenuated with lifelong (>25 years) endurance exercise in a dose-dependent manner. Remodelling of the extracellular matrix of cardiovascular structures may underpin these lifelong exercise adaptations in structural stiffness. The primary aim was to examine whether matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) levels are associated with aging and lifelong exercise-related changes in cardiac and central arterial stiffness. Plasma MMPs and TIMPs, left ventricular (LV) (LV stiffness constant) and central arterial stiffness (pulse wave velocity) were examined in healthy adults stratified into five groups based on age and lifelong weekly exercise frequency: (1) young sedentary adults (28-50 years), and older adults (>60 years) who had performed either: (a) sedentary (0-1 sessions/week), (b) casual (2-3 sessions/week), (c) committed (4-5 sessions/week) or (d) athletic (≥6 sessions/week) frequency of exercise. MMP-1 was significantly lower in young compared to older sedentary (p = 0.049). Except for TIMP-2 (p = 0.018 versus committed) and the ratio of MMP-2/TIMP-4 (p = 0.047 versus committed), MMP and TIMP expression was not significantly different in lifelong exercise groups (≥casual) compared to the older sedentary group. MMP-1, -3 had a weak positive relationship with central PWV (r = 0.17-0.25, p ≤ 0.050) but there were no significant relationships between MMPs or TIMPs and LV stiffness constant (p ≥ 0.148). In conclusion, there was not a clear or consistent difference in plasma MMPs and TIMPs with lifelong exercise dose despite exhibiting lower cardiovascular stiffness at the highest exercise levels.

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.

Relationship between cerebral blood flow estimated by transcranial Doppler ultrasound and single-photon emission computed tomography in elderly people with dementia.

Transcranial Doppler (TCD) ultrasonography is a noninvasive technique allowing continuous recording of cerebral blood flow (CBF) velocity. However, it is unclear whether the CBF estimated by TCD would be reliable for the comparison between individuals. The present study aimed to clarify the relationship between middle cerebral artery blood flow (MCA BF) measured by TCD and regional and total CBF measured by single-photon emission computed tomography (SPECT-CBF) with a quantification software program, a three-dimensional stereotaxic region of interest template. We recruited 91 elderly subjects with and without dementia. MCA blood flow velocity (MCA V) and middle cerebral artery cross-sectional area (AM) were measured by TCD and magnetic resonance angiography, respectively. MCA BF was calculated by the product of MCA V and AM. Diastolic or mean MCA V and MCA BF were significantly correlated with SPECT-CBF in several segments. Interestingly, the correlation coefficient in the temporal segment of SPECT-CBF was higher than those of the other segments. Moreover, correlations between MCA BF and SPECT-CBF were stronger as compared with those between MCA V and SPECT-CBF. These findings suggest that both mean MCA V and MCA BF with TCD ultrasonography would be useful for CBF comparison between individuals especially in the temporal region, although estimated blood flow with arterial area seems to be better than using simple flow velocity. NEW & NOTEWORTHY Correlations between middle cerebral artery blood flow (MCA BF) calculated by the product of MCA blood flow velocity (MCA V) and middle cerebral artery cross-sectional area and regional and total cerebral blood flow (CBF) measured by single-photon emission computed tomography (SPECT-CBF) were stronger as compared with those between MCA V and SPECT-CBF. These findings suggest that both mean MCA V and MCA BF would be useful for CBF comparison between individuals although estimated blood flow with arterial area seems to be better than using simple flow velocity.