The effect of age and mitigation strategies during hot water immersion on orthostatic intolerance and thermal stress.

NEW FINDINGS: What is the central question of this study? The aim was to characterize adverse responses to whole-body hot water immersion and to investigate practical strategies to mitigate these effects. What is the main finding and its importance? Whole-body hot water immersion induced transient orthostatic hypotension and impaired postural control, which recovered to baseline within 10 min. Hot water immersion was well tolerated by middle-aged adults, but younger adults suffered from a greater frequency and severity of dizziness. Cooling the face with a fan or not immersing the arms can mitigate some of these adverse responses in younger adults. ABSTRACT: Hot water immersion improves cardiovascular health and sporting performance, yet its adverse responses are understudied. Thirteen young and 17 middle-aged adults (n = 30) were exposed to 2 × 30 min bouts of whole-body 39°C water immersion. Young adults also completed cooling mitigation strategies in a randomized cross-over design. Orthostatic intolerance and selected physiological, perceptual, postural and cognitive responses were assessed. Orthostatic hypotension occurred in 94% of middle-aged adults and 77% of young adults. Young adults exhibited greater dizziness upon standing (young subjects, 3 out of 10 arbitrary units (AU) vs. middle-aged subjects, 2 out of 10 AU), with four terminating the protocol early owing to dizziness or discomfort. Despite middle-aged adults being largely asymptomatic, both age groups had transient impairments in postural sway after immersion (P < 0.05), but no change in cognitive function (P = 0.58). Middle-aged adults reported lower thermal sensation, higher thermal comfort, and higher basic affect than young adults (all P < 0.01). Cooling mitigation trials had 100% completion rates, with improvements in sit-to-stand dizziness (P < 0.01, arms in, 3 out of 10 AU vs. arms out, 2 out of 10 AU vs. fan, 4 out 10 AU), lower thermal sensation (P = 0.04), higher thermal comfort (P < 0.01) and higher basic affect (P = 0.02). Middle-aged adults were predominantly asymptomatic, and cooling strategies prevented severe dizziness and thermal intolerance in younger adults.

Gastrointestinal bleeding in children with familial dysautonomia: a case-control study.

OBJECTIVE: Familial dysautonomia (FD) is a rare inherited autosomal recessive disorder with abnormal somatosensory, enteric, and afferent autonomic neurons. We aimed to define the incidence of gastrointestinal bleeding and its associated risk factors in patients with FD. METHODS: In this retrospective case-control study, we identified all episodes of gastrointestinal bleeding in patients with FD, occurring over four decades (January 1980-December 2017), using the New York University FD registry. RESULTS: We identified 104 episodes of gastrointestinal bleeding occurring in 60 patients with FD. The estimated incidence rate of gastrointestinal bleeds in the FD population rate was 4.20 episodes per 1000 person-years. We compared the 60 cases with 94 age-matched controls. Bleeding in the upper gastrointestinal tract from gastric and duodenal ulcers occurred most frequently (64 bleeds, 75.6%). Patients were more likely to have a gastrostomy (G)-tube and a Nissen fundoplication [odds ratio (OR) 3.73, 95% confidence interval (CI) 1.303-13.565] than controls. The mean time from G-tube placement to first gastrointestinal bleed was 7.01 years. The mean time from Nissen fundoplication to bleed was 7.01 years. Cases and controls had similar frequency of intake of nonsteroidal antiinflammatory drugs (NSAID) and selective serotonin reuptake inhibitors (SSRI). CONCLUSION: The incidence of gastrointestinal bleeding in the pediatric FD population was estimated to be 4.20 per 1000 person-years, 21 times higher than in the general pediatric population (0.2 per 1000 person-years). Patients with FD with a G-tube and a Nissen fundoplication had a higher risk of a subsequent gastrointestinal bleeding.

The baroreceptor reflex brought to life outside the classroom - an e-learning based asynchronous laboratory class using a non-supervised modified Active Standing Test.

BACKGROUND: E-learning based laboratory classes can replace or enhance in-classroom laboratories. They typically offer temporal flexibility, self-determined learning speed, repeatability and do not require supervision or face-to-face contact. The aim of this feasibility study was to investigate whether the established in-classroom laboratory class on the baroreceptor reflex (BRR) can be transformed into a new e-learning based asynchronous laboratory class for untrained, non-supervised students without medical equipment. The BRR is a fundamental cardiovascular process which is regularly visualized in physiology during in-classroom laboratories by a student-performed Active Standing Test (AST). During this voluntary provocation of orthostatic stress, the BRR reliably causes a solid rise in heart rate (HR) and a stabilization or even increase in blood pressure (BP). METHODS: The conventional AST was modified by omission of BP measurements which would require medical devices and was embedded into a framework of interactive digital material allowing independent student performance. With specific adaptions, this instrument was implemented to 1st and 2nd year curricula of human medicine, dental medicine, midwifery and pharmacy. An audience response system was used to collect the students' data on HR, epidemiology, technical problems, satisfaction and orthostatic symptoms. As primary outcome, we investigated the students' correct performance of the modified AST regarding textbook conformity of the HR data. Secondary outcomes included technical feasibility, the students' satisfaction and consistency of HR data within predefined subgroups (e.g., gender, curricula). Descriptive statistics are reported. RESULTS: The class was completed by 217 students (mean age: 23 ± 8 [SD], 81% female, 19% male). Mean reported rise of HR during standing was ~ 20 bpm (~ 30%) which is highly concordant to textbooks. Reported feasibility (~ 80% negated any technical issues) and students' satisfaction (4.4 on 5-point Likert-scale) were high. The HR data were consistent within the subgroups. CONCLUSION: This study demonstrates that the highly relevant BRR can be successfully addressed in an e-learning based asynchronous laboratory class implementing a non-supervised AST restricted to HR measurements embedded in digital material. The robust HR response and the adjustable complexity allow an application to different healthcare-related curricula. This class, therefore, provides a broad audience access to a fundamental concept of cardiovascular physiology.

Incidence and Risk Factors of Orthostasis After Primary Hip and Knee Arthroplasty.

BACKGROUND: Postoperative orthostatic intolerance can limit mobilization after hip and knee arthroplasty. The literature is lacking on the incidence and risk factors associated with orthostatic intolerance after elective arthroplasty. METHODS: A retrospective case-control study of primary total hip, total knee, and unicompartmental knee arthroplasty patients was conducted. Patients with orthostatic events were identified, and potential demographic and perioperative risk factors were recorded. Orthostatic intolerance was defined as postoperative syncope, lightheadedness, or dizziness, limiting ambulation and/or requiring medical treatment. Statistical analysis was completed using Pearson's chi-square test for categorical data and t-tests for continuous data. Binary logistic regression was performed. RESULTS: A total of 500 consecutive patients were included. The overall incidence of orthostatic intolerance was 18%; 25% in total hip arthroplasty (THA) and 11% in total knee arthroplasty. On univariate analysis, significant risk factors for developing postoperative orthostatic intolerance include older age, female gender, THA surgery, lower American Society of Anesthesiologists class, absence of recreational drug use, lower estimated blood volume, lower preoperative diastolic blood pressure, spinal with monitored anesthesia care (MAC), posterior approach for THA, bupivacaine use in spinal, percent of blood loss, postoperative oxycodone or tramadol use, higher postoperative intravenous fluid volume, and lower postoperative hemoglobin. Multivariate analysis demonstrated persistent significance of female gender, THA surgery, spinal with MAC, bupivacaine use in spinal, and more intravenous fluid administered postoperatively. CONCLUSION: Orthostatic intolerance affects a significant number of arthroplasty patients. Awareness of risk factors and modification of perioperative variables linked to orthostatic intolerance may assist the surgeon in choosing the appropriate surgical setting, educating patients, and improving early postoperative recovery.

Walking instead of standing.

Background: Leg discomfort is common in the general population. Volume increase and discomfort in the lower legs especially occur in occupations with long standing or sitting periods and less movement. Are both related to each other? Patients and methods: A time-controlled standing period of 15 min was performed in this nonrandomized controlled study to investigate the change and temporal relationship of volume increase and the occurrence of lower leg discomfort. Sensations of discomfort and the urge to move were queried using a numerical rating scale from 0 to 10 (NRS). Correlation analysis was conducted between the lower leg volume and the data regarding the discomfort and urge to move in each subject. Further, linear mixed effect models were performed to detect a causal relationship between the lower leg volume and the sensations of discomfort/urge to move in the standing period. Results: Lower leg volume increased by an average of 63 ml (p<0.001) during the standing period. The sensations of discomfort increased by a mean of 3.46 points on the NRS (p<0.001) during orthostasis. Participants' urge to move increased by 3.47 points on the NRS (p<0.001) during the standing period. A significant correlation was shown between the increase of lower leg volume and the occurrence of discomfort sensation in 9 out of 15 subjects (p<0.05) and between the increase of lower leg volume and the urge to move in 11 out of 15 subjects (p<0.05). Association was shown between volume increase and symptoms in linear mixed effects models. Conclusions: Prolonged standing with lack of movement leads to an increase in the lower leg volume and a sensation of discomfort in venous healthy subjects. Causal relationships are indicated between these variables by linear mixed effects models.

Effect of ingesting a meal and orthostasis on the regulation of splanchnic and systemic hemodynamics and the responsiveness of cardiovascular α1-adrenoceptors.

Postprandial orthostasis activates mechanisms of cardiovascular homeostasis to maintain normal blood pressure (BP) and adequate blood flow to vital organs. The underlying mechanisms of cardiovascular homeostasis in postprandial orthostasis still require elucidation. Fourteen healthy volunteers were recruited to investigate the effect of an orthostatic challenge (60°-head-up-tilt for 20 min) on splanchnic and systemic hemodynamics before and after ingesting an 800-kcal composite meal. The splanchnic circulation was assessed by ultrasonography of the superior mesenteric and hepatic arteries and portal vein. Systemic hemodynamics were assessed noninvasively by continuous monitoring of BP, heart rate (HR), cardiac output (CO), and the pressor response to an intravenous infusion on increasing doses of phenylephrine, an α1-adrenoceptor agonist. Neurohumoral regulation was assessed by spectral analysis of HR and BP, plasma catecholamine and aldosterone levels and plasma renin activity. Postprandial mesenteric hyperemia was associated with an increase in CO, a decrease in SVR and cardiac vagal tone, and reduction in baroreflex sensitivity with no change in sympathetic tone. Arterial α1-adrenoceptor responsiveness was preserved and reduced in hepatic sinusoids. Postprandial orthostasis was associated with a shift of 500 mL of blood from mesenteric to systemic circulation with preserved sympathetic-mediated vasoconstriction. Meal ingestion provokes cardiovascular hyperdynamism, cardiac vagolysis, and resetting of the baroreflex without activation of the sympathetic nervous system. Meal ingestion also alters α1-adrenoceptor responsiveness in the hepatic sinusoids and participates in the redistribution of blood volume from the mesenteric to the systemic circulation to maintain a normal BP during orthostasis.NEW & NOTEWORTHY A unique integrated investigation on the effect of meal on neurohumoral mechanisms and blood flow redistribution of the mesenteric circulation during orthostasis was investigated. Food ingestion results in cardiovascular hyperdynamism, reduction in cardiac vagal tone, and baroreflex sensitivity and causes a decrease in α1-adrenoceptor responsiveness only in the venous intrahepatic sinusoids. About 500-mL blood shifts from the mesenteric to the systemic circulation during orthostasis. Accordingly, the orthostatic homeostatic mechanisms are better understood.

Lower body negative pressure enhances oxygen availability in the knee extensor muscles during intense resistive exercise in supine position.

PURPOSE: During exercise in supine posture or under microgravity in space, the gravity-dependent component of local blood pressure in leg muscles at upright posture can be simulated by lower body negative pressure (LBNP). We hypothesized that during resistive exercise LBNP favors oxygen availability in lower extremities, benefiting energy levels and performance of working muscles. METHODS: In permutated crossover design, nine subjects performed a series of fifteen slow-paced concentric (4 s) and eccentric contractions (4 s) without or with 40 mmHg LBNP and 4 s pause between repetitions. The force at knee flexion was 6% of the one repetition maximum (1-RM) and gradually increased to 60% 1RM in the first half of the individual range of motion, subsequently remaining constant until full extension. RESULTS: During the low force periods of continuous exercise, LBNP enhanced the refill of capillary blood measured by near infrared spectroscopy, amplifying the increase of total haemoglobin by about 20 µmol/l (p < 0.01) and oxyhaemoglobin by about 10 µmol/l (p < 0.01). During continuous exercise, LBNP induced a trend towards a lower EMG increment. This LBNP effect was not found when the periods of low forces at knee flexion were extended by 4 s pauses. Increased respiratory oxygen uptake (+ 0.1 l/min, p < 0.05) indicated overall enhanced muscle energy turn-over. CONCLUSIONS: Our results suggest stimulation of oxidative metabolism through LBNP enables working muscles to meet the energy demands of intense exercise. Further research is needed on the consequences for energy metabolism and the molecular control of growth and differentiation.

Modeling human orthostatic responses on the Moon and on Mars.

PURPOSE: Since manned missions to the Moon and Mars are planned, we conducted active standing tests with lunar, Martian, terrestrial, and 1.8 loads of inertial resistance (+Gz) modeled through defined parabolic flight maneuvers. We hypothesized that the cardiovascular response to active standing is proportional to the +Gz load. METHODS: During partial-+Gz parabolic flights, 14 healthy test subjects performed active stand-up maneuvers under 1 +Gz, lunar (0.16 +Gz), Martian (0.38 +Gz), and hyper inertial resistance (1.8 +Gz) while heart rate and finger blood pressure were continuously monitored. We quantified amplitudes and timing of orthostatic response immediately following standing up. RESULTS: The maximum early heart rate increase was 21 (SD ± 10) bpm with lunar, 23 (± 11) bpm with Martian, 34 (± 17) bpm with terrestrial +Gz, and 40 (± 11) bpm hyper +Gz. The time to maximum heart rate increased gradually with increasing loads of inertial resistance. The transient blood pressure reduction was most pronounced with hyper +Gz but did not differ significantly between lunar and Martian +Gz. The mean arterial pressure nadir was reached significantly later with Martian and lunar compared to 1 +Gz. Paradoxically, the time for blood pressure to recover was shortest with terrestrial +Gz. CONCLUSION: While load of inertial resistance directly affects the magnitude of the transient blood pressure reduction and heart rate response to active standing, blood pressure stabilization is most rapidly attained during terrestrial +Gz. The observation might suggest that the human cardiovascular system is tuned to cope with orthostatic stress on earth.

Knee-high compression socks minimize head-up tilt-induced cerebral and cardiovascular responses following dynamic exercise.

In healthy individuals during a non-exercised state, knee-high compression socks (CS) may reduce the magnitude of lower limb venous pooling during orthostasis but are not effective at minimizing the incidence of pre-syncopal symptoms. However, exaggerated reductions in cerebral blood flow velocity (CBV) and cardiac stroke volume (SV) occur during passive head-up tilt (HUT) testing following dynamic exercise. It is unknown if CS can minimize post-exercise HUT-induced decrements in CBV and SV in this population. To test the hypothesis that CS will attenuate the reductions in SV and CBV during 60° HUT following 60 minutes of moderate-intensity (60% VO2 peak) cycling exercise. Ten healthy volunteers (22.6 ± 2.1 years, 24.1 ± 2.5 kg/m2 ) completed pre- and post-exercise 15-minute HUT tests during randomized CS and Control (no CS) conditions. Changes in blood pressure (finger plethysmography), SV (Modelflow® method), and CBV (Transcranial Doppler) were measured during HUT and preceding supine rest periods. Pre-exercise HUT-induced similar (all, P > .47) reductions in SV (Control; -23.1 ± 11.5%, CS; -20.5 ± 10.9%) and CBV (Control; -18.1 ± 6.3%, CS; -15.3 ± 9.0%). However, larger post-exercise decreases in SV and CBV during HUT were observed in the Control versus CS condition. Specifically, CS attenuated the drop in SV (Control: -32.9 ± 5.6%, CS: -24.3 ± 11.6%; P = .01) and CBV (Control: -25.1 ± 5.8%, CS: -17.6 ± 7.8%; P = .02) during the post-exercise HUT test. These results indicate that CS attenuated HUT-induced reductions in SV and CBV following moderate-intensity cycling exercise and suggest that CS may be an effective countermeasure to reduce the incidence of post-exercise syncope in vulnerable populations.

Caffeine, gravity, and baroreceptor function: the integration of diet and cardiovascular control.

We describe a simple, cost-effective experiment to demonstrate cardiovascular integration of heart rate and blood pressure to accommodate the environmental and dietary factors of gravity and caffeine. Specific learning objectives associated with this include understanding the effects of posture on blood pressure and heart rate, coupled with the role of caffeine in modifying this response. Inclusion of ECG measurements, coupled with heart rate variability analysis, added a demonstration of the contribution made by the autonomic nervous system under these conditions. We clearly demonstrate that the cardiac work, estimated as rate-pressure product, necessary to undertake the transition from supine to standing, is fixed for a given group of subjects. However, the individual contribution of heart rate and systolic pressure to the cardiac workload is subject to the external factors of gravity and caffeine. Such an activity also demonstrates additional benefits, including unstructured teaching opportunities to augment classroom learning associated with integrative physiology and also the discussion of ethical issues with regard to human experimentation.

Blood pressure oscillations in baroreflex failure.

A 67-year-old man presented with labile hypertension and orthostatic hypotension after radical neck dissection and radiotherapy for squamus cell carcinoma. Baroreflex failure is clearly evident on autonomic testing.

Symbolic dynamics of heart rate variability - a promising tool to investigate cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD)?

We aimed to evaluate complex cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD) by using heart rate variability (HRV) nonlinear analysis - symbolic dynamics. We examined 29 boys with untreated ADHD and 25 healthy boys (age 8-13 years). ADHD symptoms were evaluated by ADHD-RS-IV scale. ECG was recorded in 3 positions: baseline supine position, orthostasis, and clinostasis. Symbolic dynamics indices were used for the assessment of complex cardiac sympathovagal regulation: normalised complexity index (NCI), normalised unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). The results showed that HRV complexity was significantly reduced at rest (NUPI) and during standing position (NCI, NUPI) in ADHD group compared to controls. Cardiac-linked sympathetic index 0V% was significantly higher during all posture positions and cardiovagal index 2LV% was significantly lower to standing in boys suffering from ADHD. Importantly, ADHD symptom inattention positively correlated with 0V%, and negatively correlated with NCI, NUPI. Concluding, symbolic dynamics revealed impaired complex neurocardiac control characterised by potential cardiac beta-adrenergic overactivity and vagal deficiency at rest and to posture changes in boys suffering from ADHD that is correlated with inattention. We suggest that symbolic dynamics indices could represent promising cardiac biomarkers in ADHD.

Aging augments renal vasoconstrictor response to orthostatic stress in humans.

The ability of the human body to maintain arterial blood pressure (BP) during orthostatic stress is determined by several reflex neural mechanisms. Renal vasoconstriction progressively increases during graded elevations in lower body negative pressure (LBNP). This sympathetically mediated response redistributes blood flow to the systemic circulation to maintain BP. However, how healthy aging affects the renal vasoconstrictor response to LBNP is unknown. Therefore, 10 young (25 ± 1 yr; means ± SE) and 10 older (66 ± 2 yr) subjects underwent graded LBNP (-15 and -30 mmHg) while beat-to-beat renal blood flow velocity (RBFV; Doppler ultrasound), arterial BP (Finometer), and heart rate (HR; electrocardiogram) were recorded. Renal vascular resistance (RVR), an index of renal vasoconstriction, was calculated as mean BP/RBFV. All baseline cardiovascular variables were similar between groups, except diastolic BP was higher in older subjects (P < 0.05). Increases in RVR during LBNP were greater in the older group compared with the young group (older: -15 mmHg Δ10 ± 3%, -30 mmHg Δ20 ± 5%; young: -15 mmHg Δ2 ± 2%, -30 mmHg Δ6 ± 2%; P < 0.05). RBFV tended to decrease more (P = 0.10) and mean BP tended to decrease less (P = 0.09) during LBNP in the older group compared with the young group. Systolic and diastolic BP, pulse pressure, and HR responses to LBNP were similar between groups. These findings suggest that aging augments the renal vasoconstrictor response to orthostatic stress in humans.

Investigating the Effects of Ultraendurance Running on Athletes' Heart Rate and Blood Pressure.

Background While the effects of exercise on the cardiovascular system are well documented, ultra-endurance sports involve distances beyond the scope of traditional marathons and have grown in popularity at a staggering pace in recent years. While short-term high-intensity exercise stimulates sympathetic rises in heart rate (HR) and blood pressure (BP), the depletion of fluid and electrolyte reserves characteristic of ultra-endurance sports may contribute to decreases in overall BP after the race. If decompensation of the autonomic safety net occurs, orthostatic hypotension as a result of fluid loss during an event may cause fatigue, dizziness, syncope, or collapse. Methodology Subjects were recruited by emails sent to race participants and at pre-race meetings, and no participants were excluded from the study. We observed BP and HR changes in subjects before and after ultramarathon activity in both supine and standing positions over multiple races of variant length and terrain from 50 to 240 km from 2013 to 2018. Participants entered races in Florida, with a mean age of 43.8 and an average body mass index (BMI) of 21.2. In addition to pre-race and post-race measurements, positional post-race BPs and HRs were analyzed for orthostatic trends. Results Of those who participated, 140 completed the events and post-race HR and BP measurements were recorded. The mean systolic blood pressure (SBP) increase from pre-race to post-race standing was 21 mmHg, while the mean diastolic blood pressure (DBP) rise was 13 mmHg. While in a supine position, there was a 15 mmHg increase in SBP from pre-race to post-race, along with a 7 mmHg rise in diastolic pressure. Post-race supine to standing average BP change was insignificant. In the supine position, the mean HR increased by 20 beats per minute (bpm) after the race and by 27 bpm while standing. After the race, the average increase in HR supine to standing was 15 bpm. Conclusions The SBP changed much more notably than diastolic pressures likely due to the increase in stroke volume associated with the sympathetic response during exercise. HR values also climbed as a result of exercise stress in the setting of catecholamine release, and the combined influence contributed to increased cardiac output despite water and electrolyte loss during the event. Post-race, no trends of orthostatic hypotension were noted either with HR or BP when rising from a supine position. The significance of the contribution of fluid intake during the race to compensatory mechanisms under neural control requires further study.

The Impact of Type 2 Diabetes on Peripheral and Cerebral Hemodynamic Responses to Active Stand.

BACKGROUND: Although type 2 diabetes mellitus (T2DM) is an established risk factor for cognitive impairment, the underlying mechanisms remain poorly explored. One potential mechanism may be through effects of T2DM on cerebral perfusion. The current study hypothesized that T2DM is associated with altered peripheral and central hemodynamic responses to orthostasis, which may in turn be associated with cognitive impairment in T2DM. METHODS: A novel use of function-on-scalar regression, which allows the entire hemodynamic response curve to be modeled, was employed to assess the association between T2DM and hemodynamic responses to orthostasis. Logistic regression was used to assess the relationship between tissue saturation index (TSI), T2DM, and cognitive impairment. All analyses used cross-sectional data from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA). RESULTS: Of 2 984 older adults (aged 64.3 ±â€…8.0; 55% female), 189 (6.3%) had T2DM. T2DM was associated with many features that are indicative of autonomic dysfunction including a blunted peak heart rate and lower diastolic blood pressure. T2DM was associated with reduced TSI and also with greater odds of impaired performance on the Montreal Cognitive Assessment (odds ratio [OR]: 1.62; confidence interval [CI: 1.07, 2.56]; p = .019). Greater TSI was associated with lower odds of impaired performance (OR: 0.90, CI [0.81-0.99]; p = .047). CONCLUSIONS: T2DM was associated with impaired peripheral and cerebral hemodynamic responses to active stand. Both T2DM and reduced cerebral perfusion were associated with impaired cognitive performance. Altered cerebral perfusion may represent an important mechanism linking T2DM and adverse brain health outcomes in older adults.

Insult of Ultraendurance Events on Blood Pressure: A Systematic Review and Meta-Analysis.

The rise of ultraendurance sports in the past two decades warrants evaluation of the impact on the heart and vessels of a growing number of athletes participating. Blood pressure is a simple, inexpensive method to evaluate one dimension of an athlete's cardiovascular health. No systematic review or meta-analysis to date has chronicled and delineated the effects of ultraendurance races, such as ultramarathons, marathons, half-marathons, and Ironman triathlon events, specifically on heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) measurements in supine and standing positions before and after the event. This meta-analysis reviews the effects of ultraendurance events on positional and calculated hemodynamic values. Data were extracted from 38 studies and analyzed using a random effects model with a total of 1,645 total blood pressure measurements. Of these, 326 values were obtained from a standing position, and 1,319 blood pressures were taken supine. Pre-race and post-race measurements were evaluated for clinical significance using established standards of hypotension and orthostasis. HR and calculated BP features, such as PP and MAP, were evaluated. Across all included studies, the mean supine post-race HR increased by 21±8 beats per minute (bpm) compared to pre-race values. The mean standing post-race HR increased by 23±14 bpm when compared with pre-race HR. Overall, there was a mean SBP decrease of 19±9 mmHg and a DBP decrease of 9±5 mmHg post-race versus pre-race values. MAP variations reflected SBP and DBP changes. The mean supine and standing pre-race blood pressures across studies were systolic (126±7; 124±14) and diastolic (76±6; 75±12), suggesting that some athletes may enter races with existing hypertension. The post-race increase in the mean HR and decline in mean blood pressure across examined studies suggest that during long-term events, ultramarathon athletes perform with relatively asymptomatic hypotension.

Relationship between sarcopenia and orthostatic blood pressure recovery in older falls clinic attendees.

PURPOSE: Sarcopenia and delayed orthostatic blood pressure (BP) recovery are two disorders increasingly associated with adverse clinical outcomes in older adults. There may exist a pathophysiological link between the two via the skeletal muscle pump of the lower limbs. Previously in a large population-based study, we found an association between probable sarcopenia and orthostatic BP recovery. Here, we sought to determine the association between confirmed sarcopenia and orthostatic BP recovery in falls clinic attendees aged 50 years or over. METHODS: One hundred and nine recruited patients (mean age 70 years, 58% women) underwent an active stand with non-invasive beat-to-beat haemodynamic monitoring. Hand grip strength and five-chair stands time were measured, and bioelectrical impedance analysis was performed. They were then classified as robust, probable sarcopenic or sarcopenic as per the European Working Group on Sarcopenia in Older People guidelines. Mixed effects models with linear splines were used to model the effect of sarcopenia status on orthostatic BP recovery, whilst controlling for potential confounders. RESULTS: Probable sarcopenia was identified in 32% of the sample and sarcopenia in 15%. Both probable and confirmed sarcopenia were independently associated with an attenuated rate of recovery of both systolic and diastolic BP in the 10-20 s period after standing. Attenuation was larger for confirmed than probable sarcopenia (systolic BP ß - 0.85 and - 0.59, respectively, P < 0.01; diastolic BP ß - 0.65, - 0.45, P < 0.001). CONCLUSION: Sarcopenia was independently associated with slower BP recovery during the early post-stand period. The potentially modifiable effect of the skeletal muscle pump in orthostatic haemodynamics requires further study.

Haemodynamic Parameters Underlying the Relationship between Sarcopenia and Blood Pressure Recovery on Standing.

BACKGROUND: Sarcopenia, delayed blood pressure (BP) recovery following standing, and orthostatic hypotension (OH) pose significant clinical challenges associated with ageing. While prior studies have established a link between sarcopenia and impaired BP recovery and OH, the underlying haemodynamic mechanisms remain unclear. METHODS: We enrolled 107 participants aged 50 and above from a falls and syncope clinic, conducting an active stand test with continuous non-invasive haemodynamic measurements. Hand grip strength and five-chair stand time were evaluated, and muscle mass was estimated using bioelectrical impedance analysis. Participants were categorised as non-sarcopenic or sarcopenic. Employing mixed-effects linear regression, we modelled the effect of sarcopenia on mean arterial pressure and heart rate after standing, as well as Modelflow®-derived parameters such as cardiac output, total peripheral resistance, and stroke volume, while adjusting for potential confounders. RESULTS: Sarcopenia was associated with diminished recovery of mean arterial pressure during the 10-20 s period post-standing (ß -0.67, p < 0.001). It also resulted in a reduced ascent to peak (0-10 s) and recovery from peak (10-20 s) of cardiac output (ß -0.05, p < 0.001; ß 0.06, p < 0.001). Furthermore, sarcopenia was associated with attenuated recovery (10-20 s) of total peripheral resistance from nadir (ß -0.02, p < 0.001) and diminished recovery from peak (10-20 s) of stroke volume (ß 0.54, p < 0.001). Notably, heart rate did not exhibit a significant association with sarcopenia status at any time interval post-standing. CONCLUSION: The compromised BP recovery observed in sarcopenia appears to be driven by an initial reduction in the peak of cardiac output, followed by attenuated recovery of cardiac output from its peak and total peripheral resistance from its nadir. This cardiac output finding seems to be influenced by stroke volume rather than heart rate. Possible mechanisms for these findings include cardio-sarcopenia, the impact of sarcopenia on the autonomic nervous system, and/or the skeletal muscle pump.

Risk factors for the development of orthostatic hypotension during autologous stem cell transplant in patients with multiple myeloma.

Orthostatic hypotension (OH) is a well-recognized phenomenon occurring in multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT), and is associated with significant morbidity and mortality. A retrospective analysis of patients admitted for first ASCT between June 2012 and April 2014 found that 161/222 (73%) patients were diagnosed with OH during the course of ASCT, including 51 patients who were found to have OH on the day of first orthostatic vitals check. Excluding these 51 patients, 110/171 (64%) patients developed OH during the peri-transplant period, at a median of 7 days post ASCT (95% CI: 6.5-8.5). OH did not significantly impact length of hospitalization, progression free and overall survival. Multivariable analysis revealed four risk factors (i.e. ≥0.5% weight loss/day, white race, gabapentin, antihypertensives) and two protective factors (i.e. antihistamine, proton pump inhibitor) associated with the development of peri-transplant OH.

Practical pearls to improve the efficacy and tolerability of levodopa in Parkinson's disease.

INTRODUCTION: Levodopa is the most effective medication for the treatment of motor symptoms of Parkinson's disease (PD). Several factors may affect the efficacy and tolerability of levodopa. These include the timing, dosage and administration of levodopa, concomitant drugs, food, PD-associated non-motor symptoms, and various neurologic and non-neurologic comorbidities. If not appropriately addressed, these issues may limit levodopa efficacy, tolerability, and compliance. AREAS COVERED: This article reviews the basics of the metabolism of orally administered levodopa, its side effects, and the factors that may affect its tolerability and efficacy. We provide several practical pearls to improve the tolerability and efficacy of levodopa. EXPERT OPINION: Protein-rich food delays and reduces levodopa absorption. Hence, levodopa should preferably be administered in a relatively empty stomach. Carbidopa dosing is crucial as it not only enhances the entry of levodopa into the central nervous system but also reduces levodopa's peripheral adverse effects. Patients experiencing the early side effects such as nausea/vomiting should be prescribed with anti-nausea medications that do not block dopamine receptors. Non-oral routes of administration can be used to obviate persistent gastrointestinal side effects. Implementation of these and other tips may help improve the tolerability and efficacy of levodopa.