Hemodynamic and Cerebrovascular Responses to an Acute Bout of Blood Flow Restriction Resistance Exercise

Blood flow restriction (BFR) training is a novel exercise modality characterized by restricting blood flow to active muscles by the use of an occlusive device. A hallmark of this training is the use of lighter resistance loads, making it a potentially valuable tool for the elderly as well as patients exercising in a rehabilitative setting. Despite the growing interest in this novel mode of exercise, no investigation has comprehensively assessed the combined arterial pressure and cerebrovascular responses (flow and oxygenation) to BFR training, factors which may limit its application for cardiac and stroke rehabilitation. One concern about these applications is the potential for an amplification of the exercise pressor reflex, which could cause an unsafe rise in arterial blood pressure. The aim of this investigation was to compare the hemodynamic and cerebrovascular responses between BFR resistance exercise and traditional resistance exercise (TE). We hypothesized that the exercise-induced elevation in arterial pressure and cerebral blood flow would be attenuated with BFR, due to the use of lower workloads. Five healthy human volunteers (3 males, 2 females; age, 25.4±1.1 years) performed 3 sets of 10 repetitions of bilateral leg press with (BFR) or without (TE) bilateral blood flow restriction (220 mmHg cuff pressure), separated by 1-min rest periods (randomized, cross-over design). BFR was performed at 20% of 1 repetition maximum (1RM) while TE was performed at 65% of 1RM. Heart rate (HR) and arterial pressures were collected via ECG and finger photoplethysmography. Middle cerebral artery blood velocity (MCAv) was measured via transcranial Doppler ultrasound, and oxygen saturation of the frontal cortex (ScO2) was measured via near-infrared spectroscopy. Rate pressure product (RPP) was calculated as systolic arterial pressure multiplied by HR, and used as an index of myocardial oxygen demand. Mean arterial pressure (MAP) and RPP were both higher during TE compared with BFR during sets 2 and 3 (MAP: TE, 116±10 mmHg vs. BFR, 104±6 mmHg for BFR, P=0.05 (Set 3); RPP: TE, 16229±2387 mmHg*bpm vs. BFR, 11889±978 mmHg*bpm, P≤0.02 (Set 3)). While MCAv and ScO2 increased with exercise (

Resting sympathetic baroreflex sensitivity in subjects with low and high tolerance to central hypovolemia induced by lower body negative pressure

Central hypovolemia elicited by orthostasis or hemorrhage triggers sympathetically-mediated baroreflex responses to maintain organ perfusion; these reflexes are less sensitive in patients with orthostatic intolerance, and during conditions of severe blood loss, may result in cardiovascular collapse (decompensatory or circulatory shock). The ability to tolerate central hypovolemia is variable and physiological factors contributing to tolerance are emerging. We tested the hypothesis that resting muscle sympathetic nerve activity (MSNA) and sympathetic baroreflex sensitivity (BRS) are attenuated in male and female subjects who have low tolerance (LT) to central hypovolemia induced by lower body negative pressure (LBNP). MSNA and diastolic arterial pressure (DAP) were recorded in 47 human subjects who subsequently underwent LBNP to tolerance (onset of presyncopal symptoms). LT subjects experienced presyncopal symptoms prior to completing LBNP of -60 mm Hg, and subjects with high tolerance (HT) experienced presyncopal symptoms after completing LBNP after -60 mmHg. Contrary to our hypothesis, resting MSNA burst incidence was not different between LT and HT subjects, and was not related to time to presyncope. BRS was assessed as the slope of the relationship between spontaneous fluctuations in DAP and MSNA during 5 min of supine rest. MSNA burst incidence/DAP correlations were greater than or equal to 0.5 in 37 subjects (LT: n= 9; HT: n=28), and BRS was not different between LT and HT (-1.8 ± 0.3 vs. -2.2 ± 0.2 bursts•(100 beats)-1•mmHg-1, p=0.29). We conclude that tolerance to central hypovolemia is not related to either resting MSNA or sympathetic BRS

Influence of Controlled Breathing on Cerebrovascular Control During Upright Tilt

Arterial pressures oscillate with the frequency of respiration, and these oscillations are translated directly to the cerebrovasculature. For this reason, intrinsic cerebrovascular control is assessed at the low frequency (LF; .07-.2 Hz). When humans breathe spontaneously, it is possible that breathing frequency encroaches on these non-respiratory rhythms, thereby confounding the interpretation of intrinsic cerebrovascular control. PURPOSE: To test the hypothesis that controlled breathing (CB) decreases, and spontaneous breathing (SB) increases the reliance of cerebral blood velocity on arterial pressure within the LF range in both the supine and upright postures. METHODS: We recorded ECG, finger arterial pressure (Finometer), transcranial Doppler ultrasound of the middle cerebral artery, and end-tidal CO₂ in 20 healthy male volunteers (24±2 yrs). Ten subjects breathed in time to a metronome set at a pace of 15 breaths/min (CB), and ten subjects breathed spontaneously (SB). Both groups were studied in the supine and head-up tilt (HUT) positions for 5-min. Reliance of mean cerebral blood velocity (CBVmean) on mean arterial pressure (MAP) was assessed over the LF with cross-spectral coherence analysis (COH). RESULTS: Respiratory rates were not different between CB and SB during supine (p=.86), but were lower for SB compared with CB during HUT (11.7±.7 vs. 14.8±.1; p\u3c.001). End-tidal CO₂ was decreased by CB during both supine and HUT (p\u3c.05). CBVmean was decreased with CB during supine (p=.04), but was similar between CB and SB during HUT (p=.14). Neither LFMAP nor LFCBVmean oscillations were different in the supine position (p\u3e.6), but were increased (with a trend for LFMAP) with SB during HUT (p=.003 for LF CBVmean and p=.09 for LFMAP). COH was not different in the supine position between CB and SB (.42±.05 for CB and .61±.06 SB; p=.13), but was lower for CB in the HUT position (.55±.05 for CB and .78±.08 for SB; p=.02). CONCLUSION: Reliance of CBVmean on MAP is increased in the LF range when subjects breathe spontaneously during HUT. We attribute changes in COH during HUT to entrainment of respiratory-mediated arterial pressure fluctuations on the cerebrovasculature. However, the potential confounding influence of hypocapnia warrants further investigation

Heart Rate Variability during Simulated Hemorrhage with Lower Body Negative Pressure in High and Low Tolerant Subjects

Heart rate variability (HRV) decreases during hemorrhage, and has been proposed as a new vital sign to assess cardiovascular stability in trauma patients. The purpose of this study was to determine if any of the HRV metrics could accurately distinguish between individuals with different tolerance to simulated hemorrhage. Specifically, we hypothesized that (1) HRV would be similar in low tolerant (LT) and high tolerant (HT) subjects at presyncope when both groups are on the verge of hemodynamic collapse; and (2) HRV could distinguish LT subjects at presyncope from hemodynamically stable HT subjects (i.e., at a submaximal level of hypovolemia). Lower body negative pressure (LBNP) was used as a model of hemorrhage in healthy human subjects, eliciting central hypovolemia to the point of presyncopal symptoms (onset of hemodynamic collapse). Subjects were classified as LT if presyncopal symptoms occurred during the −15 to −60 mmHg levels of LBNP, and HT if symptoms occurred after LBNP of −60 mmHg. A total of 20 HRV metrics were derived from R–R interval measurements at the time of presyncope, and at one level prior to presyncope (submax) in LT and HT groups. Only four HRV metrics (Long-range Detrended Fluctuation Analysis, Forbidden Words, Poincaré Plot Descriptor Ratio, and Fractal Dimensions by Curve Length) supported both hypotheses. These four HRV metrics were evaluated further for their ability to identify individual LT subjects at presyncope when compared to HT subjects at submax. Variability in individual LT and HT responses was so high that LT responses overlapped with HT responses by 85–97%. The sensitivity of these HRV metrics to distinguish between individual LT from HT subjects was 6–33%, and positive predictive values were 40–73%. These results indicate that while a small number of HRV metrics can accurately distinguish between LT and HT subjects using group mean data, individual HRV values are poor indicators of tolerance to hypovolemia

Cerebrovascular Hemodynamics during Concentric and Eccentric Phases of Heavy Resistance Exercise

Rapid and drastic fluctuations in arterial blood pressures, such as those occurring during heavy resistance exercise pose a unique challenge to the maintenance of cerebral perfusion. During high-intensity leg cycling, regulation of cerebral perfusion is reduced by rapid decreases in beat-to-beat fluctuations in blood pressure (diastolic phase) rather than rapid increases (systolic phase). The purpose of this study was to test the hypothesis that rhythmic heavy resistance exercise will similarly impair the regulation of cerebral blood flow during the diastolic phase of beat-to-beat fluctuations in pressure. We studied seven healthy male subjects. Beat-to-beat finger arterial pressures, and middle cerebral artery blood velocity (MCAv) were measured during 10 repetitions (REP) of rhythmic high intensity leg press exercise. Velocities and arterial pressures were evaluated during both the isotonic concentric and eccentric phases of each REP. The Gosling pulsatility index (PI) of MCAv of each REP was calculated as MCAv systolic-MCAv diastolic/MCAv mean. During the concentric phase, systolic arterial pressures progressively increased from REP 1 through REP 10 (P \u3c 0.001), while systolic MCAv was not different across all REPs (P \u3e0.2). Diastolic arterial pressures during the eccentric phase also increased from REP 1 through REP 10 (P = 0.03) however diastolic MCAv decreased during REPs 7-10 compared with REP 2 (P ≤ 0.02). MCAv PI also increased during REP 7-10 compared to REP 2 (P ≤ 0.02). Similar to high-intensity leg cycling, our data suggest that during rhythmic high-intensity leg press exercise, cerebral perfusion is well controlled during periods of rapid increases in blood pressure, but regulation of cerebral perfusion is impaired during the diastolic phase of beat-to-beat fluctuations in pressure

Effects of Acute Vaporized Nicotine in Non-tobacco Users at Rest and During Exercise

Smokers, and even non-smokers, may utilize vaporized nicotine delivered by electronic cigarette (EC) due to the perception that EC are “healthier” than traditional tobacco cigarettes. The effects of vaporized nicotine delivered by EC on resting blood pressure (BP) and metabolic rate (RMR), or BP and aerobic power during exercise have not been studied. This investigation tested the effects of acute vaporized nicotine inhalation by EC on resting BP and RMR and cycle exercise BP, metabolic responses, and aerobic power in young, normotensive non-smokers. Using a double-blind design, 20 subjects (10 female; 23.1±2.5 years, 1.69±0.1 m, 70.6±14.9 kg; 22.1±11.0% body fat) self-reporting as healthy and non-smoking participated. All subjects participated in two randomized trials: placebo (0 mg nicotine) or nicotine (18 mg nicotine). Participants inhaled from EC once every 30 s for 10 min (20 inhalations total) during each trial. RMR was assessed 40 min later by indirect calorimetry followed by an incremental cycle test. Participants’ pre-inhalation SBP, DBP, and HR were also not significantly different between conditions or from those averaged over the last 5 min of the indirect calorimetry protocol. Cotinine, a stable nicotine metabolite, was assessed on post-inhalation (i.e., 10 min) urine samples. The cotinine concentration ranges, as scored using the semi-quantitative urine analysis kit strips, were significantly higher (p-1) compared to placebo (0-10 ng•ml-1). RMR was assessed ~40 min after the last EC inhalation. RMR (p=0.39), VO2 (p=0.5), RQ (p=0.15), and HR (p=0.47) were not significantly different between the placebo and nicotine trials. Compared to the placebo trial, nicotine use resulted in a 3.7 mmHg lower resting SBP (p=0.04) but a 3.0 mmHg higher DBP (p=0.04). VO2peak was not different between the nicotine trial (2.3±0.8 L•min-1) and placebo trial (2.3±0.7 L•min-1) trials (p=0.77). No statistically distinguishable difference was observed for Wpeak between nicotine (201.0±53.8 W) and placebo (204.8±57.8 W) (p=0.29). There was a main effect of time over the cycle test for VO2 , energy expenditure, RQ, and HR but no between treatment effects. A main treatment effect was identified for DBP, which was higher following nicotine compared to placebo at all time points during the test (p=0.05). No time by treatment interaction was identified for any variable during exercise. Exercise DBPpeak after nicotine (79.4±7.6) was significantly higher (p=0.02) than placebo (74.9±8.3 mmHg). Peak SBP was not different between trials (p=0.14). Our results show that acute vaporized nicotine inhalation via EC increases resting and exercise DBP but does not affect RMR or cycle aerobic power in young, normotensive non-smokers

Sympathetic Responses to Central Hypovolemia: New Insights from Microneurographic Recordings

Hemorrhage remains a major cause of mortality following traumatic injury in both military and civilian settings. Lower body negative pressure (LBNP) has been used as an experimental model to study the compensatory phase of hemorrhage in conscious humans, as it elicits central hypovolemia like that induced by hemorrhage. One physiological compensatory mechanism that changes during the course of central hypovolemia induced by both LBNP and hemorrhage is a baroreflex-mediated increase in muscle sympathetic nerve activity (MSNA), as assessed with microneurography. The purpose of this review is to describe recent results obtained using microneurography in our laboratory as well as those of others that have revealed new insights into mechanisms underlying compensatory increases in MSNA during progressive reductions in central blood volume and how MSNA is altered at the point of hemodynamic decompensation. We will also review recent work that has compared direct MSNA recordings with non-invasive surrogates of MSNA to determine the appropriateness of using such surrogates in assessing the clinical status of hemorrhaging patients

Effects of Vaporized Nicotine on Resting Metabolic Rate and Physical Work Capacity

Download PD

Vaporized Nicotine Inhalation Increases Arterial Pressure in both Supine and 70o Head-up Positions

ABSTRACT Electronic cigarettes (e-cigs) are popular with smokers looking for a healthier alternative to tobacco cigarettes. E-cigs utilize a battery, activated on inhalation, to heat propylene glycol-suspended nicotine which is inhaled as vapor, and which does not include harmful poisons found in conventional cigarettes. Although the health claims of e-cigs continue to be debated, the effects of nicotine delivered as vapor on the cardiovascular system have not been studied. Because nicotine is a sympathomemetic agent, we tested the hypothesis that e-cigs would increase arterial pressure and protect against challenges associated with upright posture. Ten non-smoking subjects (5 male) participated in two experimental trials, separated by one week (randomized). Seated blood pressures were taken after a 10 min quiet rest period, and then subjects either inhaled (once every 30 s for 10 min) on an e-cig with a placebo cartridge (0 mg nicotine) or an active cartridge (18 mg nicotine). After an additional 10 min quiet seated rest, we measured blood pressure again, and then subjects provided a urine sample for analysis of cotinine (a nicotine biomarker). We recorded ECG and finger photoplethysmographic arterial pressure. Subjects breathed to a metronome set at 15 breaths/min for 5 min supine, 5 min head-up (70o), and 5 min supine (recovery). Cotinine readings failed to register the presence of nicotine in urine, but a majority of subjects experienced dizziness and nausea after the active, but not the placebo cartridge. Seated arterial pressures were similar after the placebo cartridge (p ≥ .05), but increased from 112 ± 3/62 ± 2 mmHg to 115 ± 3/67 ± 3 after the nicotine cartridge (p ≤. 05). Systolic and diastolic pressures were higher (all p ≤ .05) after the nicotine trial compared to placebo for supine (115 ± 3/69 ± 2 vs. 106 ± 4/62 ± 2 mmHg), tilt (105 ± 4/66 ± 3 vs. 93 ± 4/60 ± 3 mmHg), and recovery (117 ± 5/72 ± 2 vs. 106 ± 4/64 ± 3 mmHg). No subject experienced presyncope during tilt for either trial. We show, for the first time, that inhalation of vaporized nicotine increases arterial pressure in the seated, supine and head-up tilt positions - suggesting sympathomemetic properties. Although mild, acute increases in arterial pressure may seem harmless, it is possible that daily, continuous use of e-cigs could result in consistently elevated arterial pressure, resulting in higher afterload and chronic cardiac strain

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation