Racial and Ethnic Differences in Hospital Admission and Diagnostic Evaluation for Febrile Seizures in the Emergency Department.

OBJECTIVE: To examine differences in hospital admission and diagnostic evaluation for febrile seizure by race and ethnicity. STUDY DESIGN: We conducted a cross-sectional study among children 6 months to 6 years with simple or complex febrile seizure between January 1, 2016, and December 31, 2021, using data from the Pediatric Health Information System. The primary outcome was hospital admission. Secondary outcomes included the proportion of encounters with neuroimaging or lumbar puncture. We used mixed-effects logistic regression model with random intercept for hospital and patient to estimate the association between outcomes and race and ethnicity after adjusting for covariates, including seizure type. RESULTS: In total, 94 884 encounters were included. Most encounters occurred among children of non-Hispanic White (37.0%), Black (23.9%), and Hispanic/Latino (24.6%) race and ethnicity. Black and Hispanic/Latino children had 29% (aOR 0.71; 95% CI 0.66-0.75) and 26% (aOR 0.74; 95% CI 0.69-0.80) lower odds of hospital admission compared with non-Hispanic White children, respectively. Black and Hispanic/Latino children had 21% (aOR 0.79; 95% CI 0.73-0.86) and 22% (aOR 0.78; 95% CI 0.71-0.85) lower adjusted odds of neuroimaging compared with non-Hispanic White children. For complex febrile seizure, the adjusted odds of lumbar puncture was significantly greater among Asian children (aOR 2.12; 95% CI 1.19-3.77) compared with non-Hispanic White children. There were no racial differences in the odds of lumbar puncture for simple febrile seizure. CONCLUSIONS: Compared with non-Hispanic White children, Black and Hispanic/Latino children with febrile seizures are less likely to be hospitalized or receive neuroimaging.

Mobile Health Assessment of Traumatic Dental Injuries Using Smartphone-Acquired Photographs: A Multicenter Diagnostic Accuracy Study.

Background: Mobile health (mHealth) has an emerging potential for remote assessment of traumatic dental injuries (TDI) and support of emergency care. This study aimed to determine the diagnostic accuracy of TDI detection from smartphone-acquired photographs. Methods: The upper and lower anterior teeth of 153 individuals aged ≥ 6 years were photographed using a smartphone camera app. The photos of 148 eligible participants were reviewed independently by a dental specialist, two general dentists, and two dental therapists, using predetermined TDI classification and criteria. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and inter-rater reliability were estimated to evaluate the diagnostic performance of the photographic method relative to the reference standard established by the dental specialist. Results: Of the 1,870 teeth screened, one-third showed TDI; and one-seventh of the participants had primary or mixed dentitions. Compared between the specialist's reference standard and four dental professionals' reviews, the diagnostic sensitivity and specificity for TDI versus non-TDI were 59-95% and 47-93%, respectively, with better performance for urgent types of TDI (78-89% and 99-100%, separately). The diagnostic consistency was also better for the primary/mixed dentitions than the permanent dentition. Conclusion: This study suggested a valid mHealth practice for remote assessment of TDI. A better diagnostic performance in the detection of urgent types of TDI and examination of the primary/mixed dentition was also reported. Future directions include professional development activities involving dental photography and photographic assessment, incorporation of a machine learning technology to aid photographic reviews, and randomized controlled trials in multiple clinical settings.

The Pediatric Emergency Department Nurse and Gastrostomy Tube Replacement: How Safe Is it?

AIM: To review the outcomes of a nurse-only guideline for replacement of gastrostomy tubes (g-tubes) in a pediatric emergency department (ED) and compare rates of success, failure, length of stay (LOS), and return visits with that of ED physicians. DESIGN: Nursing g-tube guidelines, created by a nurse educator and nursing council, were instigated on January 31, 2018. Variables examined included LOS, age at visit, return visit within 72 hours, reason for replacement, and any postplacement complications. REVIEW METHODS: Data of g-tube placement by nurses and physicians were compared using t test or χ 2 analysis (IBM-SPSS version 20, New Orchard Road, Armonk, NY). The institutional review board determined the study to be exempt from human subjects. The STROBE checklist was used and completed accordingly. DATA SOURCES: Chart abstraction and data were collected from January 1, 2011 through April 13, 2020, and medical records were obtained using International Classification of Diseases, Tenth Revision (ICD-10) codes for g-tubes: Z93.1, K94.23. RESULTS: A total of 110 patients were included in our study. Fifty-eight underwent nursing-only replacements; 52 were replaced by physicians. Nurse replacement success rate was 98.3% with an average stay of 22 minutes. Physician success rate was 100% with an average stay of 86 minutes. The difference between nursing and physician LOS was 64.6 minutes. No patient in either group experienced postreplacement complications. CONCLUSIONS: The initiation of nurse-only management of dislodged g-tubes was successful, safe, and had a shorter LOS when compared with physicians in the pediatric ED. IMPACT: Our study determined the implications of nurse-only replacement of g-tubes in a pediatric ED. We found that nurses replacing g-tubes was equally safe and effective as physician counterparts. In addition, we found that it significantly reduced the LOS for patients, which has consequences on patient satisfaction and billing. PATIENT/PUBLIC CONTRIBUTION: Nursing staff were trained in g-tube replacement using guidelines created by a nurse educator and nursing council. Patients either had their dislodged g-tubes replaced by the trained nurse or a physician and comparisons on the outcomes were made. Patients were aware of the study and consented to have their medical records accessed to make the data comparisons. RELEVANCE TO CLINICAL PRACTICE: With more than 189,000 children in the United States relying on g-tubes, nursing staff will inevitably be involved in the care of patients with such a device. In addition, as pediatric EDs continue to develop longer and longer waiting times, we must learn how to better use our nursing staff for procedures within their scope and minimize LOS. Our research demonstrates the safety, feasibility, and general benefits of having the pediatric nursing staff replace g-tubes in the ED, and it is hoped that this will lead to beneficial policy changes. WHAT DOES THIS ARTICLE CONTRIBUTE TO THE WIDER GLOBAL COMMUNITY: - Demonstrates the safety and effectiveness of nurse-only g-tube replacement- Reports on the statistically significant difference in LOS between physician and nurse replacement of g-tubes in a pediatric ED- Has the ability to lead to policy change in the pediatric ED that will allow for greater patient satisfaction and decrease patient cost.

Predicting Adverse Outcomes for Shiga Toxin-Producing Escherichia coli Infections in Emergency Departments.

OBJECTIVE: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting. STUDY DESIGN: We reviewed medical records of children <18 years old infected with STEC and treated in 1 of 38 participating emergency departments in North America between 2011 and 2015. The HUS severity score (hemoglobin [g/dL] plus 2-times serum creatinine [mg/dL]) was calculated using first available laboratory results. Children with scores >13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness. RESULTS: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children <5 years old (area under the curve 0.77, 95% CI 0.68-0.87). For children <5 years, greatest net benefit was achieved for a threshold probability >26%. CONCLUSIONS: The HUS severity score was able to discriminate between high- and low-risk children <5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.

Treatment of Hypothermic Cardiac Arrest in the Pediatric Drowning Victim, a Case Report, and Systematic Review.

OBJECTIVES: Drowning is the second leading cause of death in children. Extracorporeal membrane oxygenation (ECMO) has become the criterion standard therapy to resuscitate the hypothermic drowning victim in cardiac arrest. We present our own experience treating 5 children with hypothermic cardiac arrest in conjunction with a systematic review to analyze clinical features predictive of survival. METHODS: Our search resulted in 55 articles. Inclusion criteria were as follows: (1) younger than 18 years, (2) ECMO therapy, and (3) drowning. Ten articles met our inclusion criteria. We included studies using both central and peripheral ECMO and salt or fresh water submersions. We compared clinical features of survivors to nonsurvivors. RESULTS: A total of 29 patients from the 10 different studies met our criteria. Data analyzed included presenting cardiac rhythm, time to initiation of ECMO, submersion time, pH, potassium, lactate, duration of chest compressions, and survival. There was a significant increase in mortality for presenting rhythm of asystole and with hyperkalemia (P < 0.05). CONCLUSIONS: Extracorporeal membrane oxygenation is an important resuscitation tool for the hypothermic drowning victim. Hyperkalemia and presenting cardiac rhythm correlate with survival although they are not reasons to end resuscitation. More studies are needed to compare the outcomes in using ECMO for the hypothermic drowning victim.

Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care. METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children aged <18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible. RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count ≥13.0 × 103/µL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count <250 × 103/µL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/µL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18-6.21]). CONCLUSIONS: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.

A PRESing case of visual changes and confusion.

Visual disturbances are an uncommon pediatric chief complaint. Usually, after a complete ocular exam including visual acuity, most causes are benign and not life-threatening. Children with abnormal visual complaints who have underlying medical conditions, such as SLE or other autoimmune conditions, a recipient of a transplant, renal disease, and even eclampsia require closer scrutiny. We report a 10-year-old female with a history of systemic lupus erythematosus complicated by hypertension and cardiomyopathy secondary to lupus who presented to the emergency department with a history of vision loss and headache. Head computer tomography demonstrated findings of posterior reversible encephalopathy syndrome (PRES). PRES is a clinical disease associated with cranial radiological findings of heterogenous etiologies that is often reversible. Prompt recognition and treatment are important in preventing permanent damage, long term morbidity and even death.

What is the effect of a decision aid in potentially vulnerable parents? Insights from the head CT choice randomized trial.

OBJECTIVE: To test the hypotheses that use of the Head CT Choice decision aid would be similarly effective in all parent/patient dyads but parents with high (vs low) numeracy experience a greater increase in knowledge while those with low (vs high) health literacy experience a greater increase in trust. METHODS: This was a secondary analysis of a cluster randomized trial conducted at seven sites. One hundred seventy-two clinicians caring for 971 children at intermediate risk for clinically important traumatic brain injuries were randomized to shared decision making facilitated by the DA (n = 493) or to usual care (n = 478). We assessed for subgroup effects based on patient and parent characteristics, including socioeconomic status (health literacy, numeracy and income). We tested for interactions using regression models with indicators for arm assignment and study site. RESULTS: The decision aid did not increase knowledge more in parents with high numeracy (P for interaction [Pint ] = 0.14) or physician trust more in parents with low health literacy (Pint  = 0.34). The decision aid decreased decisional conflict more in non-white parents (decisional conflict scale, -8.14, 95% CI: -12.33 to -3.95; Pint  = 0.05) and increased physician trust more in socioeconomically disadvantaged parents (trust in physician scale, OR: 8.59, 95% CI: 2.35-14.83; Pint  = 0.04). CONCLUSIONS: Use of the Head CT Choice decision aid resulted in less decisional conflict in non-white parents and greater physician trust in socioeconomically disadvantaged parents. Decision aids may be particularly effective in potentially vulnerable parents.

Ocular Injury Presenting to a Level-III Pediatric Trauma Center.

The purpose of this study is to describe pediatric ocular injuries presenting to a level-III pediatric trauma center and emergency department. METHODS: We performed a retrospective study and identified children from January 1, 2011, to January 1, 2016. Charts were reviewed for any subject, age from newborn to younger than 18 years, based on International Classification of Diseases, ninth and tenth revision, codes for any ocular injury. Data abstraction included age, sex, means of arrival, eye involved, mechanism of injury, type of ocular injury, imaging studies obtained, procedures performed, location of definitive repair (in the operating room or emergency department), and subspecialty services involved. RESULTS: In the 5-year period, we describe 356 injuries among 278 children. Males had a slightly higher rate of presentation than females (156 and 122, respectively). Forty-three children (15.46%) required repair in the operating room. Dog bites comprised of 7.19% children with outpatient follow-up, one patient (0.36%) eventually developed anophthalmia, and 30 children (10.79%) had long-term ophthalmological sequelae (ie, glaucoma and blindness). CONCLUSIONS: At our institution, a level-III trauma center, we evaluated and managed approximately 1 ocular injury case per week and children required surgical repair in the operating room at a higher rate than higher-level trauma centers. Injuries secondary to dog bites remain a clinically significant etiology.

Pediatric Trauma Experience After Transition to a Freestanding Children's Hospital.

INTRODUCTION: Transition of pediatrics services to freestanding children's hospitals is a common trend over the past 3 decades, yet there is no published information on the effect of these moves on the pediatric emergency department (ED). We looked at the effect on trauma volume and severity presenting to the ED after transitioning to a freestanding children's hospital at a location previously without dedicated pediatrics services. METHODS: We analyzed data using a retrospective chart review of pediatric trauma visits (age, <15 years) from our pediatric trauma registry. Data analyzed included trauma volume per year, injury severity score, method of trauma, and method of arrival to hospital. Patients were differentiated into groups based on premove years (2008-2010) and postmove years (2012-2014). RESULTS: A total of 833 trauma patients were admitted to the ED between 2008 and 2014. Trauma volume per year almost doubled in years after the move. Difference in injury severity score and methods of trauma were not statistically significant. In postmove years, there was an increase in emergency medical service and private vehicle visits. CONCLUSIONS: New characteristics and location of the freestanding children's hospital may suggest that easy access to the new location, parental preferences for specialized pediatrics services, and emergency medical service preferences may have positively impacted trauma volume without affecting the severity of trauma seen in our department. This study provides a unique single-center experience in understanding ED patient flow after a major department transition.

Emergency Management of the Ingested Magnet: An Algorithmic Approach.

INTRODUCTION: Accidental ingestion of foreign bodies is an increasing problem in the pediatric population. Symptoms are often nonspecific and may lead to a missed diagnosis because the ingestion event often goes unwitnessed. CASE: We present a case of a missed diagnosis of a multiple magnet ingestion event in a pediatric patient leading to operative management. A 2-year-old boy with a 4-week history of nonspecific abdominal pain presented to the emergency department (ED) with vomiting and worsening abdominal pain. He was recently seen in the ED for nonspecific abdominal pain diagnosed as acute otitis media. In this second ED visit, the child was found to be febrile and tachycardic and had signs of peritonitis. Radiographs revealed a foreign body in the right lower quadrant. The child was taken to the operating room where multiple intestinal perforations were identified and repaired. The child had an uneventful postoperative course and was discharged 7 days later. DISCUSSION: There are increasing awareness and growing concern over complications from pediatric magnet ingestion. Complications from neodymium magnet ingestion may include bowel obstruction, perforation, and fistula formation. The risk of complications is especially high with multiple-magnet ingestion. Pediatric foreign-body magnet ingestion may be a diagnostic challenge because the associated symptoms are nonspecific, and the ingestion is often unwitnessed. CONCLUSIONS: Our case represents the missed diagnosis of 4 magnets ingested separately over time. Emergency department providers may benefit from a clinical algorithm guiding the management of these increasingly prevalent patient presentations to prevent delayed diagnoses and to decrease morbidity.

Fitness-related differences in the rate of whole-body evaporative heat loss in exercising men are heat-load dependent.

NEW FINDINGS: What is the central question of this study? Aerobic fitness modulates heat loss, but the heat-load threshold at which fitness-related differences in heat loss occur in young healthy men remains unclear. What is the main finding and its importance? We demonstrate using direct calorimetry that aerobic fitness modulates heat loss in a heat-load-dependent manner, with fitness-related differences occurring between young men who have low and high fitness when the heat load is ∼≥500 W. Although aerobic fitness has been known for some time to modulate heat loss, our findings define the precise heat-load threshold at which fitness-related differences occur. The effect of aerobic fitness (defined as rate of peak oxygen consumption) on heat loss during exercise is thought to be related to the level of heat stress. However, it remains unclear at what combined exercise and environmental (net) heat-load threshold these fitness-related differences occur. To identify this, we assessed whole-body heat exchange (dry and evaporative) by direct calorimetry in young (22 ± 3 years) men matched for physical characteristics with low (Low-fit; 39.8 ± 2.5 ml O2  kg-1  min-1 ), moderate (Mod-fit; 50.9 ± 1.2 ml O2  kg-1  min-1 ) and high aerobic fitness (High-fit; 62.0 ± 4.4 ml O2  kg-1  min-1 ; each n = 8), during three 30 min bouts of cycling in dry heat (40°C, 12% relative humidity) at increasing rates of metabolic heat production of 300 (Ex1), 400 (Ex2) and 500 W (Ex3), each followed by a 15 min recovery period. Each group was exposed to a similar net heat load (metabolic plus ∼100 W dry heat gain; P = 0.83) during each exercise bout [∼400 (Ex1), ∼500 (Ex2) and ∼600 W (Ex3); P < 0.01]. Although evaporative heat loss was similar between groups during Ex1 (P = 0.33), evaporative heat loss was greater in the High-fit (Ex2, 466 ± 21 W; Ex3, 557 ± 26 W) compared with the Low-fit group (Ex2, 439 ± 22 W; Ex3, 511 ± 20 W) during Ex2 and Ex3 (P ≤ 0.03). Conversely, evaporative heat loss for the Mod-fit group did not differ from either the High-fit or Low-fit group during all exercise bouts (P ≥ 0.09). We demonstrate that aerobic fitness modulates heat loss in a heat-load-dependent manner, such that young, highly fit men display greater heat-loss capacity only at heat loads ∼≥500 W compared with their lesser trained counterparts.

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger.

OBJECTIVE: To determine the impact of a cerebrospinal fluid enterovirus polymerase chain reaction (PCR) test performance on hospital length of stay (LOS) in a large multicenter cohort of infants undergoing evaluation for central nervous system infection. STUDY DESIGN: We performed a planned secondary analysis of a retrospective cohort of hospitalized infants ≤60 days of age who had a cerebrospinal fluid culture obtained at 1 of 18 participating centers (2005-2013). After adjustment for patient age and study year as well as clustering by hospital center, we compared LOS for infants who had an enterovirus PCR test performed vs not performed and among those tested, for infants with a positive vs negative test result. RESULTS: Of 19 953 hospitalized infants, 4444 (22.3%) had an enterovirus PCR test performed and 945 (21.3% of tested infants) had positive test results. Hospital LOS was similar for infants who had an enterovirus PCR test performed compared with infants who did not (incident rate ratio 0.98 hours; 95% CI 0.89-1.06). However, infants PCR positive for enterovirus had a 38% shorter LOS than infants PCR negative for enterovirus (incident rate ratio 0.62 hours; 95% CI 0.57-0.68). No infant with a positive enterovirus PCR test had bacterial meningitis (0%; 95% CI 0-0.4). CONCLUSIONS: Although enterovirus PCR testing was not associated with a reduction in LOS, infants with a positive enterovirus PCR test had a one-third shorter LOS compared with infants with a negative enterovirus PCR test. Focused enterovirus PCR test use could increase the impact on LOS for infants undergoing cerebrospinal fluid evaluation.

The roles of KCa, KATP, and KV channels in regulating cutaneous vasodilation and sweating during exercise in the heat.

We recently showed the varying roles of Ca2+-activated (KCa), ATP-sensitive (KATP), and voltage-gated (KV) K+ channels in regulating cholinergic cutaneous vasodilation and sweating in normothermic conditions. However, it is unclear whether the respective contributions of these K+ channels remain intact during dynamic exercise in the heat. Eleven young (23 ± 4 yr) men completed a 30-min exercise bout at a fixed rate of metabolic heat production (400 W) followed by a 40-min recovery period in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC) and local sweat rate were assessed at four forearm skin sites perfused via intradermal microdialysis with: 1) lactated Ringer solution (control); 2) 50 mM tetraethylammonium (nonspecific KCa channel blocker); 3) 5 mM glybenclamide (selective KATP channel blocker); or 4) 10 mM 4-aminopyridine (nonspecific KV channel blocker). Responses were compared at baseline and at 10-min intervals during and following exercise. KCa channel inhibition resulted in greater CVC versus control at end exercise (P = 0.04) and 10 and 20 min into recovery (both P < 0.01). KATP channel blockade attenuated CVC compared with control during baseline (P = 0.04), exercise (all P ≤ 0.04), and 10 min into recovery (P = 0.02). No differences in CVC were observed with KV channel inhibition during baseline (P = 0.15), exercise (all P ≥ 0.06), or recovery (all P ≥ 0.14). With the exception of KV channel inhibition augmenting sweating during baseline (P = 0.04), responses were similar to control with all K+ channel blockers during each time period (all P ≥ 0.07). We demonstrated that KCa and KATP channels contribute to the regulation of cutaneous vasodilation during rest and/or exercise and recovery in the heat.

Intradermal administration of endothelin-1 attenuates endothelium-dependent and -independent cutaneous vasodilation via Rho kinase in young adults.

We recently showed that intradermal administration of endothelin-1 diminished endothelium-dependent and -independent cutaneous vasodilation. We evaluated the hypothesis that Rho kinase may be a mediator of this response. We also sought to evaluate if endothelin-1 increases sweating. In 12 adults (25 ± 6 yr), we measured cutaneous vascular conductance (CVC) and sweating during 1) endothelium-dependent vasodilation induced via administration of incremental doses of methacholine (0.25, 5, 100, and 2,000 mM each for 25 min) and 2) endothelium-independent vasodilation induced via administration of 50 mM sodium nitroprusside (20-25 min). Responses were evaluated at four skin sites treated with either 1) lactated Ringer solution (Control), 2) 400 nM endothelin-1, 3) 3 mM HA-1077 (Rho kinase inhibitor), or 4) endothelin-1+HA-1077. Pharmacological agents were intradermally administered via microdialysis. Relative to the Control site, endothelin-1 attenuated endothelium-dependent vasodilation (CVC at 2,000 mM methacholine, 80 ± 10 vs. 56 ± 15%max, P < 0.01); however, this response was not detected when the Rho kinase inhibitor was simultaneously administered (CVC at 2,000 mM methacholine for Rho kinase inhibitor vs. endothelin-1 + Rho kinase inhibitor sites: 73 ± 9 vs. 72 ± 11%max, P > 0.05). Endothelium-independent vasodilation was attenuated by endothelin-1 compared with the Control site (CVC, 92 ± 13 vs. 70 ± 14%max, P < 0.01). However, in the presence of Rho kinase inhibition, endothelin-1 did not affect endothelium-independent vasodilation (CVC at Rho kinase inhibitor vs. endothelin-1+Rho kinase inhibitor sites: 81 ± 9 vs. 86 ± 10%max, P > 0.05). There was no between-site difference in sweating throughout (P > 0.05). We show that in young adults, Rho kinase is an important mediator of the endothelin-1-mediated attenuation of endothelium-dependent and -independent cutaneous vasodilation, and that endothelin-1 does not increase sweating.

Nicotinic receptor activation augments muscarinic receptor-mediated eccrine sweating but not cutaneous vasodilatation in young males.

NEW FINDINGS: What is the central question of this study? Acetylcholine released from cholinergic nerves can activate both muscarinic and nicotinic receptors. Although each receptor can independently induce cutaneous vasodilatation and eccrine sweating, it remains to be elucidated whether the two receptors interact in order to mediate these responses. What is the main finding and its importance? We show that although nicotinic receptor activation does not modulate muscarinic cutaneous vasodilatation, it lowers the muscarinic receptor agonist threshold at which onset for eccrine sweating (augmentation of muscarinic eccrine sweating) occurs in young men in normothermic resting conditions. These results provide new insights into the physiological significance of nicotinic receptors in the regulation of cutaneous perfusion and eccrine sweating. Acetylcholine released from cholinergic nerves can activate both muscarinic and nicotinic receptors; each is known independently to induce cutaneous vasodilatation and eccrine sweating in humans. However, it is not known whether the two receptors interact in order to mediate cutaneous vasodilatation and eccrine sweating. In 10 young men (27 ± 6 years old), cutaneous vascular conductance and sweat rate were evaluated at intradermal microdialysis sites that were continuously perfused with either lactated Ringer's solution (control) or three different concentrations of nicotine (0.1, 1 and 10 mm), a nicotinic receptor agonist. Co-administration of methacholine, a muscarinic receptor agonist, was performed at all skin sites in a dose-proportional fashion (0.0125, 0.25, 5, 100 and 2000 mm, each for 25 min). Administration of nicotine alone caused dose-dependent transient increases in cutaneous vascular conductance and sweat rate (all P ≤ 0.05), which thereafter returned to pre-nicotine levels, except that a portion of transient responses remained with continuous administration of 10 mm nicotine (both P ≤ 0.05). Cutaneous vascular conductance was increased by administration of ≥0.25 mm methacholine at the control site, and this response was likewise observed in the presence of co-administration of all doses of nicotine used (all P ≤ 0.05). Sweat rate at the control site was increased by administration of ≥0.25 mm methacholine, but the lowest dose of methacholine (0.0125 mm) was able to increase sweat rate in the presence of 10 mm nicotine (P ≤ 0.05). We conclude that nicotinic receptor activation lowers the muscarinic receptor agonist threshold for eccrine sweating (augmentation of muscarinic sweating) but does not affect muscarinic cutaneous vasodilatation in young men in normothermic resting conditions.

The interactive contributions of Na(+) /K(+) -ATPase and nitric oxide synthase to sweating and cutaneous vasodilatation during exercise in the heat.

KEY POINTS: Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilatation during exercise in the heat. Similarly, reports show that Na(+) /K(+) -ATPase activation can modulate sweating and microvascular circulation. In light of the fact that NO can activate Na(+) /K(+) -ATPase, we evaluated whether there is an interaction between Na(+) /K(+) -ATPase and NOS in the regulation of heat loss responses during an exercise-induced heat stress. We demonstrate that Na(+) /K(+) -ATPase and NOS do not synergistically influence local forearm sweating during moderate intensity (fixed rate of metabolic heat production of 500 W) exercise in the heat (35°C). Conversely, we show an interactive role between NOS and Na(+) /K(+) -ATPase in the modulation of cutaneous vasodilatation. These findings provide novel insight regarding the mechanisms underpinning the control of sweating and cutaneous vasodilatation during exercise in the heat. Given that ouabain may be prescribed as a cardiac glycoside in clinical settings, potential heat loss impairments with ouabain administration should be explored. ABSTRACT: Nitric oxide (NO) synthase (NOS) contributes to the heat loss responses of sweating and cutaneous vasodilatation. Given that NO can activate Na(+) /K(+) -ATPase, which also contributes to sweating and microvasculature regulation, we evaluated the separate and combined influence of Na(+) /K(+) -ATPase and NOS on sweating and cutaneous vasodilatation. Thirteen young (23±3 years) males performed two 30 min semi-recumbent cycling bouts in the heat (35°C) at a fixed rate of metabolic heat production (500 W) followed by 20 and 40 min recoveries, respectively. Local sweat rate (LSR) and cutaneous vascular conductance (CVC) were measured at four forearm skin sites continuously perfused via intradermal microdialysis with either: (1) lactated Ringer solution (Control); (2) 6 mᴍ ouabain (Ouabain), a Na(+) /K(+) -ATPase inhibitor; (3) 10 mᴍ l-N(G) -nitroarginine methyl ester (l-NAME), a NOS inhibitor; or (4) 6 mᴍ ouabain and 10 mᴍ l-NAME (Ouabain+l-NAME). At the end of both exercise bouts relative to Control, LSR was attenuated with Ouabain (54-60%), l-NAME (12-13%) and Ouabain+l-NAME (68-74%; all P < 0.05). Moreover, the sum of attenuations from Control induced by independent administration of Ouabain and l-NAME was similar to the combined infusion of Ouabain+l-NAME (both P ≥ 0.74). Compared to Control, CVC at the end of both exercise bouts was similar with Ouabain (both P ≥ 0.30), but attenuated with l-NAME (%CVCmax reduction from Control, 24-25%). Furthermore, CVC at the Ouabain+l-NAME site (38-39%; all P < 0.01) was attenuated compared to Control and did not differ from baseline resting values (both P ≥ 0.81). We show that Na(+) /K(+) -ATPase and NOS do not synergistically mediate sweating, whereas they influence cutaneous blood flow in an interactive manner during exercise in the heat.

K+ channel mechanisms underlying cholinergic cutaneous vasodilation and sweating in young humans: roles of KCa, KATP, and KV channels?

Acetylcholine released from cholinergic nerves is involved in heat loss responses of cutaneous vasodilation and sweating. K(+) channels are thought to play a role in regulating cholinergic cutaneous vasodilation and sweating, though which K(+) channels are involved in their regulation remains unclear. We evaluated the hypotheses that 1) Ca(2+)-activated K(+) (KCa), ATP-sensitive K(+) (KATP), and voltage-gated K(+) (KV) channels all contribute to cholinergic cutaneous vasodilation; and 2) KV channels, but not KCa and KATP channels, contribute to cholinergic sweating. In 13 young adults (24 ± 5 years), cutaneous vascular conductance (CVC) and sweat rate were evaluated at intradermal microdialysis sites that were continuously perfused with: 1) lactated Ringer (Control), 2) 50 mM tetraethylammonium (KCa channel blocker), 3) 5 mM glybenclamide (KATP channel blocker), and 4) 10 mM 4-aminopyridine (KV channel blocker). At all sites, cholinergic cutaneous vasodilation and sweating were induced by coadministration of methacholine (0.0125, 0.25, 5, 100, and 2,000 mM, each for 25 min). The methacholine-induced increase in CVC was lower with the KCa channel blocker relative to Control at 0.0125 (1 ± 1 vs. 9 ± 6%max) and 5 (2 ± 5 vs. 17 ± 14%max) mM methacholine, whereas it was lower in the presence of KATP (69 ± 7%max) and KV (57 ± 14%max) channel blocker compared with Control (79 ± 6%max) at 100 mM methacholine. Furthermore, methacholine-induced sweating was lower at the KV channel blocker site (0.42 ± 0.17 mg·min(-1)·cm(-2)) compared with Control (0.58 ± 0.15 mg·min(-1)·cm(-2)) at 2,000 mM methacholine. In conclusion, we show that KCa, KATP, and KV channels play a role in cholinergic cutaneous vasodilation, whereas only KV channels contribute to cholinergic sweating in normothermic resting humans.