Cerebral blood velocity during concurrent supine cycling, lower body negative pressure, and head-up tilt challenges: implications for concussion rehabilitation.

Introduction. The effect of concurrent head-up tilt and lower body negative pressure (LBNP) have been examined on middle cerebral artery velocity (MCAv) at rest; however, it is unknown the superimposed effect these factors have on blunting the elevation in cerebral blood velocity associated with moderate-intensity exercise.Methods. 23 healthy adults (11 females / 12 males, 20-33 years) completed three visits. The first consisted of a maximal ramp supine cycling test to identify the wattage associated with individualized maximal MCAv. Subsequent visits included randomized no LBNP (control) or LBNP at -40 Torr (experimental) with successively increasing head-up tilt stages of 0, 15, 30, and 45 degrees during the pre-described individualized wattage. Transcranial Doppler ultrasound was utilized to quantify MCAv. Two-factorial repeated measures analysis of variance with effect sizes were used to determine differences between days and tilt stages.Results. Between-day baseline values for MCAv, heart rate, and blood pressure displayed low variability with <5% variation. With no LBNP, MCAv was above baseline on average for all participants; however, 15 degrees and 30 degrees tilt with concurrent -40 Torr LBNP was sufficient to return MCAv to 100% of baseline values in females and males, respectively. Body-weight did not impact the association between tilt and pressure (R2range: 0.01-0.12).Conclusion. Combined LBNP and tilt were sufficient to reduce the increase in MCAv associated with moderate-intensity exercise. This exercise modality shows utility to enable individuals with a concussion to obtain the positive physiological adaptions associated with exercise while minimizing symptom exacerbation due to the notion of the Monro-Kellie doctrine.

Acute regulation of erythropoietin via lower body negative pressure: Influence of sex and age.

The regulation of erythropoiesis via hemodynamic stimuli such as reduced central blood volume (CBV) remains uncertain in women and elderly individuals. This study assessed the acute effects of lower body negative pressure (LBNP) on key endocrine biomarkers regulating erythropoiesis, that is, erythropoietin (EPO) and copeptin, in young and older women and men (n = 87). Transthoracic echocardiography and hemodynamics were assessed throughout incremental LBNP levels for 1 hour, or until presyncope, with established methods. Venous blood samples were collected at baseline and immediately after termination of the orthostatic tolerance (OT) test for subsequent hormone analyses. The average age of young women and men (33.1 ± 6.0 vs. 29.5 ± 6.9 yr) and older women and men (63.8 ± 8.0 vs. 65.3 ± 8.9 yr) as well as their physical activity levels were matched within each age and sex group. CBV, as determined by right atrial volume, was reduced in all individuals at the end of the OT test (p < 0.001). The average OT time ranged from 50.1 to 58.1 min in all individuals. LBNP increased circulating EPO in young women (p = 0.023) but not in young men or older individuals. Copeptin was increased in all individuals with LBNP but was exclusively associated with EPO in men (r = 0.39, p = 0.013). The present study indicates that the acute hemodynamic regulation of EPO production is both sex- and age-dependent.

A Comparison of Haemodynamic Responses between Head-Up Tilt and Lower Body Negative Pressure.

Orthostatic intolerance (OI), a disorder of the autonomic nervous system, it is the development of symptoms when standing upright which are relieved when reclining. Head-up tilt (HUT) table test is a common test for assessing orthostatic tolerance. However, HUT is limited with low sensitivity and specificity. Another approach to stimulate the changing direction and value of the gravity field vector is the lower body negative pressure (LBNP) chamber. The aims of the study is to evaluate the physiological responses of healthy subjects on HUT and LBNP, and examine the relations of two tests. A total of 19 subjects were recruited. A validated wearable device, Sotera Visi Mobile was use to collect physiological signals simultaneously throughout the experiment procedures. Each subject went through a baseline supine rest, 70o of HUT test, another round of baseline supine rest, followed by activation of LBNP test. Three level of suction were applied, i.e. -30 mmHg, -40 mmHg, and -50 mmHg. In this pilot study, healthy subjects showed significantly increased of heart rate, and decreased of systolic blood pressure and diastolic blood pressure, in both HUT and LBNP tests. Although both tests are capable of stimulating a decreased blood volume in the central circulation, but the physiological responses behaved differently and shown only very week correlation. This suggesting that a combination of LBNP test with HUT test might work the best in orthostatic intolerance assessment.

Influence of head-up tile and lower body negative pressure on the internal jugular vein.

Head-up tilt (HUT)-induced gravitational stress causes collapse of the internal jugular vein (IJV) by decreasing central blood volume and through mass-effect from the surrounding tissues. Besides HUT, lower body negative pressure (LBNP) is used to stimulate orthostatic stress as an experimental model. Compared to HUT, LBNP has less of a gravitational effect because of the supine position; therefore, we hypothesized that LBNP causes less of a decrease in the cross-sectional area of the IJV compared to HUT. We tested the hypothesis by measuring the cross-sectional area of the IJV using B-mode ultrasonography while inducing orthostatic stress at levels of -40 mmHg LBNP and 60° HUT. The cross-sectional area of IJV decreased from the resting baseline during both LBNP and HUT trials, but the LBNP-induced decrease in the cross-sectional area of IJV was smaller than that of HUT (right, -45% ± 49% vs. -78% ± 27%, p = 0.008; left, -49% ± 27% vs. -78% ± 20%, p = 0.004). Since changes in venous outflow may affect cerebral arterial circulation, the findings of the present study suggest that orthostatic stress induced by different techniques modulates cerebral blood flow regulation through its effect on venous outflow.

The design and use of a simple device for the MRI assessment of changes in cardiovascular function by lower-body negative-pressure-simulated reduction of central blood volume.

AIM: To use a locally designed and simple lower-body negative-pressure (LBNP) device and 1.5 T magnetic resonance imaging (MRI) to demonstrate the ability to assess changes in cardiovascular function during preload reduction. These effects were evaluated on ventricular volumes and great vessel flow in healthy volunteers, for which there are limited published data. MATERIAL AND METHODS: After ethical review, 14 volunteers (mean age 33.9 ± 7 years, mean body mass index [BMI] 23.1 ± 2.5) underwent LBNP prospectively at 0, -5, -10, and -20 mmHg pressure, using a locally designed LBNP box. Expiratory breath-hold biventricular volumes, and free-breathing flow imaging of the ascending aorta and main pulmonary artery were acquired at each level of LBNP. RESULTS: At -5 mmHg, there was no change in aortic flow or left ventricular volumes versus baseline. Right ventricular output (p=0.013) and pulmonary net flow (p=0.026) decreased. At -20 mmHg, aortic and pulmonary net flow (p<0.001) decreased, as were left and right ventricular end diastolic volume (p<0.001) and left and right end systolic volumes (p=0.038 and p=0.003 respectively). CONCLUSIONS: Use of a MRI-compatible LBNP device is feasible to measure changes in ventricular volume and great arterial flow in the same experiment. This may enhance further research into the effects of preload reduction by MRI in a wide range of important cardiovascular pathologies.

The effect of hypercapnia on regional cerebral blood flow regulation during progressive lower-body negative pressure.

PURPOSE: Previous work indicates that dynamic cerebral blood flow (CBF) regulation is impaired during hypercapnia; however, less is known about the impact of resting hypercapnia on regional CBF regulation during hypovolemia. Furthermore, there is disparity within the literature on whether differences between anterior and posterior CBF regulation exist during physiological stressors. We hypothesized: (a) lower-body negative pressure (LBNP)-induced reductions in cerebral blood velocity (surrogate for CBF) would be more pronounced during hypercapnia, indicating impaired CBF regulation; and (b) the anterior and posterior cerebral circulations will exhibit similar responses to LBNP. METHODS: In 12 healthy participants (6 females), heart rate (electrocardiogram), mean arterial pressure (MAP; finger photoplethosmography), partial pressure of end-tidal carbon dioxide (PETCO2), middle cerebral artery blood velocity (MCAv) and posterior cerebral artery blood velocity (PCAv; transcranial Doppler ultrasound) were measured. Cerebrovascular conductance (CVC) was calculated as MCAv or PCAv indexed to MAP. Two randomized incremental LBNP protocols were conducted (- 20, - 40, - 60 and - 80 mmHg; three-minute stages), during coached normocapnia (i.e., room air), and inspired 5% hypercapnia (~ + 7 mmHg PETCO2 in normoxia). RESULTS: The main findings were: (a) static CBF regulation in the MCA and PCA was similar during normocapnic and hypercapnic LBNP trials, (b) MCA and PCA CBV and CVC responded similarly to LBNP during normocapnia, but (c) PCAv and PCA CVC were reduced to a greater extent at - 60 mmHg LBNP (P = 0.029; P < 0.001) during hypercapnia. CONCLUSION: CBF regulation during hypovolemia was preserved in hypercapnia, and regional differences in cerebrovascular control may exist during superimposed hypovolemia and hypercapnia.

High-intensity interval exercise reduces tolerance to a simulated haemorrhagic challenge in heat-stressed individuals.

NEW FINDINGS: What is the central question of this study? In heat-stressed individuals, does high-intensity interval exercise reduce tolerance to a simulated haemorrhagic challenge (lower body negative pressure, LBNP) relative to steady state exercise? What is the main finding and its importance? LBNP tolerance was lower in heat-stressed individuals following high-intensity interval exercise relative to steady state exercise. This was likely owing to the greater cardiovascular strain required to maintain arterial blood pressure prior to and early during LBNP following high-intensity interval exercise. These findings are of importance for individuals working in occupations in which combined heat stress and intense intermittent exercise are common and where the risk of haemorrhagic injury is increased. ABSTRACT: This study investigated whether tolerance to a simulated haemorrhagic challenge (lower body negative pressure, LBNP) was lower in heat-stressed individuals following high-intensity interval exercise relative to steady state exercise. Nine healthy participants completed two trials (Steady State and Interval). Participants cycled continuously at ∼38% (Steady State) or alternating between 10 and ∼88% (Interval) of the maximal power output whilst wearing a hot water perfused suit until core temperatures increased ∼1.4°C. Participants then underwent LBNP to pre-syncope. LBNP tolerance was quantified as cumulative stress index (CSI; mmHg min). Mean skin and core temperatures were elevated in both trials following exercise prior to LBNP (to 38.1 ± 0.6°C and 38.3 ± 0.2°C, respectively, both P < 0.001 relative to baseline) but not different between trials (both P > 0.05). In the Interval trial, heart rate was greater (122 ± 12 beats min-1 ) prior to LBNP, relative to the Steady State trial (107 ± 8 beats min-1 , P < 0.001) while mean arterial pressure was similarly reduced in both trials prior to LBNP (from baseline 89 ± 5 to 77 ± 7 mmHg; P = 0.001) and at pre-syncope (to 62 ± 9 mmHg, P < 0.001). CSI was lower in the Interval trial (280 ± 194 vs. 550 ± 234 mmHg min; P = 0.0085). In heat-stressed individuals, tolerance to a simulated haemorrhagic challenge is reduced following high-intensity interval exercise relative to steady state exercise.

Intracranial Hypertension and Intra-abdominal Pressure. Is it Worth Measuring?

Patients with refractory intracranial hypertension who have already undergone all the measures recommended by the current guidelines can benefit from having their intraabdominal pressure monitored since its increase generates hemodynamic repercussions and secondary elevation of intracranial pressure. In this context, a bibliographic research was performed on PubMed with the terms intra-abdominal pressure, abdominal compartment syndrome, intracranial pressure, intracranial hypertension. Altogether, 146 articles were observed, 87 of which were from the year 2000, and only 15 articles were considered relevant to the topic. These studies indicate that patients with refractory intracranial hypertension can benefit fromthe measurement of intraabdominal pressure, since there is evidence that an increase in this pressure leads to organic dysfunctions with an indirect impact on cerebral venous return and, consequently, an increase in intracranial pressure. In thosewho underwent decompression laparotomy, direct effectswere observed in reducing intracranial hypertension and survival.

Analysis of changes in cardiac circadian rhythms of RR and QT induced by a 60-day head-down bed rest with and without nutritional countermeasure.

PURPOSE: Prolonged weightlessness exposure generates cardiovascular deconditioning, with potential implications on ECG circadian rhythms. Head-down (- 6°) tilt (HDT) bed rest is a ground-based analogue model for simulating the effects of reduced motor activity and fluids redistribution occurring during spaceflight. Our aim was to evaluate the impact of 60-day HDT on the circadianity of RR and ventricular repolarization (QTend) intervals extracted from 24-h Holter ECG recordings, scheduled 9 days before HDT (BDC-9), the 5th (HDT5), 21st (HDT21) and 58th (HDT58) day of HDT, the 1st (R + 0) and 8th (R + 7) day after HDT. Also, the effectiveness of a nutritional countermeasure (CM) in mitigating the HDT-related changes was tested. METHODS: RR and QTend circadian rhythms were evaluated by Cosinor analysis, resulting in maximum and minimum values, MESOR (a rhythm-adjusted mean), oscillation amplitude (OA, half variation within a night-day cycle), and acrophase (φ, the time at which the fitting sinusoid's amplitude is maximal) values. RESULTS: RR and QTend MESOR increased at HDT5, and the OA was reduced along the HDT period, mainly due to the increase of the minima. At R + 0, QTend OA increased, particularly in the control group. The φ slightly anticipated during HDT and was delayed at R + 0. CONCLUSION: 60-Day HDT affects the characteristics of cardiac circadian rhythm by altering the physiological daily cycle of RR and QTend intervals. Scheduled day-night cycle and feeding time were maintained during the experiment, thus inferring the role of changes in the gravitational stimulus to determine these variations. The applied nutritional countermeasure did not show effectiveness in preventing such changes.

Evidence for misleading decision support in characterizing differences in tolerance to reduced central blood volume using measurements of tissue oxygenation.

BACKGROUND: The physiological response to hemorrhage includes vasoconstriction in an effort to shunt blood to the heart and brain. Hemorrhaging patients can be classified as "good" compensators who demonstrate high tolerance (HT) or "poor" compensators who manifest low tolerance (LT) to central hypovolemia. Compensatory vasoconstriction is manifested by lower tissue oxygen saturation (StO2 ), which has propelled this measure as a possible early marker of shock. The compensatory reserve measurement (CRM) has also shown promise as an early indicator of decompensation. METHODS: Fifty-one healthy volunteers (37% LT) were subjected to progressive lower body negative pressure (LBNP) as a model of controlled hemorrhage designed to induce an onset of decompensation. During LBNP, CRM was determined by arterial waveform feature analysis. StO2 , muscle pH, and muscle H+ concentration were calculated from spectrum using near-infrared spectroscopy (NIRS) on the forearm. RESULTS: These values were statistically indistinguishable between HT and LT participants at baseline (p ≥ 0.25). HT participants exhibited lower (p = 0.01) StO2 at decompensation compared to LT participants. CONCLUSIONS: Lower StO2 measured in patients during low flow states associated with significant hemorrhage does not necessarily translate to a more compromised physiological state, but may reflect a greater resistance to the onset of shock. Only the CRM was able to distinguish between HT and LT participants early in the course of hemorrhage, supported by a significantly greater ROC AUC (0.90) compared with STO2 (0.68). These results support the notion that measures of StO2 could be misleading for triage and resuscitation decision support.

Neurovascular coupling is not influenced by lower body negative pressure in humans.

Cerebral blood flow is tightly coupled with local neuronal activation and metabolism, i.e., neurovascular coupling (NVC). Studies suggest a role of sympathetic nervous system in the regulation of cerebral blood flow. However, this is controversial, and the sympathetic regulation of NVC in humans remains unclear. Since impaired NVC has been identified in several chronic diseases associated with a heightened sympathetic activity, we aimed to determine whether reflex-mediated sympathetic activation via lower body negative pressure (LBNP) attenuates NVC in humans. NVC was assessed using a visual stimulation protocol (5 cycles of 30 s eyes closed and 30 s of reading) in 11 healthy participants (aged 24 ± 3 yr). NVC assessments were made under control conditions and during LBNP at -20 and -40 mmHg. Posterior (PCA) and middle (MCA) cerebral artery mean blood velocity (Vmean) and vertebral artery blood flow (VAflow) were simultaneously determined with cardiorespiratory variables. Under control conditions, the visual stimulation evoked a robust increase in PCAVmean (∆18.0 ± 4.5%), a moderate rise in VAflow (∆9.6 ± 4.3%), and a modest increase in MCAVmean (∆3.0 ± 1.9%). The magnitude of NVC response was not affected by mild-to-moderate LBNP (all P > 0.05 for repeated-measures ANOVA). Given the small change that occurred in partial pressure of end-tidal CO2 during LBNP, this hypocapnia condition was matched via voluntary hyperventilation in absence of LBNP in a subgroup of participants (n = 8). The mild hypocapnia during LBNP did not exert a confounding influence on the NVC response. These findings indicate that the NVC is not influenced by LBNP or mild hypocapnia in humans.NEW & NOTEWORTHY Visual stimulation evoked a robust increase in posterior cerebral artery velocity and a modest increase in vertebral artery blood flow, i.e., neurovascular coupling (NVC), which was unaffected by lower body negative pressure (LBNP) in humans. In addition, although LBNP induced a mild hypocapnia, this degree of hypocapnia in the absence of LBNP failed to modify the NVC response.

Hypercapnia augments resistive exercise-induced elevations in intraocular pressure in older individuals.

NEW FINDINGS: What is the central question of this study? Astronauts on-board the International Space Station (ISS) perform daily exercises designed to prevent muscle atrophy and bone demineralization: what is the effect of resistive exercise performed by subjects while exposed to the same level of hypercapnia as on the ISS on intraocular pressure (IOP)? What is the main finding and its importance? The static exercise-induced elevation in IOP during 6° prone head-down tilt (simulating the headward shift of body fluids in microgravity) is augmented by hypercapnia and exceeds the ocular hypertension threshold. ABSTRACT: The present study assessed the effect of 6° head-down (establishing the cephalad fluid displacement noted in astronauts in microgravity) prone (simulating the effect on the eye) tilt during rest and exercise (simulating exercise performed by astronauts to mitigate the sarcopenia induced by unloading of weight-bearing limbs), in normocapnic and hypercapnic conditions (the latter simulating conditions on the International Space Station) on intraocular pressure (IOP). Volunteers (mean age = 57.8 ± 6 years, n = 10) participated in two experimental sessions, each comprising: (i) 10 min rest, (ii) 3 min static handgrip exercise (30% max), and (iii) 2 min recovery, inspiring either room air (NCAP) or a hypercapnic mixture (1% CO2 , HCAP). We measured IOP in the right eye, cardiac output (CO), stroke volume (SV), heart rate (HR) and mean arterial pressure (MAP) at regular intervals. Baseline IOP in the upright seated position while breathing room air was 14.1 ± 2.9 mmHg. Prone 6° head-down tilt significantly (P < 0.01) elevated IOP in all three phases of the NCAP (rest: 27.0 ± 3.7 mmHg; exercise: 32.2 ± 4.8 mmHg; recovery: 27.4 ± 4.0 mmHg) and HCAP (rest: 27.3 ± 4.3 mmHg; exercise: 34.2 ± 6.0 mmHg; recovery: 29.1 ± 5.8 mmHg) trials, with hypercapnia augmenting the exercise-induced elevation in IOP (P < 0.01). CO, SV, HR and MAP were significantly increased during handgrip dynamometry, but there was no effect of hypercapnia. The observed IOP measured during prone 6° HDT in all phases of the NCAP and HCAP trials exceeded the threshold pressure defining ocular hypertension. The exercise-induced increase in IOP is exacerbated by hypercapnia.

Sympathetic activation by lower body negative pressure decreases kidney perfusion without inducing hypoxia in healthy humans.

PURPOSE: There is ample evidence that systemic sympathetic neural activity contributes to the progression of chronic kidney disease, possibly by limiting renal blood flow and thereby inducing renal hypoxia. Up to now there have been no direct observations of this mechanism in humans. We studied the effects of systemic sympathetic activation elicited by a lower body negative pressure (LBNP) on renal blood flow (RBF) and renal oxygenation in healthy humans. METHODS: Eight healthy volunteers (age 19-31 years) were subjected to progressive LBNP at - 15 and - 30 mmHg, 15 min per level. Brachial artery blood pressure was monitored intermittently. RBF was measured by phase-contrast MRI in the proximal renal artery. Renal vascular resistance was calculated as the MAP divided by the RBF. Renal oxygenation (R2*) was measured for the cortex and medulla by blood oxygen level dependent (BOLD) MRI, using a monoexponential fit. RESULTS: With a LBNP of - 30 mmHg, pulse pressure decreased from 50 ± 10 to 43 ± 7 mmHg; MAP did not change. RBF decreased from 1152 ± 80 to 1038 ± 83 mL/min to 950 ± 67 mL/min at - 30 mmHg LBNP (p = 0.013). Heart rate and renal vascular resistance increased by 38 ± 15% and 23 ± 8% (p = 0.04) at - 30 mmHg LBNP, respectively. There was no change in cortical or medullary R2* (20.3 ± 1.2 s-1 vs 19.8 ± 0.43 s-1; 28.6 ± 1.1 s-1 vs 28.0 ± 1.3 s-1). CONCLUSION: The results suggest that an increase in sympathetic vasoconstrictor drive decreases kidney perfusion without a parallel reduction in oxygenation in healthy humans. This in turn indicates that sympathetic activation suppresses renal oxygen demand and supply equally, thus allowing adequate tissue oxygenation to be maintained.

Cerebral Blood Flow Response to Simulated Hypovolemia in Essential Hypertension: A Magnetic Resonance Imaging Study.

Hypertension is associated with raised cerebral vascular resistance and cerebrovascular remodeling. It is currently unclear whether the cerebral circulation can maintain cerebral blood flow (CBF) during reductions in cardiac output (CO) in hypertensive patients thereby avoiding hypoperfusion of the brain. We hypothesized that hypertension would impair the ability to effectively regulate CBF during simulated hypovolemia. In the present study, 39 participants (13 normotensive, 13 controlled, and 13 uncontrolled hypertensives; mean age±SD, 55±10 years) underwent lower body negative pressure (LBNP) at -20, -40, and -50 mmHg to decrease central blood volume. Phase-contrast MR angiography was used to measure flow in the basilar and internal carotid arteries, as well as the ascending aorta. CBF and CO decreased during LBNP (P<0.0001). Heart rate increased during LBNP, reaching significance at -50 mmHg (P<0.0001). There was no change in mean arterial pressure during LBNP (P=0.3). All participants showed similar reductions in CBF (P=0.3, between groups) and CO (P=0.7, between groups) during LBNP. There was no difference in resting CBF between the groups (P=0.36). In summary, during reductions in CO induced by hypovolemic stress, mean arterial pressure is maintained but CBF declines indicating that CBF is dependent on CO in middle-aged normotensive and hypertensive volunteers. Hypertension is not associated with impairments in the CBF response to reduced CO.

Efficacy and safety of active abdominal compression-decompression versus standard CPR for cardiac arrests: A systematic review and meta-analysis of 17 RCTs.

BACKGROUND & AIM: Active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR), which applies to cardiac arrests with contraindication of standard chest compressions (SCC) CPR, has been utilized in cardiac arrest. However, the efficacy and safety of AACD-CPR still remained controversy. This analysis was designed to comprehensively compare AACD versus SCC-CPR in patients with cardiac arrest. METHODS: We searched the Cochrane Library, PubMed, EMBASE, Web of Science and CNKI up to April 22, 2019. Mean difference (MD) and risk ratio (RR) with its 95% confidence intervals (CIs) were estimated to compare outcomes of the groups. Our primary outcomes were restoration of spontaneous circulation (ROSC) and short-term survival. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2 and Stata 12.0. RESULTS: A total of seventeen studies (N = 1647 patients) were identified for the present analysis. Compared with standard CPR, AACD-CPR was superior in restoration of spontaneous circulation (ROSC) and short-term survival, with pooled RRs of 1.38 (95% CI 1.23-1.55; P < 0.00001) and RRs of 2.05 (95% CI 1.69-2.50; P < 0.00001) respectively. In addition, significant superiority of AACD-CPR was found in incidence of fracture, long-term survival, pressure of end-tidal carbon dioxide (PETCO2), coronary perfusion pressure (CPP) and adverse events. No significant difference was observed in incidence of vomiting. CONCLUSIONS: Generally, in this combined analysis we found a statistically significant improvement in survival and ROSC with the use of AACD-CPR as compared with the use of standard CPR. There was also significant improvement in incidence of fracture, long-term survival, PETCO2 and CPP with AACD-CPR in comparison with standard CPR; results were not statistically different between the groups regarding to vomiting rate and adverse events. The standardized, diversified and individualized methods of clinical operation of AACD-CPR need exploration and expectingly serve as a guideline for clinical application of AACD-CPR in the future.

Responses of cerebral blood velocity and tissue oxygenation to low-frequency oscillations during simulated haemorrhagic stress in humans.

NEW FINDINGS: What is the central question of this study? Do low-frequency oscillations in arterial pressure and cerebral blood velocity protect cerebral blood velocity and oxygenation during central hypovolaemia? What is the main finding and its importance? Low-frequency oscillations in arterial pressure and cerebral blood velocity attenuate reductions in cerebral oxygen saturation but do not protect absolute cerebral blood velocity during central hypovolaemia. This finding indicates the potential importance of haemodynamic oscillations in maintaining cerebral oxygenation and therefore viability of tissues during challenges to cerebral blood flow and oxygen delivery. ABSTRACT: Tolerance to both real and simulated haemorrhage varies between individuals. Exaggerated low-frequency (∼0.1 Hz) oscillations in mean arterial pressure and brain blood flow [indexed via middle cerebral artery velocity (MCAv)] have been associated with improved tolerance to reduced central blood volume. The mechanism for this association has not been explored. We hypothesized that inducing low-frequency oscillations in arterial pressure and cerebral blood velocity would attenuate reductions in cerebral blood velocity and oxygenation during simulated haemorrhage. Fourteen subjects (11 men and three women) were exposed to oscillatory (0.1 and 0.05 Hz) and non-oscillatory (0 Hz) lower-body negative pressure profiles with an average chamber pressure of -60 mmHg (randomized and counterbalanced order). Measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and cerebral oxygenation of the frontal lobe via near-infrared spectroscopy. Tolerance was higher during the two oscillatory profiles compared with the 0 Hz profile (0.05 Hz, P = 0.04; 0.1 Hz, P = 0.09), accompanied by attenuated reductions in stroke volume (P < 0.001) and cerebral oxygenation of the frontal lobe (P ≤ 0.02). No differences were observed between profiles for reductions in mean arterial pressure (P = 0.17) and MCAv (P = 0.30). In partial support of our hypothesis, cerebral oxygenation, but not cerebral blood velocity, was protected during the oscillatory profiles. Interestingly, more subjects tolerated the oscillatory profiles compared with the static 0 Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of haemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissues during haemorrhagic stress.

Coagulation changes induced by lower-body negative pressure in men and women.

We investigated whether lower-body negative pressure (LBNP) application leads to coagulation activation in whole blood (WB) samples in healthy men and women. Twenty-four women and 21 men, all healthy young participants, with no histories of thrombotic disorders and not on medications, were included. LBNP was commenced at -10 mmHg and increased by -10 mmHg every 5 min until a maximum of -40 mmHg. Recovery up to 10 min was also monitored. Blood samples were collected at baseline, at end of LBNP, and end of recovery. Hemostatic profiling included comparing the effects of LBNP on coagulation values in both men and women using standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and markers of thrombin formation. LBNP led to coagulation activation determined in both plasma and WB samples. At baseline, women were hypercoagulable compared with men, as evidenced by their shorter "lag times" and higher thrombin peaks and by shorter "coagulation times" and "clot formation times." Moreover, men were more susceptible to LBNP, as reflected in their elevated factor VIII levels and decreased lag times following LBNP. LBNP-induced coagulation activation was not accompanied by endothelial activation. Women appear to be relatively hypercoagulable compared with men, but men are more susceptible to coagulation changes during LBNP. The application of LBNP might be a useful future tool to identify individuals with an elevated risk for thrombosis, in subjects with or without history of thrombosis. NEW & NOTEWORTHY LBNP led to coagulation activation determined in both plasma and whole blood samples. At baseline, women were hypercoagulable compared with men. Men were, however, more susceptible to coagulation changes during LBNP. LBNP-induced coagulation activation was not accompanied by endothelial activation. The application of LBNP might be a useful future tool to identify individuals with an elevated risk for thrombosis, in subjects with or without history of thrombosis.

Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults.

IMPACT STATEMENT: We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F2-isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.

Negative pressure therapy with instillation for the treatment of infected wounds: recommendations of utilization based on evidence.

OBJECTIVE: To establish recommendations related to negative pressure therapy  with instillation according to effectiveness, safety, efficiency, consensus guidelines and stability data of instillation solutions. METHOD: A literature search was conducted to compare the available evidence  regarding effectiveness, safety and efficiency of negative pressure therapy with  instillation, as well as the existence of consensus guidelines for use. The articles  were classified according to the "Scale of evidence classification for therapeutic  studies" of the American Society of Plastic and Reconstructive Surgery. RESULTS: A total of 13 studies were included, of which five were comparative cohort studies (level II and III of evidence), and the rest  corresponded to case series (level IV of evidence). Two consensus guidelines  were selected with recommendations regarding the type of wound, instillation solution, solution retention time, vacuum pressure and appropriate  vacuum time. According to literature and available evidence, recommendations were proposed and established on negative pressure therapy  with instillation in our hospital, including stability data of the proposed solutions. CONCLUSIONS: This paper provides preliminary guidelines on the application of  negative pressure therapy with instillation until new evidence supports or  modifies these recommendations.

Objetivo: Establecer recomendaciones relacionadas con la terapia de presión negativa con instilación según efectividad, seguridad, eficiencia, guías de  consenso y estabilidades contrastadas de las soluciones de instilación. Método: Se realizó una búsqueda bibliográfica para contrastar la evidencia disponible en cuanto a efectividad, seguridad y eficiencia de la terapia de presión negativa con instilación, así como la existencia de guías de consenso de utilización. Se clasificaron los artículos en función de la "Escala de clasificación de evidencia para estudios terapéuticos" según la  Sociedad Americana de Cirugía Plástica y Reconstructiva.Resultados: Se incluyeron 13 estudios, de los cuales cinco fueron estudios de  cohortes comparativos (nivel II y III de evidencia), y el resto correspondieron a  series de casos (nivel IV de evidencia). Se seleccionaron dos guías de consenso  con recomendaciones según tipo de herida, solución de instilación, tiempo de  retención de solución, presión de vacío y tiempo de vacío apropiado. Según la  literatura y la evidencia disponible, se propusieron y establecieron recomendaciones sobre la terapia de presión negativa con  instilación en nuestro hospital, incluyendo datos de estabilidad de las soluciones  propuestas.Conclusiones: Este manuscrito proporciona pautas preliminares para la aplicación de la terapia de presión negativa con instilación hasta que nuevas evidencias apoyen o modifiquen estas recomendaciones.

Hemostatic responses to exercise, dehydration, and simulated bleeding in heat-stressed humans.

Heat stress followed by an accompanying hemorrhagic challenge may influence hemostasis. We tested the hypothesis that hemostatic responses would be increased by passive heat stress, as well as exercise-induced heat stress, each with accompanying central hypovolemia to simulate a hemorrhagic insult. In aim 1, subjects were exposed to passive heating or normothermic time control, each followed by progressive lower-body negative pressure (LBNP) to presyncope. In aim 2 subjects exercised in hyperthermic environmental conditions, with and without accompanying dehydration, each also followed by progressive LBNP to presyncope. At baseline, pre-LBNP, and post-LBNP (<1, 30, and 60 min), hemostatic activity of venous blood was evaluated by plasma markers of hemostasis and thrombelastography. For aim 1, both hyperthermic and normothermic LBNP (H-LBNP and N-LBNP, respectively) resulted in higher levels of factor V, factor VIII, and von Willebrand factor antigen compared with the time control trial (all P < 0.05), but these responses were temperature independent. Hyperthermia increased fibrinolysis [clot lysis 30 min after the maximal amplitude reflecting clot strength (LY30)] to 5.1% post-LBNP compared with 1.5% (time control) and 2.7% in N-LBNP ( P = 0.05 for main effect). Hyperthermia also potentiated increased platelet counts post-LBNP as follows: 274 K/µl for H-LBNP, 246 K/µl for N-LBNP, and 196 K/µl for time control ( P < 0.05 for the interaction). For aim 2, hydration status associated with exercise in the heat did not affect the hemostatic activity, but fibrinolysis (LY30) was increased to 6-10% when subjects were dehydrated compared with an increase to 2-4% when hydrated ( P = 0.05 for treatment). Central hypovolemia via LBNP is a primary driver of hemostasis compared with hyperthermia and dehydration effects. However, hyperthermia does induce significant thrombocytosis and by itself causes an increase in clot lysis. Dehydration associated with exercise-induced heat stress increases clot lysis but does not affect exercise-activated or subsequent hypovolemia-activated hemostasis in hyperthermic humans. Clinical implications of these findings are that quickly restoring a hemorrhaging hypovolemic trauma patient with cold noncoagulant fluids (crystalloids) can have serious deleterious effects on the body's innate ability to form essential clots, and several factors can increase clot lysis, which should therefore be closely monitored.