Blunted autonomic response to standing up and head-up tilt in individuals with intellectual disabilities.

Previous research suggests individuals with intellectual disabilities (ID) may experience autonomic dysfunction, however, this has not been thoroughly investigated. The aim of this study was to compare the autonomic response to standing up (active orthostasis) and head-up tilt (passive orthostasis) in individuals with ID to a control group without ID. Eighteen individuals with and 18 individuals without ID were instrumented with an ECG-lead and finger-photoplethysmography for continuous heart rate and blood pressure recordings. The active and passive orthostasis protocol consisted of 10-min supine rest, 10-min standing, 10-min supine recovery, 5-min head-up tilt at 70°, followed by 10-min supine recovery. The last 5 min of each position was used to calculate hemodynamic and autonomic function (time- and frequency-domain heart rate and blood pressure variability measures and baroreflex sensitivity). Individuals with ID had higher heart rate during baseline and recovery (P < 0.05), and an attenuated hemodynamic (stroke volume, heart rate) and heart rate variability response to active and passive orthostasis (interaction effect P < 0.05) compared with individuals without ID. Mean arterial pressure (MAP) was higher in individuals with ID at all timepoints. Individuals with ID demonstrated altered hemodynamic and autonomic regulation compared with a sex- and age-matched control group, evidenced by a higher mean arterial pressure and a reduced response in parasympathetic modulation to active and passive orthostasis.NEW & NOTEWORTHY Individuals with ID demonstrated altered hemodynamic and autonomic regulation to the clinical autonomic function tasks standing up and head-up tilt (active and passive orthostasis). Higher resting heart rate and higher MAP throughout the protocol suggest a higher arousal level, and individuals with ID showed a blunted response in parasympathetic modulation. Further research should investigate the relationship of these findings with clinical outcomes.

Weighing the evidence for using vascular conductance, not resistance, in comparative cardiovascular physiology.

Vascular resistance and conductance are reciprocal indices of vascular tone that are often assumed to be interchangeable. However, in most animals in vivo, blood flow (i.e. cardiac output) typically varies much more than arterial blood pressure. When blood flow changes at a constant pressure, the relationship between conductance and blood flow is linear, whereas the relationship between resistance and blood flow is non-linear. Thus, for a given change in blood flow, the change in resistance depends on the starting point, whereas the attendant change in conductance is proportional to the change in blood flow regardless of the starting conditions. By comparing the effects of physical activity at different temperatures or between species - concepts at the heart of comparative cardiovascular physiology - we demonstrate that the difference between choosing resistance or conductance can be marked. We also explain here how the ratio of conductance in the pulmonary and systemic circulations provides a more intuitive description of cardiac shunt patterns in the reptilian cardiovascular system than the more commonly used ratio of resistance. Finally, we posit that, although the decision to use conductance or resistance should be made on a case-by-case basis, in most circumstances, conductance is a more faithful portrayal of cardiovascular regulation in vertebrates.

Sex Differences in Aortic Hemodynamics Following Acute Exercise: Wave Separation Analysis.

The importance of sex differences in the control of blood pressure responses to exercise is controversial. It is unknown whether the potential sex differences are a result of magnitude differences in forward or reflected pressure waves. The purpose of this study was to investigate sex differences in BP following acute exercise using wave separation analysis. Sixty-eight adults (36 females) participated in the study. Aerobic capacity was measured during a graded cycle ergometry test. Central pulse wave analysis was derived from the radial pulse using applanation tonometry and separated into forward and reflected pressure waves before, and 15 min and 30 min after maximum aerobic exercise. Both males and females exhibited significantly decreased brachial SBP (p<0.05) following acute exercise. However, only males exhibited a significant decrease in forward wave pressure (p<0.05). Reflected wave pressure was decreased following exercise in both sex (p<0.05) with no sex difference. Males and females differ in blood pressure control following maximal exercise. Results show that males rely on both central and peripheral hemodynamic modifications, whereas females mostly rely on peripheral modifications. The preferential peripheral adaptations in females may provide insight regarding mechanisms of blood pressure control and the disproportionate development of hypertension in young men compared to women.

Healthy aging and carotid performance: strain measures and ß-stiffness index.

Arterial stiffness is related to the risk of cardiovascular disease (CVD) and increases with aging. Functional impairment of the arterial wall can occur before structural changes and can be detectable before CVD symptoms. The elastic properties of the carotid arterial wall during the cardiac cycle can be evaluated by standard 2-dimensional (2D) ultrasound longitudinal or circumferential imaging of vascular deformation (strain) using speckle tracking. The purpose of this study was to compare standard 2D ultrasound circumferential and longitudinal images of vascular tissue motion and strain using speckle tracking in young and older individuals. Participants underwent recording of 2D ultrasound circumferential and longitudinal images of the common carotid artery. Circumferential carotid strain (CS) and CS rate were obtained and analyzed via speckle tracking software. Following the strain analysis, the circumferential strain ß-stiffness (C-ß) was calculated. Conventional longitudinal ß-stiffness (L-ß) was calculated and non-invasive blood pressure measurements were obtained from carotid artery pressure measurements in a resting supine position using applanation tonometry. C-ß was significantly higher than L-ß, and the association with age was greater (r = .824 vs. r = .547). CS and CS rate were significantly higher in the young compared to the older group. L-ß does not explain as much of the age-dependent differences in the carotid artery compared with C-ß. This is possibly due to the inclusion of whole arterial wall motion and deformation observed in the CS image. The ability of C-ß to accurately predict the future risk of CVD independent of age still needs further investigation.

Effect of upper body position on arterial stiffness: influence of hydrostatic pressure and autonomic function.

OBJECTIVE: To evaluate changes in arterial stiffness with positional change and whether the stiffness changes are due to hydrostatic pressure alone or if physiological changes in vasoconstriction of the conduit arteries play a role in the modulation of arterial stiffness. METHODS: Thirty participants' (male = 15, 24 ±â€Š4 years) upper bodies were positioned at 0, 45, and 72° angles. Pulse wave velocity (PWV), cardio-ankle vascular index, carotid beta-stiffness index, carotid blood pressure (cBP), and carotid diameters were measured at each position. A gravitational height correction was determined using the vertical fluid column distance (mmHg) between the heart and carotid artery. Carotid beta-stiffness was calibrated using three methods: nonheight corrected cBP of each position, height corrected cBP of each position, and height corrected cBP of the supine position (theoretical model). Low frequency systolic blood pressure variability (LFSAP) was analyzed as a marker of sympathetic activity. RESULTS: PWV and cardio-ankle vascular index increased with position (P < 0.05). Carotid beta-stiffness did not increase if not corrected for hydrostatic pressure. Arterial stiffness indices based on Method 2 were not different from Method 3 (P = 0.65). LFSAP increased in more upright positions (P < 0.05) but diastolic diameter relative to diastolic pressure did not (P > 0.05). CONCLUSION: Arterial stiffness increases with a more upright body position. Carotid beta-stiffness needs to be calibrated accounting for hydrostatic effects of gravity if measured in a seated position. It is unclear why PWV increased as this increase was independent of blood pressure. No difference between Methods 2 and 3 presumably indicates that the beta-stiffness increases are only pressure dependent, despite the increase in vascular sympathetic modulation.

N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects.

NEW FINDINGS: What is the central question of this study? This study evaluated the following central question: does N-acetylcysteine (N-AC), an antioxidant that readily penetrates the blood-brain barrier, have the capability to reduce the increase in sympathetic nerve activity observed during hyperacute intermittent hypoxia? What is the main finding and its importance? We demonstrate that N-AC decreases muscle sympathetic nerve activity in response to hyperacute intermittent hypoxia versus placebo control. This finding suggests that antioxidants, such as N-AC, have therapeutic potential in obstructive sleep apnoea. This investigation tested the following hypotheses: that (i) N-acetylcysteine (N-AC) attenuates hyperacute intermittent hypoxia-induced sympathoexcitation, (ii) without elevating superoxide measured in peripheral venous blood. Twenty-eight healthy human subjects were recruited to the study. One hour before experimentation, each subject randomly ingested either 70 mg kg(-1) of N-AC (n = 16) or vehicle placebo (n = 12). Three-lead ECG and arterial blood pressure, muscle sympathetic nerve activity (n = 17) and whole-blood superoxide concentration (using electron paramagnetic resonance spectroscopy; n = 12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia training (hAIHT) protocol that consisted of cyclical end-expiratory apnoeas with 100% nitrogen. N-AC decreased muscle sympathetic nerve activity after hAIHT compared with placebo (P < 0.02). However, N-AC did not alter superoxide concentrations in venous blood compared with placebo (P > 0.05). Moreover, hAIHT did not increase superoxide concentrations in the peripheral circulation as measured by electron paramagnetic resonance (P > 0.05). Based on these findings, we contend that (i) hAIHT and (ii) the actions of N-AC in hAIHT are primarily mediated centrally rather than peripherally, although central measurements of reactive oxygen species are difficult to obtain in human subjects, thus making this assertion difficult to verify. This investigation suggests the possibility of developing a pharmaceutical therapy to inhibit the sympathoexcitation associated with obstructive sleep apnoea.

Methods and considerations for the analysis and standardization of assessing muscle sympathetic nerve activity in humans.

The technique of microneurography and the assessment of muscle sympathetic nerve activity (MSNA) are used in laboratories throughout the world. The variables used to describe MSNA, and the criteria by which these variables are quantified from the integrated neurogram, vary among studies and laboratories and, therefore, can become confusing to those starting to learn the technique. Therefore, the purpose of this educational review is to discuss guidelines and standards for the assessment of sympathetic nervous activity through the collection and analysis of MSNA. This review will reiterate common practices in the collection of MSNA, but will also introduce considerations for the evaluation and physiological inference using MSNA.

Caffeine delays autonomic recovery following acute exercise.

BACKGROUND: Impaired autonomic recovery of heart rate (HR) following exercise is associated with an increased risk of sudden death. Caffeine, a potent stimulator of catecholamine release, has been shown to augment blood pressure (BP) and sympathetic nerve activity; however, whether caffeine alters autonomic function after a bout of exercise bout remains unclear. METHODS: In a randomized, crossover study, 18 healthy individuals (26 ± 1 years; 23.9 ± 0.8 kg·m(-2)) ingested caffeine (400 mg) or placebo pills, followed by a maximal treadmill test to exhaustion. Autonomic function and ventricular depolarization/repolarization were determined using heart rate variability (HRV) and corrected QT interval (QTc), respectively, at baseline, 5, 15, and 30 minutes post-exercise. RESULTS: Maximal HR (HRmax) was greater with caffeine (192 ± 2 vs. 190 ± 2 beat·min(-1), p < 0.05). During recovery, HR, mean arterial pressure (MAP), and diastolic blood pressure (DBP) remained elevated with caffeine (p < 0.05). Natural log transformation of low-to-high frequency ratio (LnLF/LnHF) of HRV was increased compared with baseline at all time points in both trials (p < 0.05), with less of an increase during 5 and 15 minutes post-exercise in the caffeine trial (p < 0.05). QTc increased from baseline at all time points in both trials, with greater increases in the caffeine trial (p < 0.05). CONCLUSIONS: Caffeine ingestion disrupts post-exercise autonomic recovery because of increased sympathetic nerve activity. The prolonged sympathetic recovery time could subsequently hinder baroreflex function during recovery and disrupt the stability of autonomic function, potentiating a pro-arrhythmogenic state in young adults.

Novel Split Chest Tube Improves Post-Surgical Thoracic Drainage.

OBJECTIVE: Conventional, separate mediastinal and pleural tubes are often inefficient at draining thoracic effusions. DESCRIPTION: We developed a Y-shaped chest tube with split ends that divide within the thoracic cavity, permitting separate intrathoracic placement and requiring a single exit port. In this study, thoracic drainage by the split drain vs. that of separate drains was tested. METHODS: After sternotomy, pericardiotomy, and left pleurotomy, pigs were fitted with separate chest drains (n=10) or a split tube prototype (n=9) with internal openings positioned in the mediastinum and in the costo-diaphragmatic recess. Separate series of experiments were conducted to test drainage of D5W or 0.58 M sucrose, an aqueous solution with viscosity approximating that of plasma. One litre of fluid was infused into the thorax, and suction was applied at -20 cm H2O for 30 min. RESULTS: When D5W was infused, the split drain left a residual volume of 53 ± 99 ml (mean value ± SD) vs. 148 ± 120 for the separate drain (P=0.007), representing a drainage efficiency (i.e. drained vol/[drained + residual vol]) of 95 ± 10% vs. 86 ± 12% for the separate drains (P = 0.011). In the second series, the split drain evacuated more 0.58 M sucrose in the first minute (967 ± 129 ml) than the separate drains (680 ± 192 ml, P<0.001). By 30 min, the split drain evacuated a similar volume of sucrose vs. the conventional drain (1089 ± 72 vs. 1056 ± 78 ml; P = 0.5). Residual volume tended to be lower (25 ± 10 vs. 62 ± 72 ml; P = 0.128) and drainage efficiency tended to be higher (98 ± 1 vs. 95 ± 6%; P = 0.111) with the split drain vs. conventional separate drains. CONCLUSION: The split chest tube drained the thoracic cavity at least as effectively as conventional separate tubes. This new device could potentially alleviate postoperative complications.

Autonomic neural control of heart rate during dynamic exercise: revisited.

UNLABELLED: The accepted model of autonomic control of heart rate (HR) during dynamic exercise indicates that the initial increase is entirely attributable to the withdrawal of parasympathetic nervous system (PSNS) activity and that subsequent increases in HR are entirely attributable to increases in cardiac sympathetic activity. In the present review, we sought to re-evaluate the model of autonomic neural control of HR in humans during progressive increases in dynamic exercise workload. We analysed data from both new and previously published studies involving baroreflex stimulation and pharmacological blockade of the autonomic nervous system. Results indicate that the PSNS remains functionally active throughout exercise and that increases in HR from rest to maximal exercise result from an increasing workload-related transition from a 4 : 1 vagal-sympathetic balance to a 4 : 1 sympatho-vagal balance. Furthermore, the beat-to-beat autonomic reflex control of HR was found to be dependent on the ability of the PSNS to modulate the HR as it was progressively restrained by increasing workload-related sympathetic nerve activity. IN CONCLUSION: (i) increases in exercise workload-related HR are not caused by a total withdrawal of the PSNS followed by an increase in sympathetic tone; (ii) reciprocal antagonism is key to the transition from vagal to sympathetic dominance, and (iii) resetting of the arterial baroreflex causes immediate exercise-onset reflexive increases in HR, which are parasympathetically mediated, followed by slower increases in sympathetic tone as workloads are increased.

Pyruvate-enriched resuscitation: metabolic support of post-ischemic hindlimb muscle in hypovolemic goats.

Tourniquet-imposed ischemia-reperfusion of extremities generates reactive oxygen and nitrogen species (RONS), which can disrupt intermediary metabolism and ATP production. This study tested the hypothesis that fluid resuscitation with pyruvate, a natural antioxidant and metabolic fuel, ameliorates the deleterious effects of ischemia-reperfusion on intermediary metabolism in skeletal muscle. Anesthetized male goats (∼25 kg) were bled to a mean arterial pressure of 48 ± 1 mmHg and then subjected to 90 min hindlimb ischemia with a tourniquet and femoral crossclamp, followed by 4-h reperfusion. Lactated Ringers (LR) or pyruvate Ringers (PR) was infused intravenous for 90 min, from 30 min ischemia to 30 min reperfusion, to deliver 0.05 mmol kg(-1) min(-1) lactate or pyruvate. Time controls (TC) underwent neither hemorrhage nor hindlimb ischemia. Lipid peroxidation product 8-isoprostane, RONS-sensitive aconitase and creatine kinase activities, antioxidant superoxide dismutase activity, and phosphocreatine phosphorylation potential ([PCr]/[{Cr}{P(i)}]), an index of tissue energy state, were measured in reperfused gastrocnemius at 90 min resuscitation (n = 6 all groups) and 3.5 h post-resuscitation (n = 8 TC, 9 LR, 10 PR). PR more effectively than LR suppressed 8-isoprostane formation, prevented inactivation of aconitase and creatine kinase, doubled superoxide dismutase activity, and augmented [PCr]/([Cr][P(i)]). Pyruvate-enriched Ringer's is metabolically superior to Ringer's lactate for fluid resuscitation of tourniqueted muscle.

Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia.

AIM: To test the hypothesis that fluid resuscitation with Ringer's solution enriched with pyruvate (PR), a physiological antioxidant and energy substrate, affords protection of myocardial metabolism and electrophysiological performance superior to lactated Ringer's (LR) during hypovolemia and hindlimb ischemia-reperfusion. METHODS: Male domestic goats (25-30 kg) were exsanguinated to a mean arterial pressure of 48 ± 1 mmHg. Right hindlimb ischemia was imposed for 90 min by applying a tourniquet and femoral crossclamp. LR or PR, infused iv, delivered 0.05 mmol/kg per minute L-lactate or pyruvate, respectively, from 30 min hindlimb ischemia until 30 min post-ischemia. Time controls (TC) underwent neither hemorrhage, hindlimb ischemia nor resuscitation. Goats were sacrificed and left ventricular myocardium biopsied at 90 min fluid resuscitation (n = 6 per group) or 3.5 h later (n = 9 LR, 10 PR, 8 TC). RESULTS: Myocardial 8-isoprostane content, phosphocreatine phosphorylation potential, creatine kinase activity, and heart rate-adjusted QT interval (QTc) variability were evaluated at 90 min resuscitation and 3.5 h post-resuscitation. PR sharply lowered pro-arrhythmic QTc variability vs LR (P < 0.05); this effect persisted 3.5 h post-resuscitation. PR lowered myocardial 8-isoprostane content, a product of oxidative stress, by 39 and 37% during and 3.5 h after resuscitation, respectively, vs LR. Creatine kinase activity fell 42% post-LR vs TC (P < 0.05), but was stable post-PR (P < 0.02 vs post-LR). PR doubled phosphocreatine phosphorylation potential, a measure of ATP free energy state, vs TC and LR (P < 0.05); this energetic enhancement persisted 3.5 h post-resuscitation. CONCLUSION: By augmenting myocardial energy state and protecting creatine kinase activity, pyruvate-enriched resuscitation stabilized cardiac electrical function during central hypovolemia and hindlimb ischemia-reperfusion.

Comparison of irrigation solutions and devices in a contaminated musculoskeletal wound survival model.

BACKGROUND: There is much to learn about the effectiveness of different methods currently used for the irrigation of open wounds. The purpose of this study was to compare various approaches in a survival animal model. METHODS: We used an established goat model involving the creation of a reproducible complex musculoskeletal wound followed by inoculation with Pseudomonas aeruginosa (lux) bacteria. This genetically altered luminescent bacterium provides the ability for quantitative analysis with a photon-counting camera system. For Study 1, wound irrigation was performed six hours after the injury and inoculation; the goats were assigned to four treatment groups: normal saline solution, bacitracin solution, castile soap, and benzalkonium chloride. All wounds received sharp débridement and irrigation with use of a pulsatile lavage device (19 psi). Images and photon counts were obtained prior to irrigation, after irrigation, and forty-eight hours after injury and inoculation. For Study 2, we used the same animal model and compared bulb syringe and pulsatile lavage irrigation with saline solution. RESULTS: In Study 1, the irrigation treatment lowered the bacterial counts in all treatment groups. The greatest reduction was seen with castile soap, which lowered the photon count to 13% of the pretreatment level. This was followed by benzalkonium chloride, bacitracin, and saline solution at 18%, 22%, and 29%, respectively. At forty-eight hours, imaging showed a rebound in bacterial counts in every group. The highest rebound was measured in the castile soap group, which rebounded to 120% of the pretreatment level. The benzalkonium chloride group experienced a rebound to 94% of the pretreatment level. These were followed by bacitracin solution (89%) and normal saline solution (68%). In Study 2, both treatment methods were effective in removing 75% of the bacteria initially. At forty-eight hours, the bacterial levels in the pulsed lavage group rebounded to 94% of the original levels (compared with 48% in the bulb syringe group). The difference in the mean photon count ratios at forty-eight hours was significant (p = 0.048). CONCLUSIONS: Approaches used to remove bacteria from wounds, such as irrigants other than saline solution or high-pressure devices, may not have the best clinical outcome.

Incidence of major tendon ruptures and anterior cruciate ligament tears in US Army soldiers.

BACKGROUND: Although a rare event, the prevalence of major tendon rupture has increased in recent decades. Identification of risk factors is important for prevention purposes. HYPOTHESIS: Race is a risk factor for major tendon ruptures. STUDY DESIGN: Cohort study (prevalence); Level of evidence, 2. METHODS: All patients admitted for surgical management of a rupture of a major tendon at Womack Army Medical Center, Fort Bragg, North Carolina, in 1995 and 1996 were identified and evaluated for risk factors. RESULTS: The authors identified 52 major tendon ruptures: 29 Achilles, 12 patellar, 7 pectoralis major, and 4 quadriceps tendon ruptures. All patients were active-duty soldiers, and 1 was a female soldier. Forty-one tendon ruptures occurred among black soldiers, 8 occurred among white soldiers, and 3 occurred among Latino soldiers. The population at risk included 93,224 exposures during the 2-year period, of which 67.1% were white, 24.5% were black, and 8.4% were self-classified as other race. The rate ratio for tendon rupture, adjusted for gender and age, was 13.3 (95% confidence interval, 6.2-28.5) between blacks and whites and 2.9 (95% confidence interval, 0.8-10.9) between Latinos and whites. CONCLUSION: The rate of major tendon rupture was 13 times greater for black men in this study population when compared with whites. Interventions among those at a higher risk for injury should be considered.

Extremity trauma research in the United States Army.

Extremity wounds compose the burden of injury in the global war on terrorism, and there is a great need for research to improve the treatment of soldiers who incur these devastating injuries. The mission of the United States Army Institute of Surgical Research is to conduct combat casualty care research in several areas, including explosive injury mechanisms, field tourniquet use, external fixator pin coating, wound irrigation optimization, antibiotic-impregnated bone graft substitutes, segmental muscle defects, and outcomes research. Future research directions include development of bone and soft-tissue regenerative technologies, prevention and treatment of heterotopic ossification, and bacteriology of unique pathogens.