Respiratory Reflexes Research Articles

Analgosedation in Pediatric Emergency Care: A Comprehensive Scoping Review

Effective management of pain and anxiety in pediatric emergency room is crucial for ensuring both the physical and emotional well-being of young patients. Analgosedation, a combination of analgesia and sedation, is commonly used to facilitate various procedures in children. However, selecting the optimal agent and administration route remains challenging due to the unique pharmacological profiles and side effects of available drugs. This scoping review aims to provide a comprehensive analysis of the pharmacological agents used for procedural analgosedation in pediatric emergency settings, focusing on their efficacy, safety, administration routes, and potential side effects. A systematic review of the literature was conducted, focusing on key agents such as ketamine, midazolam, dexmedetomidine, fentanyl, and nitrous oxide. Studies were included based on their relevance to pediatric procedural sedation, particularly in emergency settings. Literature analysis showed that ketamine and fentanyl are effective for managing moderate to severe pain, with a rapid onset of action. Fentanyl is preferred for acute pain management following fractures and burns, while ketamine and midazolam are commonly used for emergency analgosedation. Dexmedetomidine, which induces sedation similar to natural sleep, is particularly effective in preventing pain and agitation during procedures and is well tolerated in children, especially those with developmental disorders. Nitrous oxide, when used in a 50% oxygen mixture, offers a valuable option for conscious sedation during mildly to moderately painful procedures, maintaining respiratory and airway reflexes. No single drug is ideal for all pediatric patients and procedures and the choice of agent should be tailored to the specific clinical scenario, considering both the sensory and affective components of pain. Future research should prioritize large-scale comparative studies, the exploration of combination therapies, and the development of non-pharmacological adjuncts to enhance the safety and efficacy of pediatric analgosedation.

The Respiratory Reflex of Cough: A Comparative Study of Contemporary Medicine and Unani Concepts

Cough suddenly and frequently helps to remove mucus, irritants, foreign substances, and bacteria from the airways. It can be a symptom of a respiratory infection like the common cold, bronchitis, tuberculosis, influenza, smoking, or other health issues. Contemporary texts describe several kinds of coughs, including acute, chronic, and subacute coughs, coughs that produce or do not produce mucus, and specific types like Reflex cough, voluntary cough, and evoked cough. In Unani texts, cough is referred to as diseases rather than symptoms. it is also called as “Sual” in Arabic, “Surfa” in Persian, khansi in Hindi, and cough in English. In Unani medicine, Sual is attributed to three causes: Ashab-e-badiya (extrinsic factor), Asbab-i- Wassila (intrinsic factor), and Iltehab (inflammation). The primary categories of Sual identified in Unani texts are Sual yabis and Sual Ratab, which are further subdivided into various types. This paper examines the concept, causes, types, and treatment approaches to Sual/Cough as described in both classical and modern literature. Keywords: Cough, Sual, Surfa, Modern concept Unani literature, sual yabis, sual ratab.

Intrinsic molecular proton sensitivity underlies GPR4 effects on retrotrapezoid nucleus (RTN) neuronal activation and CO2-stimulated breathing.

An interoceptive homeostatic reflex monitors levels of CO2/H+ to maintain blood gas homeostasis and rapidly regulate tissue acid-base balance by driving lung ventilation and CO2 excretion - this CO2-evoked increase in respiration is the hypercapnic ventilatory reflex (HCVR). Retrotrapezoid nucleus (RTN) neurons provide crucial excitatory drive to downstream respiratory rhythm/pattern-generating circuits, and their activity is directly modulated by changes in CO2/H+ RTN neurons express GPR4 and TASK-2, global deletion of which abrogates CO2/H+ activation of RTN neurons and the HCVR. It has not been determined if the intrinsic pH sensitivity of these proton detectors is required for these effects. We used CRISPR/Cas9 genome editing to generate mice with mutations in either of two pH-sensing histidine residues in GPR4 to determine effects on RTN neuronal CO2/H+ sensitivity and the HCVR. In global GPR4(H81F) and GPR4(H167F) mice, CO2-stimulated breathing and CO2-induced RTN neuronal activation were strongly blunted, with no effect on hypoxia-stimulated breathing. In brainstem slices from GPR4(H81F) mice, peak firing of RTN neurons during bath acidification was significantly reduced compared to GPR4 wild type mice, and a subpopulation of RTN neurons was rendered pH-insensitive, phenocopying previous results from GPR4-deleted mice. These effects were independent of changes in RTN number/distribution, neuronal excitability or transcript levels for GPR4 and TASK-2. CO2-stimulated breathing was reduced to a similar extent in GPR4(H81F) and TASK-2-deleted mice, with combined mutation yielding no additional deficit in the HCVR. Together, these data demonstrate that the intrinsic pH sensitivity of GPR4 is necessary for full elaboration of the HCVR.Significance Statement Among the critical mechanisms for whole-body homeostasis, the hypercapnic ventilatory reflex (HCVR) regulates lung ventilation in order to maintain physiological levels of arterial PCO2 and acid-base balance. GPR4 is a proton-activated receptor and putative molecular proton sensor in retrotrapezoid nucleus (RTN) neurons, which are a crucial neural component of this respiratory reflex. In this work, we developed multiple lines of mice in which the intrinsic pH sensitivity of GPR4 was globally disabled by mutations in key histidine residues; in those mice, CO2/H+-sensitivity of RTN neurons and the HCVR were strongly blunted. These data support a role for GPR4 as a direct molecular sensor for CO2/H+ in support of this important homeostatic reflex.

Dual role of transient receptor potential ankyrin 1 in respiratory and gastrointestinal physiology: From molecular mechanisms to therapeutic targets.

The transient receptor potential ankyrin 1 (TRPA1) channel plays a pivotal role in the respiratory and gastrointestinal tracts. Within the respiratory system, TRPA1 exhibits diverse distribution patterns across key cell types, including epithelial cells, sensory nerves, and immune cells. Its activation serves as a frontline sensor for inhaled irritants, triggering immediate protective responses, and influencing airway integrity. Furthermore, TRPA1 has been implicated in airway tissue injury, inflammation, and the transition of fibroblasts, thereby posing challenges in conditions, such as severe asthma and fibrosis. In sensory nerves, TRPA1 contributes to nociception, the cough reflex, and bronchoconstriction, highlighting its role in both immediate defense mechanisms and long-term respiratory reflex arcs. In immune cells, TRPA1 may modulate the release of pro-inflammatory mediators, shaping the overall inflammatory landscape. In the gastrointestinal tract, the dynamic expression of TRPA1 in enteric neurons, epithelial cells, and immune cells underscores its multifaceted involvement. It plays a crucial role in gut motility, visceral pain perception, and mucosal defense mechanisms. Dysregulation of TRPA1 in both tracts is associated with various disorders such as asthma, Chronic Obstructive Pulmonary Disease, Irritable Bowel Syndrome, and Inflammatory Bowel Disease. This review emphasizes the potential of TRPA1 as a therapeutic target and discusses the efficacy of TRPA1 antagonists in preclinical studies and their promise for addressing respiratory and gastrointestinal conditions. Understanding the intricate interactions and cross-talk of TRPA1 across different cell types provides insight into its versatile role in maintaining homeostasis in vital physiological systems, offering a foundation for targeted therapeutic interventions.

Decoding the role of genetically-distinct sensory nerves in controlling cardiopulmonary reflexes

Activation of airway sensory nerves causes respiratory and autonomic reflexes. The majority of the airway sensory afferents are only sensitive to noxious stimuli, such as inflammation, irritants, and pollutants. Activation of these nociceptive afferents evokes protective mechanisms such as apnea, cough, and bradycardia. These reflexes may contribute to disease morbidity when excessively activated. Airway nociceptors, largely projecting from the vagal ganglia (nodose and jugular ganglion), are heterogeneous with respect to gene expression and neuroanatomy, and our objective is to characterize the reflexes evoked by activation of specific afferent subsets using chemogenetics. To selectively activate vagal afferent subpopulations in vivo, mice were exposed to nebulized selective stimuli such as capsaicin (transient receptor potential (TRP) vanilloid 1 (V1) agonist), allyl isothiocyanate (AITC, TRP ankyrin 1 (A1) agonist), and clozapine-N-oxide (CNO, selective agonist for the designer receptor exclusively activated by designer drug (DREADD) stimulatory receptor hM3Dq). hM3Dq expression by ROSA26-loxP-STOP-loxP mice was selectively expressed in sensory subpopulations by breeding with Cre recombinase-expressing mice: TRPV1 (all nociceptors), Tac1-Cre (peptidergic/jugular-originating nerves), and P2X2-Cre (nodose-originating nerves). An intersectional approach using TRPV1-flp mice and the above Cre mice combined with bilateral vagal injections of an AAV delivering dual recombinase-dependent DREADD constructs was used to express hM3Dq in afferent populations defined by two genes (e.g. TRPV1+ and P2X2+). ECGS were recorded via radiotelemetry, and respiration was measured via whole-body plethysmography. CNO administration in TRPV1-hM3Dq mice, P2X2-hM3Dq mice, and Tac1-hM3Dq mice evoked bradypnea and bradycardia. When CNO was administered in the dual recombinase-dependent ConFon (Cre-On/Flp-On) Tac1-Cre/TRPV1-Flp mouse (selectively activating the vagal jugular nociceptors), a significant bradypnea was evoked; however, when CNO was administered in the dual recombinase-dependent ConFon P2X2-Cre/TRPV1-Flp mouse (selectively activating the nodose nociceptors), no bradypnea was observed. Our preliminary data suggest that functionally-distinct nociceptive subpopulations differentially regulate the cardiopulmonary reflexes. NIH R01: 152219, NIH T32: HL160529. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Concurrent, dual perturbations of the 5-HT and NA systems reveal dynamic interplay in regulating the neonate autoresuscitation reflex

Sudden Infant Death Syndrome (SIDS) is a leading cause of infant mortality worldwide. Failure of the neonate auto-resuscitation reflex is hypothesized to be a common endpoint in many SIDS cases. Although SIDS is idiopathic, postmortem studies indicate abnormalities in the serotonergic (5-HT) and noradrenergic (NA) systems of the respiratory network. To better understand the contributions and interactions of these two systems in autoresuscitation, we combined a novel series of Cre- and FLPo- recombinase driver mouse lines and conditional inhibitory and excitatory DREADD lines for singular excitation or inhibition of either the whole 5-HT or whole NA systems. These models were then uniquely combined to further enable 1) concurrent excitation or inhibition of both systems in the same neonate or 2) inhibition of one system while exciting the other system in the same neonate. In total, we developed 8 distinct sets of conditional genetic mouse models for singular and combined 5-HT and NA system perturbation paradigms. The 8 experimental groups and 2 control groups were repeatedly assayed for the autoresuscitation reflex using a robotic neonate cardiorespiratory assessment platform, Looper. Neonates are repeatedly tested until they succumb. Resulting data were analyzed with our recently published waveform analysis software, Breathe Easy, to calculate operant outcomes. In 320 mice total, we found 4 groups with decreased autoresuscitation success: NA activation, NA activation + 5-HT activation, NA activation + 5-HT inhibition, and 5-HT activation. There was no change in survival in any of the other groups including 5-HT inhibition. Preliminary results suggest a potential cardiovascular mechanism of autoresuscitation failure independent of respiratory outcomes. At baseline, all 4 groups with decreased survival showed increased heart rate (HR) whereas the other groups either had the same HR or a decreased HR. During early recovery, defined as beginning at the 10th breath following the primary gasp until recovery, the 4 groups with decreased survival show higher HR than the other groups following the 1st bout of autoresuscitation. As recovery progressed in these groups, HR continued to increase as well until the next autoresuscitation test. Ventilatory frequency, tidal volume, and ventilation all increased in the 3 groups where NA was activated either in isolation or in combination, but there were decreases in all other groups, including 5-HT activation. As the underlying genetic and environmental mechanisms driving SIDS are likely to have pleiotropic effects across multiple neural systems, our first-of-its-kind dual 5-HT and NA system modulations set the stage to more comprehensively model key aspects of SIDS neuropathology that reveal a previously uncharacterized dynamic functional interplay between the NA and 5-HT systems in protective respiratory reflexes. NIH: 1F32HL160073-01A1, R01HL130249 44617-S4. BCM McNair Scholar Program, March of Dimes Basil O'Connor Research Award, Parker B. Francis Fellowship, CJ Foundation for SIDS. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Role of OPRM1 in the Neonatal Autoresuscitation Reflex and Sudden Infant Death Syndrome

Opioid receptors are widely expressed throughout the brain and integral in nociception as well as homeostatic regulation of autonomic processes including respiration through modulation of respiratory rhythmogenesis and chemosensory responses. Perturbations to homeostatic mu opioid receptor (MOR) signaling via opiate overdose results in respiratory depression, aberrant breathing, and often death. With the rise of opioid use over the last two decades, many infants are being diagnosed with Neonatal Abstinence Syndrome (NAS), a congenital cardio-respiratory disorder resulting from prenatal exposure to opioids. Infants born with NAS have a fourfold increased risk for Sudden Infant Death Syndrome (SIDS). SIDS and related Sudden Unexpected Infant Death takes the lives of approximately 3,400 infants annually under the age of one and its etiology remains mostly unknown. Currently SIDS is explained via the triple risk model that proposes that SIDS occurs in a vulnerable infant during a critical developmental period when triggered by an external stressor, converging on the failure of the neonate autoresuscitation reflex in most cases. Recently a study identified an association between a mutation in the OPRM1 gene encoding MORs and SIDS cases. However, how this gene and perturbations in its native function modulates respiratory regulation are poorly understood. We hypothesize that native OPRM1 function is integral to protective neonate respiratory reflexes and that perturbation of native OPRM1 signaling negatively affects the neonatal autoresuscitation reflex. Male and female OPRM1 loss of function mice were assayed for their autoresuscitation reflex on our novel testbed, Looper. Mice were exposed to repeated bouts of anoxia and allowed to autoresuscitate until death occurred. Preliminary data suggest that loss of OPRM1 function results in a higher mortality rate on the autoresuscitation assay with OPRM1 KO mice surviving significantly less anoxic challenges compared to wild type controls. No sex differences were observed between male and female survival for all genotype groups. Results indicate that perturbation of the native function of OPRM1 produces a vulnerability to autoresuscitation dysfunction and mitigated survival. Our data demonstrate the first functional assessment of OPRM1 in neonatal cardiovascular function and autoresuscitation and reveal an important risk factor that may be implicated in perpetuating SIDS and NAS phenotypes. Additional analyses of distinct parameters from respiratory trace data for OPRM1 loss of function mice will aid in a deeper, mechanistic understanding of features implicated in autoresuscitation dysfunction. Future studies aim to characterize specific splice variants of OPRM1, known to produce neomorphic function and model the SIDS associated VUS, to further characterize the implication of OPRM1 and its variants in congenital respiratory diseases. Funding sources NIH/NHLBI R01HLN161142-01 and R01HL130249-07. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Regulation of vagally-evoked respiratory responses by the lateral parabrachial nucleus in the mouse

Vagal sensory inputs to the brainstem can alter breathing through the modulation of pontomedullary respiratory circuits. In this study, we set out to investigate the localised effects of modulating lateral parabrachial nucleus (LPB) activity on vagally-evoked changes in breathing pattern. In isoflurane-anaesthetised and instrumented mice, electrical stimulation of the vagus nerve (eVNS) produced stimulation frequency-dependent changes in diaphragm electromyograph (dEMG) activity with an evoked tachypnoea and apnoea at low and high stimulation frequencies, respectively. Muscimol microinjections into the LPB significantly attenuated eVNS-evoked respiratory rate responses. Notably, muscimol injections reaching the caudal LPB, previously unrecognised for respiratory modulation, potently modulated eVNS-evoked apnoea, whilst muscimol injections reaching the intermediate LPB selectively modulated the eVNS-evoked tachypnoea. The effects of muscimol on eVNS-evoked breathing rate changes occurred without altering basal eupneic breathing. These results highlight novel roles for the LPB in regulating vagally-evoked respiratory reflexes.

Metoprolol for prevention of bucking at orotracheal extubation: a double-blind, placebo-controlled randomised trial

BackgroundRespiratory responses to extubation can cause serious postoperative complications. Beta-blockers, such as metoprolol, can interfere with the cough pathway. However, whether metoprolol can effectively control respiratory reflexes during extubation remains unclear. The objective of this study is to evaluate the efficacy of intravenous metoprolol in attenuating respiratory responses to tracheal extubation. MethodsRandomized, double-blinded, placebo-controlled trial. Setting: Tertiary referral center located in Brasília, Brazil. Recruitment: June 2021 to December 2021. Sample: 222 patients of both sexes with an American Society of Anesthesiologists (ASA) physical status I–III aged 18–80 years. Patients were randomly assigned to receive intravenous metoprolol 5 mg IV or placebo at the end of surgery. The primary outcome was the proportion of patients who developed bucking secondary to endotracheal tube stimulation of the tracheal mucosa during extubation. Secondary outcomes included coughing, bronchospasm, laryngospasm, Mean Blood Pressure (MAP), and Heart Rate (HR) levels. ResultsTwo hundred and seven participants were included in the final analysis: 102 in the metoprolol group and 105 in the placebo group. Patients who received metoprolol had a significantly lower risk of bucking (43.1% vs. 64.8%, Relative Risk [RR = 0.66], 95% Confidence Interval [95% CI 0.51–0.87], p = 0.003). In the metoprolol group, 6 (5.9%) patients had moderate/severe coughing compared with 33 (31.4%) in the placebo group (RR = 0.19; 95% CI 0.08–0.43, p < 0.001). ConclusionMetoprolol reduced the risk of bucking at extubation in patients undergoing general anesthesia compared to placebo.

MATHEMATICAL MODELING OF SARS-COV-2 PARTICLES’ PROPAGATION DURING HUMAN REFLEXES

An unknown virus, which was detected in Wuhan city in 2019, had changed fate of the world immediately causing an economic loss, decrease in total population and etc. A penetration of coronavirus contaminated particles to a human cell is able to cause an overproduction of cytokines and antibodies. This process gives a rise to fatal cases. Hence, because of SARS-CoV-2’s pathogenicity, severity and unexpectedness, effective safety measures should be implemented. Along with safe social distancing and wearing a mask, a presence of air conditioning, ventilation system and open windows can reduce the coronavirus propagation in enclosed spaces. The present article focuses on the modeling of coronavirus particles’ propagation during human respiratory reflexes within a constructed three-dimensional confined space with inlet and outlet boundary conditions. Momentum and continuity equations, k-ε turbulence model and Lagrangian dispersion model were utilized to solve the problem. SIMPLE is a main method to solve all governing equations. The primary objectives of this work are to demonstrate the efficiency of air conditioning and open windows in preventing the spread of viruses and to examine particle behavior in the computational domain.

Trigeminal Function in Sino-Nasal Health and Disease.

The upper airway (nasal passages, paranasal sinuses, pharynx, and glottis) provides the sentinel portion of the human respiratory tract, with the combined senses of olfaction (cranial nerve I) and trigeminal sensation (cranial nerve V) signaling the quality of inspired air. Trigeminal function also complements the sense of taste (in turn mediated by cranial nerves VII, IX and X), and participates in the genesis of taste aversions. The ability of trigeminal stimulation in the upper aero-digestive tract to trigger a variety of respiratory and behavioral reflexes has long been recognized. In this context, the last three decades has seen a proliferation of observations at a molecular level regarding the mechanisms of olfaction, irritation, and gustation. Concurrently, an ever-widening network of physiological interactions between olfaction, taste, and trigeminal function has been uncovered. The objective of this review is to summarize the relatively recent expansion of research in this sub-field of sensory science, and to explore the clinical and therapeutic implications thereof.

Concurrent, dual perturbations of the 5-HT and NA systems reveal dynamic interplay in regulating the neonate autoresuscitation reflex

Sudden Infant Death Syndrome (SIDS) is a leading cause of infant mortality worldwide. Postmortem studies indicate abnormalities in the serotonergic (5-HT) and noradrenergic (NA) systems of the respiratory network. To better understand the relative and potential combined contributions and interactions of these two neurotransmitter systems to SIDS pathology, we developed a novel series of conditionally expressed inhibitory (hM4De) and excitatory (hM3D) DREADD models that allows for singular excitation or inhibition of either the whole 5-HT or whole NA systems as defined by cre- and FLPo- drivers. These models were then uniquely combined to further enable 1) concurrent stimulation or inhibition of both the NA and 5-HT systems in the same animal or 2) inhibition of one system while exciting the other system in the same animal. In total, after two years of complex breeding combining 3 loci and 6 alleles, we developed 8 distinct sets of conditional genetic mouse models for various singular and combined 5-HT and NA system perturbation paradigms.Failure of the neonate auto-resuscitation reflex is hypothesized to be a common endpoint in many SIDS cases. The autoresuscitation reflex can be readily assayed in neonate mice by repeated bouts of exposure to an anoxic gas to induce bradycardia and apnea followed by restoration of room air to observe successful or failed autoresuscitation. The 8 experimental groups and 2 control groups were repeatedly assayed for the autoresuscitation reflex using a new closed loop robotic neonate cardiorespiratory assessment platform and outcomes were analyzed with our recently developed comprehensive respiratory analysis platform, Breathe Easy, to calculate operant outcomes. In &gt;170 mouse pups (≈17 pups per group) assayed over three months, we found that singular DREADD-mediated activation or inhibition of the NA system results in decreased survival. Interestingly, we found that DREADD-mediated 5-HT activation decreases survival. In contrast to previous studies, we found that DREADD-mediated 5-HT inhibition does not impact survival, particularly when all neonates are challenged to autoresuscitation failure. Furthermore, we show survival is restored to control levels when NA inhibition is combined with 5-HT inhibition; however, failure via NA activation is not rescued by 5-HT inhibition. Controls used for comparison were CNO-injected controls as we also show an effect of CNO on survival that cannot be attributed to time of day, rig, experimenter, weight, background genotype, etc. As the underlying genetic and environmental mechanisms driving SIDS are likely to have pleiotropic effects across multiple neural systems, our first-of-its-kind dual 5-HT and NA system modulations sets the stage to more comprehensively model key aspects of SIDS neuropathology that reveal a previously uncharacterized dynamic functional interplay between the NA and 5-HT systems in protective respiratory reflexes. NIH: 1F32HL160073-01A1, R01HL130249 44617-S4. BCM McNair Scholar Program, March of Dimes Basil O'Connor Research Award, Parker B. Francis Fellowship, CJ Foundation for SIDS. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Performance simulations of human trachea during respiratory reflexes after stent implantation

Performance simulations of human trachea during respiratory reflexes after stent implantation

Asystole, A Rare Cardiac Complication of Lateral Medullary Infarction: Case report and Literature Review. (P2-5.010)

<h3>Objective:</h3> We report a case of lateral medullary infarction leading to asystole, and we discuss the diagnosis, management, and prognosis of patients with this rare complication. <h3>Background:</h3> Clinical presentations of lateral medullary stroke vary. Wallenberg syndrome is the most common presentation, which includes vertigo with nystagmus, ataxia, ipsilateral sensory deficits in the face, bulbar muscle weakness, and ipsilateral Horner’s syndrome. The nucleus tractus solitarius, the dorsal vagal nucleus, and the nucleus ambiguous in the lateral medulla oblongata play a critical role in autonomic regulation and have centers for respiratory, cardiac, and vasomotor reflexes. Despite this, cardiac arrhythmias such as asystole are a rare clinical manifestation of lateral medullary stroke. <h3>Design/Methods:</h3> Case report and literature review. <h3>Results:</h3> A 64-year-old man with hypertension, previously involved in a motor vehicle accident, presented with acute onset dysphagia, left facial droop, and left eye ptosis. CT of the head did not show any acute stroke or hemorrhage. CT angiography of the head and neck showed left vertebral artery (V3/V4 segment) occlusion. He received IV thrombolysis. Post thrombolysis, he had bradycardia evolving to asystole and brief cardiac arrest. MRI of the brain revealed acute left posterior lateral medullary stroke and MR angiography showed left vertebral artery dissection. Cardiac work-up was unrevealing, and he eventually required placement of a dual-chamber pacemaker. Given the absence of respiratory factors and structural heart disease, the bradycardia and asystole were attributed to the lateral medullary stroke. <h3>Conclusions:</h3> Despite the recognized role of the lateral medulla in autonomic regulation, cardiac arrhythmias are rarely associated with lateral medullary infarction. Precise mechanisms are yet to be elucidated, but it remains important to recognize them as a potential complication of this stroke. <b>Disclosure:</b> Dr. Gutierrez Quiceno has nothing to disclose. Dr. Gowda has nothing to disclose. Dr. Kakadia has nothing to disclose.

The Nasal Solitary Chemosensory Cell Signaling Pathway Triggers Mouse Avoidance Behavior to Inhaled Nebulized Irritants.

The nasal epithelium houses a population of solitary chemosensory cells (SCCs). SCCs express bitter taste receptors and taste transduction signaling components and are innervated by peptidergic trigeminal polymodal nociceptive nerve fibers. Thus, nasal SCCs respond to bitter compounds, including bacterial metabolites, and these reactions evoke protective respiratory reflexes and innate immune and inflammatory responses. We tested whether SCCs are implicated in aversive behavior to specific inhaled nebulized irritants using a custom-built dual-chamber forced-choice device. The behavior of mice was recorded and analyzed for the time spent in each chamber. Wild-type (WT) mice exhibited an aversion to 10 mm denatonium benzoate (Den) or cycloheximide and spent more time in the control (saline) chamber. The SCC-pathway knock-out (KO) mice did not exhibit such an aversion response. The bitter avoidance behavior of WT mice was positively correlated with the concentration increase of Den and the number of exposures. Bitter-ageusic P2X2/3 double KO mice similarly showed an avoidance response to nebulized Den, excluding the taste system's involvement and pointing to an SCC-mediated major contributor to the aversive response. Interestingly, SCC-pathway KO mice showed an attraction to higher Den concentrations; however, chemical ablation of the olfactory epithelium eliminated this attraction attributed to the smell of Den. These results demonstrate that activation of SCCs leads to a rapid aversive response to certain classes of irritants with olfaction, but not gustation, contributing to the avoidance behavior during subsequent irritant exposures. This SCC-mediated avoidance behavior represents an important defense mechanism against the inhalation of noxious chemicals.

Irritant-evoked reflex tachyarrhythmia in spontaneously hypertensive rats is reduced by inhalation of TRPM8 agonists l-menthol and WS-12.

Inhalation of noxious irritants activates nociceptive sensory afferent nerves innervating the airways, inducing reflex regulation of autonomic networks and the modulation of respiratory drive and cardiovascular (CV) parameters such as heart rate and blood pressure. In healthy mammals, irritant-evoked pulmonary-cardiac reflexes cause parasympathetic-mediated bradycardia. However, in spontaneously hypertensive (SH) rats, irritant inhalation also increases sympathetic drive to the heart. This remodeled pulmonary-cardiac reflex may contribute to cardiovascular risk caused by inhalation of air pollutants/irritants in susceptible individuals with cardiovascular disease (CVD). Previous studies have shown that the cooling mimic l-menthol, an agonist for the cold-sensitive transient receptor potential melastatin 8 (TRPM8), can alleviate nasal inflammatory symptoms and respiratory reflexes evoked by irritants. Here, we investigated the impact of inhalation of TRPM8 agonists l-menthol and WS-12 on pulmonary-cardiac reflexes evoked by inhalation of the irritant allyl isothiocyanate (AITC) using radiotelemetry. l-Menthol, but not its inactive analog d-menthol, significantly reduced the AITC-evoked reflex tachycardia and premature ventricular contractions (PVCs) in SH rats but had no effect on the AITC-evoked bradycardia in either SH or normotensive Wistar-Kyoto (WKY) rats. WS-12 reduced AITC-evoked tachycardia and PVCs in SH rats, but this more potent TRPM8 agonist also reduced AITC-evoked bradycardia. l-Menthol had no effect on heart rate when given alone, whereas WS-12 evoked a minor bradycardia in WKY rats. We conclude that stimulation of TRPM8-expressing afferents within the airways reduces irritant-evoked pulmonary-cardiac reflexes, especially the aberrant reflex tachyarrhythmia in SH rats. Airway menthol treatment may be an effective therapy for reducing pollution-associated CV exacerbations.NEW & NOTEWORTHY Irritant-evoked pulmonary-cardiac reflexes are remodeled in spontaneously hypertensive (SH) rats-causing de novo sympathetic reflexes that drive tachyarrhythmia. This remodeling may contribute to air pollution-associated risk in susceptible individuals with cardiovascular disease. We found that inhalation of TRPM8 agonists, l-menthol and WS-12, but not the inactive analog d-menthol, selectively reduces the reflex tachyarrhythmia evoked by allyl isothiocyanate (AITC) inhalation in SH rats. Use of menthol may protect susceptible individuals from pollution-associated CV exacerbations.

Lumbar Epidural Anesthesia in a High-Risk Patient with Advanced Lung Cancer, Multi-Organ Metastasis and Hydropneumothorax

Epidural anesthesia (EA) can be applied in the perioperative period (PP) in addition to general anesthesia (GA) or as a stand-alone anesthesia technique. EA provides better hemodynamic stability in high-risk patients, reduced neurohormonal surgical stress response, and preserved airway reflexes with spontaneous breathing. In addition, EA prevents pulmonary dysfunction through decreasing multifactorial mediators, improves pulmonary functions by reducing the decrease in functional residual capacity, and protects spontaneous respiratory and airway reflexes. Herein, we wanted to emphasize the importance of the perioperative approach, the choice of anesthesia technique, and the effects of this choice on the postoperative period in a high-risk patient with incidental stage four lung adenocarcinoma, right parietal brain, lumbar vertebral, liver, and adrenal metastasis, as well as hydropneumothorax. With a successful epidural catheterization and anesthesia, the patient was follow-up without any problems. As in our patient, we should adopt a multimodal approach in the perioperative period, perform a detailed examination before the operation, and evaluate all risks and benefits comparatively when choosing the most appropriate anesthesia technique. Thus, it should be kept in mind that the chosen technique will significantly affect perioperative complications, morbidity and mortality, drug use, length of hospital stay, and cost.

Dexmedetomidine decreases stress post-operative in pediatrics

ABSTRACT Introduction Tracheal extubation causes hypertension and tachycardia. These associated hemodynamic changes are due to sympathetic discharge due to epipharyngeal and laryngeal stimulation.(1) Aim of work Dexmedetomidine is an effective sedative and analgesic agent, it helps in opioid sparing and multimodal techniques in pediatric anesthesia and reduces the toxicity of common anesthetics, and it has been approved by the end of 1999 by the FDA for human use for sedation in the intensive care unit (ICU). Dexmedetomidine is notable for its ability to provide sedation without risk of respiratory depression and can provide cooperative or arousable sedation. The aim of this study is to assess the effect of administering dexmedetomidine near the end of surgery versus a control group regarding the change in circulatory reflexes (represented by MAP) and the incidence of adverse events such as cough, laryngeal spasm or desaturation. Study design This study was designed as a prospective randomized controlled study. It was conducted in the Pediatrics orthopedic surgery theatre (Abo El Reesh pediatric Hospital) belonging to Cairo university hospitals on 70 patients divided into two groups 35 patients each and aged from 3–12 years planned for elective isolated limb anomaly correction. Result Dexmedetomidine injection near the end of the operation decreased the stress induced during extubation with almost no change in HR or MAP and less cough score, which indicated smoother extubation. Conclusion Dexmedetomidine is a potent alpha 2 receptor agonist, having analgesic and sedative effects and sparing usage of opioids without compromising respiratory reflexes or attenuating cardiovascular response during extubation.

MANAJEMEN ASUHAN KEBIDANAN KOMPLEKS PADA BAYI BARU LAHIR DENGAN ASFIKSIA RINGAN DI BPM SURATMI KOTA BATAM TAHUN 2022

Asphyxia neonatorum is a condition in which the baby cannot breathe spontaneously and regularly immediately after birth. Asphyxia occupies the number 3 mortality rate in newborns with a rate of 23%. This task aims to understand midwifery care in complex cases of newborns with asphyxia. This case study uses a descriptive method with a case study approach and reference collection. Care is carried out by clearing the airway, stimulating respiratory reflexes, and maintaining body temperature. Based on the results of the case study, it can be concluded that BY. X with midwifery care of newborns with asphyxia went well marked by a Normal Apgar Score, the conclusion is the importance of assessing the Apgar Score in newborns with asphyxia with action in accordance with evidence based.

SPARC: Intersectional labeling of vagal afferent nerve subsets using Cre and FLP dependent dual reporter strain

Respiratory reflexes are tightly controlled by distinct types of vagal sensory afferent nerves. Afferent nerves can be categorized by their conduction velocity, axon diameter, myelination, responses to stimuli, ion channels/receptor expression, and embryological origin. Some airway vagal afferent nerves are sensitive to noxious stimuli (i.e. nociceptive). TRPV1, the capsaicin receptor, is selectively expressed on most vagal nociceptors. Vagal ganglia are comprised of jugular ganglia (neural crest origin) and nodose ganglia (placodal origin). Tac1 encodes Tachykinin1, the substance P precursor protein, and is mainly expressed in the jugular ganglia. P2X2, a purinergic receptor, is exclusively expressed in nodose ganglia. Previous data suggests that activation of jugular nociceptors and nodose nociceptors causes distinct reflexes. Here, we used intersectional genetics to simultaneously visualize nodose and jugular nociceptors. We generated a transgenic mouse model with dual recombinase responsive allele using Cre‐Lox and Flp‐FRT (Flippase‐Flp recognition target) systems. With the ROSA26‐RC::FLTG allele, cells with only Flp show tdTomato expression (by excising of FRT‐flanked STOP cassette) while cells with both Flp and Cre have GFP expression (by excising of both FRT‐flanked STOP cassette and loxP‐flanked tdTomato). We generated TRPV1‐FLP:Tac1‐Cre:ROSA and TRPV1‐FLP:P2X2‐Cre:ROSA strains. Offspring (6 to 8 weeks old) were used for characterization. Vagal ganglia, lung and brainstem were collected and fixed with 4% paraformaldehyde. Tissue were cryosectioned for immunohistochemistry. In TRPV1‐FLP:Tac1‐Cre:ROSA, the majority of tdTomato expressing cells were in nodose ganglia and GFP expressing neurons were in jugular ganglia. In TRPV1‐FLP:P2X2‐Cre:ROSA, as expected, GFP expressing neurons were only observed in nodose ganglia while tdTomato expressing neurons were observed in both nodose and jugular ganglia. Reporter expressing neurons in both strains overlapped with anti‐TRPV1 antibody staining indicating they were all nociceptive. In the brainstem, reporter expression was mainly in the nucleus of solitary tract (nTS) in both strains. In TRPV1‐FLP:Tac1‐Cre:ROSA strain, GFP expression (jugular nociceptors) was also observed in the paratrigeminal nucleus (Pa5). In the lung, most TRPV1+ fibers expressing Tac1 were found in close proximity to the epithelial layer of bronchi and bronchioles. Whereas TRPV1+ fibers expressing P2X2 often projected away from the conducting airways into the alveolar tissue. Taken together, we have developed cell type specific‐dual reporter mouse models using a combinatorial/intersectional Cre and FLP strategy to successfully identify distinct nociceptive subtypes of afferent nerves in vagal ganglia, brainstem, and lung.