Retrospective analysis of a STEM outreach event reveals positive influences on student attitudes toward STEM careers but not scientific methodology.

Substantial, involved, and expensive efforts to promote the dissemination of scientific knowledge and career interest in Science, Technology, Engineering, and Mathematics (STEM) are enthusiastically supported by many scientific, federal, and local organizations. The articulated underlying goals for these efforts include an enhanced public understanding of science and science-related policy, an increased diversity in STEM careers, and an increase in the future STEM workforce. This effort is primarily driven by an underperformance of the United States that includes poor test performance and limited number of students pursuing STEM degrees. Despite this investment, attitudes toward STEM have not notably changed. The goal of this project was to determine students' attitudes toward STEM in response to a previously established scientific outreach event. This event was used to address three common goals in STEM outreach: STEM literacy, diversity and inclusion, and career preparedness. We found there was a notable difference in the attitudes toward scientific activities and interest in pursuing a "Science Career" after participation in this event. Strikingly, interest in hypothesis development, the keystone of all STEM disciplines, was the least liked of all the activities offered during the event. Our data suggest that events designed to enhance interest in pursuing a STEM career may benefit from different elements compared with events designed to increase understanding of STEM literacy concepts, such as hypothesis development.

Unmasking the Hypovolemic Shock Continuum: The Compensatory Reserve.

Hypovolemic shock exists as a spectrum, with its early stages characterized by subtle pathophysiologic tissue insults and its late stages defined by multi-system organ dysfunction. The importance of timely detection of shock is well known, as early interventions improve mortality, while delays render these same interventions ineffective. However, detection is limited by the monitors, parameters, and vital signs that are traditionally used in the intensive care unit (ICU). Many parameters change minimally during the early stages, and when they finally become abnormal, hypovolemic shock has already occurred. The compensatory reserve (CR) is a parameter that represents a new paradigm for assessing physiologic status, as it comprises the sum total of compensatory mechanisms that maintain adequate perfusion to vital organs during hypovolemia. When these mechanisms are overwhelmed, hemodynamic instability and circulatory collapse will follow. Previous studies involving CR measurements demonstrated their utility in detecting central blood volume loss before hemodynamic parameters and vital signs changed. Measurements of the CR have also been used in clinical studies involving patients with traumatic injuries or bleeding, and the results from these studies have been promising. Moreover, these measurements can be made at the bedside, and they provide a real-time assessment of hemodynamic stability. Given the need for rapid diagnostics when treating critically ill patients, CR measurements would complement parameters that are currently being used. Consequently, the purpose of this article is to introduce a conceptual framework where the CR represents a new approach to monitoring critically ill patients. Within this framework, we present evidence to support the notion that the use of the CR could potentially improve the outcomes of ICU patients by alerting intensivists to impending hypovolemic shock before its onset.

An outreach program with hands-on, physiology-based exercises generates questions about STEM career expectations.

Scientific advocacy and outreach programs are encouraged to increase public understanding of scientific knowledge and generate interest in science, technology, engineering, and mathematics (STEM) careers. However, evaluation of these events' effectiveness is difficult and somewhat rare. This study's purpose was to better understand how effective an established physiology-based outreach program was in generating interest in STEM careers, while simultaneously providing information that can be used to increase the effectiveness of future events. We partnered with a private school located in Omaha, Nebraska, where 64-80 students participated in 3 h of physiology-based activities presented by volunteers from the University of Nebraska Medical Center. The event included a brief presentation of the eye, sensory, heart, and lung systems, followed by hands-on demonstrations and activities. Each session concluded with 15 min of questions and answers (Q&A), where students were encouraged to engage the volunteers in inquiries about what they just learned, career-related questions, or any topic of their choosing. Each Q&A session was audio recorded and evaluated using thematic analysis to identify patterns in the Q&A data. Two major themes of questions were identified: 1) scientific content (animal circulatory systems and how organs are affected by disease or stimulus); and 2) career-related content, including typical day-to-day activities of a scientist and the volunteers' satisfaction with a scientific career. We conclude that hands-on physiology-based learning opportunities are effective in generating short-term interest in STEM content and careers. The results of this study will also facilitate informed modification of event content to better suit student's interests.

Increased Brain-Derived Neurotrophic Factor in Lumbar Dorsal Root Ganglia Contributes to the Enhanced Exercise Pressor Reflex in Heart Failure.

An exaggerated exercise pressor reflex (EPR) is associated with excessive sympatho-excitation and exercise intolerance in the chronic heart failure (CHF) state. We hypothesized that brain-derived neurotrophic factor (BDNF) causes the exaggerated EPR via sensitizing muscle mechanosensitive afferents in CHF. Increased BDNF expression was observed in lumbar dorsal root ganglia (DRGs) from CHF rats compared to sham rats. Immunofluorescence data showed a greater increase in the number of BDNF-positive neurons in medium and large-sized DRG subpopulations from CHF rats. Patch clamp data showed that incubation with BDNF for 4⁻6 h, significantly decreased the current threshold-inducing action potential (AP), threshold potential and the number of APs during current injection in Dil-labeled isolectin B4 (IB4)-negative medium-sized DRG neurons (mainly mechano-sensitive) from sham rats. Compared to sham rats, CHF rats exhibited an increased number of APs during current injection in the same DRG subpopulation, which was significantly attenuated by 4-h incubation with anti-BDNF. Finally, chronic epidural delivery of anti-BDNF attenuated the exaggerated pressor response to either static contraction or passive stretch in CHF rats whereas this intervention had no effect on the pressor response to hindlimb arterial injection of capsaicin. These data suggest that increased BDNF in lumbar DRGs contributes to the exaggerated EPR in CHF.

A day of immersive physiology experiments increases knowledge and excitement towards physiology and scientific careers in Native American students.

Underserved minority groups are disproportionately absent from the pursuit of careers in science, technology, engineering, and mathematics (STEM) fields. One such underserved population, Native Americans, are particularly underrepresented in STEM fields. Although recent advocacy and outreach designed toward increasing minority involvement in health care-related occupations have been mostly successful, little is known about the efficacy of outreach programs in increasing minority enthusiasm toward careers in traditional scientific professions. Furthermore, very little is known about outreach among Native American schools toward increasing involvement in STEM. We collaborated with tribal middle and high schools in South Dakota and Nebraska through a National Institutes of Health Science Education Partnership Award to hold a day-long physiology, activity-based event to increase both understanding of physiology and enthusiasm to scientific careers. We recruited volunteer biomedical scientists and trainees from the University of Nebraska Medical Center, Nebraska Wesleyan University, and University of South Dakota. To evaluate the effectiveness of the day of activities, 224 of the ~275-300 participating students completed both a pre- and postevent evaluation assessment. We observed increases in both students self-perceived knowledge of physiology and enthusiasm toward scientific career opportunities after the day of outreach activities. We conclude that activity-based learning opportunities in underserved populations are effective in increasing both knowledge of science and interest in scientific careers.

Renal nerves dynamically regulate renal blood flow in conscious, healthy rabbits.

Despite significant clinical interest in renal denervation as a therapy, the role of the renal nerves in the physiological regulation of renal blood flow (RBF) remains debated. We hypothesized that the renal nerves physiologically regulate beat-to-beat RBF variability (RBFV). This was tested in chronically instrumented, healthy rabbits that underwent either bilateral surgical renal denervation (DDNx) or a sham denervation procedure (INV). Artifact-free segments of RBF and arterial pressure (AP) from calmly resting, conscious rabbits were used to extract RBFV and AP variability for time-domain, frequency-domain, and nonlinear analysis. Whereas steady-state measures of RBF, AP, and heart rate did not statistically differ between groups, DDNx rabbits had greater RBFV than INV rabbits. AP-RBF transfer function analysis showed greater admittance gain in DDNx rabbits than in INV rabbits, particularly in the low-frequency (LF) range where systemic sympathetic vasomotion gives rise to AP oscillations. In the LF range, INV rabbits exhibited a negative AP-RBF phase shift and low coherence, consistent with the presence of an active control system. Neither of these features were present in the LF range of DDNx rabbits, which showed no phase shift and high coherence, consistent with a passive, Ohm's law pressure-flow relationship. Renal denervation did not significantly affect nonlinear RBFV measures of chaos, self-affinity, or complexity, nor did it significantly affect glomerular filtration rate or extracellular fluid volume. Cumulatively, these data suggest that the renal nerves mediate LF renal sympathetic vasomotion, which buffers RBF from LF AP oscillations in conscious, healthy rabbits.

Exercise training attenuates chemoreflex-mediated reductions of renal blood flow in heart failure.

In chronic heart failure (CHF), carotid body chemoreceptor (CBC) activity is increased and contributes to increased tonic and hypoxia-evoked elevation in renal sympathetic nerve activity (RSNA). Elevated RSNA and reduced renal perfusion may contribute to development of the cardio-renal syndrome in CHF. Exercise training (EXT) has been shown to abrogate CBC-mediated increases in RSNA in experimental heart failure; however, the effect of EXT on CBC control of renal blood flow (RBF) is undetermined. We hypothesized that CBCs contribute to tonic reductions in RBF in CHF, that stimulation of the CBC with hypoxia would result in exaggerated reductions in RBF, and that these responses would be attenuated with EXT. RBF was measured in CHF-sedentary (SED), CHF-EXT, CHF-carotid body denervation (CBD), and CHF-renal denervation (RDNX) groups. We measured RBF at rest and in response to hypoxia (FiO2 10%). All animals exhibited similar reductions in ejection fraction and fractional shortening as well as increases in ventricular systolic and diastolic volumes. Resting RBF was lower in CHF-SED (29 ± 2 ml/min) than in CHF-EXT animals (46 ± 2 ml/min, P < 0.05) or in CHF-CBD animals (42 ± 6 ml/min, P < 0.05). In CHF-SED, RBF decreased during hypoxia, and this was prevented in CHF-EXT animals. Both CBD and RDNX abolished the RBF response to hypoxia in CHF. Mean arterial pressure increased in response to hypoxia in CHF-SED, but was prevented by EXT, CBD, and RDNX. EXT is effective in attenuating chemoreflex-mediated tonic and hypoxia-evoked reductions in RBF in CHF.

Validation of pulse rate variability as a surrogate for heart rate variability in chronically instrumented rabbits.

Heart rate variability (HRV) is a function of cardiac autonomic tone that is widely used in both clinical and animal studies. In preclinical studies, HRV measures are frequently derived using the arterial pulse waveform from an implanted pressure telemetry device, termed pulse rate variability (PRV), instead of the electrocardiogram signal in accordance with clinical guidelines. The acceptability of PRV as a surrogate for HRV in instrumented animals is unknown. Using rabbits implanted with intracardiac leads and chronically implanted pressure transducers, we investigated the correlation and agreement of time-domain, frequency-domain, and nonlinear indexes of HRV and PRV at baseline. We also investigated the effects of ventricular pacing and autonomic blockade on both measures. At baseline, HRV and PRV time- and frequency-domain parameters showed robust correlations and moderate to high agreement, whereas nonlinear parameters showed slightly weaker correlations and varied agreement. Ventricular pacing almost completely eliminated HRV, and spectral analysis of the PRV signal revealed a HRV-independent rhythm. After cardiac autonomic blockade with atropine or metoprolol, the changes in time- and non-normalized frequency-domain measures of PRV continued to show strong correlations and moderate to high agreement with corresponding changes in HRV measures. Blockade-induced changes in nonlinear PRV indexes correlated poorly with HRV changes and showed weak agreement. These results suggest that time- and frequency-domain measures of PRV are acceptable surrogates for HRV even in the context of changing cardiac autonomic tone, but caution should be used when nonlinear measures are a primary end point or when HRV is very low as HRV-independent rhythms may predominate.

Unilateral renal denervation improves autonomic balance in conscious rabbits with chronic heart failure.

A hallmark of chronic heart failure (CHF) is an increased sympathetic tone resulting in autonomic imbalance. Renal denervation (DNx) in CHF patients has resulted in symptomatic improvement, but the protective mechanisms remain unclear. We hypothesized in CHF, unilateral renal DNx would improve cardiac autonomic balance. The present study used conscious, chronically instrumented New Zealand White rabbits undergoing renal DNx prior to pacing-induced CHF. Four treatment groups were used: nonpace, non-DNx [Sham-Innervated (Sham-INV)], nonpace DNx (sham-DNx), pace non-DNx (CHF-INV) or pace DNx (CHF-DNx). We examined several markers indicative of autonomic balance. Baroreflex sensitivity and time domain heart rate variability (HRV) were both decreased in the CHF-INV group compared with sham-INV and were restored to sham levels by renal DNx. Power spectral analysis indicated an increase in low-frequency/high-frequency (LF/HF) ratio in the CHF-INV compared with the sham-INV, which was normalized to sham levels by DNx. To assess whether this was due to a withdrawal of sympathetic tone or an increase in parasympathetic tone, the heart rate response was measured after an intravenous bolus of metoprolol or atropine. Bradycardia induced by intravenous metoprolol (indicative of cardiac sympathetic tone) was exacerbated in CHF-INV rabbits compared with sham-INV but was normalized in CHF-DNx. Conversely, the tachycardia in response to intravenous atropine (indicative of cardiac vagal tone) was not improved in CHF-DNx vs. CHF-INV animals. Renal DNx also prevented the increase in circulating plasma NE seen in CHF-INV rabbits. These results suggest renal DNx improves cardiac autonomic balance in CHF by a reduction of sympathetic tone.

Creation of a High-Fidelity, Low-Cost, Intraosseous Line Placement Task Trainer via 3D Printing.

The description of procedural task trainers includes their use as a training tool to hone technical skills through repetition and rehearsal of procedures in a safe environment before ultimately performing the procedure on a patient. Many procedural task trainers available to date suffer from several drawbacks, including unrealistic anatomy and the tendency to develop user-created 'landmarks' after the trainer tissue undergoes repeated manipulations, potentially leading to inappropriate psychomotor skill development. To ameliorate these drawbacks, a process was created to produce a high-fidelity procedural task trainer, created from anatomy obtained from computed tomography (CT) scans, that utilize ubiquitous three-dimensional (3D) printing technology and off-the-shelf commodity supplies. This method includes creating a 3D printed tissue mold capturing the tissue structure surrounding the skeletal element of interest to encase the bony skeletal structure suspended within the tissue, which is also 3D printed. A tissue medium mixture, which approximates tissue in both high-fidelity geometry and tissue density, is then poured into a mold and allowed to set. After a task trainer has been used to practice a procedure, such as intraosseous line placement, the tissue media, molds, and bones are reclaimable and may be reused to create a fresh task trainer, free of puncture sites and manipulation defects, for use in subsequent training sessions.

Cardiac Spinal Afferent Denervation Attenuates Renal Dysfunction in Rats With Cardiorenal Syndrome Type 2.

Cardiorenal syndrome type 2 (CRS2) is defined as a chronic cardiovascular disease, usually chronic heart failure (CHF), resulting in chronic kidney disease. We hypothesized that the cardiac spinal afferent reflex (CSAR) plays a critical role in the development of CRS2. Our data suggest that cardiac afferent ablation by resiniferatoxin not only improves cardiac function but also benefits the kidneys and increases long-term survival in the myocardial infarction model of CHF. We also found that renal denervation has a similar reno-protective effect in CHF rats. We believe this novel work contributes to the development of a unique neuromodulation therapy to treat CHF patients.

Safety and efficacy of renal denervation in patients with heart failure with reduced ejection fraction (HFrEF): A systematic review and meta-analysis.

INTRODUCTION: A systematic analysis of clinical trials was performed in order to assess the effectiveness and risks of bilateral renal denervation (RDN) in patients with chronic heart failure with reduced ejection fraction (HFrEF). METHODS: A systematic review was conducted of all clinical trials exploring the effectiveness of RDN in patients with HF who had reduced (<50%) EF. Primary outcomes were NYHA class, 6-min walk test, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, left ventricular ejection fraction (LVEF) and other cardiac parameters including left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), and left atrium diameter (LAD). Secondary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), glomerular filtration rate (GFR), and creatinine. RESULTS: Seven studies were included in this analysis. From baseline to 6 months after RDN, the pooled mean NYHA class was decreased (mean difference [MD], -0.9; 95% confidence interval [CI], -1.6 to -0.2; P = 0.018), the mean 6-min walk test was increased (MD, 79.5 m; 95% CI, 26.9 to 132.1; P = 0.003), and the average NT-proBNP level was decreased (MD, -520.6 pg/mL; 95% CI, -1128.4 to 87.2; P = 0.093). Bilateral RDN increased the LVEF (MD, 5.7%; 95% CI, 1.6 to 9.6; P = 0.004), decreased the LVESD (MD, -0.4 cm; 95% CI, -0.5 to -0.2; P < 0.001), decreased the LVEDD (MD, -0.5 cm; 95% CI, -0.6 to -0.3; P < 0.001), and decreased the LAD (MD, -0.4 cm; 95% CI, -0.8 to 0; P = 0.045). In addition, RDN significantly decreased systolic BP (MD, -9.4 mmHg; 95% CI, -16.3 to -2.4; P = 0.008) and diastolic BP (MD, -4.9 mmHg; 95% CI, -9.5 to -0.4; P = 0.033), and decreased HR (MD, -4.5 bpm; 95% CI, -8.2to -0.9; P = 0.015). RDN did not significantly change GFR (MD, 7.9; 95% CI, -5.0 to 20.8; P = 0.230), or serum creatinine levels (MD, -7.2; 95% CI, -23.7 to 9.4; P = 0.397). CONCLUSION: Bilateral RDN appears safe and well-tolerated in patients with HF. RDN improved the signs and symptoms of HF and slightly decreased systolic and diastolic BP without affecting renal function in the clinical trials performed to date.

3D printing of face shields to meet the immediate need for PPE in an anesthesiology department during the COVID-19 pandemic.

BACKGROUND: Anesthesia providers are at risk for contracting COVID-19 due to close patient contact, especially during shortages of personal protective equipment. We present an easy to follow and detailed protocol for producing 3D printed face shields and an effective decontamination protocol, allowing their reuse. METHODS: The University of Nebraska Medical Center (UNMC) produced face shields using a combination of 3D printing and assembly with commonly available products, and produced a simple decontamination protocol to allow their reuse. To evaluate the effectiveness of the decontamination protocol, we inoculated bacterial suspensions of E. coli and S. aureus on to the face shield components, performed the decontamination procedure, and finally swabbed and enumerated organisms onto plates that were incubated for 12-24 hours. Decontamination effectiveness was evaluated using the average log10 reduction in colony counts. RESULTS: Approximately 112 face shields were constructed and made available for use in 72 hours. These methods were successfully implemented for in-house production at UNMC and at Tripler Army Medical Center (Honolulu, Hawaii). Overall, the decontamination protocol was highly effective against both E. coli and S. aureus, achieving a ≥4 log10 (99.99%) reduction in colony counts for every replicate from each component of the face shield unit. DISCUSSION: Face shields not only act as a barrier against the soiling of N95 face masks, they also serve as more effective eye protection from respiratory droplets over standard eye shields. Implementation of decontamination protocols successfully allowed face shield and N95 mask reuse, offering a higher level of protection for anesthesiology providers at the onset of the COVID-19 pandemic. CONCLUSIONS: In a time of urgent need, our protocol enabled the rapid production of face shields by individuals with little to no 3D printing experience, and provided a simple and effective decontamination protocol allowing reuse of the face shields.

Quantification of Renal Sympathetic Vasomotion as a Novel End Point for Renal Denervation.

Renal sympathetic denervation, a potentially revolutionary interventional treatment for hypertension, faces an existential problem due to the inability to confirm successful ablation of the targeted renal sympathetic nerves. Based on the observation that renal sympathetic nerve activity exerts rhythmic, baroreflex-driven, and vasoconstrictive control of the renal vasculature, we developed a novel technique for identifying rhythmic sympathetic vascular control using a time-varying, 2-component Windkessel model of the renal circulation. This technology was tested in 2 different animal models of renal denervation; 10 rabbits underwent chronic, surgical renal denervation, and 9 pigs underwent acute, functional renal denervation via intrathecal administration of ropivacaine. Both methods of renal denervation reduced negative admittance gain, negative phase shift renal vascular control at known sympathetic vasomotor frequencies, consistent with a reduction in vasoconstrictive, baroreflex-driven renal sympathetic vasomotion. Classic measures like mean renal blood flow and mean renal vascular resistance were not significantly affected in either model of renal denervation. Renal sympathetic vasomotion monitoring could provide intraprocedural feedback for interventionists performing renal denervation and serve more broadly as a platform technology for the evaluation and treatment of diseases affecting the sympathetic nervous system.

Predictors of hemodynamic decompensation in progressive hypovolemia: Compensatory reserve versus heart rate variability.

BACKGROUND: Hemorrhage remains the leading cause of death following traumatic injury in both civilian and military settings. Heart rate variability (HRV) and heart rate complexity (HRC) have been proposed as potential "new vital signs" for monitoring trauma patients; however, the added benefit of HRV or HRC for decision support remains unclear. Another new paradigm, the compensatory reserve measurement (CRM), represents the integration of all cardiopulmonary mechanisms responsible for compensation during relative blood loss and was developed to identify current physiologic status by estimating the progression toward hemodynamic decompensation. In the present study, we hypothesized that CRM would provide greater sensitivity and specificity to detect progressive reductions in central circulating blood volume and onset of decompensation as compared with measurements of HRV and HRC. METHODS: Continuous, noninvasive measurements of compensatory reserve and electrocardiogram signals were made on 101 healthy volunteers during lower-body negative pressure (LBNP) to the point of decompensation. Measures of HRV and HRC were taken from electrocardiogram signal data. RESULTS: Compensatory reserve measurement demonstrated a superior sensitivity and specificity (receiver operator characteristic area under the curve [ROC AUC] = 0.93) compared with all HRV measures (ROC AUC ≤ 0.84) and all HRC measures (ROC AUC ≤ 0.86). Sensitivity and specificity values at the ROC optimal thresholds were greater for CRM (sensitivity = 0.84; specificity = 0.84) than HRV (sensitivity, ≤0.78; specificity, ≤0.77), and HRC (sensitivity, ≤0.79; specificity, ≤0.77). With standardized values across all levels of LBNP, CRM had a steeper decline, less variability, and explained a greater proportion of the variation in the data than both HRV and HRC during progressive hypovolemia. CONCLUSION: These findings add to the growing body of literature describing the advantages of CRM for detecting reductions in central blood volume. Most importantly, these results provide further support for the potential use of CRM in the triage and monitoring of patients at highest risk for the onset of shock following blood loss.

Comparisons of Traditional Metabolic Markers and Compensatory Reserve as Early Predictors of Tolerance to Central Hypovolemia in Humans.

Circulatory shock remains a leading cause of death in both military and civilian trauma. Early, accurate and reliable prediction of decompensation is necessary for the most efficient interventions and clinical outcomes. Individual tolerance to reduced central blood volume can serve as a model to assess the sensitivity and specificity of vital sign measurements. The compensatory reserve (CRM) is the measurement of this capacity. Measurements of muscle oxygen saturation (SmO2), blood lactate, and end tidal CO2 (EtCO2) have recently gained attention as prognostic tools for early assessment of the status of patients with progressive hemorrhage, but lack the ability to adequately differentiate individual tolerance to hypovolemia. We hypothesized that the CRM would better predict hemodynamic decompensation and provide greater specificity and sensitivity than metabolic measures. To test this hypothesis, we employed lower body negative pressure on healthy human subjects until symptoms of presyncope were evident. Receiver operating characteristic area under the curve (ROC AUC), sensitivity, and specificity were used to evaluate the ability of CRM, partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), SmO2, lactate, EtCO2, potential of hydrogen (pH), base excess and hematocrit (Hct) to predict hemodynamic decompensation. The ROC AUC for CRM (0.94) had a superior ability to predict decompensation compared with pO2 (0.85), pCO2 (0.62), SmO2 (0.72), lactate (0.57), EtCO2 (0.74), pH (0.55), base excess (0.59), and Hct (0.67). Similarly, CRM also exhibited the greatest sensitivity and specificity. These findings support the notion that CRM provides superior detection of hemodynamic compensation compared with commonly used clinical metabolic measures.

Eppur Si Muove: The dynamic nature of physiological control of renal blood flow by the renal sympathetic nerves.

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation.

The physiology of blood loss and shock: New insights from a human laboratory model of hemorrhage.

The ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of the various physiological mechanisms that are active during volume loss and that have the ability to stave off hemodynamic collapse. This review provides new insights about the physiology that underlies blood loss and shock in humans through the development of a simulated model of hemorrhage using lower body negative pressure. In this review, we present controlled experimental results through utilization of the lower body negative pressure human hemorrhage model that provide novel insights on the integration of physiological mechanisms critical to the compensation for volume loss. We provide data obtained from more than 250 human experiments to classify human subjects into two distinct groups: those who have a high tolerance and can compensate well for reduced central blood volume (e.g. hemorrhage) and those with low tolerance with poor capacity to compensate.We include the conceptual introduction of arterial pressure and cerebral blood flow oscillations, reflex-mediated autonomic and neuroendocrine responses, and respiration that function to protect adequate tissue oxygenation through adjustments in cardiac output and peripheral vascular resistance. Finally, unique time course data are presented that describe mechanistic events associated with the rapid onset of hemodynamic failure (i.e. decompensatory shock). Impact Statement Hemorrhage is the leading cause of death in both civilian and military trauma. The work submitted in this review is important because it advances the understanding of mechanisms that contribute to the total integrated physiological compensations for inadequate tissue oxygenation (i.e. shock) that arise from hemorrhage. Unlike an animal model, we introduce the utilization of lower body negative pressure as a noninvasive model that allows for the study of progressive reductions in central blood volume similar to those reported during actual hemorrhage in conscious humans to the onset of hemodynamic decompensation (i.e. early phase of decompensatory shock), and is repeatable in the same subject. Understanding the fundamental underlying physiology of human hemorrhage helps to test paradigms of critical care medicine, and identify and develop novel clinical practices and technologies for advanced diagnostics and therapeutics in patients with life-threatening blood loss.

The neurovascular complexity index as a potential indicator of traumatic brain injury severity: A case-series study.

BACKGROUND: Multimodal monitoring of brain physiology following a traumatic brain injury (TBI) shows promise as a strategy to improve management and outcomes of TBI patients within civilian and military trauma. Valid and reliable measures of different aspects of brain physiology following a TBI could prove critical to accurately capturing these changes. METHODS: Using a case-series design with a control subject group comparison, we evaluated a new proprietary algorithm called the Neurovascular Complexity Index (NCI) using transcranial Doppler to noninvasively obtain measures of cerebral blood flow variability. Baseline NCI data from 169 control subjects were compared with 12 patients with moderate to severe TBI. RESULTS: Patients with TBI exhibited significantly greater mean and variability in NCI scores compared with control subjects (F = 195.48; p < 0.001). The mean absolute deviation (MAD) of NCI scores increased significantly and in a monotonic fashion with severity of injury, where control subjects exhibited a small MAD of 0.44, patients with moderate TBI had a higher MAD of 4.20, and patients with severe TBI had an MAD of 6.51 (p < 0.001). CONCLUSIONS: Advancement in multimodal monitoring of TBI patients is important in reducing the potential risk of secondary injury. This study reports results indicating that a new noninvasive quantifiable assessment of TBI based on a noninvasive measure of cerebral blood flow variability shows potential for continuous monitoring and early identification of brain-injured patients, deployable in far-forward military environments, to better inform individualized management. LEVEL OF EVIDENCE: Case series, level IV.