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BACKGROUND: Airway obstruction is the second leading cause of potentially preventable death on the battlefield. The treatment for airway obstruction is intubation or advanced airway adjunct, which has a known risk of aspiration. We sought to describe the variables associated with aspiration pneumonia after prehospital airway intervention. METHODS: This is a sub-analysis of previously described data from the Department of Defense Trauma Registry (DoDTR) from 2007 to 2020. We included casualties that had at least one prehospital airway intervention with documentation of subsequent aspiration pneumonia or pneumonia within three days of the intervention. We used a generalized linear model with Firth bias estimates to test for associations. RESULTS: There were 1,509 casualties that underwent prehospital airway device placement. Of these, 41 (2.7%) met inclusion criteria into the aspiration pneumonia cohort. The demographics had no statistical difference between the groups. The non-aspiration cohort had fewer median ventilator days (2 versus 6, p < 0.001), intensive care unit days (2 versus 7, p < 0.001, and hospital days [3 versus 8, p < 0.001]). Survival was lower in the non-aspiration cohort (74.2% versus 90.2%, p = 0.017). The administration of succinylcholine was higher in the non-aspiration cohort (28.0% versus 12.2%, p = 0.031). In our multivariable model, only the administration of succinylcholine was significant and was associated with lower probability of aspiration pneumonia (odds ratio 0.56). CONCLUSION: Overall, the incidence of aspiration pneumonia was low in our cohort. The administration of succinylcholine was associated with a lower odds of developing aspiration pneumonia.
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Obstrucción de las Vías Aéreas , Servicios Médicos de Urgencia , Neumonía por Aspiración , Humanos , Manejo de la Vía Aérea , Succinilcolina , Obstrucción de las Vías Aéreas/terapia , Neumonía por Aspiración/epidemiología , Neumonía por Aspiración/etiología , Sistema de RegistrosRESUMEN
BACKGROUND: Airway obstruction is the second leading cause of potentially survivable death on the battlefield. Assessing outcomes associated with airway interventions is important, and temporal trends can reflect the influence of training, technology, the system of care, and other factors. We assessed mortality among casualties undergoing prehospital airway intervention occurring over the course of combat operations during 2007-2019. METHODS: This is a retrospective analysis of a previously described dataset from the Department of Defense Trauma Registry (DODTR). We included only casualties with documented placement of an endotracheal tube, cricothyrotomy, or supraglottic airway (SGA) in the prehospital setting. RESULTS: Within the DODTR from January 2007 to December 2019, there were 25,849 adult encounters with documentation of any prehospital activity. Within that group, there were 251 documented cricothyrotomies, 1,147 documented intubations, and 35 documented supraglottic airways placed. Cricothyrotomy recipients had a median age of 25. Within this group, the largest proportion were non-North Atlantic Treaty Organization (NATO) military personnel (35%), were injured by explosives (54%), had a median injury severity score (ISS) of 24, and 60% survived to hospital discharge. Intubation recipients had a median age of 24. Within this group, the largest proportion were non-NATO military personnel (37%), were injured by explosives (57%), had a median ISS of 18, and 76% survived to hospital discharge. SGA recipients had a median age of 28. Within this group, the largest proportion were non-NATO military (37%), were injured by firearms (48%), had a median ISS of 25, and 54% survived to hospital discharge. A downward trend existed in the quantity of all procedures performed during the study period. In both unadjusted and adjusted regression models, we identified no year-to-year differences in survival after prehospital cricothyrotomy or SGA placement. In the unadjusted and adjusted models, we noted a decrease in mortality during the 2007-2008 (odds ratio [OR] for death 0.47, 95% CI 0.26-0.86) and an increase from 2012-2013 (OR 2.10, 95% CI 1.09-4.05) for prehospital intubation. CONCLUSION: Mortality among combat casualties undergoing prehospital or emergency department airway interventions showed no sustained change during the study period. These findings suggest that advances in airway resuscitation are necessary to achieve mortality improvements in potentially survivable airway injuries in the prehospital setting.
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Obstrucción de las Vías Aéreas , Servicios Médicos de Urgencia , Personal Militar , Heridas y Lesiones , Adulto , Humanos , Estudios Retrospectivos , Intubación Intratraqueal/métodos , Servicios Médicos de Urgencia/métodos , Manejo de la Vía Aérea/métodos , Obstrucción de las Vías Aéreas/terapia , Sistema de Registros , Heridas y Lesiones/terapia , Heridas y Lesiones/complicacionesRESUMEN
Tracheal intubation is the preferred method of airway management, a common emergency trauma medicine problem. Currently, methods for confirming tracheal tube placement are lacking, and we propose a novel technology, spectral reflectance, which may be incorporated into the tracheal tube for verification of placement. Previous work demonstrated a unique spectral profile in the trachea, which allowed differentiation from esophageal tissue in ex vivo swine, in vivo swine, and human cadavers. The goal of this study is to determine if spectral reflectance can differentiate between trachea and other airway tissues in living humans and whether the unique tracheal spectral profile persists in the presence of an inhalation injury. Reflectance spectra were captured using a custom fiber-optic probe from the buccal mucosa, posterior oropharynx, and trachea of healthy humans intubated for third molar extraction and from the trachea of patients admitted to a burn intensive care unit with and without inhalation injury. Using ratio comparisons, we found that the tracheal spectral profile was significantly different from buccal mucosa or posterior oropharynx, but the area under the curve values are not high enough to be used clinically. In addition, inhalation injury did not significantly alter the spectral reflectance of the trachea. Further studies are needed to determine the utility of this technology in a clinical setting and to develop an algorithm for tissue differentiation.
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Intubación Intratraqueal , Tráquea , Animales , Cadáver , Tecnología de Fibra Óptica , Humanos , Respiración Artificial , Porcinos , Tráquea/lesionesRESUMEN
Airway management is one of the most challenging problems in prehospital combat casualty care. Airway assessment and intervention are second only to hemorrhage control in priority in the initial treatment of trauma patients, and airway compromise continues to account for approximately 1 in 10 preventable battlefield deaths. Combat medics often provide care in no- or low-light conditions, surrounded by the chaos of combat, and with the limited dexterity that accompanies bulky body armor, gloves, and heavy equipment. Far-forward medical care is also limited by available resources, which are often only what a combat medic can fit in the aid bag. Therefore, a procedure such as airway management that currently requires a high degree of skill becomes substantially more complex. Improved airway devices are listed among the top five in a comprehensive list of battlefield research and development priorities by the Defense Health Board, yet the challenge of airway management has received little investment compared to other causes of preventable battlefield death such as exsanguinating hemorrhage and traumatic brain injury.
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Manejo de la Vía Aérea , Hemorragia , Hemorragia/prevención & control , HumanosRESUMEN
Airway management is important in trauma and critically ill patients. Prolonged mechanical ventilation results in overventilation-induced lung barotrauma, but few studies have examined the consequence of acute (1 h or less) overventilation. We hypothesized that acute hyperventilation, as might inadvertently be performed in prehospital settings, would elevate systemic inflammation and cause lung damage. Female Yorkshire pigs (40-50 kg, n = 10/group) were anesthetized, instrumented for hemodynamic measurements and blood sampling, and underwent a 25% controlled hemorrhage followed by 1 h of 1) spontaneous breathing, 2) "normal" bag ventilation (4.8 L·min volume, â¼400 mL tidal volume, 12 breaths/minute), 3) bag hyperventilation (9 L·min volume, â¼750 mL tidal volume, 12 breaths/minute), 4) maximum hyperventilation (15 L·min volume, â¼750 mL tidal volume, 20 breaths/minute), or 5) mechanical ventilation. Pigs then regained consciousness and recovered for 24 h, followed by euthanasia and collection of blood and tissue samples. No level of manual ventilation had any significant impact on hemodynamic variables. Blood markers of tissue damage and plasma cytokines were not statistically different between groups with the exception of a transient increase in IL-1ß; all values returned to baseline by 24 h. On pathological review, severity and distribution of lung edema or other gross pathologies were not significantly different between groups. These data indicate hyperventilation causes no adverse effects, to include inflammation and tissue damage, and that acute overventilation, as could be seen in the prehospital phase of trauma care, does not produce evidence of adverse effects on the lungs following moderate hemorrhage.NEW & NOTEWORTHY Appropriate airway management is essential in trauma and critically ill patients. Prolonged mechanical ventilation can result in overventilation-induced lung barotrauma, but few studies have examined the consequence of acute overventilation. We investigated the outcome of hemorrhage followed by 1 h of overventilation in swine. We found that acute overventilation, as could be seen in the prehospital phase of trauma care, does not produce evidence of adverse effects on otherwise healthy lungs following moderate hemorrhage.
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Pulmón , Respiración Artificial , Animales , Femenino , Hemodinámica , Hemorragia/etiología , Humanos , Respiración Artificial/efectos adversos , Porcinos , Volumen de Ventilación PulmonarRESUMEN
Endotracheal intubation is a common life-saving procedure implemented in emergency care to ensure patient oxygenation, but it is difficult and often performed in suboptimal conditions leading to high rates of patient complications. Undetected misplacement in the esophagus is a preventable complication that can lead to fatalities in 5-10% of patients who undergo emergency intubation. End-tidal carbon dioxide monitoring and other proper placement detection methods are useful, yet the problem of misplacement persists. Our previous work demonstrated the utility of spectral reflectance sensors for differentiating esophageal and tracheal tissues, which can be used to confirm proper endotracheal tube placement. In this study, we examine the effectiveness of spectral characterization in the presence of saline, blood, "vomit", and soot in the trachea. Our results show that spectral properties of the trachea that differentiate it from the esophagus persist in the presence of these substances. This work further confirms the potential usefulness of this novel detection technology in field applications.
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Intubación Intratraqueal , Hollín , Tráquea , Dióxido de Carbono/análisis , Esófago , Humanos , Monitoreo FisiológicoRESUMEN
INTRODUCTION: Airway compromise is the second leading cause of potentially survivable death on the battlefield. The purpose of this study was to better understand wartime prehospital airway patients. MATERIALS AND METHODS: The Role 2 Database (R2D) was retrospectively reviewed for adult patients injured in Afghanistan between February 2008 and September 2014. Of primary interest were prehospital airway interventions and mortality. Prehospital combat mortality index (CMI-PH), hemodynamic interventions, injury mechanism, and demographic data were also included in various statistical analyses. RESULTS: A total of 12,780 trauma patients were recorded in the R2D of whom 890 (7.0%) received prehospital airway intervention. Airway intervention was more common in patients who ultimately died (25.3% vs. 5.6%); however, no statistical association was found in a multivariable logistic regression model (OR 1.28, 95% CI 0.98-1.68). Compared with U.S. military personnel, other military patients were more likely to receive airway intervention after adjusting for CMI-PH (OR 1.33, 95% CI 1.07-1.64). CONCLUSIONS: In the R2D, airway intervention was associated with increased odds of mortality, although this was not statistically significant. Other patients had higher odds of undergoing an airway intervention than U.S. military. Awareness of these findings will facilitate training and equipment for future management of prehospital/prolonged field care airway interventions.
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Manejo de la Vía Aérea/métodos , Servicios Médicos de Urgencia/métodos , Adolescente , Adulto , Campaña Afgana 2001- , Afganistán , Manejo de la Vía Aérea/instrumentación , Manejo de la Vía Aérea/normas , Distribución de Chi-Cuadrado , Servicios Médicos de Urgencia/estadística & datos numéricos , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Personal Militar/estadística & datos numéricos , Oportunidad Relativa , Estudios RetrospectivosRESUMEN
Loss of a patent airway is a significant cause of prehospital death. Endotracheal intubation is the gold standard of care but has a high rate of failure and complications, making development of new devices vital. We previously showed that tracheal tissue has a unique spectral profile which could be utilized to confirm correct airway device placement. Therefore, the goals of this study were twofold: 1- to develop an airway obstruction model and 2- use that model to assess how airway compromise affects tissue reflectance. Female swine were anesthetized, intubated, and instrumented. Pigs were allowed to breathe spontaneously and underwent either slow- or rapid-onset obstruction until a real-time pulse oximeter reading of ≤50%. At baseline, 25%, 50%, 75%, and 100% obstruction, a fiber-optic reflection probe was inserted into the trachea and esophagus to capture reflectance spectra. Both slow- and rapid-onset obstruction significantly decreased arterial oxygen concentration (sO2 ) and increased partial pressure of CO2 (pCO2 ). The presence of the tracheal-defining spectral profile was confirmed and remained consistent despite changes in sO2 and pCO2 . This study validated a model of slow- and rapid-airway obstruction that results in significant hypoxia and hypercapnia. This is valuable for future testing of airway device components that may improve airway management. Additionally, our data support the ability of spectral reflectance to differentiate between tracheal and esophageal tissues in the presence of a clinical condition that decreases oxygen saturation.
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Obstrucción de las Vías Aéreas , Modelos Animales de Enfermedad , Hipercapnia , Hipoxia , Imagen Óptica/métodos , Obstrucción de las Vías Aéreas/complicaciones , Animales , Femenino , Hipercapnia/etiología , Hipoxia/etiología , Intubación Intratraqueal , Procesamiento de Señales Asistido por Computador , PorcinosRESUMEN
BACKGROUND: Airway compromise is the second leading cause of preventable death on the battlefield. Unlike a cricothyrotomy, supraglottic airway (SGA) placement does not require an incision and is less technically challenging. We compare survival of causalities undergoing cricothyrotomy versus SGA placement. METHODS: We used a series of emergency department (ED) procedure codes to search within the Department of Defense Trauma Registry (DoDTR) from January 2007 to August 2016. This is a subanalysis of that dataset. RESULTS: During the study period, 194 casualties had a documented cricothyrotomy and 22 had a documented SGA as the sole airway intervention. The two groups had similar proportions of explosive injuries (57.7% versus 63.6%, p = .328), similar composite injury severity scores (25 versus 27.5, p = .168), and similar AIS for the head, face, extremities, and external body regions. The cricothyrotomy group had lower AIS for the thorax (0 versus 3, p = .019) a trend toward lower AIS for the abdomen (0 versus 0, p = .077), more serious injuries to the head (67.5% versus 45.5%, p = .039), and similar rates of serious injuries to the face (4.6% versus 4.6%, p = .984). Glasgow Coma Scale (GCS) scores were similar upon arrival to the ED (3 versus 3, p = .467) as were the proportion of patients surviving to discharge (45.4% versus 40.9%, p = .691). On repeated multivariable analyses, the odds ratios (ORs) for survival were not significantly different between the two groups. CONCLUSION: We found no difference in short-term outcomes between combat casualties who received an SGA vs cricothyrotomy. Military prehospital personnel rarely used either advanced airway intervention during the recent conflicts in Afghanistan and Iraq.
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Manejo de la Vía Aérea/métodos , Servicios Médicos de Urgencia , Heridas Relacionadas con la Guerra/terapia , Humanos , Análisis de Supervivencia , Resultado del Tratamiento , Heridas Relacionadas con la Guerra/mortalidadRESUMEN
BACKGROUND: Airway obstruction is the second most common cause of potentially preventable death on the battlefield. We compared survival in the combat setting among patients undergoing prehospital versus emergency department (ED) intubation. METHODS: Patients were identified from the Department of Defense Trauma Registry (DODTR) from January 2007 to August 2016. We defined the prehospital cohort as subjects undergoing intubation prior to arrival to a forward surgical team (FST) or combat support hospital (CSH), and the ED cohort as subjects undergoing intubation at an FST or CSH. We compared study variables between these cohorts; survival was our primary outcome. RESULTS: There were 4341 intubations documented in the DODTR during the study period: 1117 (25.7%) patients were intubated prehospital and 3224 (74.3%) were intubated in the ED. Patients intubated prehospital had a lower median age (24 versus 25 years, p < .001), composed a higher proportion of host nation forces (36.1% versus 29.1%, p < .001), had a lower proportion of injuries from explosives (57.6% versus 61.0%, p = .030), and had higher median injury severity scores (20 versus 18, p = .045). A lower proportion of the prehospital cohort survived to hospital discharge (76.4% versus 84.3%, p < .001). The prehospital cohort had lower odds of survival to hospital discharge in both univariable (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.51-0.71) and multivariable analyses controlling for confounders (OR 0.70, 95% CI 0.58-0.85). In a subgroup analysis of patients with a head injury, the lower odds of survival persisted in the multivariable analysis (OR 0.49, 95% CI 0.49-0.82). CONCLUSIONS: Patients intubated in the prehospital setting had a lower survival than those intubated in the ED. This finding persisted after controlling for measurable confounders.
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Obstrucción de las Vías Aéreas/terapia , Servicios Médicos de Urgencia/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Intubación Intratraqueal/estadística & datos numéricos , Heridas Relacionadas con la Guerra/terapia , Adulto , Afganistán/epidemiología , Obstrucción de las Vías Aéreas/mortalidad , Estudios de Cohortes , Humanos , Irak/epidemiología , Sistema de Registros , Análisis de Supervivencia , Resultado del Tratamiento , Heridas Relacionadas con la Guerra/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Airway compromise is the second leading cause of preventable death on the battlefield. Unlike a cricothyrotomy, supraglottic airway (SGA) placement does not require an incision and is less technically challenging. We compare the survival of causalities undergoing cricothyrotomy versus SGA placement. METHODS: We used a series of emergency department (ED) procedure codes to search within the Department of Defense Trauma Registry (DODTR) from January 2007 to August 2016. This is a subanalysis of that data set. RESULTS: During the study period, 194 casualties had a documented cricothyrotomy and 22 had a documented SGA as the sole airway intervention. The two groups had similar proportions of explosive injuries (57.7% versus 63.6%, p = .328), similar composite injury severity scores (25 versus 27.5, p = .168), and similar AIS for the head, face, extremities, and external body regions. The cricothyrotomy group had lower AIS for the thorax (0 versus 3, p = .019), a trend toward lower AIS for the abdomen (0 versus 0, p = .077), more serious injuries to the head (67.5% versus 45.5%, p = .039), and similar rates of serious injuries to the face (4.6% versus 4.6%, p = .984). Glasgow Coma Scale (GCS) scores were similar on arrival to the ED (3 versus 3, p = .467) as were the proportion of patients surviving to discharge (45.4% versus 40.9%, p = .691). On repeated multivariable analyses, the odds ratios for survival were not significantly different between the two groups. CONCLUSIONS: We found no difference in short-term outcomes between combat casualties who received an SGA vs those who received a cricothyrotomy. Military prehospital personnel rarely used either advanced airway intervention during the recent conflicts in Afghanistan and Iraq.
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Manejo de la Vía Aérea/métodos , Servicios Médicos de Urgencia/estadística & datos numéricos , Intubación Intratraqueal/métodos , Traqueostomía/estadística & datos numéricos , Heridas Relacionadas con la Guerra/terapia , Afganistán/epidemiología , Manejo de la Vía Aérea/instrumentación , Humanos , Intubación Intratraqueal/instrumentación , Irak/epidemiología , Análisis de Supervivencia , Resultado del Tratamiento , Heridas Relacionadas con la Guerra/mortalidadRESUMEN
OBJECTIVES: Airway failures are the second leading cause of potentially preventable death on the battlefield. Improvements in airway management depend on identifying current challenges. We sought to build on previously reported data on prehospital, combat airway management. METHODS: We used a series of emergency department procedure codes to identify patients within the Department of Defense Trauma Registry from January 2007 to August 2016. This is a subanalysis of those with a documented prehospital airway intervention. RESULTS: Of the 28,222 patients in our dataset, 1379 (4.9%) had a documented prehospital airway intervention. Airway devices consisted of 49 airway adjuncts (17 nasopharyngeal airways, 2 oropharyngeal airways, remainder listed as unspecified), 230 cricothyrotomies, 1117 endotracheal intubations, and 27 supraglottic airways. Patients undergoing airway intervention were mostly members of the US military (42.2%). Compared with those without airway intervention, they were slightly younger (median 24 vs 25 years, P < 0.001), more frequently injured by explosives (57.7% vs 55.2%, P < 0.001) and gunshot wound (28.7% vs 23.3%, P < 0.001), with higher injury severity scores (composite and by body region) except the superficial body region, and less likely to survive to discharge (73.5% vs 96.6%, P < 0.001). Vecuronium (35.4%) and midazolam (27.9%) were the most frequently used paralytic and sedative, respectively. CONCLUSIONS: Patients undergoing airway intervention were most frequently injured by explosive or gunshot wound. Intubations and cricothyrotomies were the most frequent airway interventions performed. Patients undergoing interventions were more critically injured, with higher mortality rates. Further research is needed to determine methods to reduce mortality in this critically injured population.
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Manejo de la Vía Aérea/métodos , Servicios Médicos de Urgencia/métodos , Personal Militar , Heridas Relacionadas con la Guerra/terapia , Adulto , Afganistán , Femenino , Humanos , Irak , Masculino , Sistema de Registros , Índices de Gravedad del Trauma , Resultado del Tratamiento , Estados Unidos , Heridas Relacionadas con la Guerra/diagnóstico , Heridas Relacionadas con la Guerra/mortalidadRESUMEN
BACKGROUND: Airway management is of critical importance in combat trauma patients. Airway compromise is the second leading cause of potentially survivable death on the battlefield and accounts for approximately 1 in 10 preventable deaths. Reports from the Iraq and Afghanistan wars indicate 4% to 7% incidence of airway interventions on casualties transported to combat hospitals. The goal of this study was to describe airway management in the prehospital combat setting and document airway devices used on the battlefield. METHODS: This study is a retrospective review of casualties that required a prehospital lifesaving airway intervention during combat operations in Afghanistan. We obtained data from the Prehospital Trauma Registry that was linked to the Department of Defense Trauma Registry for outcome data for the time period between January 2013 and September 2014. RESULTS: Seven hundred five total trauma patients were included, 16.9% required a prehospital airway management procedure. There were 132 total airway procedures performed, including 83 (63.4%) endotracheal intubations and 26 (19.8%) nasopharyngeal airway placements. Combat medics were involved in 48 (36.4%) of airway cases and medical officers in 73 (55.3%). Most (94.2%) patients underwent airway procedures due to battle injuries caused by explosion or gunshot wounds. Casualties requiring airway management were more severely injured and less likely to survive as indicated by Injury Severity Score, responsiveness level, Glascow Coma Scale, and outcome. CONCLUSION: Percentages of airway interventions more than tripled from previous reports from the wars in Afghanistan and Iraq. These changes are significant, and further study is needed to determine the causes. Casualties requiring airway interventions sustained more severe injuries and experienced lower survival than patients who did not undergo an airway procedure, findings suggested in previous reports. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level III.
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Manejo de la Vía Aérea/estadística & datos numéricos , Servicios Médicos de Urgencia/estadística & datos numéricos , Heridas Relacionadas con la Guerra/terapia , Campaña Afgana 2001- , Manejo de la Vía Aérea/métodos , Servicios Médicos de Urgencia/métodos , Femenino , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Medicina Militar/métodos , Medicina Militar/estadística & datos numéricos , Estudios Retrospectivos , Resultado del Tratamiento , Estados UnidosRESUMEN
Blackburn MB, Andrade MA, Toney GM. Hypothalamic PVN contributes to acute intermittent hypoxia-induced sympathetic but not phrenic long-term facilitation. J Appl Physiol 124: 1233-1243, 2018. First published December 19, 2017; doi: 10.1152/japplphysiol.00743.2017 .- Acute intermittent hypoxia (AIH) repetitively activates the arterial chemoreflex and triggers a progressive increase of sympathetic nerve activity (SNA) and phrenic nerve activity (PNA) referred to as sympathetic and phrenic long-term facilitation (S-LTF and P-LTF), respectively. Neurons of the hypothalamic paraventricular nucleus (PVN) participate in the arterial chemoreflex, but their contribution to AIH-induced LTF is unknown. To determine this, anesthetized rats were vagotomized and exposed to 10 cycles of AIH, each consisting of ventilation for 3 min with 100% O2 followed by 3 min with 15% O2. Before AIH, rats received bilateral PVN injections of artificial cerebrospinal fluid (aCSF; vehicle) or the GABA-A receptor agonist muscimol (100 pmol in 50 nl) to inhibit neuronal activity. Thirty minutes after completing the AIH protocol, during which rats were continuously ventilated with 100% O2, S-LTF and P-LTF were quantified from recordings of integrated splanchnic SNA and PNA, respectively. PVN muscimol attenuated increases of SNA during hypoxic episodes occurring in later cycles (6-10) of AIH ( P < 0.03) and attenuated post-AIH S-LTF ( P < 0.001). Muscimol, however, did not consistently affect peak PNA responses during hypoxic episodes and did not alter AIH-induced P-LTF. These findings indicate that PVN neuronal activity contributes to sympathetic responses during AIH and to subsequent generation of S-LTF. NEW & NOTEWORTHY Neural circuits mediating acute intermittent hypoxia (AIH)-induced sympathetic and phrenic long-term facilitation (LTF) have not been fully elucidated. We found that paraventricular nucleus (PVN) inhibition attenuated sympathetic activation during episodes of AIH and reduced post-AIH sympathetic LTF. Neither phrenic burst patterning nor the magnitude of AIH-induced phrenic LTF was affected. Findings indicate that PVN neurons contribute to AIH-induced sympathetic LTF. Defining mechanisms of sympathetic LTF could improve strategies to reduce sympathetic activity in cardiovascular and metabolic diseases.
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Hipoxia/fisiopatología , Potenciación a Largo Plazo/fisiología , Núcleo Hipotalámico Paraventricular/fisiopatología , Nervio Frénico/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Animales , Masculino , Ratas , Ratas Sprague-Dawley , RespiraciónRESUMEN
ANG II-salt hypertension selectively increases splanchnic sympathetic nerve activity (sSNA), but the extent to which this reflects increased respiratory versus cardiac rhythmic bursting is unknown. Here, integrated sSNA was elevated in ANG II-infused rats fed a high-salt (2% NaCl) diet (ANG II-HSD) compared with vehicle-infused rats fed a normal-salt (0.4% NaCl) diet (Veh-NSD; P < 0.01). Increased sSNA was not accompanied by increased inspiratory or expiratory bursting, consistent with no group difference in central inspiratory drive. Consistent with preserved inhibitory baroreflex entrainment of elevated sSNA in ANG II-HSD rats, the time integral ( P < 0.05) and amplitude ( P < 0.01) of cardiac rhythmic sSNA were increased. Consistent with activity of hypothalamic paraventricular nucleus (PVN) neurons supporting basal SNA in ANG II-salt hypertension, inhibition of PVN with the GABA-A receptor agonist muscimol reduced mean arterial pressure (MAP) and integrated sSNA only in the ANG II-HSD group ( P < 0.001). PVN inhibition had no effect on respiratory rhythmic sSNA bursting in either group but reduced cardiac rhythmic sSNA in ANG II-HSD rats only ( P < 0.01). The latter likely reflected reduced inhibitory baroreflex entrainment subsequent to the fall of MAP. Of note is that MAP as well as integrated and rhythmic burst patterns of sSNA were similar in vehicle-infused rats whether they were fed a normal or high-salt diet. Findings indicate that PVN neurons support elevated sSNA in ANG II-HSD rats by driving a tonic component of activity without altering respiratory or cardiac rhythmic bursting. Because sSNA was unchanged in Veh-HSD rats, activation of PVN-driven tonic sSNA appears to require central actions of ANG II. NEW & NOTEWORTHY ANG II-salt hypertension is strongly neurogenic and depends on hypothalamic paraventricular nucleus (PVN)-driven splanchnic sympathetic nerve activity (sSNA). Here, respiratory and cardiac bursts of sSNA were preserved in ANG II-salt rats and unaltered by PVN inhibition, suggesting that PVN neurons drive a tonic component of sSNA rather than modulating dominant patterns of burst discharge.