Cardiovascular physiology and pathophysiology in Down syndrome.

Down syndrome (Ds) is the most common chromosomal cause of intellectual disability that results from triplication of chromosome 21 genes. Individuals with Ds demonstrate cognitive deficits in addition to comorbidities including cardiac defects, pulmonary arterial hypertension (PAH), low blood pressure (BP), and differences in autonomic regulation. Many individuals with Ds are born with heart malformations and some can be surgically corrected. Lower BP at rest and in response to exercise and other stressors are a prevalent feature in Ds. These reduced cardiovascular responses may be due to underlying autonomic dysfunction and have been implicated in lower exercise/work capacity in Ds, which is an important correlate of morbidity, mortality and quality of life. Exercise therapy can be beneficial to normalize autonomic function and may help prevent the development of co-morbidities in Ds. We will review cardiovascular physiology and pathophysiology in individuals with Ds, along with exercise therapy and special considerations for these individuals.

Effect of acute high-intensity resistance exercise on optic nerve sheath diameter and ophthalmic artery blood flow pulsatility.

Exertional hypertension associated with acute high-intensity resistance exercise (RE) increases both intravascular and intracranial pressure (ICP), maintaining cerebrovascular transmural pressure. Carotid intravascular pressure pulsatility remains elevated after RE. Whether ICP also remains elevated after acute RE in an attempt to maintain the vessel wall transmural pressure is unknown. Optic nerve sheath diameter (ONSD), a valid proxy of ICP, was measured in 20 participants (6 female; 24 ± 4 yr, 24.2 ± 3.9 kg m(-)(2)) at rest (baseline), following a time-control condition, and following RE (5 sets, 5 repetition maximum bench press, 5 sets 10 repetition maximum biceps curls) using ultrasound. Additionally, intracranial hemodynamic pulsatility index (PI) was assessed in the ophthalmic artery (OA) by using Doppler. Aortic pulse wave velocity (PWV) was obtained from synthesized aortic pressure waveforms obtained via a brachial oscillometric cuff and carotid pulse pressure was measured by using applanation tonometry. Aortic PWV (5.2 ± 0.5-6.0 ± 0.7 m s(-1), P < 0.05) and carotid pulse pressure (45 ± 17-59 ± 19 mm Hg, P < 0.05) were significantly elevated post RE compared with baseline. There were no significant changes in ONSD (5.09 ± 0.7-5.09 ± 0.7 mm, P > 0.05) or OA flow PI (1.35 ± 0.2-1.38 ± 0.3, P > 0.05) following acute RE. In conclusion, during recovery from acute high-intensity RE, there are increases in aortic stiffness and extracranial pressure pulsatility in the absence of changes in ICP and flow pulsatility. These findings may have implications for alterations in cerebral transmural pressure and cerebral aneurysmal wall stress following RE.

Effect of a single bout of resistance exercise on arterial stiffness following a high-fat meal.

Consumption of a high-fat meal (HFM) causes postprandial lipemia and vascular dysfunction. Acute resistance exercise (RE) alone may also have a negative effect on vascular function. The purpose of this study was to measure arterial stiffness and postprandial lipemia after a HFM with or without acute RE. 9 recreationally active men (age 24±5 years, BMI 25±3 kg/m2) completed both: (1) HFM alone and (2) HFM+RE in a randomized order. Pulse wave velocity (PWV) from carotid to femoral artery and carotid to radial artery were used as measures of central/aortic and peripheral arterial stiffness, respectively. Circulating triglycerides (TRG) were obtained from finger stick samples as a marker of lipemia. There was a significant condition-by-time interaction for TRG (p<0.05). TRG levels increased significantly following both conditions with a significantly attenuated increase following HFM+RE (p<0.05). There was a significant condition-by-time interaction for peripheral PWV as this parameter increased following HFM, but decreased following HFM+RE (p=0.021). Central PWV did not change with HFM or HFM+RE (p>0.05). Following a HFM, acute RE attenuates postprandial lipemia and improves peripheral arterial stiffness without having a negative effect on central arterial stiffness.

Effect of resistance training on biomarkers of vascular function and oxidative stress in young African-American and Caucasian men.

African Americans (AA) have an earlier onset of hypertension and a different vascular profile than their Caucasian (Cau) peers. Research suggests that biological mediators of vascular inflammation are different among these groups in hypertensive populations. Resistance training (RT) is an important exercise modality that improves the vascular profile of young AA men. We examined the role of RT on biomarkers of vascular function and oxidative stress in body mass index-matched AA and Cau men. RT for 6 weeks elicited significant changes in circulating matrix metalloprotease-9 (MMP-9) and 8-Isoprostane (8-IsoP) in young AA men (n=14, AA; n=18, Cau; 18-35 years). MMP-9 was lower and decreased in AA (pre: P=0.02; post: P<0.001) and a time × group interaction for MMP-9 (F(1, 30)=4.81; P=0.036) and 8-IsoP (F(1, 24)=7.09; P=0.014) was detected. 8-IsoP decreased in AA (P=0.026) but did not change in Cau (P=0.309). Notably, the increase in strength (1-repetition maximum (1-RM)) was correlated with the decrease in MMP-9 (r=-0.398; P=0.022). Furthermore, these adaptations were independent of any improvement in cardiorespiratory fitness. We demonstrate that RT effectively reduces matrix remodeling proteins and oxidative stress in young AA men. Increasing strength may be beneficial for improving vascular health and offsetting novel cardiovascular risk factors of hypertension in young AA men.

Aortic reservoir function, estimated myocardial demand and coronary perfusion pressure following steady-state and interval exercise.

Aortic reservoir function is a measure of the aorta's ability to distribute blood during diastole, attenuating the pulsatility of blood flow, and is important in balancing cardiac flow. Effects of acute high versus moderate exercise intensity on reservoir function and cardiac energetics is unknown. Eighteen athletes completed a interval (INT) and steady-state (SS) cycling bout at 60% of VO(2) peak. Reservoir function was calculated as the ratio of diastolic run-off to stroke volume and expressed as a percentage. Coronary perfusion pressure was derived from tissue Doppler imaging and echocardiography. Systolic tension-time integral (TTI) from the aortic pressure waveform served as a measure of myocardial oxygen consumption. All measures were made at rest, 30-min postexercise and 60-min postexercise. Average reservoir function before SS was 76%, which was reduced to 62% 30-min post-SS and 67% 60-min post-SS (P<0.05). Significantly greater reductions in reservoir function were seen following INT (from 71% pre-INT to 45% 30-min post-INT and 53% 60-min INT, P<0.05). Estimated coronary perfusion pressure was reduced 30 min following INT but not SS; both bouts reduced coronary perfusion pressure at 60-min postexercise (P<0.05). TTI increased following both INT and SS at 30- and 60-min postexercise with greater increases following INT (P<0.05). Following exercise, reservoir function was associated with TTI (P<0.05), but not coronary perfusion pressure (P>0.05). We conclude that reservoir function is attenuated following acute SS and INT, but these reductions were greater post-INT, suggesting that exercise intensity affects reservoir function. Reduction of reservoir function following exercise is related to TTI, a reflection of myocardial oxygen consumption but apparently not associated with coronary perfusion pressure.

Carotid artery stiffness, high-density lipoprotein cholesterol and inflammation in men with pre-hypertension.

Low circulating levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased risk for cardiovascular events. HDL-C has a variety of poorly understood atheroprotective effects, including altering lipid metabolism and reducing inflammation. Increased arterial stiffness is an important predictor of subsequent cardiovascular risk. Therefore, in this study, we sought to determine whether HDL-C levels are associated with carotid arterial stiffness. In addition, we examined potential correlates of this association, such as inflammatory factors, cardiorespiratory fitness and body fat percentage. Carotid artery beta-stiffness was measured by ultrasound in 47 (23 years old) healthy pre-hypertensive men. Low HDL-C was defined as <1.0 mmol l(-1). Body fat was measured by air displacement plethysmography. Cardiorespiratory fitness was measured using a maximal exercise test, with metabolic gas analysis and inflammatory markers consisting of C-reactive protein (CRP), white blood cell (WBC) count and absolute neutrophil count. Men with a low HDL-C had significantly higher carotid artery stiffness, CRP, WBC count, neutrophil count, body fat, fasting glucose and lower cardiorespiratory fitness (P<0.05). Co-varying for cardiorespiratory fitness, % body fat and glucose had no effect on group differences in carotid artery stiffness. Co-varying for inflammatory markers resulted in groups having similar carotid artery stiffness. Pre-hypertensive men with low HDL-C have a higher carotid artery stiffness when compared with those with higher HDL-C. The detrimental effects of low HDL-C on large artery stiffness in pre-hypertensive men may be mediated by inflammation and not by cardiorespiratory fitness or body fat levels.

Acute resistance exercise reduces heart rate complexity and increases QTc interval.

Acute resistance exercise (RE) has been shown to reduce cardiac vagal control. Whether this would in turn affect QTc interval (an index of ventricular depolarization/repolarization) or heart rate complexity is not known. Heart rate variability (HRV), heart rate complexity (SampEn), and QT interval (rate corrected using Bazett, Fridericia, Hodges, and Framingham) were measured before and 5 min after an acute RE bout in twelve healthy young men. Normalized high frequency power of HRV (an index of cardiac parasympathetic modulation; HF (nu)), and SampEn were reduced following RE (p < 0.05). Bazett corrected QTc interval increased following RE (p < 0.05). Change in HF (nu) from rest to recovery was correlated with both change in SampEn (r = 0.51, p < 0.05) and change in QTc interval for each method of correction (r = - 0.67 to - 0.70, p < 0.05). Acute RE reduced HF spectral power of HRV and this was related to both reduced heart rate complexity and increased QTc length. Thus, during recovery from acute RE, there is prolongation of depolarization and repolarization of the ventricles concomitant with reduced cardiac irregularity, and this may be related to a reduction in cardiac vagal control.

Gender differences in QTc interval in young, trained individuals with lower spinal cord injury.

STUDY DESIGN: Cross-sectional comparison. OBJECTIVE: To examine gender differences in rate-corrected QT interval (QTc), an index of ventricular depolarization/repolarization, in young, trained men and women with lower spinal cord injury (SCI) and able-bodied (AB) controls. SETTING: University of Illinois at Urbana-Champaign, Exercise and Cardiovascular Research Lab, USA. METHODS: Subjects consisted of 16 athletes with SCI (eight men and eight women) and 16 age-matched AB active controls (eight men and eight women). QT interval dynamics was derived from ECG recordings and rate corrected using the Bazett formula. RESULTS: Men with SCI had QTc similar to that of AB men (369.3+/-7.5 versus 357.9+/-3.0 ms, P>0.05). Women with SCI had QTc similar to that of AB women (400.0+/-4.6 versus 385.2+/-6.5 ms, P>0.05). AB women had longer QTc interval than AB men, and SCI women had longer QTc than SCI men (P<0.05). CONCLUSIONS: Gender differences in ventricular depolarization/repolarization are present in trained individuals with SCI. Thus, similar to their AB gender-matched peers, women with SCI have longer QTc intervals and may be at greater risk for the development of untoward cardiac arrhythmias than men with SCI.

Arterial stiffness and baroreflex sensitivity following bouts of aerobic and resistance exercise.

We examined arterial stiffness, baroreflex sensitivity (BRS), and systolic arterial pressure (SAP) variability after an acute bout of aerobic exercise compared to resistance exercise. We hypothesized that arterial stiffness would be reduced after aerobic exercise, while it would be increased after resistance exercise, and these alterations would be associated with differential changes in BRS and SAP variability. Arterial stiffness, BRS, and SAP variability were assessed before and 20 min after a bout of aerobic exercise and resistance exercise in 13 male participants. Pulse wave velocity (PWV) was used to measure central (carotid-femoral) and peripheral (femoral-dorsalis pedis) arterial stiffness. BRS was derived via the sequence technique. Spectral decomposition of beat-to-beat SAP variability was used as an estimate of sympathetic vasomotor tone. A mode-by-time interaction (p < 0.001) was detected for central PWV, due to an increase in PWV (p < 0.05) following resistance exercise and a decrease in PWV following aerobic exercise (p < 0.05). A mode-by-time interaction was also detected for peripheral PWV (p < 0.05), due to a decrease in peripheral PWV following aerobic exercise (p < 0.05) with no change following resistance exercise. BRS was significantly lower following resistance compared with aerobic exercise (p < 0.004). SAP variability increased following resistance exercise (p < 0.05) but there was no interaction. In conclusion, aerobic exercise decreased both central and peripheral arterial stiffness, while resistance exercise significantly increased central arterial stiffness only. BRS was reduced after both bouts of exercise, but significantly greater reductions were seen following resistance exercise.