Rectal sensorimotor dysfunction in women with fecal incontinence

The rate and pattern of rectal distension affect rectal distensibility, perception, and anal relaxation in health. Because rectal urgency is a prominent symptom in fecal incontinence (FI), we assessed rectal distensibility, contractions, perception, and anal pressures during rectal distention in 21 healthy, asymptomatic women (age 61 +/- 2 yr, mean +/- SE) and 51 women with FI (60 +/- 2 yr). Rectal staircases (0-32 mmHg, 4-mm steps) and ramp distensions [0-200 ml at 25, 50, and 100 ml/min with a phase of sustained distension (SD), lasting 1 min, between inflation and deflation]. The rectum was stiffer during rapid than slow ramp distention. This effect was more prominent at a lower volume (50 ml) and was also more pronounced in older subjects and in FI. A rectal contractile response was observed not only during inflation but also during SD and during deflation. During inflation, this contractile response was rate dependent in controls but not in FI. During staircase but not ramp distentions, the threshold for the desire to defecate was lower in FI. During ramp distentions, the duration of perception was significantly longer in FI. The rate of distention did not affect rectal perception (i.e., sensory thresholds or duration of perception) during ramp distentions. Baseline anal pressures and the magnitude of anal relaxation during rectal distention were also reduced in FI. In addition to reduced rectal capacity and compliance, women with FI had an exaggerated rate-dependent reduction in rectal distensibility, lower sensory thresholds, and more prolonged perception, indicative of rectoanal dysfunctions.     

Anal sphincteric neurogenic injury in asymptomatic nulliparous women and fecal incontinence

While anal sphincter neurogenic injury documented by needle electromyography (EMG) has been implicated to cause fecal incontinence (FI), most studies have been uncontrolled. Normal values and the effects of age on anal sphincter motor unit potentials (MUP) are ill defined. The functional significance of anal sphincter neurogenic injury in FI is unclear. Anal pressures and EMG were assessed in 20 asymptomatic nulliparous women (age, 38 ± 5 yr; mean ± SE) and 20 women with FI (54 ± 3 yr). A computerized program quantified MUP duration and phases. These parameters and MUP recruitment were also semiquantitatively assessed by experienced electromyographers in real time. Increasing age was associated with longer and more polyphasic MUP in nulliparous women by quantitative analysis. A higher proportion of FI patients had prolonged (1 control, 7 patients, P = 0.04) and polyphasic MUP (2 controls, 9 patients, P = 0.03) at rest but not during squeeze. Semiquantitative analyses identified neurogenic or muscle injury in the anal sphincter (11 patients) and other lumbosacral muscles (4 patients). There was substantial agreement between quantitative and semiquantitative analyses (κ statistic 0.63 ± 95% CI: 0.32-0.96). Anal resting and squeeze pressures were lower (P ≤ 0.01) in FI than controls. Anal sphincter neurogenic or muscle injury assessed by needle EMG was associated (P = 0.01) with weaker squeeze pressures (83 ± 10 mmHg vs. 154 ± 30 mmHg) and explained 19% (P = 0.01) of the variation in squeeze pressure. Anal sphincter MUP are longer and more polyphasic in older than younger nulliparous women. Women with FI have more severe neurogenic or muscle anal sphincter injury, which is associated with lower squeeze pressures.     

Reduction of coronary flow reserve in patients with increased aortic stiffness

Aortic stiffness is thought to affect coronary blood flow, but little is known about its influence on coronary flow reserve (CFR). The objective of the present study was to investigate the relationship between aortic stiffness and CFR in matched patients with and without increased aortic stiffness. Stress transoesophageal echocardiography (TEE) as the CFR measurement and coronary angiography were performed in all cases. Increased aortic stiffness was defined if elastic modulus Ep > 680 mmHg. The following patient populations free of coronary artery disease were compared: 36 subjects with normal aortic distensibility and 19 age-, sex-, and risk factor-matched patients with increased aortic stiffness. CFR was significantly reduced in patients with increased aortic stiffness as compared with cases with normal aortic distensibility (2.64 +/- 1.16 vs. 2.12 +/- 0.58, p <0.01). Hyperaemic diastolic flow velocities were reduced in patients with increased aortic stiffness (129.5 +/- 36.6 cm/s vs. 102.1 +/- 39.8 cm/s, p <0.05). Negative correlations were found between Ep and hyperaemic diastolic coronary flow velocity (r = -0.41, p < 0.01) and CFR (r = -0.21, p < 0.05). CFR is reduced in patients with increased aortic stiffness and negative correlations exist between these functional parameters.     

Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women

The mechanisms mediating arterial stiffening with aging and menopause are not completely understood. We determined whether administration of tetrahydrobiopterin (BH(4)), a critical cofactor for endothelial nitric oxide synthase to produce nitric oxide, would increase vascular endothelial-dependent vasodilatory tone and decrease arterial stiffness in estrogen-deficient postmenopausal women. Additionally, we examined whether the beneficial effects of estrogen on vascular function were possibly related to BH(4). Arterial stiffness (carotid artery compliance) and endothelial-dependent vasodilation [brachial artery flow-mediated dilation (FMD)] were measured in postmenopausal (n = 24; 57 ± 1 yr, mean ± SE) and eumenorrheic premenopausal (n = 9; 33 ± 2 yr) women before and 3 h after the oral administration of BH(4). Subsequently, in postmenopausal women, vascular testing (before and after BH(4)) was repeated following randomization to either 2 days of transdermal estradiol or placebo. Baseline carotid artery compliance and brachial artery FMD were lower in postmenopausal than in premenopausal women (P < 0.0001). BH(4) administration increased carotid artery compliance (0.61 ± 0.05 to 0.73 ± 0.04 mm(2)·mmHg(-1)·10(-1) vs. baseline, P < 0.0001) and brachial artery FMD (P < 0.001) in postmenopausal women but had no effect in premenopausal women (P = 0.62). Carotid artery compliance (0.59 ± 0.05 to 0.78 ± 0.06 mm(2)·mmHg(-1)·10(-1), P < 0.001) and FMD increased in postmenopausal women in response to estradiol (P = 0.02) but were not further improved with the coadministration of BH(4), possibly because estrogen increased BH(4) bioavailability. Carotid artery compliance and FMD increased with BH(4) in the placebo group (P = 0.02). Although speculative, these results suggest that reduced vascular BH(4) may be an important contributor to arterial stiffening in estrogen-deficient postmenopausal women, related in part to reduced endothelial-dependent vasodilatory tone.     

Effect of airway smooth muscle tone on airway distensibility measured by the forced oscillation technique in adults with asthma

Airway distensibility appears to be unaffected by airway smooth muscle (ASM) tone, despite the influence of ASM tone on the airway diameter-pressure relationship. This discrepancy may be because the greatest effect of ASM tone on airway diameter-pressure behavior occurs at low transpulmonary pressures, i.e., low lung volumes, which has not been investigated. Our study aimed to determine the contribution of ASM tone to airway distensibility, as assessed via the forced oscillation technique (FOT), across all lung volumes with a specific focus on low lung volumes. We also investigated the accompanying influence of ASM tone on peripheral airway closure and heterogeneity inferred from the reactance versus lung volume relationship. Respiratory system conductance and reactance were measured using FOT across the entire lung volume range in 22 asthma subjects and 19 healthy controls before and after bronchodilator. Airway distensibility (slope of conductance vs. lung volume) was calculated at residual volume (RV), functional residual capacity (FRC), and total lung capacity. At baseline, airway distensibility was significantly lower in subjects with asthma at all lung volumes. After bronchodilator, distensibility significantly increased at RV (64.8%, P < 0.001) and at FRC (61.8%, P < 0.01) in subjects with asthma but not in control subjects. The increased distensibility at RV and FRC in asthma were not associated with the accompanying changes in the reactance versus lung volume relationship. Our findings demonstrate that, at low lung volumes, ASM tone reduces airway distensibility in adults with asthma, independent of changes in airway closure and heterogeneity.     

Influence of hyperglycemia during and after pregnancy on postpartum vascular function

Endothelial dysfunction is commonly observed in women with a previous diagnosis of gestational diabetes mellitus (GDM). Whether arterial stiffness is also related to pregnancy and/or postpartum glucose intolerance has not been determined. We examined the influence of GDM during pregnancy and hyperglycemia in the postpartum period on arterial function. Thirty postpartum women were stratified into one of three groups: 1) normoglycemic pregnancy, normoglycemic postpartum (NORM), 2) GDM during pregnancy, normoglycemic postpartum (GDM-N); and 3) GDM during pregnancy, hyperglycemic postpartum (GDM-H). Ten never-pregnant controls were also recruited (Control). All measures were made at 2 mo postpartum or in the early follicular phase in Control women. Arterial stiffness was assessed by pulse wave velocity (PWV) and brachial and carotid artery distensibility. Endothelial function was determined by flow-mediated dilation (FMD). PWV was not different between the four groups. Distensibility of the brachial and carotid arteries was lower in GDM-N women (brachial: 1.1 × 10(-3) mmHg(-1) ± 3.6 × 10(-4); carotid: 2.0 × 10(-3) ± 3.3 × 10(-4)) and GDM-H (brachial: 1.4 × 10(-3) mmHg(-1) ± 4.1 × 10(-4); carotid: 1.8 × 10(-3) mmHg(-1) ± 5.0 × 10(-4)) compared with NORM women (brachial: 3.4 × 10(-3) mmHg(-1) ± 7.0 × 10(-4); carotid: 3.9 × 10(-3) ± 7.4 × 10(-4)). However, only brachial artery distensibility returned to Control levels by 2 mo postpartum in the NORM women. FMD was lower in previously GDM women (GDM-N: 4.1% ± 2.3; GDM-H: 4.4% ± 0.9) compared with NORM women (10.8% ± 1.3; P < 0.01). These findings suggest that the vascular function of women in the early postpartum period is influenced by GDM during pregnancy and the persistence of clinical and/or subclinical hyperglycemia after delivery.     

Very low-frequency blood pressure variability depends on voltage-gated L-type Ca2+ channels in conscious rats

The mechanisms generating high- frequency (HF) and low-frequency (LF) blood pressure variability (BPV) are reasonably well understood. However, little is known about the origin of very low-frequency (VLF) BPV. We tested the hypothesis that VLF BPV is generated by L-type Ca(2+) channel-dependent mechanisms. In conscious rats, arterial blood pressure was recorded during control conditions (n = 8) and ganglionic blockade (n = 7) while increasing doses (0.01-5.0 mg.100 micro l(-1).h(-1)) of the L-type Ca(2+) channel blocker nifedipine were infused intravenously. VLF (0.02-0.2 Hz), LF (0.2-0.6 Hz), and HF (0.6-3.0 Hz) BPV were assessed by spectral analysis of systolic blood pressure. During control conditions, nifedipine caused dose-dependent declines in VLF and LF BPV, whereas HF BPV was not affected. At the highest dose of nifedipine, VLF BPV was reduced by 86% compared with baseline, indicating that VLF BPV is largely mediated by L-type Ca(2+) channel-dependent mechanisms. VLF BPV appeared to be relatively more dependent on L-type Ca(2+) channels than LF BPV because lower doses of nifedipine were required to significantly reduce VLF BPV than to reduce LF BPV. Ganglionic blockade markedly reduced VLF and LF BPV and abolished the nifedipine-induced dose-dependent declines in VLF and LF BPV, suggesting that VLF and LF BPV require sympathetic activity to be evident. In conclusion, VLF BPV is largely mediated by L-type Ca(2+) channel-dependent mechanisms. We speculate that VLF BPV is generated by myogenic vascular responses to spontaneously occurring perturbations of blood pressure. Other factors, such as sympathetic nervous system activity, may elicit a permissive effect on VLF BPV by increasing vascular myogenic responsiveness.     

Altered L-type Ca(2+) channel currents in vascular smooth muscle cells from experimental diabetic rats

Vascular complications of diabetes are associated with abnormal Ca(2+) handling by vascular smooth muscle cells (SMCs) in which the alteration in L-type voltage-dependent Ca(2+) channel (VDCC) currents may play an important role. In the present study, the characteristics of L-type VDCC currents in tail artery SMCs from streptozotocin-induced diabetic rats were examined. The densities, but not the voltage dependence, of L-type VDCC currents were reduced as diabetes progressed from 1 wk to 3 mo. The inhibitory effect of dibutyryl-cAMP on L-type VDCC currents was greater in diabetic SMCs than in age-matched control cells (P < 0.01). Both the stimulatory effect of BAY K 8644 and the inhibitory effect of nifedipine on L-type VDCC currents were significantly enhanced in diabetic cells. The diabetes-related abnormalities in L-type VDCC currents were mimicked by culturing SMCs with a high concentration of glucose. Our results suggest that the properties of L-type VDCC in diabetic vascular SMCs were significantly altered, partially related to the increased L-type VDCC sensitivity to cAMP and hyperglycemia.     

Nifedipine in hypertensive emergencies.

The effects and safety of using oral nifedipine 10-20 mg as acute antihypertensive treatment were studied in a single-blind placebo-controlled study of 25 consecutive patients with very high blood pressure requiring emergency reduction. In addition the effect of this treatment on cerebral blood flow was investigated using xenon-133 in 10 patients randomly allocated to receive oral nifedipine or intravenous clonidine. Whereas placebo did not alter the blood pressure, oral nifedipine significantly reduced the systolic and diastolic blood pressures in all 25 patients (from 221 +/- 22/126 +/- 14 mm Hg to 152 +/- 20/89 +/- 12 mm Hg after 30 minutes, p less than 0.001). Heart rate increased from 74 +/- 11 to 84 +/- 11 beats/minute (p less than 0.01); this effect was inversely related to age (r = -0.65, p less than 0.01). The falls in systolic and diastolic blood pressures were closely related to the blood pressures before treatment ) r = 0.67, p less than 0.001 for systolic, and r = -0.58, p less than 0.01 for diastolic values). No serious unwanted effects were observed. Measurement of cerebral blood flow after nifedipine showed an increase in flow in four out of five patients. Clonidine, by contrast, reduced cerebral blood flow in all patients by up to 28%. Nifedipine is a simple, effective, and safe alternative drug for managing hypertensive emergencies, especially when continuous monitoring of the patient cannot be guaranteed.     

Acute hemorrhagic shock decreases airway resistance in anesthetized rat

We studied the relation between changes in pulmonary and systemic hemodynamics to those in the airway resistance, respiratory tissue mechanics, and thoracic gas volume (TGV) following acute hemorrhage and blood reinfusion in rats. Forced oscillation technique was used to measure airway resistance (Raw), respiratory tissue damping, and elastance at baseline and after stepwise 1-ml blood withdrawals up to 5 ml total, followed by stepwise reinfusion up to full restoration. Mean systemic (Pam) and pulmonary arterial pressures and suprarenal aortic blood flow were measured at each step. In supplemental animals, plethysmographic TGV, Pam, and respiratory mechanics measurements were performed. Blood volume loss (BVL) led to proportional decreases in Raw (66.5 ± 8.8 vs. 44.8 ± 9.0 cmH(2)O·s·l(-1) with 5 ml, P < 0.001), Pam, and aortic blood flow. In contrast, tissue damping increased significantly (1,070 ± 91 vs. 1,235 ± 105 cmH(2)O/l, P = 0.009 with 5 ml BVL), whereas tissue elastance did not change significantly. TGV significantly increased with acute BVL (3.7 ± 0.2 vs. 4.2 ± 0.2 ml, P = 0.01). Stepwise reinfusions produced opposite changes in the above parameters, with Raw reaching a higher value than baseline (P = 0.001) upon full volume restoration. Both adrenalin (P = 0.015) and noradrenalin levels were elevated (P = 0.010) after 5-ml blood withdrawal. Our data suggest that the decreases in Raw following BVL may be attributed to the following: 1) an increased TGV enhancing airway parenchymal tethering forces; and 2) an increase in circulating catecholamines. The apparent beneficial effect of a reduction in Raw in acute hemorrhagic shock is counteracted by an increase in dead space and the appearance of peripheral mechanical heterogeneities due to de-recruitment of the pulmonary vasculature.     

Carotid distensibility characterized via the isometric exercise pressor response

Distensibility of the large elastic arteries is a key index for cardiovascular health. Distensibility, usually estimated from resting values in humans, is not a static characteristic but a negative curvilinear function of pressure. We hypothesized that differences in vascular function with gender and age may only be recognized if distensibility is quantified over a range of pressures. We used isometric handgrip exercise to induce progressive increases in pressures and carotid diameters, thereby enhancing the characterization of distensibility. In 30 volunteers, evenly distributed by gender and age across the third to fifth decades of life, we derived pulsatile distensibility slopes as a function of arterial pressure for a dynamic distensibility index and compared it with a traditional static index at a reference pressure of 95 mmHg. We also assessed intima-media thickness (IMT). We found that women had greater distensibility slopes within each decade, despite comparable IMT. Furthermore, declines in distensibility slope with increasing age were correlated to increased IMT. The static distensibility index failed to show gender-related differences in distensibility but did show age-related differences. Our results indicate that gender- and age-related differences can be manifest even in young, healthy adults and may only be identified with techniques that assess carotid distensibility across a range of pressures.     

Congestive heart failure with preserved ejection fraction is associated with severely impaired dynamic Starling mechanism

Sedentary aging leads to increased cardiovascular stiffening, which can be ameliorated by sufficient amounts of lifelong exercise training. An even more extreme form of cardiovascular stiffening can be seen in heart failure with preserved ejection fraction (HFpEF), which comprises ~40~50% of elderly patients diagnosed with congestive heart failure. There are two major interrelated hypotheses proposed to explain heart failure in these patients: 1) increased left ventricular (LV) diastolic stiffness and 2) increased arterial stiffening. The beat-to-beat dynamic Starling mechanism, which is impaired with healthy human aging, reflects the interaction between ventricular and arterial stiffness and thus may provide a link between these two mechanisms underlying HFpEF. Spectral transfer function analysis was applied between beat-to-beat changes in LV end-diastolic pressure (LVEDP; estimated from pulmonary artery diastolic pressure with a right heart catheter) and stroke volume (SV) index. The dynamic Starling mechanism (transfer function gain between LVEDP and the SV index) was impaired in HFpEF patients (n = 10) compared with healthy age-matched controls (n = 12) (HFpEF: 0.23 ± 0.10 ml·m?2·mmHg?1 and control: 0.37 ± 0.11 ml·m?2·mmHg?1, means ± SD, P = 0.008). There was also a markedly increased (3-fold) fluctuation of LV filling pressures (power spectral density of LVEDP) in HFpEF patients, which may predispose to pulmonary edema due to intermittent exposure to higher pulmonary capillary pressure (HFpEF: 12.2 ± 10.4 mmHg2 and control: 3.8 ± 2.9 mmHg2, P = 0.014). An impaired dynamic Starling mechanism, even more extreme than that observed with healthy aging, is associated with marked breath-by-breath LVEDP variability and may reflect advanced ventricular and arterial stiffness in HFpEF, possibly contributing to reduced forward output and pulmonary congestion.     

Carotid Stiffness and Physical Activity in Elderly—A Short Report of the SAPALDIA 3 Cohort Study

Introduction

Regular physical activity has been shown to reduce cardiovascular disease risk in the general population. While smaller studies in specified groups (highly trained versus untrained individuals) indicate a certain dose-dependent effect of physical activity on the reduction of carotid stiffness (an indicator of subclinical vascular disease), it is unclear whether this association is present in a representative sample. Thus, we investigated this question cross-sectionally in participants from the population-based Swiss Cohort Study on Air Pollution And Lung and Heart Diseases In Adults (SAPALDIA).

Methods

Self-reported total, moderate and vigorous physical activity and distensibility as a measure of local arterial stiffness among 1636 participants aged 50 to 81 years without clinically manifest diseases were evaluated. Mixed regression models were used to examine associations of physical activity intensity with distensibility.

Results

Vigorous physical activity, but not total nor moderate physical activity, was significantly associated with increased distensibility (= reduced carotid stiffness) in univariate analyses (percent change in the geometric mean and 95% confidence interval per 1 standard deviation increment in vigorous physical activity = 2.54 (0.69; 4.43), p<0.01; in total physical activity = 1.62 (-0.22; 3.50), p = 0.08; in moderate physical activity = 0.70 (-1.12; 2.56), p = 0.45). These associations disappeared when we additionally adjusted for age.

Conclusion

After adjustment for the most important confounders and risk factors, we found no evidence for an association of physical activity with carotid stiffness in the general middle aged to elderly population.     

Acute exercise and training alter blood lipid and lipoprotein profiles differently in overweight and obese men and women

Our purpose was to elucidate effects of acute exercise and training on blood lipids-lipoproteins, and high-sensitivity C-reactive protein (hsCRP) in overweight/obese men (n = 10) and women (n = 8); age, BMI, body fat percentage, and VO(2)max were (mean ± SEM): 45 ± 2.5 years, 31.9 ± 1.4 kg·m(-2), 41.1 ± 1.5%, and 25.2 ± 1.3 mlO(2)·kg(-1)·min(-1). Before exercise training subjects performed an acute exercise session on a treadmill (70% VO(2)max, 400 kcal energy expenditure), followed by 12 weeks of endurance exercise training (land-based or aquatic-based treadmill): 3 sessions·week(-1), progressing to 500 kcal·session(-1) during which subjects maintained accustomed dietary habits. After training, the acute exercise session was repeated. Blood samples, obtained immediately before and 24 h after acute exercise sessions, were analyzed for serum lipids, lipoproteins, and hsCRP adjusted for plasma volume shifts. Exercise training increased VO(2)max (+3.67 mlO(2)·kg(-1)·min(-1), P < 0.001) and reduced body weight (-2.7 kg, P < 0.01). Training increased high-density lipoprotein (HDL) and HDL(2b)-cholesterol (HDL-C) concentrations (+3.7 and +2.4 mg·dl(-1), P < 0.05) and particle numbers (+588 and +206 nmol·l(-1), P < 0.05) in men. In women despite no change in total HDL-C, subfractions shifted from HDL(3)-C (-3.2, P < 0.01) to HDL(2b)-C (+3.5, P < 0.05) and HDL(2a)-C (+2.2 mg·dl(-1), P < 0.05), with increased HDL(2b) particle number (+313 nmol·l(-1), P < 0.05). Training reduced LDL(3) concentration and particle number in women (-1.6 mg·dl(-1) and -16 nmol·l(-1), P < 0.05). Acute exercise reduced the total cholesterol (TC): HDL-C ratio in men (-0.16, P < 0.01) and increased hsCRP in all subjects (+0.05 mg·dl(-1), P < 0.05), regardless of training. Training did not affect acute exercise responses. Our data support the efficacy of endurance training, without dietary intervention, to elicit beneficial changes in blood lipids-lipoproteins in obese men and women.     

Gadolinium prevents stretch-mediated contractile dysfunction in isolated papillary muscles

We tested the hypothesis that overstretching the myocardium could induce and/or exacerbate contractile dysfunction via stretch-activated (SA) ion channels. Maximum developed tension (T(max)), normalized to a control value, was compared in guinea pig papillary muscles held at one of three resting lengths (physiological stretch, overstretch, and unloaded) for 85 min. Overstretched muscles exhibited decreased contractile force (T(max) = 0.77 +/- 0.03) compared with physiological and unloaded muscles (T(max) = 0.93 +/- 0.05 and 1.03 +/- 0.07, respectively). Gd(3+), an SA channel antagonist, eliminated the adverse effect of overstretching (T(max) = 0.98 +/- 0.06), but nifedipine, a dihydropyridine (DHP) antagonist of L-type calcium channels, did not (T(max) = 0.82 +/- 0.04). Exposure to modified hypoxia-reoxygenation (MHR) during physiological stretch resulted in decreased contractility (T(max) = 0.63 +/- 0.07), an effect that was exacerbated by overstretching (T(max) = 0.44 +/- 0.04). Gd(3+) mitigated the effects of overstretch during MHR (T(max) = 0.64 +/- 0.05), but DHP did not (T(max) = 0.48 +/- 0.04). These data suggest that overstretching of the myocardium contributes to contractile abnormalities via SA channels that are distinct from L-type calcium channels.     

Progressive resistance training without volume increases does not alter arterial stiffness and aortic wave reflection

Endurance exercise is efficacious in reducing arterial stiffness. However, the effect of resistance training (RT) on arterial stiffening is controversial. High-intensity, high-volume RT has been shown to increase arterial stiffness in young adults. We tested the hypothesis that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume would not elicit increases in either central or peripheral arterial stiffness or alter aortic pressure wave reflection in young men and women. The RT group (n = 24; 21 +/- 1 years) performed two sets of 8-12 repetitions to volitional fatigue on seven exercise machines on 3 days/week for 12 weeks, whereas the control group (n = 18; 22 +/- 1 years) did not perform RT. Central and peripheral arterial pulse wave velocity (PWV), aortic pressure wave reflection (augmentation index; AIx), brachial flow-mediated dilation (FMD), and plasma levels of nitrate/nitrite (NOx) and norepinephrine (NE) were measured before and after RT. RT increased the one-repetition maximum for the chest press and the leg extension (P < 0.001). RT also increased lean body mass (P < 0.01) and reduced body fat (%; P < 0.01). However, RT did not affect carotid-radial, carotid-femoral, and femoral-distal PWV (8.4 +/- 0.2 vs. 8.0 +/- 0.2 m/sec; 6.5 +/- 0.1 vs. 6.3 +/- 0.2 m/sec; 9.5 +/- 0.3 vs. 9.5 +/- 0.3 m/sec, respectively) or AIx (2.5% +/- 2.3% vs. 4.8% +/- 1.8 %, respectively). Additionally, no changes were observed in brachial FMD, NOx, NE, or blood pressures. These results suggest that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume does not increase central or peripheral arterial stiffness or alter aortic pressure wave characteristics in young subjects.     

Preserved structural and functional characteristics of common carotid artery in properly treated normoglycemic women with gestational diabetes mellitus

Women with gestational diabetes mellitus (GDM) are at high risk of subsequently developing type 2 diabetes mellitus which is an important cardiovascular risk factor. We have evaluated whether preclinical morphological and functional arterial changes are present in GDM. Diameter, intima-media thickness (IMT), intima-media cross-section area (IMCSA) and elasticity features (compliance, distensibility coefficient, circumferential strain, stiffness index (SI) α and β, incremental elastic modulus) of the common carotid arteries (CCA) were studied in the 3rd trimester in 25 women with GDM, and 17 normal pregnant women matched for age and body mass index using an ultrasonographic vessel wall-movement tracking system and applanation tonometry. Mean IMT, IMCSA and SI α tended to be larger, whereas compliance was smaller in women with GDM but none of these differences were significant. Serum glucose (4.99 ± 0.51 vs. 4.79 ± 0.61 mmol/L, p=0.37) and HbA1c (5.33 ± 0.27 vs. 5.36 ± 0.47 mmol/L, p=0.85) proved normoglycemia in both groups. In conclusion, by the combination of methods we applied in this case control study, neither morphological nor functional characteristics of large elastic arteries differ significantly between well-treated normoglycemic women with GDM and non-diabetic pregnant women in the 3rd trimester.     

Impact of age and hyperglycemia on the mechanical behavior of intact human coronary arteries: an ex vivo intravascular ultrasound study

Despite their advantages, percutaneous coronary interventional procedures are less effective in diabetic patients. Changes in the mechanical properties of vascular walls secondary to long-term hyperglycemia as well as other factors such as age may influence coronary distensibility. This investigation is aimed at deciphering the extent of these effects on distensibility of postmortem human coronary arteries in a controlled manner. Excised human left anterior descending (LAD) coronary arteries were obtained within 24 h postmortem. With the use of intravascular ultrasound, vascular deformation was analyzed at midregions of 51 moderate lesions. Intraluminal pressure was systematically altered using a computerized pressure pump system and monitored by a pressure-sensing guidewire. Distensibility, a normalized compliance term, was defined as the change in lumen area normalized by the initial reference area over a given pressure interval. With the use of multivariate analysis and repeated-measures ANOVA, coronary distensibility was independently influenced by hyperglycemia and age (P < 0.05) through the entire pressure range. Within physiological pressure range, distensibility was significantly reduced with age in nonhyperglycemic coronary specimens (10.55 +/- 4.41 vs. 6.99 +/- 2.45, x10(3) kPa(-1), P = 0.01), whereas the hyperglycemic vessels were stiff even in the younger group (7.90 +/- 5.82 vs. 7.20 +/- 3.36, x10(3) kPa(-1), P = 0.79). Similar results were observed with stiffness index and elastic modulus of the arteries. Hyperglycemia and age independently influenced the distensibility of moderately atherosclerotic LAD coronary arteries. The stiffening with age was overshadowed in the hyperglycemic group by as-yet-undetermined factors.     

Chronic hypoxia augments uterine artery distensibility and alters the circumferential wall stress-strain relationship during pregnancy.

Pregnancy-associated increases in uterine artery (UA) blood flow are due, in part, to vasoactive and growth-related changes that enlarge UA diameter. Although active and passive mechanical factors can contribute to this enlargement, their role is less well understood. We hypothesized that pregnancy increased UA distensibility and/or decreased myogenic tone. Given the fetal growth restriction and lower UA flow seen under chronic hypoxia, we further hypothesized that chronic hypoxia opposed these normal active and passive mechanical changes. UA were isolated from 12 nonpregnant and 12 pregnant (0.7 gestation) guinea pigs housed under normoxia or chronic hypoxia (3,960 m) and studied by pressure myography. Pregnancy increased UA diameter similarly under normoxia and hypoxia. Although chronic hypoxia raised resting tone in UA from nonpregnant guinea pigs to approximately 20% and tone was greater in preconstricted pregnant chronically hypoxic vs. normoxic UA (both P<0.01), there was an absence of myogenic response (i.e., an increase in tone with rising pressure) in all groups. Pregnancy increased UA distensibility 1.5-fold but did not change stiffness or the stress-strain relationship. Compared with vessels from normoxic pregnant animals, hypoxic pregnancy raised UA distensibility fourfold, decreased stiffness (rate constant b=3.80+/-1.06 vs. 8.92+/-1.25, respectively, P<0.01), lowered elastin by 50%, and shifted the stress-strain relationship upward such that four times as much strain was present at a given stress. We concluded that increased distensibility and low myogenic tone contribute to enlarging UA diameter and raising UA blood flow during pregnancy. Chronic hypoxia exaggerates the rise in distensibility and alters the stress-strain relationship in ways that may provoke vascular injury.     

Relationships between maximal muscle oxidative capacity and blood lactate removal after supramaximal exercise and fatigue indexes in humans.

The present study investigated whether blood lactate removal after supramaximal exercise and fatigue indexes measured during continuous and intermittent supramaximal exercises are related to the maximal muscle oxidative capacity in humans with different training status. Lactate recovery curves were obtained after a 1-min all-out exercise. A biexponential time function was then used to determine the velocity constant of the slow phase (gamma(2)), which denoted the blood lactate removal ability. Fatigue indexes were calculated during all-out (FI(AO)) and repeated 10-s cycling sprints (FI(Sprint)). Biopsies were taken from the vastus lateralis muscle, and maximal ADP-stimulated mitochondrial respiration (V(max)) was evaluated in an oxygraph cell on saponin-permeabilized muscle fibers with pyruvate + malate and glutamate + malate as substrates. Significant relationships were found between gamma(2) and pyruvate + malate V(max) (r = 0.60, P < 0.05), gamma(2) and glutamate + malate V(max) (r = 0.66, P < 0.01), and gamma(2) and citrate synthase activity (r = 0.76, P < 0.01). In addition, gamma(2), glutamate + malate V(max), and pyruvate + malate V(max) were related to FI(AO) (gamma(2) - FI(AO): r = 0.85; P < 0.01; glutamate + malate V(max) - FI(AO): r = 0.70, P < 0.01; and pyruvate + malate V(max) - FI(AO): r = 0.63, P < 0.01) and FI(Sprint) (gamma(2) - FI(Sprint): r = 0.74, P < 0.01; glutamate + malate V(max) - FI(Sprint): r = 0.64, P < 0.01; and pyruvate + malate V(max) - FI(Sprint): r = 0.46, P < 0.01). In conclusion, these results suggested that the maximal muscle oxidative capacity was related to blood lactate removal ability after a 1-min all-out test. Moreover, maximal muscle oxidative capacity and blood lactate removal ability were associated with the delay in the fatigue observed during continuous and intermittent supramaximal exercises in well-trained subjects.