Protecting athletes from sudden cardiac death.
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Adolescent↗
Biomedical subjects
Benjamin D Levine
Publications and source records attributed to Benjamin D Levine.
Vasomotor sympathetic neural control is maintained during sustained upright posture in humans.
Vasomotor sympathetic activity plays an important role in arterial pressure maintenance via the baroreflex during acute orthostasis in humans. If orthostasis is prolonged, blood pressure may be supported additionally by humoral factors with a possible reduction in sympathetic baroreflex sensitivity. We tested the hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA) decreases during prolonged upright posture. MSNA and haemodynamics were measured supine and during 45 min 60 deg upright tilt in 13 healthy individuals. Sympathetic baroreflex sensitivity was quantified using the slope of the linear correlation between MSNA and diastolic pressure during spontaneous breathing. It was further assessed as the relationship between MSNA and stroke volume, with stroke volume derived from cardiac output (C2H2 rebreathing) and heart rate. Total peripheral resistance was calculated from mean arterial pressure and cardiac output. We found that MSNA increased from supine to upright (17+/-8 (S.D.) versus 38+/-12 bursts min-1; P<0.01), and continued to increase to a smaller degree during sustained tilt (39+/-11, 41+/-12, 43+/-13 and 46+/-15 bursts min-1 after 10, 20, 30 and 45 min of tilt; between treatments P<0.01). Sympathetic baroreflex sensitivity increased from supine to upright (-292+/-180 versus -718+/-362 units beat-1 mmHg-1; P<0.01), but remained unchanged as tilting continued (-611+/-342 and -521+/-221 units beat-1 mmHg-1 after 20 and 45 min of tilt; P=0.49). For each subject, changes in MSNA were associated with changes in stroke volume (r=0.88+/-0.13, P<0.05), while total peripheral resistance was related to MSNA during 45 min upright tilt (r=0.82+/-0.15, P<0.05). These results suggest that the vasoconstriction initiated by sympathetic adrenergic nerves is maintained by ongoing sympathetic activation during sustained (i.e. 45 min) orthostasis without obvious changes in vasomotor sympathetic neural control.
Adult↗
Increased serum erythropoietin but not red cell production after 4 wk of intermittent hypobaric hypoxia (4,000-5,500 m).
This study tested the hypothesis that athletes exposed to 4 wk of intermittent hypobaric hypoxia exposure (3 h/day, 5 days/wk at 4,000-5,500 m) or double-blind placebo increase their red blood cell volume (RCV) and hemoglobin mass (Hbmass) secondary to an increase in erythropoietin (EPO). Twenty-three collegiate level athletes were measured before (Pre) and after (Post) the intervention for RCV via Evans blue (EB) dye and in duplicate for Hbmass using CO rebreathing. Hematological indexes including EPO, soluble transferrin receptor, and reticulocyte parameters were measured on 8-10 occasions spanning the intervention. The subjects were randomly divided among hypobaric hypoxia (Hypo, n = 11) and normoxic (Norm, n = 12) groups. Apart from doubling EPO concentration 3 h after hypoxia there was no increase in any of the measures for either Hypo or Norm groups. The mean change in RCV from Pre to Post for the Hypo group was 2.3% (95% confidence limits = -4.8 to 9.5%) and for the Norm group was -0.2% (-5.7 to 5.3%). The corresponding changes in Hbmass were 1.0% (-1.3 to 3.3%) for Hypo and -0.3% (-2.6 to 3.1%) for Norm. There was good agreement between blood volume (BV) from EB and CO: EB BV = 1.03 x CO BV + 142, r2 = 0.85, P < 0.0001. Overall, evidence from four independent techniques (RCV, Hbmass, reticulocyte parameters, and soluble transferrin receptor) suggests that intermittent hypobaric hypoxia exposure did not accelerate erythropoiesis despite the increase in serum EPO.
Adaptation, Physiological↗
Cascade model of ventricular-arterial coupling and arterial-cardiac baroreflex function for cardiovascular variability in humans.
Cardiovascular variability reflects autonomic regulation of blood pressure (BP) and heart rate (HR). However, systolic BP (SBP) variability also may be induced by fluctuations in stroke volume through left ventricular end-diastolic pressure (LVEDP) variability via dynamic ventricular-arterial coupling during respiration. We hypothesized that dynamic ventricular-arterial coupling is modulated by changes in left ventricular compliance associated with altered preload and that a cascade control mechanism of ventricular-arterial coupling with arterial-cardiac baroreflex function contributes to the genesis of cardiovascular variability at the respiratory frequency. Seven healthy young subjects underwent 6-min recordings of beat-by-beat LVEDP, SBP, and HR in the supine position with controlled respiration at 0.2 Hz during hyper- and hypovolemia. Spectral and transfer function analysis of these variables was conducted between 0.18 and 0.22 Hz. Dynamic ventricular-arterial coupling gain (Gain LVEDP-SBP) was smaller by 25% (P = 0.009) during hypervolemia than during hypovolemia, whereas arterial-cardiac baroreflex function gain (Gain SBP-HR) was similar. As predicted from a cascade model, a linear relationship between Gain LVEDP-HR and LVEDP-SBP times Gain SBP-HR was identified (R(2) = 0.93, P < 0.001). Gain LVEDP-HR was smaller by 40% (P = 0.04) during hypervolemia than during hypovolemia, leading to a reduction in spectral power of HR variability by 45% (P = 0.08). We conclude that dynamic ventricular-arterial coupling gain is reduced during hypervolemia because of a decrease in left ventricular compliance. A cascade model of ventricular-arterial coupling with the arterial-cardiac baroreflex contributes to the genesis of cardiovascular variability at the respiratory frequency.
Adult↗
Scaling of diastolic intraventricular pressure gradients is related to filling time duration.
In early diastole, pressure is lower in the apex than in the base of the left ventricle (LV). This early intraventricular pressure difference (IVPD) facilitates LV filling. We assessed how LV diastolic IVPD and intraventricular pressure gradient (IVPG), defined as IVPD divided by length, scale to the heart size and other physiological variables. We studied 10 mice, 10 rats, 5 rabbits, 12 dogs, and 21 humans by echocardiography. Color Doppler M-mode data were postprocessed to reconstruct IVPD and IVPG. Normalized LV filling time was calculated by dividing filling time by RR interval. The relationship between IVPD, IVPG, normalized LV filling time, and LV end-diastolic volume (or mass) as fit to the general scaling equation Y = kM beta, where M is LV heart size parameter, Y is a dependent variable, k is a constant, and beta is the power of the scaling exponent. LV mass varied from 0.049 to 194 g, whereas end-diastolic volume varied from 0.011 to 149 ml. The beta values relating normalized LV filling time with LV mass and end-diastolic volume were 0.091 (SD 0.011) and 0.083 (SD 0.009), respectively (P < 0.0001 vs. 0 for both). The beta values relating IVPD with LV mass and end-diastolic volume were similarly significant at 0.271 (SD 0.039) and 0.243 (SD 0.0361), respectively (P < 0.0001 vs. 0 for both). Finally, beta values relating IVPG with LV mass and end-diastolic volume were -0.118 (SD 0.013) and -0.104 (SD 0.011), respectively (P < 0.0001 vs. 0 for both). As a result, there was an inverse relationship between IVPG and normalized LV filling time (r = -0.65, P < 0.001). We conclude that IVPD decrease, while IVPG increase with decreasing animal size. High IVPG in small mammals may be an adaptive mechanism to short filling times.
Adult↗
Women have higher left ventricular ejection fractions than men independent of differences in left ventricular volume: the Dallas Heart Study.
BACKGROUND: Although gender-specific criteria are common for defining cardiac traits such as left ventricular hypertrophy, left ventricular ejection fraction (LVEF) thresholds widely used in clinical practice have traditionally been the same for women and men, perhaps because it remains uncertain whether there is a systematic difference in LVEF between genders. METHODS AND RESULTS: Using cardiac magnetic resonance imaging in a probability-based sample of Dallas County residents aged 30 to 65 years (1435 women and 1183 men), we compared LVEF in women and men. The association of gender with stroke volume independent of end-diastolic volume (EDV) or other potential confounders was assessed by multivariable analysis. Gender-specific thresholds for a low LVEF were defined at the 2.5th percentile in women and men from a healthy reference subpopulation. The median (25th, 75th percentile) LVEF was higher in women than in men (75% [70%, 79%] in women versus 70% [65%, 75%] in men, P<0.001). Left ventricular EDV and end-systolic volume indexed to body surface area were smaller in women than in men (P<0.001 for both). Gender remained significantly associated with stroke volume, independent of EDV and other potential confounders in multivariable analysis. A low LVEF was defined as below 61% in women and below 55% in men. CONCLUSIONS: Women have a higher LVEF than men in the general population, secondary to a higher stroke volume for a given EDV independent of known potential confounders.
Adult↗
Coronary artery calcium score, risk factors, and incident coronary heart disease events.
BACKGROUND: Whether the absence of coronary artery calcium, or conversely the presence of high volumes of coronary artery calcium, may alter assessment of coronary heart disease risk based on traditional risk factors is uncertain. We sought to identify a potential threshold of coronary artery calcium for clinical use and examine the predictive power of coronary artery calcium in individuals categorized using conventional coronary heart disease risk assessment. METHODS: The study included 10,746 men and women (36.3%) with a mean age of 53.8+/-9.9 years who were either physician- or self-referred for electron beam tomography scanning to a preventive medical clinic. Coronary heart disease risk factors were elicited by use of a questionnaire. RESULTS: During a mean follow-up of 3.5 years, 81 primary events (coronary heart disease death or nonfatal myocardial infarction) occurred. Among individuals with a coronary artery calcium score of zero, the primary event rate was very low (0.4 events per 1000 person-years of observation). When participants were stratified by self-reported coronary heart disease risk factors (0-2, or 3-4), a coronary artery calcium score >or=100 was associated with substantially increased risk of coronary heart disease events within each level of stratification. In a subgroup of participants with available clinical data, similar results were found when participants were categorized by Framingham risk scores. CONCLUSIONS: Coronary artery calcium score can identify individuals at increased risk for coronary heart disease events who otherwise would be considered low-risk based on clinical assessment. A coronary artery calcium score of zero is associated with very low risk for coronary heart disease in the short to intermediate term ( approximately 3.5 years) regardless of the number of risk factors present.
Adult↗
Cerebral hemodynamics during orthostatic stress assessed by nonlinear modeling.
The effects of orthostatic stress, induced by lower body negative pressure (LBNP), on cerebral hemodynamics were examined in a nonlinear context. Spontaneous fluctuations of beat-to-beat mean arterial blood pressure (MABP) in the finger, mean cerebral blood flow velocity (MCBFV) in the middle cerebral artery, as well as breath-by-breath end-tidal CO2 concentration (P(ET(CO2))) were measured continuously in 10 healthy subjects under resting conditions and during graded LBNP to presyncope. A two-input nonlinear Laguerre-Volterra network model was employed to study the dynamic effects of MABP and P(ET(CO2)) changes, as well as their nonlinear interactions, on MCBFV variations in the very low (VLF; below 0.04 Hz), low (LF; 0.04-0.15 Hz), and high frequency (HF; 0.15-0.30 Hz) ranges. Dynamic cerebral autoregulation was described by the model terms corresponding to MABP, whereas cerebral vasomotor reactivity was described by the model P(ET(CO2)) terms. The nonlinear model terms reduced the output prediction normalized mean square error substantially (by 15-20%) and had a prominent effect in the VLF range, both under resting conditions and during LBNP. Whereas MABP fluctuations dominated in the HF range and played a significant role in the VLF and LF ranges, changes in P(ET(CO2)) accounted for a considerable fraction of the VLF and LF MCBFV variations, especially at high LBNP levels. The magnitude of the linear and nonlinear MABP-MCBFV Volterra kernels increased substantially above -30 mmHg LBNP in the VLF range, implying impaired dynamic autoregulation. In contrast, the magnitude of the P(ET(CO2))-MCBFV kernels reduced during LBNP at all frequencies, suggesting attenuated cerebral vasomotor reactivity under dynamic conditions. We speculate that these changes may reflect a progressively reduced cerebrovascular reserve to compensate for the increasingly unstable systemic circulation during orthostatic stress that could ultimately lead to cerebral hypoperfusion and syncope.
Adult↗
Hypertension and antihypertensive therapy in elderly women: how much do we really know?
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Aged↗
Coronary artery calcium, exercise tolerance, and CHD events in asymptomatic men.
Coronary artery calcium (CAC) scores >/=100 are predictive of CHD events in asymptomatic men. Exercise tolerance of >/=10METs predicts lower event rates in CHD patients; however, its relationship with events in individuals with subclinical atherosclerosis is less known. Participants were 710 asymptomatic men from the Aerobics Center Longitudinal Study whose exercise tolerance (ET) was quantified (<10 or >/=10METs) and whose CAC score was >/=100 as measured by electron beam tomography. During 3.5 years of follow-up 59 CHD events occurred. The age-adjusted hazard ratio (HR) of CHD events was 0.26 (95% CI=0.15-0.45) in men whose ET was >/=10METs compared with men whose ET was <10METs. Adjustment for CHD risk factors and abnormal exercise ECG did not change the association between ET and CHD. The extent of underlying atherosclerosis did not influence the association between ET and CHD; for example, the HR for CHD events in the >/=10MET group among men with CAC scores <400 and >/=400 was 0.16 (95% CI=0.05-0.56) and 0.23 (95% CI=0.11-0.46), respectively. In asymptomatic men with subclinical coronary atherosclerosis, an ET of >/=10METs identifies patients at lower risk for manifest CHD.
Calcium↗
Urine acid-base compensation at simulated moderate altitude.
Acute exposure to high altitude elicits respiratory alkalosis, and this is partially corrected by renal compensation. To determine the time course and magnitude of renal compensation during short-term moderate altitude exposure, we measured urine gas tensions and acid-base status in 48 healthy men and women at four levels of simulated altitude exposures. Each subject was exposed in pseudorandom order to simulated altitudes of 1780, 2085, 2455, and 2800 m in a decompression chamber for 24 h, separated by 1 week at sea level. Fresh urine was collected anaerobically at sea level and after 6 and 24 h of each altitude exposure. Urine pH increased significantly (p < 0.01) after 6 h at all altitudes and returned to baseline values by 24 h at the lowest altitudes. In contrast, urine pH remained elevated at the highest altitudes. The mean value of urine HCO at sea level was 1.67 +/- 0.25 mmol/L, increased significantly after 6 h at all altitudes, and then returned to near baseline after 24 h at three lower altitudes (1780, 2085, and 2455 m). However, it remained elevated at 2800 m. PCO2 in urine was significantly increased after 6 h and returned to baseline after 24 h at all altitudes. These results suggest that (1) short-term low to moderate altitude exposure results in a marked HCO diuresis, which may be caused by inhibition of the secretion of renal tubular H+, and (2) renal HCO compensation was completed by 24 h at low to moderate altitude, but still incomplete at higher altitude.
Acid-Base Equilibrium↗
Should "artificial" high altitude environments be considered doping?
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Altitude↗
Medical director responsibilities for outpatient cardiac rehabilitation/secondary prevention programs: a scientific statement from the American Heart Association/American Association for Cardiovascular and Pulmonary Rehabilitation.
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Ambulatory Care↗
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↗
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↗
Sudden death in patients with myocardial infarction.
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Death, Sudden, Cardiac↗
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↗
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↗