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Biomedical subjects

Benjamin D Levine

Publications and source records attributed to Benjamin D Levine.

At least 37 records · Page 2Linked to original sources
PubMed2005

Relationship among diastolic intraventricular pressure gradients, relaxation, and preload: impact of age and fitness.

Diastolic intraventricular pressure gradients (IVPGs) are a measure of the ability of the ventricle to facilitate its filling using diastolic suction. We assessed 15 healthy young but sedentary subjects, aged <50 yr (young subjects; age, 35 +/- 9 yr); 13 healthy but sedentary seniors, aged >65 yr with known reductions in ventricular compliance (elderly sedentary subjects; age, 70 +/- 4 yr); and 12 master athletes, aged >65 yr, previously shown to have preserved ventricular compliance (elderly fit subjects; age, 68 +/- 3 yr). Pulmonary capillary wedge pressure (PCWP) and echocardiography measurements were performed at baseline, during load manipulation by lower body negative pressure at -15 and -30 mmHg, and after saline infusion of 10 and 20 ml/kg (elderly) or 15 and 30 ml/kg (young). IVPGs were obtained from color M-mode Doppler echocardiograms. Baseline IVPGs were lower (1.2 +/- 0.4 vs. 2.4 +/- 0.7 mmHg, P < 0.0001), and the time constant of pressure decay (tau(0)) was longer (60 +/- 10 vs. 46 +/- 6 ms, P < 0.0001) in elderly sedentary than in young subjects, with no difference in PCWP. Although PCWP changes during load manipulations were similar (P = 0.70), IVPG changes were less prominent in elderly sedentary than in young subjects (P = 0.02). Changes in stroke volume and IVPGs during loading manipulations correlated (r = 0.96, P = 0.0002). PCWP and tau(0) were strong multivariate correlates of IVPGs (P < 0.001, for both). IVPG response to loading interventions in elderly sedentary and elderly fit subjects was similar (P = 0.33), despite known large differences in ventricular compliance. The ability to regulate IVPGs during changes in preload is impaired with aging. Preserving ventricular compliance during aging by lifelong exercise training does not prevent this impairment.

Adult↗
PubMed2005

Effects of heat stress on thermoregulatory responses in congestive heart failure patients.

BACKGROUND: Clinical observations suggest that tolerance to heat stress may be impaired in patients with cardiovascular diseases, particularly those associated with impaired ventricular function and congestive heart failure (CHF). However, thermoregulatory function during a controlled heat stress challenge in patients with CHF has not been studied. METHODS AND RESULTS: To test the hypothesis that thermoregulatory responses are attenuated in such patients, we assessed cutaneous vasodilation and sweat rate in patients with stable class II-III CHF and in matched healthy subjects during passive whole-body heating. Whole-body heating induced a similar increase in internal temperature (approximately 0.85 degrees C) in both groups. The sweating responses in patients with CHF were not significantly different from that in control subjects. In contrast, the elevation in forearm cutaneous vascular conductance in patients with CHF was reduced by nearly 50% relative to the control subjects (3.8+/-0.8 versus 6.9+/-1.0 mL/100 mL tissue per minute per 100 mm Hg, P=0.04). Moreover, maximal cutaneous vasodilator capacity to direct local heating in patients with CHF was also significantly lower than in control subjects, suggesting that vascular remodeling may be limiting cutaneous vasodilation during hyperthermia. CONCLUSIONS: These observations suggest that patients with CHF exhibit attenuated cutaneous vasodilator responses to both whole-body and local heating, whereas sweating responses are preserved. Attenuated cutaneous vasodilation may be a potential mechanism for heat intolerance in patients with CHF.

Body Temperature Regulation↗
PubMed2005

Coronary artery calcium score and coronary heart disease events in a large cohort of asymptomatic men and women.

Coronary artery calcium (CAC), a measure of subclinical coronary heart disease (CHD), may be useful in identifying asymptomatic persons at risk of CHD events. The current study included 10,746 adults who were 22-96 years of age, were free of known CHD, and had their CAC quantified by electron-beam tomography at baseline as part of a preventive medical examination at the Cooper Clinic (Dallas, Texas) during 1995-2000. During a mean follow-up of 3.5 years, 81 hard events (CHD death, nonfatal myocardial infarction) and 287 total events (hard events plus coronary revascularization) occurred. Age-adjusted rates (per 1,000 person-years) of hard events were computed according to four CAC categories: no detectable CAC and incremental sex-specific thirds of detectable CAC; these rates were, respectively, 0.4, 1.5, 4.8, and 8.7 (trend p<0.0001) for men and 0.7, 2.3, 3.1, and 6.3 (trend p=0.02) for women. CAC levels also were positively associated with rates of total CHD events for women and men (trend p<0.0001 each). The association between CAC and CHD events remained significant after adjustment for CHD risk factors. CAC was associated with CHD events in persons with no baseline CHD risk factors and in younger (aged <40 years) and older (aged >65 years) study participants. These findings show that CAC is associated with an increased risk of CHD events in asymptomatic women and men.

Adult↗
PubMed2005

Effect of skin surface cooling on central venous pressure during orthostatic challenge.

Orthostatic stress leads to a reduction in central venous pressure (CVP), which is an index of cardiac preload. Skin surface cooling has been shown to improve orthostatic tolerance, although the mechanism resulting in this outcome is unclear. One possible mechanism may be that skin surface cooling attenuates the drop in CVP during an orthostatic challenge, thereby preserving cardiac filling. To test this hypothesis, CVP, arterial blood pressure, heart rate, and skin blood flow, as well as skin and sublingual temperatures, were recorded in nine healthy subjects during lower body negative pressure (LBNP) in both normothermic and skin surface cooling conditions. Cardiac output was also measured via acetylene rebreathing. Progressive LBNP was applied at -10, -15, -20, and -40 mmHg at 5 min/stage. Before LBNP, skin surface cooling lowered mean skin temperature, increased CVP, and increased mean arterial blood pressure (all P < 0.001) but did not change mean heart rate (P = 0.38). Compared with normothermic conditions, arterial blood pressure remained elevated throughout progressive LBNP. Although progressive LBNP decreased CVP under both thermal conditions, during cooling CVP at each stage of LBNP was significantly greater relative to normothermia. Moreover, at higher levels of LBNP with skin cooling, stroke volume was significantly greater relative to normothermic conditions. These data indicate that skin surface cooling induced an upward shift in CVP throughout LBNP, which may be a key factor for preserving preload, stroke volume, and blood pressure and improving orthostatic tolerance.

Adaptation, Physiological↗
PubMed2005

Vasoconstriction during venous congestion: effects of venoarteriolar response, myogenic reflexes, and hemodynamics of changing perfusion pressure.

We dissected the relative contribution of arteriovenous hemodynamics, the venoarteriolar response (VAR), and the myogenic reflex toward a decrease in local blood flow induced by venous congestion. Skin blood flow (SkBF) was measured in 12 supine subjects via laser-Doppler flowmetry 1) over areas of forearm and calf skin, in which the VAR was blocked by using eutectic mixture of local anesthetics (EMLA sites) and 2) over the contralateral forearm or calf skin (control sites), using two different techniques: limb dependency of 23-37 cm below the heart and cuff inflation to 40 mmHg. During limb dependency, SkBF decreased at the control sites, whereas it remained unchanged at the EMLA sites. In contrast, during cuff inflation, SkBF decreased at the control sites and also decreased at the EMLA sites. The percent change in SkBF from baseline was greater during cuff inflation than limb dependency at both the control sites and the EMLA sites. Estimated skin vascular resistance remained unchanged at the EMLA sites during cuff inflation, as well as limb dependency. Thus the decrease in SkBF during venous congestion with cuff inflation is not solely due to the cutaneous VAR but also to a reduction in local perfusion pressure. The VAR is therefore most specifically quantified by venous congestion induced by limb dependency, rather than cuff inflation. Finally, from both techniques, we calculated that during venous congestion induced by limb dependency (calf), approximately 45% of the nonbaroreflex vasoconstriction is induced by the VAR and approximately 55% by the myogenic reflex.

Adult↗
PubMed2005

Dose-response relationship of endurance training for autonomic circulatory control in healthy seniors.

Aging results in marked abnormalities of cardiovascular regulation. Regular exercise can improve many of these age-related abnormalities. However, it remains unclear how much exercise is optimal to achieve this improvement or whether the elderly can ever improve autonomic control by exercise training to a degree similar to that observed in healthy young individuals. Ten healthy sedentary seniors [71 +/- 3 (SD) yr] trained for 12 mo; training involved progressive increases in volume and intensity. Static hemodynamics were measured, and R-wave-R-wave interval (RRI), beat-to-beat blood pressure (BP) variability, and transfer function gain between systolic BP and RRI were calculated at baseline and every 3 mo during training. Data were compared with those obtained in 12 Masters athletes (68 +/- 3 yr) and 11 healthy sedentary young individuals (29 +/- 6 yr) at baseline. Additionally, the adaptation of these variables after completion of identical training loads was compared between the seniors and the young. Indexes of RRI variability and baroreflex gain were decreased in the sedentary seniors but preserved in the Masters athletes compared with the young at baseline. With training in the seniors, baroreflex gain and resting BP showed a peak adaptation after moderate doses of training following 3-6 mo. Indexes of RRI variability continued to improve with increasing doses of training and increased to the same magnitude as the young at baseline after heavy doses of training for 12 mo; however, baroreflex gain never achieved values equivalent to the young at baseline, even after a year of training. The magnitude of the adaptation of these variables to identical training loads was similar (no interaction effects of age x training) between the seniors and the young. Thus RRI variability in seniors improves with increasing "dose" of exercise over 1 yr of training. In contrast, more moderate doses of training for 3-6 mo may optimally improve baroreflex sensitivity, associated with a modest hypotensive effect; however, higher doses of training do not lead to greater enhancement of these changes. Seniors retain a similar degree of "trainability" as young subjects for cardiac autonomic function to dynamic exercise.

Adaptation, Physiological↗
PubMed2005

Abnormalities of Doppler measures of diastolic function in the healthy elderly are not related to alterations of left atrial pressure.

BACKGROUND: Normal healthy aging results in changes in Doppler indexes of diastolic function. One widely accepted explanation for these alterations that is based on animal data is an age-associated impairment of myocardial relaxation resulting from abnormal myocyte calcium handling. However, an alternative theory based on altered left atrial compliance with aging has been proposed in which early left atrial pressure could be low in the aged heart but rise rapidly during atrial diastole, resulting in a higher late atrial pressure and thus a normal mean pressure. We sought to explore this issue directly by performing a detailed analysis of the pulmonary capillary wedge pressure waveform obtained by right-heart catheterization during 5 different loading conditions. METHODS AND RESULTS: Twelve healthy elderly sedentary subjects (mean age, 69.8+/-3 years) were recruited for the seniors group. An additional 12 young sedentary subjects (mean age, 35+/-8 years) made up the young group. All subjects were rigorously screened for comorbidities. All subjects underwent transthoracic echocardiography to determine Doppler variables of early and late transmitral filling (E and A velocities) and isovolumetric relaxation time. Each subject also underwent pulmonary artery catheterization with measurement of pulmonary capillary wedge pressure waveform during 5 different loading conditions: baseline, lower-body negative pressures of -15 and -30 mm Hg, and rapid saline infusions of 10 to 15 and 20 to 30 mL/kg. Pressure was measured at 6 points of the waveform: point 1, peak of the atrial contraction (a wave); point 2, the left atrial pressure during the start of ventricular systole; point 3, peak of atrial filling (v wave); point 4, earliest left atrial pressure during ventricular filling; and the line between points 5 and 6, pressure during diastasis. Aging resulted in a decrease in the E/A ratio (P<0.001) and a prolongation of the isovolumetric relaxation time (P<0.001) as assessed by echocardiography, but there was no effect of age on pulmonary capillary wedge pressure at any point throughout the cardiac cycle (P=0.290). Specifically, at no measured point at any level of cardiac filling volume was the pulmonary capillary wedge pressure of the seniors lower than that of the young subjects. CONCLUSIONS: We conclude that the age-related echocardiographic change of decreasing E/A ratio is not the result of a lowering of early diastolic left atrial pressure.

Adult↗
PubMed2005

Effects of gender and hypovolemia on sympathetic neural responses to orthostatic stress.

We tested the hypothesis that women have blunted sympathetic neural responses to orthostatic stress compared with men, which may be elicited under hypovolemic conditions. Muscle sympathetic nerve activity (MSNA) and hemodynamics were measured in eight healthy young women and seven men in supine position and during 6 min of 60 degrees head-up tilt (HUT) under normovolemic and hypovolemic conditions (randomly), with approximately 4-wk interval. Acute hypovolemia was produced by diuretic (furosemide) administration approximately 2 h before testing. Orthostatic tolerance was determined by progressive lower body negative pressure to presyncope. We found that furosemide produced an approximately 13% reduction in plasma volume, causing a similar increase in supine MSNA in men and women (mean +/- SD of 5 +/- 7 vs. 6 +/- 5 bursts/min; P = 0.895). MSNA increased during HUT and was greater in the hypovolemic than in the normovolemic condition (32 +/- 6 bursts/min in normovolemia vs. 44 +/- 15 bursts/min in hypovolemia in men, P = 0.055; 35 +/- 9 vs. 45 +/- 8 bursts/min in women, P < 0.001); these responses were not different between the genders (gender effect: P = 0.832 and 0.814 in normovolemia and hypovolemia, respectively). Total peripheral resistance increased proportionately with increases in MSNA during HUT; these responses were similar between the genders. However, systolic blood pressure was lower, whereas diastolic blood pressure was similar in women compared with men during HUT, which was associated with a smaller stroke volume or stroke index. Orthostatic tolerance was lower in women, especially under hypovolemic conditions. These results indicate that men and women have comparable sympathetic neural responses during orthostatic stress under normovolemic and hypovolemic conditions. The lower orthostatic tolerance in women is predominantly because of a smaller stroke volume, presumably due to less cardiac filling during orthostasis, especially under hypovolemic conditions, which may overwhelm the vasomotor reserve available for vasoconstriction or precipitate neurally mediated sympathetic withdrawal and syncope.

Adult↗
PubMed2005

Dynamic autoregulation of cutaneous circulation: differential control in glabrous versus nonglabrous skin.

The purpose of this project was to test the hypothesis that, independent of neural control, glabrous and nonglabrous cutaneous vasculature is capable of autoregulating blood flow. In 10 subjects, spectral and transfer function analyses of arterial pressure and skin blood flow (laser-Doppler flowmetry) from glabrous (palm) and nonglabrous (forearm) regions were performed under three conditions: baseline, ganglionic blockade via intravenous trimethaphan administration, and trimethaphan plus oscillatory lower body negative pressure (LBNP; -5 to -10 mmHg) from 0.05 to 0.07 Hz. Oscillatory LBNP was applied to regenerate mean arterial pressure variability that was abolished by ganglionic blockade. Ganglionic blockade was verified by an absence of a heart rate response to a Valsalva maneuver. Spectral power and transfer function gain between blood pressure and skin blood flow were calculated in this oscillatory frequency range (0.05-0.07 Hz). Within this frequency range, ganglionic blockade significantly decreased spectral power of blood flow in both the forearm and palm, whereas regeneration of arterial blood pressure oscillations significantly increased spectral power of forearm blood flow but not palm blood flow. During oscillatory LBNP, transfer function gain between blood pressure and skin blood flow was significantly elevated at the forearm (0.28 +/- 0.03 to 0.53 +/- 0.02 flux units/mmHg; P < 0.05) but was reduced at the palm (4.7 +/- 0.5 to 1.2 +/- 0.1 flux units/mmHg; P < 0.05). These data show that independent of neural control of blood flow, glabrous skin has the ability to buffer blood pressure oscillations and demonstrates a degree of dynamic autoregulation. Conversely, these data suggest that nonglabrous skin has diminished dynamic autoregulatory capabilities.

Adult↗
PubMed2005

Persistent sympathetic activation during chronic antihypertensive therapy: a potential mechanism for long term morbidity?

Previous studies have demonstrated that antihypertensive treatment resets baroreflex control of heart rate (HR) and increases cardiac vagal baroreflex sensitivity. However, it is uncertain whether baroreflex control of muscle sympathetic nerve activity (MSNA) also resets after treatment. We tested the hypothesis that chronic antihypertensive therapy alters baroreflex regulation of MSNA in patients with untreated moderate hypertension. Seven newly diagnosed patients with systolic blood pressure (BP) of 159+/-5 mm Hg (mean+/-SE) and diastolic BP of 103+/-4 mm Hg were studied before and after 1 to 2 weeks ' and 3 months (chronic) of antihypertensive treatment with losartan-hydrochlorothiazide (Hyzaar). MSNA and hemodynamics were measured supine, during a Valsalva maneuver (VM), and at 70 degrees head-up tilt (HUT) for 10 minutes. Data were compared with those obtained in 7 age-matched healthy controls. We found that Hyzaar lowered mean BP acutely and chronically by 20+/-4 and 23+/-3 mm Hg (both P<0.01) but did not change HR. Supine MSNA increased by 43+/-11% and 34+/-11% after acute and chronic treatment (both P<0.01). However, MSNA responses to VM and HUT did not differ after treatment compared with before treatment, indicating unchanged reflex control. These data indicate that sympathetic neural activity was augmented substantially by antihypertensive treatment with Hyzaar, consistent with an ongoing baroreflex unloading, and did not return to baseline or "reset" after 3 months of therapy. We speculate that persistent and marked sympathetic activation by the baroreflex may be a potential mechanism for hypertension that is refractory to antihypertensive therapy and may provide a target mechanism for persistent morbidity despite adequate BP control.

Adult↗
PubMed2004

Vasoconstrictor reserve and sympathetic neural control of orthostasis.

BACKGROUND: We tested the hypothesis that individual variability in orthostatic tolerance is dependent on the degree of neural and vasomotor reserve available for vasoconstriction. METHODS AND RESULTS: Muscle sympathetic nerve activity (MSNA) and hemodynamics were measured in 12 healthy young volunteers during 60 degrees head-up tilt (HUT), followed by a cold pressor test (CPT) in HUT. Orthostatic tolerance was determined by progressive lower-body negative pressure (LBNP) to presyncope. The same protocols were performed randomly in normovolemic and hypovolemic conditions. We found that mean arterial pressure increased and stroke volume decreased, whereas heart rate (HR), MSNA, and total peripheral resistance (TPR) increased during HUT (all P<0.01). Application of the CPT in HUT did not increase HR or decrease stroke volume further but elevated mean arterial pressure (P<0.01) and increased MSNA and TPR in some subjects. There was a positive correlation between the time to presyncope from -50 mm Hg LBNP (equivalent to 60 degrees HUT alone) and the changes in MSNA produced by the CPT under both conditions (r=0.442, P=0.039). Those who had greater increases in MSNA had greater increases in TPR during the CPT and longer time to presyncope (both P<0.05). One subject had dramatic increases in MSNA but small increases in TPR during the CPT, which indicates a disassociation between sympathetic activity and the increase in peripheral vascular resistance. CONCLUSIONS: These results support our hypothesis and suggest that vasoconstrictor capability is a contributor to orthostatic tolerance in humans. Vasoconstrictor reserve therefore may be one mechanism underlying individual variability in orthostatic intolerance.

Adult↗