Benjamin D Levine

Brigham and Women's Hospital , Boston, MA, USA

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Publications (140)718.43 Total impact

  • Article: Cerebral vasomotor reactivity during hypo- and hypercapnia in sedentary elderly and Masters athletes.
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    ABSTRACT: Physical activity may influence cerebrovascular function. The objective of this study was to determine the impact of life-long aerobic exercise training on cerebral vasomotor reactivity (CVMR) to changes in end-tidal CO2 (EtCO2) in older adults. Eleven sedentary young (SY, 27±5 years), 10 sedentary elderly (SE, 72±4 years), and 11 Masters athletes (MA, 72±6 years) underwent the measurements of cerebral blood flow velocity (CBFV), arterial blood pressure, and EtCO2 during hypocapnic hyperventilation and hypercapnic rebreathing. Baseline CBFV was lower in SE and MA than in SY while no difference was observed between SE and MA. During hypocapnia, CVMR was lower in SE and MA compared with SY (1.87±0.42 and 1.47±0.21 vs. 2.18±0.28 CBFV%/mm Hg, P<0.05) while being lowest in MA among all groups (P<0.05). In response to hypercapnia, SE and MA exhibited greater CVMR than SY (6.00±0.94 and 6.67±1.09 vs. 3.70±1.08 CBFV1%/mm Hg, P<0.05) while no difference was observed between SE and MA. A negative linear correlation between hypo- and hypercapnic CVMR (R(2)=0.37, P<0.001) was observed across all groups. Advanced age was associated with lower resting CBFV and lower hypocapnic but greater hypercapnic CVMR. However, life-long aerobic exercise training appears to have minimal effects on these age-related differences in cerebral hemodynamics.Journal of Cerebral Blood Flow & Metabolism advance online publication, 17 April 2013; doi:10.1038/jcbfm.2013.66.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 04/2013; · 5.46 Impact Factor
  • Article: Day/Night Variability in Blood Pressure: Influence of Posture and Physical Activity.
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    ABSTRACT: BACKGROUND Blood pressure (BP) is highest during the day and lowest at night. Absence of this rhythm is a predictor of cardiovascular morbidity and mortality. Contributions of changes in posture and physical activity to the 24-hour day/night rhythm in BP are not well understood. We hypothesized that postural changes and physical activity contribute substantially to the day/night rhythm in BP.METHODS Fourteen healthy, sedentary, nonobese, normotensive men (aged 19-50 years) each completed an ambulatory and a bed rest condition during which BP was measured every 30-60 minutes for 24 hours. When ambulatory, subjects followed their usual routines without restrictions to capture the "normal" condition. During bed rest, subjects were constantly confined to bed in a 6-degree head-down position; therefore posture was constant, and physical activity was minimized. Two subjects were excluded from analysis because of irregular sleep timing.RESULTSThe systolic and diastolic BP reduction during the sleep period was similar in ambulatory (-11±2mmHg/-8±1mmHg) and bed rest conditions (-8±3mmHg/-4±2mmHg; P = 0.38/P = 0.12). The morning surge in diastolic BP was attenuated during bed rest (P = 0.001), and there was a statistical trend for the same effect in systolic BP (P = 0.06).CONCLUSIONSA substantial proportion of the 24-hour BP rhythm remained during bed rest, indicating that typical daily changes in posture and/or physical activity do not entirely explain 24-hour BP variation under normal ambulatory conditions. However, the morning BP increase was attenuated during bed rest, suggesting that the adoption of an upright posture and/or physical activity in the morning contributes to the morning BP surge.
    American Journal of Hypertension 03/2013; · 3.18 Impact Factor
  • Article: Life-long aerobic exercise preserved baseline cerebral blood flow but reduced vascular reactivity to CO2.
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    ABSTRACT: PURPOSE: To examine the potential benefits of life-long aerobic exercise on brain health, in particular cerebrovascular function. MATERIALS AND METHODS: Ten Masters athletes (MA) (seven males, three females; 74.5 ± 5.8 years) and 10 sedentary elderly individuals (SE) (eight males, two females; 75.4 ± 5.6 years) were recruited and baseline cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) to CO2 were measured on a 3T MRI scanner. Nine sedentary young subjects were also recruited to serve as a control group to verify the age effect. RESULTS: When compared to the SE group, MA showed higher CBF in posterior cingulate cortex/precuneus, which are key regions of the default-mode-network and are known to be highly sensitive to age and dementia. CVR in the MA brains were paradoxically lower than that in SE. This effect was present throughout the brain. Within the MA group, individuals with higher VO2max had an even lower CVR, suggesting a dose-response relationship. CONCLUSION: Life-long aerobic exercise preserved blood supply in the brain's default-mode-network against age-related degradation. On the other hand, its impact on the cerebral vascular system seems to be characterized by a dampening of CO2 reactivity, possibly because of desensitization effects due to a higher lifetime exposure. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 03/2013; · 2.70 Impact Factor
  • Article: Response to creatine kinase and pressor response to orthostatic tolerance.
    Yoshiyuki Okada, Benjamin D Levine, Qi Fu
    Hypertension 02/2013; 61(2):e24. · 6.21 Impact Factor
  • Article: Sympathetic Neural and Hemodynamic Responses to Upright Tilt in Patients with Pulsatile and Non-Pulsatile Left Ventricular Assist Devices.
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    ABSTRACT: BACKGROUND: -Left ventricular assist devices (LVADs) are now widely accepted as an option for patients with advanced heart failure. First generation devices were pulsatile, but they had poor longevity and durability. Newer generation devices are non-pulsatile and more durable, but remain associated with an increased risk of stroke and hypertension. Moreover, little is understood about the physiological effects of the chronic absence of pulsatile flow in humans. METHODS AND RESULTS: -We evaluated patients with pulsatile (n=6) and non-pulsatile (n=11) LVADs and healthy controls (n=9) during head-up tilt (HUT) while measuring hemodynamics and muscle sympathetic nerve activity (MSNA). Patients with non-pulsatile devices had markedly elevated supine and upright MSNA (mean±SD: 43±15 supine and 60±21 bursts/min at 60° HUT) compared to patients with pulsatile devices (24±7 and 35±8 bursts/min; P<0.01) and controls (11±6 and 31±6 bursts/min; P<0.01); however, MSNA was not different between patients with pulsatile flow and controls (P=0.34). Heart rate, mean arterial pressure, and total peripheral resistance were greater, while cardiac output was smaller, in LVAD patients compared to controls in both supine and upright postures. However, these hemodynamic variables were not significantly different between patients with pulsatile and non-pulsatile flow. CONCLUSIONS: -Heart failure patients with continuous, non-pulsatile LVADs have marked sympathetic activation, which is likely due, at least in part, to baroreceptor unloading. We speculate that such chronic sympathetic activation may contribute to, or worsen end-organ diseases, and reduce the possibility of ventricular recovery. Strategies to provide some degree of arterial pulsatility, even in continuous flow LVADs may be necessary to achieve optimal outcomes in these patients.
    Circulation Heart Failure 12/2012; · 6.29 Impact Factor
  • Article: Cardiovascular effects of 1 year of progressive endurance exercise training in patients with heart failure with preserved ejection fraction.
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    ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) is a disease of the elderly with cardiovascular stiffening and reduced exercise capacity. Exercise training appears to improve exercise capacity and cardiovascular function in heart failure with reduced ejection fraction. However, it is unclear whether exercise training could improve cardiovascular stiffness, exercise capacity, and ventricular-arterial coupling in HFpEF. Eleven HFpEF patients and 13 healthy controls underwent invasive measurements with right heart catheterization to define Starling and left ventricular (LV) pressure-volume curves; secondary functional outcomes included Doppler echocardiography, arterial stiffness, cardiopulmonary exercise testing with cardiac output measurement, and ventricular-arterial coupling assessed by the dynamic Starling mechanism. Seven of 11 HFpEF patients (74.9 ± 6 years; 3 men/4 women) completed 1 year of endurance training followed by repeat measurements. Pulmonary capillary wedge pressures and LV end-diastolic volumes were measured at baseline during decreased and increased cardiac filling. LV compliance was assessed by the slope of the pressure-volume curve. Beat-to-beat LV end-diastolic pressure (estimated from pulmonary arterial diastolic pressure) and stroke volume index were obtained, and spectral transfer function analysis was used to assess the dynamic Starling mechanism. Before training, HFpEF patients had reduced exercise capacity, distensibility and dynamic Starling mechanism but similar LV compliance and end-diastolic volumes compared to controls albeit with elevated filling pressure and increased wall stress. One year of training had little effect on LV compliance and volumes, arterial stiffness, exercise capacity or ventricular-arterial coupling. Contrary to our hypothesis, 1 year of endurance training failed to impart favorable effects on cardiovascular stiffness or function in HFpEF.
    American heart journal 12/2012; 164(6):869-77. · 4.65 Impact Factor
  • Article: Hemodynamic Responses to Rapid Saline Loading: The Impact of Age, Sex, and Heart Failure.
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    ABSTRACT: BACKGROUND: Hemodynamic assessment after volume challenge has been proposed as a way to identify heart failure with preserved ejection fraction (HFpEF). However, the normal hemodynamic response to a volume challenge and how age and sex affect this relationship remains unknown. METHODS AND RESULTS: Sixty healthy subjects underwent right heart catheterization to measure age- and sex-related normative responses of pulmonary capillary wedge pressure (PCWP) and mean pulmonary arterial pressure (MPAP) to volume loading with rapid saline infusion (100-200 ml/min). Hemodynamic responses to saline infusion in HFpEF (n=11) were then compared to healthy young (<50yrs) and older-aged (≥50yrs) subjects. In healthy subjects, PCWP increased from 10±2 to 16±3 mmHg after ~1L and to 20±3 mmHg after ~2L of saline infusion. Older women displayed a steeper increase in PCWP relative to volume infused (16±4mmHg·L(-1)·m(2)) than the other 3 groups (p≤0.019). Saline infusion resulted in a greater increase in MPAP relative to cardiac output in women compared to men, irrespective of age. Subjects with HFpEF exhibited a steeper increase in PCWP relative to infused volume (25±12 mmHg·L(-17)·m(2)) than healthy young and older subjects (p≤0.005). CONCLUSIONS: Filling pressures rise significantly with volume loading, even in normal volunteers. Older women and patients with HFpEF exhibit the largest increases in PCWP and MPAP.
    Circulation 11/2012; · 14.74 Impact Factor
  • Article: The Effect of Age-related Differences in Body Size and Composition on Cardiovascular Determinants of VO2max.
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    ABSTRACT: BACKGROUND: A reduction in maximal stroke volume (SV(max)) and total blood volume (TBV) has been hypothesized to contribute to the decline in maximal oxygen uptake (VO(2)max) with healthy aging. However, these variables have rarely been collected simultaneously in a board age range to support or refute this hypothesis. It is also unclear to what extent scaling size-related cardiovascular determinants of VO(2)max affects the interpretation of age-related differences. METHODS: A retrospective analysis of VO(2)max, maximal cardiac output (Q(C)max), TBV, and body composition including fat-free mass (FFM) in 95 (51% M) healthy adults ranging from 19-86 years. RESULTS: Absolute and indexed VO(2)max, Q(C)max, and maximal heart rate decreased in both sexes with age (p ≤ .031). SV(max) declined with age when scaled to total body mass or body surface area (p ≤ .047) but not when expressed in absolute levels (p = .120) or relative to FFM (p = .464). Absolute and indexed TBVs (mL/kg; mL/m(2)) were not significantly affected by age but increased with age in both sexes when scaled to FFM (p ≤ .013). A lower arteriovenous oxygen difference (a-vO(2)diff) contributed to the reduction in VO(2)max with age in treadmill exercisers (p = .004) but not in the entire cohort (p = .128). CONCLUSION: These results suggest (a) a reduction in absolute SV(max), and TBV do not contribute substantially to the age-related reduction in VO(2)max, which instead results from a smaller Q(C)max due to a lower maximal heart rate, and (b) body composition scaling methods should be used to accurately describe the effect of aging on physical function and cardiovascular variables.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 11/2012; · 4.60 Impact Factor
  • Article: Cardiac Baroreflex Function and Dynamic Cerebral Autoregulation In Elderly Masters Athletes.
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    ABSTRACT: Purpose: Cerebral blood flow (CBF) is maintained stable through combined effects of blood pressure (BP) regulation and cerebral autoregulation. Previous studies suggest that aerobic exercise training improves cardiac baroreflex function and beneficially affects BP regulation, but may negatively affect cerebral autoregulation. The purpose of this study was to reveal the impact of lifelong exercise on cardiac baroreflex function and dynamic cerebral autoregulation (dCA) in older adults. Methods: Eleven Masters athletes (MA) (8 males, 3 females, mean age 73±6 yrs, aerobic training >15 yrs) and 12 healthy sedentary elderly (SE) (7 males, 5 females, mean age 71±6 yrs) participated in this study. BP, CBF velocity (CBFV) and heart rate were measured during resting conditions and repeated sit-stand maneuvers to enhance BP variability. Baroreflex gain was assessed using transfer function analysis of spontaneous changes in systolic BP and R-R interval in the low frequency range (0.05-0.15 Hz). dCA was assessed during sit-stand induced changes in mean BP and CBFV at 0.05 Hz (10s sit, 10s stand). Results: Cardiac baroreflex gain was more than doubled in MA compared to SE (MA: 7.69±7.95, SE: 3.18±1.29, ms/mmHg, P=0.018). However, dCA was similar in the two groups (normalized gain: MA: 1.50±0.56, SE: 1.56±0.42, %CBFV/mmHg, P=0.792). Conclusion: These findings suggest that lifelong exercise improves cardiac baroreflex function, but does not alter dCA. Thus, beneficial effects of exercise training on BP regulation can be achieved in older adults without compromising dynamic regulation of CBF.
    Journal of Applied Physiology 11/2012; · 3.75 Impact Factor
  • Article: The Importance of the Muscle and Ventilatory Blood Pumps During Exercise in Patients Without a Subpulmonary Ventricle (Fontan Operation).
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    ABSTRACT: OBJECTIVES: The aim of this study was to determine the relative contribution of the muscle and ventilatory pumps to stroke volume in patients without a subpulmonic ventricle. BACKGROUND: In patients with Fontan circulation, it is unclear how venous return is augmented to increase stroke volume and cardiac output during exercise. METHODS: Cardiac output (acetylene rebreathing), heart rate (electrocardiography), oxygen uptake (Douglas bag technique), and ventilation were measured in 9 patients age 15.8 ± 6 years at 6.1 ± 1.8 years after Fontan operation and 8 matched controls. Data were obtained at rest, after 3 min of steady-state exercise (Ex) on a cycle ergometer at 50% of individual working capacity, during unloaded cycling at 0 W (muscle pump alone), during unloaded cycling with isocapnic hyperpnea (muscle and ventilatory pump), during Ex plus an inspiratory load of 12.8 ± 1.5 cm water, and during Ex plus an expiratory load of 12.8 ± 1.6 cm water. RESULTS: In Fontan patients, the largest increases in stroke volume and stroke volume index were during zero-resistance cycling. An additional increase with submaximal exercise occurred in controls only. During Ex plus expiratory load, stroke volume indexes were reduced to baseline, non-exercise levels in Fontan patients, without significant changes in controls. CONCLUSIONS: With Fontan circulation increases in cardiac output and stroke volume during Ex were due to the muscle pump, with a small additional contribution by the ventilatory pump. An increase in intrathoracic pressure played a deleterious role in Fontan circulation by decreasing systemic venous return and stroke volume.
    Journal of the American College of Cardiology 10/2012; · 14.16 Impact Factor
  • Article: Left atrial structure and function and clinical outcomes in the general population.
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    ABSTRACT: AimsLeft atrial (LA) structural and functional abnormalities may be subclinical phenotypes, which identify individuals at increased risk of adverse outcomes.Methods and resultsMaximum LA volume (LAmax) and LA emptying fraction (LAEF) were measured via cardiac magnetic resonance imaging in 1802 participants in the Dallas Heart Study. The associations of LAEF and LAmax indexed to body surface area (LAmax/BSA) with traditional risk factors, natriuretic peptide levels, and left ventricular (LV) structure [end-diastolic volume (EDV) and concentricity(0.67) (mass/EDV(0.67))] and function (ejection fraction) were assessed using linear regression analysis. The incremental prognostic value of LAmax/BSA and LAEF beyond traditional risk factors, LV ejection fraction, and LV mass was assessed using the Cox proportional-hazards model. Both increasing LAmax/BSA and decreasing LAEF were associated with hypertension and natriuretic peptide levels (P < 0.05 for all). In multivariable analysis, LAmax/BSA was most strongly associated with LV end-diastolic volume/BSA, while LAEF was strongly associated with LV ejection fraction and concentricity(0.67). During a median follow-up period of 8.1 years, there were 81 total deaths. Decreasing LAEF [hazard ratio (HR) per 1 standard deviation (SD) (8.0%): 1.56 (1.32-1.87)] but not increasing LAmax/BSA [HR per 1 SD (8.6 mL/m(2)): 1.14 (0.97-1.34)] was independently associated with mortality. Furthermore, the addition of LAEF to a model adjusting Framingham risk score, diabetes, race, LV mass, and ejection fraction improved the c-statistic (c-statistics: 0.78 vs. 0.77; P < 0.05, respectively), whereas the addition of LAmax/BSA did not (c-statistics: 0.76, P = 0.20).Conclusion In the general population, both LAmax/BSA and LAEF are important subclinical phenotypes but LAEF is superior and incremental to LAmax/BSA.
    European Heart Journal 07/2012; · 10.48 Impact Factor
  • Article: Elderly blacks have a blunted sympathetic neural responsiveness but greater pressor response to orthostasis than elderly whites.
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    ABSTRACT: Neural control of blood pressure (BP) has been reported to differ between young blacks and whites. We hypothesized that elderly blacks have enhanced sympathetic neural responses during orthostasis compared with elderly whites. Muscle sympathetic nerve activity, arm-cuff BP, and heart rate were recorded continuously, and cardiac output, stroke volume, and total peripheral resistance were measured intermittently during supine and 5-minute 60° upright tilt in 10 blacks (65 [SD, 4] years; 4 women) and 20 whites (68 [6] years; 8 women). We found that muscle sympathetic nerve activity burst frequency was similar between blacks and whites in the supine position (44 [10] versus 42 [7] bursts per minute) and during upright tilt (59 [11] versus 60 [9] bursts per minute; P=0.846 for race, P<0.001 for posture, and P=0.622 for interaction). However, upright total muscle sympathetic nerve activity was smaller in blacks than in whites (162 [39] versus 243 [112]%; P=0.003). Systolic BP, heart rate, cardiac output, and stroke volume were not different between groups. Diastolic BP was similar in the supine position, increased in all of the subjects during tilting; upright diastolic BP was greater in blacks than in whites (80 [10] versus 71 [7] mmHg; P=0.008). Total peripheral resistance did not differ between blacks and whites in the supine position or during upright tilt (P=0.354 for race, P<0.001 for posture, P=0.825 for interaction). Thus, elderly blacks have a blunted sympathetic neural responsiveness but enhanced pressor response to orthostasis compared with elderly whites, which may be attributable to an augmented sympathetic vascular transduction and/or nonadrenergic vasoconstrictor mechanisms (ie, angiotensin II or the venoarteriolar response).
    Hypertension 07/2012; 60(3):842-8. · 6.21 Impact Factor
  • Article: Sympathetic activation during early pregnancy in humans.
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    ABSTRACT: 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.
    The Journal of Physiology 06/2012; 590(Pt 15):3535-43. · 4.72 Impact Factor
  • Article: Effect of healthy aging on left ventricular relaxation and diastolic suction.
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    ABSTRACT: Doppler ultrasound measures of left ventricular (LV) active relaxation and diastolic suction are slowed with healthy aging. It is unclear to what extent these changes are related to alterations in intrinsic LV properties and/or cardiovascular loading conditions. Seventy carefully screened individuals (38 female, 32 male) aged 21-77 were recruited into four age groups (young: <35; early middle age: 35-49; late middle age: 50-64 and seniors: ≥65 yr). Pulmonary capillary wedge pressure (PCWP), stroke volume, LV end-diastolic volume, and Doppler measures of LV diastolic filling were collected at multiple loading conditions, including supine baseline, lower body negative pressure to reduce LV filling, and saline infusion to increase LV filling. LV mass, supine PCWP, and heart rate were not affected significantly by aging. Measures of LV relaxation, including isovolumic relaxation time and the time constant of isovolumic pressure decay increased progressively, whereas peak early mitral annular longitudinal velocity decreased with advancing age (P < 0.001). The propagation velocity of early mitral inflow, a noninvasive measure of LV suction, decreased with aging with the greatest reduction in seniors (P < 0.001). Age-related differences in LV relaxation and diastolic suction were not attenuated significantly when PCWP was increased in older subjects or reduced in the younger subjects. There is an early slowing of LV relaxation and diastolic suction beginning in early middle age, with the greatest reduction observed in seniors. Because age-related differences in LV dynamic diastolic filling parameters were not diminished significantly with significant changes in LV loading conditions, a decline in ventricular relaxation is likely responsible for the alterations in LV diastolic filling with senescence.
    AJP Heart and Circulatory Physiology 06/2012; 303(3):H315-22. · 3.71 Impact Factor
  • Article: Syncope in the athletic patient.
    Jeffrey L Hastings, Benjamin D Levine
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    ABSTRACT: Syncope is a common but concerning event in athletic patients. As such, efforts must be made to distinguish presyncope from syncope with a critical distinction of syncope during exercise and postexercise syncope. Syncope most often occurs just after exercise and is usually benign; however, syncope during exercise may be a sign of pathologic structural or electrical cardiac issues. Solving this diagnostic puzzle mandates a detailed history and examination frequently augmented with diagnostic testing and imaging studies. Recommendations for treatment and potential restriction from activity also present challenging decisions to the health care provider.
    Progress in cardiovascular diseases 03/2012; 54(5):438-44. · 4.25 Impact Factor
  • Article: Effect of rowing ergometry and oral volume loading on cardiovascular structure and function during bed rest.
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    ABSTRACT: This study examined the effectiveness of a short-duration but high-intensity exercise countermeasure in combination with a novel oral volume load in preventing bed rest deconditioning and orthostatic intolerance. Bed rest reduces work capacity and orthostatic tolerance due in part to cardiac atrophy and decreased stroke volume. Twenty seven healthy subjects completed 5 wk of -6 degree head down bed rest. Eighteen were randomized to daily rowing ergometry and biweekly strength training while nine remained sedentary. Measurements included cardiac mass, invasive pressure-volume relations, maximal upright exercise capacity, and orthostatic tolerance. Before post-bed rest orthostatic tolerance and exercise testing, nine exercise subjects were given 2 days of fludrocortisone and increased salt. Sedentary bed rest led to cardiac atrophy (125 ± 23 vs. 115 ± 20 g; P < 0.001); however, exercise preserved cardiac mass (128 ± 38 vs. 137 ± 34 g; P = 0.002). Exercise training preserved left ventricular chamber compliance, whereas sedentary bed rest increased stiffness (180 ± 170%, P = 0.032). Orthostatic tolerance was preserved only when exercise was combined with volume loading (-10 ± 22%, P = 0.169) but not with exercise (-14 ± 43%, P = 0.047) or sedentary bed rest (-24 ± 26%, P = 0.035) alone. Rowing and supplemental strength training prevent cardiovascular deconditioning during prolonged bed rest. When combined with an oral volume load, orthostatic tolerance is also preserved. This combined countermeasure may be an ideal strategy for prolonged spaceflight, or patients with orthostatic intolerance.
    Journal of Applied Physiology 02/2012; 112(10):1735-43. · 3.75 Impact Factor
  • Article: Cardiac output and sympathetic vasoconstrictor responses during upright tilt to presyncope in healthy humans.
    Qi Fu, Bart Verheyden, Wouter Wieling, Benjamin D Levine
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    ABSTRACT: Syncope is a common clinical condition occurring even in healthy people without manifest cardiovascular disease. The purpose of this study was to determine the role of cardiac output and sympathetic vasoconstriction in neurally mediated (pre)syncope. Twenty-five subjects (age 15–51) with no history of recurrent syncope but who had presyncope during 60 deg upright tilt were studied; 10 matched controls who completed 45 min tilting were analysed retrospectively. Beat-to-beat haemodynamics (Modelflow), muscle sympathetic nerve activity (MSNA) and sympathetic baroreflex sensitivity (MSNA–diastolic pressure relation) were measured. MSNA, haemodynamic responses and baroreflex sensitivity during early tilting were not different between presyncopal subjects and controls. Hypotension was mediated by a drop in cardiac output in all presyncopal subjects, accompanied by a decrease in total peripheral resistance in 16 of them (64%, group A). In the other 9 subjects, total peripheral resistance was well maintained even at presyncope (36%, group B). Cardiac output was smaller (3.26 ± 0.34 (SEM) vs. 5.02 ± 0.40 l min(−1), P = 0.01), while total peripheral resistance was greater (1327 ± 117 vs. 903 ± 80 dyn s cm(−5), P < 0.01) in group B than group A at presyncope. The steeper fall in cardiac output in group B was due to a drop in heart rate. MSNA decreased rapidly at presyncope after the onset of hypotension. Thus, a moderate fall in cardiac output with coincident vasodilatation or a marked fall in cardiac output with no changes in peripheral vascular resistance may contribute to (pre)syncope. However, an intrinsic impairment of vasomotor responsiveness and sympathetic baroreflex function is not the cause of neurally mediated (pre)syncope in this population.
    The Journal of Physiology 02/2012; 590(Pt 8):1839-48. · 4.72 Impact Factor
  • Article: Effect of ageing on left ventricular compliance and distensibility in healthy sedentary humans.
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    ABSTRACT: 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; 21–77 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): 21–34 years, G(35−49): 35–49 years, G5(0−64): 50–64 years, G(≥65): ≥65 years. All subjects underwent invasive haemodynamic measurements with right heart catheterization to define Starling and left ventricular (LV) pressure–volume 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 pressure–volume 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, pressure–volume 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.
    The Journal of Physiology 02/2012; 590(Pt 8):1871-80. · 4.72 Impact Factor
  • Article: Effect of exercise training on biologic vascular age in healthy seniors.
    Shigeki Shibata, Benjamin D Levine
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    ABSTRACT: 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.
    AJP Heart and Circulatory Physiology 01/2012; 302(6):H1340-6. · 3.71 Impact Factor
  • Article: Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction.
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    ABSTRACT: Peak oxygen uptake (VO(2)) is diminished in patients with heart failure with preserved ejection fraction (HFpEF) suggesting impaired cardiac reserve. To test this hypothesis, we assessed the haemodynamic response to exercise in HFpEF patients. Eleven HFpEF patients (73 ± 7 years, 7 females/4 males) and 13 healthy controls (70 ± 4 years, 6 females/7 males) were studied during submaximal and maximal exercise. The cardiac output (Q(c), acetylene rebreathing) response to exercise was determined from linear regression of Q(c) and VO(2) (Douglas bags) at rest, ∼30% and ∼60% of peak VO(2), and maximal exercise. Peak VO(2) was lower in HFpEF patients than in controls (13.7 ± 3.4 vs. 21.6 ± 3.6 mL/kg/min; P < 0.001), while indices of cardiac reserve were not statistically different: peak cardiac power output [CPO = Q(c) × mean arterial pressure (MAP); HFpEF 1790 ± 509 vs. controls 2119 ± 581 L/mmHg/min; P = 0.20]; peak stroke work [SW = stroke volume (SV) × MAP; HFpEF 13 429 ± 2269 vs. controls 13 200 ± 3610 mL/mmHg; P = 0.80]. The ΔQ(c)/ΔVO(2) slope was abnormally elevated in HFpEF patients vs. controls (11.2 ±3.6 vs. 8.3 ± 1.5; P = 0.015). Contrary to our hypothesis, cardiac reserve is not significantly impaired in well-compensated outpatients with HFpEF. The abnormal haemodynamic response to exercise (decreased peak VO(2), increased ΔQ(c)/ΔVO(2) slope) is similar to that observed in patients with mitochondrial myopathies, suggesting an element of impaired skeletal muscle oxidative metabolism. This impairment may limit functional capacity by two mechanisms: (i) premature skeletal muscle fatigue and (ii) metabolic signals to increase the cardiac output response to exercise which may be poorly tolerated by a left ventricle with impaired diastolic function.
    European Journal of Heart Failure 12/2011; 13(12):1296-304. · 4.90 Impact Factor

Institutions

  • 2013
    • Brigham and Women's Hospital
      • Division of Sleep Medicine
      Boston, MA, USA
  • 2002–2013
    • University of Texas Southwestern Medical Center
      • • Institute for Exercise and Environmental Medicine
      • • Department of Internal Medicine
      Dallas, TX, USA
    • Pennsylvania State University
      • Department of Kinesiology
      University Park, MD, USA
    • Michigan Technological University
      • Department of Biomedical Engineering
      Houghton, MI, USA
  • 2007–2012
    • Texas Health Resources
      Southlake, TX, USA
    • University of Colorado Colorado Springs
      Colorado Springs, CO, USA
  • 2011
    • John Peter Smith Hospital
      Fort Worth, TX, USA
  • 2010–2011
    • Indiana University Bloomington
      • Department of Kinesiology
      Bloomington, IN, USA
  • 2009
    • New York Presbyterian Hospital
      New York City, NY, USA
    • Radboud Universiteit Nijmegen
      Nijmegen, Provincie Gelderland, Netherlands
  • 2008
    • VU University Amsterdam
      • Faculty of Human Movement Sciences
      Amsterdam, North Holland, Netherlands
  • 2006
    • Qinghai University
      Xining, Qinghai Sheng, China
    • Australian Institute of Sport (AIS)
      Canberra, Australian Capital Territory, Australia