Effects of aerobic and strength training on aerobic capacity, muscle strength, and gene expression of lymphomonocytes in patients with stable CAD.

This study examined the effectiveness, suitability, and safety of a mixed interval-type aerobic and strength training program (MIAST) on physical fitness in patients with stable coronary artery disease (CAD) without history of myocardial infarction (MI). Twenty-three patients with stable CAD were randomly assigned to a MIAST (n = 12; mean age 58.6 years) or control (n = 11; 63.3 years) group. The MIAST group participated in the progressive training program twice a week for 21 weeks. Peak oxygen uptake (VO2peak), workload, and exercise time were measured as were maximal muscle strength, serum lipids, glucose concentration, and the cross-sectional area (CSA) of knee extensors. The safety and suitability of the program were assessed by wireless electrocardiogram (ECG) monitoring and exercise diaries. VO2peak (6.9%; P < 0.05) and exercise time (11.2%; P < 0.05) improved significantly after 12 weeks of training in the MIAST group compared to the control group. Muscle strength (19.9%; P < 0.05) and CSA (2.2%; P < 0.05) increased, and serum lipids and blood glucose tended to decrease after the training. The successful training program (increase in maximal oxygen uptake) increased the gene expression of oxygen metabolism and decreased the gene expression of inflammation pathways in lymphomonocytes. The MIAST program, including interval-type aerobic and strength training, was safe, did not cause any adverse effects, and led to significant improvements in physical fitness in patients with stable CAD.

Females have a blunted cardiovascular response to one year of intensive supervised endurance training.

Cross-sectional studies in athletes suggest that endurance training augments cardiovascular structure and function with apparently different phenotypes in athletic males and females. It is unclear whether the longitudinal response to endurance training leads to similar cardiovascular adaptations between sexes. We sought to determine whether males and females demonstrate similar cardiovascular adaptations to 1 yr of endurance training, matched for training volume and intensity. Twelve previously sedentary males (26 ± 7, n = 7) and females (31 ± 6, n = 5) completed 1 yr of progressive endurance training. All participants underwent a battery of tests every 3 mo to determine maximal oxygen uptake (V̇o2max) and left ventricle (LV) function and morphology (cardiac magnetic resonance imaging). Pulmonary artery catheterization was performed before and after 1 yr of training, and pressure-volume and Starling curves were constructed during decreases (lower-body negative pressure) and increases (saline infusion) in cardiac volume. Males progressively increased V̇o2max, LV mass, and mean wall thickness, before reaching a plateau from month 9 to 12 of training. In contrast, despite exactly the same training, the response in females was markedly blunted, with V̇o2max, LV mass, and mean wall thickness plateauing after only 3 mo of training. The response of LV end-diastolic volume was not influenced by sex (males +20% and females +18%). After training Starling curves were shifted upward and left, but the effect was greatest in males (interaction P = 0.06). We demonstrate for the first time clear sex differences in response to 1 yr of matched endurance training, such that the development of ventricular hypertrophy and increase in V̇o2max in females is markedly blunted compared with males.

Cardiac remodeling in response to 1 year of intensive endurance training.

BACKGROUND: It is unclear whether, and to what extent, the striking cardiac morphological manifestations of endurance athletes are a result of exercise training or a genetically determined characteristic of talented athletes. We hypothesized that prolonged and intensive endurance training in previously sedentary healthy young individuals could induce cardiac remodeling similar to that observed cross-sectionally in elite endurance athletes. METHODS AND RESULTS: Twelve previously sedentary subjects (aged 29±6 years; 7 men and 5 women) trained progressively and intensively for 12 months such that they could compete in a marathon. Magnetic resonance images for assessment of right and left ventricular mass and volumes were obtained at baseline and after 3, 6, 9, and 12 months of training. Maximum oxygen uptake ( max) and cardiac output at rest and during exercise (C2H2 rebreathing) were measured at the same time periods. Pulmonary artery catheterization was performed before and after 1 year of training, and pressure-volume and Starling curves were constructed during decreases (lower body negative pressure) and increases (saline infusion) in cardiac volume. Mean max rose from 40.3±1.6 to 48.7±2.5 mL/kg per minute after 1 year (P<0.00001), associated with an increase in both maximal cardiac output and stroke volume. Left and right ventricular mass increased progressively with training duration and intensity and reached levels similar to those observed in elite endurance athletes. In contrast, left ventricular volume did not change significantly until 6 months of training, although right ventricular volume increased progressively from the outset; Starling and pressure-volume curves approached but did not match those of elite athletes. CONCLUSIONS: One year of prolonged and intensive endurance training leads to cardiac morphological adaptations in previously sedentary young subjects similar to those observed in elite endurance athletes; however, it is not sufficient to achieve similar levels of cardiac compliance and performance. Contrary to conventional thinking, the left ventricle responds to exercise with initial concentric but not eccentric remodeling during the first 6 to 9 months after commencement of endurance training depending on the duration and intensity of exercise. Thereafter, the left ventricle dilates and restores the baseline mass-to-volume ratio. In contrast, the right ventricle responds to endurance training with eccentric remodeling at all levels of training.

[Prevention of arterial diseases in the 2010s: the European treatment guideline]. / Valtimosairauksien ehkäisy 2010-luvulla: eurooppalainen hoitosuositus.

Reduction of risk factors at the population level forms the basis of the European recommendation of 2012 for the prevention of arterial diseases. Actions at the individual level arise from risk assessment. The risk of arterial disease is graded into four categories, the uppermost ones comprising patients who have already developed the disease, diabetics, those suffering from renal insufficiency and those carrying a serious gene defect. In Finland the risk among healthy people is assessed by using the FINRISKI tool. Non-smoking, healthy diet and regular exercise are suitable for all. Statins are an effective and safe means of prevention for those at high risk regardless of lipid values.

Day/night variability in blood pressure: influence of posture and physical activity.

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. RESULTS: The 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). CONCLUSIONS: A 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.

The effect of integrated cardiac rehabilitation versus treatment as usual for atrial fibrillation patients treated with ablation: the randomised CopenHeartRFA trial protocol.

INTRODUCTION: Atrial fibrillation affects almost 2% of the population in the Western world. To preserve sinus rhythm, ablation is undertaken in symptomatic patients. Observational studies show that patients with atrial fibrillation often report a low quality of life and are less prone to be physically active due to fear of triggering fibrillation. Small trials indicate that exercise training has a positive effect on exercise capacity and mental health, and both patients with recurrent atrial fibrillation and in sinus rhythm may benefit from rehabilitation in managing life after ablation. No randomised trials have been published on cardiac rehabilitation for atrial fibrillation patients treated with ablation that includes exercise and psychoeducational components. AIM: To test the effects of an integrated cardiac rehabilitation programme versus treatment as usual for patients with atrial fibrillation treated with ablation. METHODS AND ANALYSIS DESIGN: The trial is a multicentre parallel arm design with 1:1 randomisation to the intervention and control group with blinded outcome assessment. 210 patients treated for atrial fibrillation with radiofrequency ablation will be included. The intervention consists of a rehabilitation programme including four psychoeducative consultations with a specially trained nurse and 12 weeks of individualised exercise training, plus the standard medical follow-up. Patients in the control group will receive the standard medical follow-up. The primary outcome measure is exercise capacity measured by the VO(2) peak. The secondary outcome measure is self-rated mental health measured by the Short Form 36 questionnaire. Postintervention, qualitative interviews will be conducted in 10% of the intervention group. ETHICS AND DISSEMINATION: The protocol is approved by the regional research ethics committee (number H-1-2011-135), the Danish Data Protection Agency (reg. nr. 2007-58-0015) and follows the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and may possibly impact on rehabilitation guidelines. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01523145.

Comparison of QT peak and QT end interval responses to autonomic adaptation in asymptomatic LQT1 mutation carriers.

BACKGROUND: LQT1 subtype of long QT syndrome is characterized by defective I(Ks) , which is intrinsically stronger in the epicardium than in the midmyocardial region. Electrocardiographic QT peak and QT end intervals may reflect complete repolarization of epicardium and midmyocardial region of the ventricular wall, respectively. Repolarization abnormalities in LQT1 carriers may therefore be more easily detected in the QT peak intervals. METHODS: Asymptomatic KCNQ1 mutation carriers (LQT1, n=9) and unaffected healthy controls (n=8) were studied during Valsalva manoeuvre, mental stress, handgrip and supine exercise. Global QT peak and QT end intervals derived from 25 simultaneous electrocardiographic leads were measured beat to beat with an automated method. RESULTS: In unaffected subjects, the percentage shortening of QT peak was greater than that of QT end during mental stress and during the recovery phases of Valsalva and supine exercise. In LQT1 carriers, the percentage shortening of the intervals was similar. At the beginning of Valsalva strain under abrupt endogenous sympathetic activation, QT peak shortened in LQT1 but not in control patients yielding increased electrocardiographic transmural dispersion of repolarization in LQT1. CONCLUSIONS: In asymptomatic KCNQ1 mutation carriers, repolarization abnormalities are more evident in the QT peak than in the QT end interval during adrenergic adaptation, possibly related to transmural differences in the degree of I(Ks) block.

Supine cycling plus volume loading prevent cardiovascular deconditioning during bed rest.

There are two possible mechanisms contributing to the excessive fall of stroke volume (and its contribution to orthostatic intolerance) in the upright position after bed rest or spaceflight: reduced cardiac filling due to hypovolemia and/or a less distensible heart due to cardiac atrophy. We hypothesized that preservation of cardiac mechanical function by exercise training, plus normalization of cardiac filling with volume infusion, would prevent orthostatic intolerance after bed rest. Eighteen men and three women were assigned to 1) exercise countermeasure (n=14) and 2) no exercise countermeasure (n=7) groups during bed rest. Bed rest occurred in the 6 degrees head-down tilt position for 18 days. The exercise regimen was prescribed to compensate for the estimated cardiac work reduction between bed rest and ambulatory periods. At the end of bed rest, the subjects were further divided into two additional groups for post-bed rest testing: 1) volume loading with intravenous dextran to normalize cardiac filling pressure and 2) no volume loading. Dextran infusion was given to half of the exercise group and all of the sedentary group after bed rest, leading ultimately to three groups: 1) exercise plus volume infusion; 2) exercise alone; and 3) volume infusion alone. Exercise training alone preserved left ventricular mass and distensibility as well as upright exercise capacity, but lower body negative pressure (LBNP) tolerance was still depressed. LBNP tolerance was maintained only when exercise training was accompanied by dextran infusion. Dextran infusion alone following bed rest without exercise maintained neither orthostatic tolerance nor upright exercise capacity. We conclude that daily supine cycle exercise sufficient to prevent cardiac atrophy can prevent orthostatic intolerance after bed rest only when combined with plasma volume restoration. This maintenance of orthostatic tolerance was achieved by neither exercise nor dextran infusion alone. Cardiac atrophy and hypovolemia are likely to contribute independently to orthostatic intolerance after bed rest.

Effects of 32-year leisure time physical activity discordance in twin pairs on health (TWINACTIVE study): aims, design and results for physical fitness.

The physically active lifestyle is associated with low future morbidity and mortality, but the causality between physical activity and health is not always clear. As some inherited biological characteristics and childhood experiences may cause selection bias in observational studies, we sought to take them into account by identifying 16 twin pairs (7 MZ, 9 DZ, mean age 60 years) discordant for leisure time physical activity habits for thirty years. We conducted detailed health-related examinations among these twin pairs. Our main aims were to study the effects of physical activity and genes on fitness and body composition, with special reference to body fat compartments, metabolic syndrome components and related diseases and risk factor levels, status of arteries, structure and function of the heart, bone properties, and muscle and fat tissue-related mechanisms linked to physical activity and chronic disease development. Our physical activity assessments showed that inactive co-twins were on average 8.8 MET hours/day less active than their active co-twins through out their midlife (2.2+/-2.3 vs. 11.0+/-4.1 MET h/day, p< .001). Follow-up fitness tests showed that physically inactive co-twins were less fit than their active co-twins (estimated VO(2peak) 26.4+/-4.9 vs. 32.5+/-5.5 ml/kg/min, p< .001). Similar differences were found in both MZ and DZ pairs. On the basis of earlier epidemiological observations on nonrelated individuals, these physical activity and fitness differences are large enough to cause differences in many mechanisms and risk factors related to the development of chronic diseases and to permit future analyses.

Effects of long-term physical activity on cardiac structure and function: a twin study.

Previous studies have shown that athletic training or other physical activity causes structural and functional adaptations in the heart, but less is known how long-term physical activity affects heart when genetic liability and childhood environment are taken into account. The aim of this study was to investigate the effects of long-term physical activity vs. inactivity on cardiac structure and function in twin pairs discordant for physical activity for 32 years. Twelve same-sex twin pairs (five monozygotic and seven dizygotic, 50-67 years) were studied as a part of the TWINACTIVE study. Discordance in physical activity was initially determined in 1975 and it remained significant throughout the follow-up. At the end of the follow-up in 2007, resting echocardiographic and electrocardiographic measurements were performed. During the follow-up period, the active co-twins were on average 8.2 (SD 4.0) MET hours/day more active than their inactive co-twins (p < 0.001). At the end of the follow-up, resting heart rate was lower in the active than inactive co-twins [59 (SD 5) vs. 68 (SD 10) bpm, p=0.03]. The heart rate-corrected QT interval was similar between the co-twins. Also, there was a tendency for left ventricular mass per body weight to be greater and T wave amplitude in lead II to be higher in the active co-twins (18% and 15%, respectively, p=0.08 for both). Similar trends were found for both monozygotic and dizygotic twin pairs. In conclusion, the main adaptation to long- term physical activity is lowered resting heart rate, even after partially or fully controlling for genetic liability and childhood environment. Key pointsThe main adaptation to long-term physical activity is lowering of resting heart rate, even after controlling for genetic liability.VO2peak is increased in the active co-twins compared with their inactive co-twins and accordingly, also submaximal heart rates during the clinical exercise test are lower in physically active co-twins.There is a tendency for increased LVM per body weight and heightened T wave amplitude in the active co-twins.

Electrocardiographic interventricular dispersion of repolarization during autonomic adaptation in LQT1 subtype of long QT syndrome.

OBJECTIVES: In LQT1 subtype of inherited long QT syndrome, repolarization abnormalities originating from defective I(Ks) render patients vulnerable to ventricular arrhythmia during sudden sympathetic activation. Experimental studies show lower I(Ks) density and longer action potential duration in left (LV) than in right (RV) ventricle. We studied interventricular dispersion of repolarization in patients with I(Ks) defect during autonomic tests. DESIGN: We measured interventricular (difference of QT intervals between LV and RV type leads) and transmural electrocardiographic dispersion of repolarization from 25-lead electrocardiograms in nine asymptomatic KCNQ1 mutation carriers (LQT1) and eight controls during rest, Valsalva maneuver, mental stress, sustained handgrip and supine exercise. RESULTS: LQT1 carriers showed increased interventricular dispersion of repolarization (13+/-9 ms vs. 4+/-4 ms, p=0.03) during all tests. Valsalva strain increased the difference between the study groups. In LQT1 carriers, interventricular dispersion of repolarization correlated weakly with electrocardiographic transmural dispersion of repolarization. CONCLUSIONS: Asymptomatic KCNQ1 mutation carriers exhibit increased and by abrupt sympathetic activation augmented interventricular difference in electrocardiographic repolarization times. Interventricular and transmural repolarization dispersion behave similarly in patients with I(Ks) defect.

Diastolic suction is impaired by bed rest: MRI tagging studies of diastolic untwisting.

Bed rest deconditioning leads to physiological cardiac atrophy, which may compromise left ventricular (LV) filling during orthostatic stress by reducing diastolic untwisting and suction. To test this hypothesis, myocardial-tagged magnetic resonance imaging (MRI) was performed, and maximal untwisting rates of the endocardium, midwall, and epicardium were calculated by Harmonic Phase Analysis (HARP) before and after -6 degrees head-down tilt bed rest for 18 days with (n = 14) and without exercise training (n = 10). LV mass and LV end-diastolic volume were measured using cine MRI. Exercise subjects cycled on a supine ergometer for 30 min, three times per day at 75% maximal heart rate (HR). After sedentary bed rest, there was a significant reduction in maximal untwisting rates of the midwall (-46.8 +/- 14.3 to -35.4 +/- 12.4 degrees /s; P = 0.04) where untwisting is most reliably measured, and to a lesser degree of certainty in the endocardium (-50.3 +/- 13.8 to -40.1 +/- 18.5 degrees /s; P = 0.09); the epicardium was unchanged. In contrast, when exercise was performed in bed, untwisting rates were enhanced at the endocardium (-48.4 +/- 20.8 to -72.3 +/- 22.3 degrees /ms; P = 0.05) and midwall (-39.2 +/- 12.2 to -59.0 +/- 19.6 degrees /s; P = 0.03). The differential response was significant between groups at the endocardium (interaction P = 0.02) and the midwall (interaction P = 0.004). LV mass decreased in the sedentary group (156.4 +/- 30.3 to 149.5 +/- 27.9 g; P = 0.07), but it increased slightly in the exercise-trained subjects (156.4 +/- 34.3 to 162.3 +/- 40.5 g; P = 0.16); (interaction P = 0.03). We conclude that diastolic untwisting is impaired following sedentary bed rest. However, exercise training in bed can prevent the physiological cardiac remodeling associated with bed rest and preserve or even enhance diastolic suction.

System for ECG and heart rate monitoring during group training.

We present a system for measuring ECG signals simultaneously from multiple persons during a group training session. The system transmits the signals to a coordinating computer where heart rate and other parameters are calculated from the signals. The heart rate values can then be shown for example through a video projector on a large display along with individual information about the training intensity.

Ventricular repolarization and heart rate responses during cardiovascular autonomic function testing in LQT1 subtype of long QT syndrome.

BACKGROUND: In the most prevalent LQT1 form of inherited long QT syndrome symptoms often occur during abrupt physical or emotional stress. Sympathetic stimulation aggravates repolarization abnormalities in experimental LQT1 models. We hypothesized that autonomic function tests might reveal the abnormal repolarization in asymptomatic LQT1 patients. METHODS: We measured heart rates (HRs) and QT intervals in nine asymptomatic carriers of a C-terminal KCNQ1 mutation and 8 unaffected healthy subjects using an approach of global QT values derived from 28 simultaneous electrocardiographic leads on beat-to-beat base during Valsalva maneuver, mental stress, sustained handgrip, and light supine exercise. RESULTS: LQT1 patients exhibited impaired shortening of both QTpeak and QTend intervals during autonomic interventions but exaggerated lengthening of the intervals--a QT overshoot--during the recovery phases. The number of tests with a QT overshoot was 2.4 +/- 1.7 in LQT1 patients and 0.8 +/- 0.7 in unaffected subjects (P = 0.02). Valsalva strain prolonged T wave peak to T wave end interval (TPE) in LQT1 but not in unaffected patients. LQT1 patients showed diminished HR acceleration in response to adrenergic challenge whereas HR responses to vagal stimuli were similar in both groups. CONCLUSIONS: Standard cardiovascular autonomic provocations induce a QT interval overshoot during recovery in asymptomatic KCNQ1 mutation carriers. Valsalva maneuver causes an exaggerated fluctuation of QT and TPE intervals partly explaining the occurrence of cardiac events during abrupt bursts of autonomic activity in LQT1 patients.

Effect of physical training on ventricular repolarization in type 1 long QT syndrome: a pilot study in asymptomatic carriers of the G589D KCNQ1 mutation.

AIMS: High-intensity physical exercise and competitive sports have been traditionally avoided in long QT syndrome. However, endurance training increases vagal activity and thus may improve cardiac electrical stability in healthy subjects. We hypothesized that controlled submaximal endurance training would not adversely affect ventricular repolarization in asymptomatic carriers of a KCNQ1 gene mutation of type 1 long QT syndrome (LQT1). METHODS AND RESULTS: Previously, sedentary carriers of a missense mutation of KCNQ1 gene (LQT1, n=7) and healthy controls (n=8) exercised on a bicycle ergometer 3-4 times a week, 30 min a day at 60-75% of maximal heart rate (HR) for a maximum of 3 months. Body surface potential mapping (BSPM) was recorded and QT intervals were determined automatically from 14 channels over the left chest area. Maximal work capacity increased by 4+/-1% in LQT1 and by 14+/-2% in controls (both P<0.05), and left ventricular (LV) mass by 8+/-1% and 9+/-1%, respectively (P<0.05). Resting corrected QT interval shortened by 10+/-1% (P<0.05) and QT interval dispersion by 25+/-9% (P<0.05) in LQT1, but not significantly in controls. QT intervals at specified HRs during workload and recovery phases were not changed in either group. CONCLUSION: In this pilot study of asymptomatic carriers of a KNCQ1 gene mutation, submaximal endurance training did not harmfully affect arrhythmia risk markers. Confirmatory studies in a broader spectrum of LQT1 genotypes are needed before any generalization can be made.

Reduced baroreflex control of heart period after bed rest is normalized by acute plasma volume restoration.

Adaptation to spaceflight or head-down-tilt bed rest leads to hypovolemia and an apparent abnormality of baroreflex regulation of cardiac period. In a previous study, we demonstrated that both chronic (2 wk) head-down-tilt bed rest and acute induced hypovolemia led to similar impairments in spontaneous baroreflex control of cardiac period, suggesting that a reduction in plasma volume may be responsible for this abnormality after bed rest. Therefore we hypothesized that this reduced "baroreflex function" could be restored by intravenous volume infusion equivalent to the reduction in plasma volume after bed rest. Six healthy subjects underwent 2 wk of -6 degrees head-down bed rest. Beat-by-beat arterial blood pressure and ECG were recorded during 6 min of spontaneous respiration and fixed-rate breathing (0.2 Hz), and transfer function analysis between systolic blood pressure and R-R interval was performed. Plasma volume was measured with Evans blue dye, and cardiac filling pressures were directly measured (Swan-Ganz catheter). After bed rest, studies were repeated before and after plasma volume restoration, with which both plasma volume and left ventricular end-diastolic pressure were restored to pre-bed rest levels by intravenous dextran40 infusion (288 +/- 31 ml). Transfer function gain in the high-frequency range, used as an index of vagally mediated arterial-cardiac baroreflex function, decreased significantly (13.4 +/- 3.1 to 8.1 +/- 2.9 ms/mmHg, P < 0.05) after bed rest. However, reduced transfer function gain was normalized to the pre-bed rest level (12.2 +/- 3.6 ms/mmHg) after precise plasma volume restoration. This result confirms that reductions in plasma volume, rather than a unique autonomic nervous system adaptation to bed rest, are largely responsible for the observed changes in spontaneous arterial-cardiac baroreflex function after bed rest.

Hemodynamics of orthostatic intolerance: implications for gender differences.

Women have a greater incidence of orthostatic intolerance than men. We hypothesized that this difference is related to hemodynamic effects on regulation of cardiac filling rather than to reduced responsiveness of vascular resistance during orthostatic stress. We constructed Frank-Starling curves from pulmonary capillary wedge pressure (PCWP), stroke volume (SV), and stroke index (SI) during lower body negative pressure (LBNP) and saline infusion in 10 healthy young women and 13 men. Orthostatic tolerance was determined by progressive LBNP to presyncope. LBNP tolerance was significantly lower in women than in men (626.8 +/- 55.0 vs. 927.7 +/- 53.0 mmHg x min, P < 0.01). Women had steeper maximal slopes of Starling curves than men whether expressed as SV (12.5 +/- 2.0 vs. 7.1 +/- 1.5 ml/mmHg, P < 0.05) or normalized as SI (6.31 +/- 0.8 vs. 4.29 +/- 0.6 ml.m-2.mmHg-1, P < 0.05). During progressive LBNP, PCWP dropped quickly at low levels, and reached a plateau at high levels of LBNP near presyncope in all subjects. SV was 35% and SI was 29% lower in women at presyncope (both P < 0.05). Coincident with the smaller SV, women had higher heart rates but similar mean arterial pressures compared with men at presyncope. Vascular resistance and plasma norepinephrine concentration were similar between genders. We conclude that lower orthostatic tolerance in women is associated with decreased cardiac filling rather than reduced responsiveness of vascular resistance during orthostatic challenges. Thus cardiac mechanics and Frank-Starling relationship may be important mechanisms underlying the gender difference in orthostatic tolerance.