Circadian variations in aortic stiffness, sympathetic vasoconstriction, and post-ischemic vasodilation in adults with and without type 2 diabetes.

The current literature reveals a lack of information on the circadian variations of some important cardiovascular risk factors related to the work of the heart or the capacity to provide blood and oxygen to various tissues. These factors include aortic stiffness, peripheral vasoconstrictor responsiveness, and post-ischemic vasodilation capacity. Furthermore, it is not clear whether the impact of an external stressor capable of activating the sympathetic nervous system could have greater repercussions on the cardiovascular system in the morning than in the evening. Given the higher incidence of acute cardiovascular events in the morning than in the evening, the studies undertaken in this thesis aim to investigate the circadian variations of these factors that are linked to cardiovascular risk, both at rest and during acute activation of the sympathetic nervous system. Type 2 diabetes (T2DM) is a condition that induces deleterious changes in cardiovascular function, impacting cardiovascular mortality and morbidity. Thus, the impact of diabetes will be evaluated. As a secondary purpose, considering the sex differences in the incidence and prognosis of cardiovascular disease, the effect of sex will be evaluated. Aortic stiffness proved not to be increased in the morning compared to the evening at specific times when the cardiovascular risk is significantly different, both at rest and during sympathetic activation. However, while healthy older women show similar aortic stiffness values compared to their male counterparts during acute stress, older women with T2DM reported greater aortic stiffness compared to men with T2DM. The post-ischemic forearm vasodilation is blunted in the morning compared to the evening in healthy elderly and such an attenuated vasodilation capacity impairs blood flow supply towards the ischemic area. The presence of T2DM does not affect vasodilation capacity and reactive hyperemia, but induces circadian variations in arterial pressure. The peripheral vasoconstriction triggered by a standardized sympathetic stressor is similar between morning and evening, regardless of the presence of T2DM and reduced baseline vascular conductance values in the morning. However, the peripheral vasoconstriction responsiveness is blunted in individuals with T2DM than in healthy ones as sympathetic activation induces vasodilation on the contralateral forearm in individuals with T2DM and vasoconstriction in healthy age-matched subjects. This finding highlights a neurovascular response to an external stressor altered by T2DM. Taken together, our findings suggest that the baseline state of constriction of the peripheral vascular tissue is greater in the morning than in the evening, but this fact is not due to greater sympathetic vasoconstriction responsiveness in the morning. Higher morning vasoconstriction at baseline however affects the capacity of a vascular tissue to dilate and, in turn, to supply blood to an ischemic tissue. Similar sympathetic vasoconstriction responsiveness between morning and evening is a likely factor explaining similar or lower values of central artery stiffness in the morning than in the evening, not only at rest but also during sympathetic excitation. Paradoxically, adults with T2DM report an increase in sympathetic-mediated dilatation capacity on the vascular tissue, which might be a defense mechanism that allows to reduce the central pressor response during sympathetic excitation

Sympathetic-mediated blunting of forearm vasodilation is similar between young men and women

Background: The in-vivo regulation of vascular conductance (VC) is a continuous balance between endothelial vasodilation and sympathetic vasoconstriction. Although women may report blunted sympathetic vasoconstriction along with higher endothelial vasodilation than men, it is currently unknown whether the interaction between vasoconstriction and vasodilation leads to different regulation of VC between sexes. This study assessed sex differences in sympathetic-mediated blunting of endothelial vasodilation after a brief period of ischemia and whether any restriction of vasodilation blunts tissue blood flow (BF) and re-oxygenation. Methods: 13 young women and 12 young men underwent two 5-min forearm circulatory occlusions followed by reperfusion, one in basal conditions and the other during cold pressor test-induced sympathetic activation (SYMP). Brachial artery diameter and BF, mean arterial pressure, total peripheral resistance (TPR), and thenar eminence oxygenation were collected. Percent changes normalized to baseline values of forearm VC, brachial artery BF and flow-mediated dilation (FMD), TPR, and hand oxygenation after circulatory reperfusion were calculated. Results: TPR increased during SYMP in men (p = 0.019) but not in women (p = 0.967). Women showed a greater brachial artery FMD than men (p = 0.004) at rest, but sex differences disappeared after normalization to shear rate and baseline diameter (p > 0.11). The percent increases from baseline of peak and average forearm VC after circulatory reperfusion did not differ between sexes in basal conditions (p > 0.98) or during SYMP (p > 0.97), and were restrained by SYMP similarly in both sexes (p < 0.003) without impairing the hand re-oxygenation (p > 0.08) or average hyperemic response (p > 0.09). Conclusions: Although women may report blunted sympathetic vasoconstriction than men when assessed separately, the similar sympathetic-mediated restriction of vasodilation suggests a similar dynamic regulation of VC between sexes. SYMP-mediated restrictions of the normal forearm vasodilation do not impair the average hyperemic response and hand re-oxygenation in both sexes

Circadian and sex differences in carotid-femoral pulse wave velocity in young individuals and elderly with and without type 2 diabetes

The incidence of cardiovascular events is higher in the morning than in the evening and differs between sexes. We tested the hypothesis that aortic stiffness, a compelling cardiovascular risk factor, increases in the morning than in the evening in young, healthy individuals between 18 and 30 years (H18-30) or in older individuals between 50 and 80 years, either healthy (H50-80) or with type 2 diabetes (T2DM50-80). Sex differences were also investigated. Carotid-femoral pulse wave velocity (cf-PWV) recorded via Doppler Ultrasound, blood pressure and heart rate were checked at 6 a.m. and 9 p.m., at rest and during acute sympathetic activation triggered by handgrip exercise. Cf-PWV values were lower in the morning compared to the evening in all groups (p < 0.01) at rest and lower (p = 0.008) in H18-30 but similar (p > 0.267) in the older groups during sympathetic activation. At rest, cf-PWV values were lower in young women compared to young men (p = 0.001); however, this trend was reversed in the older groups (p < 0.04). During sympathetic activation, the cf-PWV was lower in women in H18-30 (p = 0.001), similar between sexes in H50-80 (p = 0.122), and higher in women in T2DM50-80 (p = 0.004). These data do not support the hypothesis that aortic stiffness increases in the morning compared to the evening within any of the considered groups in both rest and sympathetic activation conditions. There are differences between the sexes, which vary according to age and diabetes status. In particular, aortic stiffness is higher in older women than in men with diabetes during acute stress

Postexercise cardiovascular hemodynamics assessment before and after a 30-minute standing still recovery

Background: Although postexercise syncope usually occurs shortly after physical exercise conclusion, athletes commonly reveal symptoms of postexercise hypotension several tens of minutes after exercise completion. Currently, no studies have investigated central hemodynamic regulation during posture changes occurring several tens of minutes after exercise compared to immediately after cessation. Methods: This study examined changes in mean arterial pressure (MAP), heart rate (HR), systemic vascular conductance (SVC), cardiac output, and stroke volume during two sets of tilt tests performed before vs. after a 30-minute standing still recovery, respectively. Tilt tests were performed after a short-lasting supramaximal test (WNG) and long-lasting maximal incremental test (INC) in 12 young endurance-trained individuals. Results: The key findings were that, regardless of the exercise type, the 30-minute recovery augmented (P<0.01) the increase in HR and the drop in SVC during the transition from supine to upright, although the MAP drop was similar (P=0.99) after vs. before recovery. INC led to greater increases (P<0.01) in HR and drops (P<0.01) in SVC compared to WNG during postural transitions both before and after the recovery. Conclusions: These findings suggest that, in a population that tolerates postexercise hypotension, MAP neural control is more challenged after a 30-minute standing still recovery than before, as evidenced by an augmented vasodilation capacity along with an increased HR buffering response during posture changes. Moreover, our data suggest that effective MAP control is resulting from an equally effective HR buffering response on MAP. Therefore, exercises that induce greater systemic vasodilation lead to greater HR buffering responses

Mental stress augments central artery stiffness in young individuals of both sexes

Mental stress is a daily stimulus that can acutely activate the sympathetic nervous system. Whether sympathetic stimulation can augment central artery stiffness (CAS) has not yet been well documented. Moreover, sex differences in sympathetic neurovascular transduction have been reported. We assessed whether mental stress augments CAS in both sexes and whether any CAS increase is blunted in women compared with men. The hf-PWV (heart-femoral pulse wave velocity; index of CAS), MAP (mean arterial pressure), PP (pulse pressure), TPR (total peripheral resistance), and HR (heart rate) were measured in 26 young individuals (13 men, 13 women) at rest and throughout a 10-minute bout of stress induced by mental arithmetic. Data over the mental stress period were compared to the preceding baseline values and between sexes. Mental stress increased hf-PWV, MAP, PP, and HR from baseline throughout the entire stimulation period (p < .005). TPR diminished in the first minute of stimulation (p < .001) in both sexes and increased in the last minutes in women only (p < .005). Hf-PWV was lower in women than men (p < .001) at rest and during mental stress, but the changes from baseline were similar in both sexes. There were sex differences in the PP and TPR changes, which were evident at different times of stimulation. Mental stress increased CAS in both sexes throughout the stimulation period. Although values of CAS were lower in women both at rest and during mental stress, the CAS increase due to mental stress was similar in both sexes

Prolonged visual reaction time after strenuous endurance exercise: higher increment in male compared to female recreational runners

Purpose: This project aimed to evaluate the simple visual reaction time (SVRT) changes in runners of both sexes before and after a 21.1 km run. Methods: 20 male (age 35.3 ± 17.1 years, BMI 23.5 ± 3.3 kg/m2) and 20 female (age 32.2 ± 14.3 years, BMI 24.8 ± 4.2 kg/m2) amateur runners were evaluated 30 min before and after a half-marathon run under competing conditions. Subjects were asked to push an electronic switch at the lighting of a lamp for 11 trials randomly divided to one another between 1 and 10 s. Effort-perception data were collected through a Borg CR100 scale and SVRT data using an electronic chronometric device. A two-way RM ANOVA assessed the effects of exercise and biological sex on SVRT. Results: Borg effort data were similar (M: 82.4 ± 3.9 vs W: 84.7 ± 4.9 AU, p = 0.68). SVRT was lower in men than women before (M: 234.05 ± 3.33 vs F: 239.47 ± 6.1 ms, p < 0.05) but not after the race (M: 249.9 ± 7.18 vs F: 252.09 ± 16.93 ms, p = 0.7). Exercise lengthened the SVRT (M: + 7%; F: + 5%; p < 0.05). Response accuracy was greater in men both before and after exercise. Conclusion: Previous studies suggested exercise lengthened SVRT due to an exercise intensity-related reduced post-exercise cerebral oxygenation that decreases cognitive processes efficiency. In our results, this reduction seemed higher in men. The sex-related response accuracy might be due to different estrogen effects in brain areas implicated in information processing, motor performance, and attention and to different processing and attention focus strategies between the sexes or anticipatory strategies in females. © 2019, Springer-Verlag Italia S.r.l., part of Springer Nature

Polydimethylsiloxanes biocompatibility in PC12 neuronal cell line

Cochlear implants, the only way to recover from severe/profound hearing loss, may cause adverse effects, among which reactions to silicone materials coating implant electrodes, leading to apoptosis and necrosis of spiral ganglion cells. Our aim was to evaluate whether three polydimethylsiloxane (PDMS) compounds (hexadimethylsiloxane, octamethyltrisiloxane, decamethylcyclopentasiloxane) used in silicone rods could exert toxic effects on an in vitro neuronal cell model (PC12). Cell viability, morphology and mRNA expression levels of apoptotic markers were evaluated on PC12 cells at different PDMS dilutions up to 6 days of exposure. The results showed that at the highest concentrations tested cell viability was reduced by hexadimethylsiloxane and octamethyltrisiloxane at all times of exposure, but only from 72\u2009h onwards by decamethylcyclopentasiloxane. The number of neurites per cell was not affected by hexadimethylsiloxane, but was significantly reduced from 24\u2009h onwards by octamethyltrisiloxane and decamethylcyclopentasiloxane. Neurite length was reduced by hexadimethylsiloxane only at 24\u2009h, and by octamethyltrisiloxane and decamethylcyclopentasiloxane at all exposure intervals. In controls exposed to silicone or glass rods cell viability was reduced only after 24\u2009h, but neurite number and length was never reduced at any exposure interval. Biomolecular investigations showed that apoptotic markers did not change in any experimental condition, suggesting that PDMS are biocompatible. The reduction of cell viability and neurite number and length caused by exposure to these compounds was probably caused by a PDMS surface film formed over the cell medium, preventing air exchange, and not by the release of cytotoxic molecules

Pedaling cadence variability increases by worsening the bike fitting across most but not all workloads

Cyclic motion variability reflects the movement error correction. Since movement motor control generally worsens with impaired biomechanical setups, we assessed whether the pedaling cadence variability (PCV) increases by worsening the bike fitting across multiple workloads. Sixteen cyclists performed multiple 5-min bouts of constant load cycling exercise at 0, 20, 40, 55, 70, 85% of their maximum workload (MWL) capacity at 60 rpm with proper (PROPER) and worsened (WORSENED; 15 cm saddle height drop) bike fittings. Cycle-by-cycle duration series were collected. PCV was calculated as the standard deviation of each series. In both PROPER and WORSENED, PCV showed a U-shaped feature by increasing workload (minimum PCV values at 55% MWL). PCV was higher in WORSENED than PROPER, except at 55% MWL (0% MWL: 36.69 ± 10.06 vs. 42.21 ± 11.3, p < 0.01; 55% MWL: 18.87 ± 3.51 vs. 19.74 ± 4.73, p = 0.3; 85% MWL: 34.93 ± 10.51 vs. 39.52 ± 11.84, p < 0.01; ms; PROPER vs. WORSENED, respectively). PCV seems to be a workload-dependent variable, being greater at low and high workloads. At intermediate workloads, the moderate force expression to continue the movement, along with the effect of the workload itself in counteracting the natural extension of the leg, might explain a lower need for continuous motion adjustments and, consequently, a lower PCV in both bike setups

Effect of acute sympathetic activation on leg vasodilation before and after endurance exercise

Vascular conductance (VC) regulation involves a continuous balance between metabolic vasodilation and sympathetic vasoconstriction. Endurance exercise challenges the sympathetic control on VC due to attenuated sympathetic receptor responsiveness and persistence of muscle vasodilation, especially in endurance athletes, predisposing them to blood pressure control dysfunctions. This study assessed whether acute handgrip-mediated sympathetic activation (SYMP) restrains sudden leg vasodilation before and after a half-marathon. Prior to, and within the 20 min following the race, 11 well-trained runners underwent two single passive leg movement (SPLM) tests to suddenly induce leg vasodilation, one without and the other during SYMP. Leg blood flow and mean arterial pressure were measured to assess changes in leg VC. Undertaking 60 sec of SYMP reduced the baseline leg VC both before (4.0 ± 1.0 vs. 3.3 ± 0.7 ml/min/mmHg; P=0.01; NO SYMP vs. SYMP, respectively) and after the race (4.6 ± 0.8 vs. 3.9 ± 0.8 ml/min/mmHg; P=0.01). However, SYMP did not reduce leg peak vasodilation immediately after the SPLM either before (11.5 ± 4.0 vs. 12.2 ± 3.8 ml/min/mmHg; P=0.35) or after the race (7.2 ± 2.0 vs. 7.3 ± 2.6 ml/min/mmHg; P=0.96). Furthermore, SYMP did not blunt the mean leg vasodilation over the 60 sec after the SPLM before (5.1 ± 1.7 vs. 5.9 ± 2.5 ml/min/mmHg; P=0.14) or after the race (4.8 ± 1.3 vs. 4.2 ± 1.5 ml/min/mmHg; P=0.26). This data suggest that the release of local vasoactive agents effectively opposes any preceding handgrip-mediated augmented vasoconstriction in endurance athletes before and after a half-marathon. Handgrip-mediated SYMP might improve normal vasoconstriction while athletes are still, but not necessarily while they move, as movements can induce a release of vasoactive molecules