5-HT Receptor Antagonism Attenuates the Ischemia-Reperfusion Injury After Rabbit Lung Preservation

Arreola-Ramírez, José Luis; Alquicira-Mireles, Jesús; Morales-Hernández, Pablo Ernesto; Vargas, Mario H.; Villalba-Caloca, Jaime; Segura-Medina, Patricia

doi:10.1016/j.transproceed.2015.04.089

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…In addition, 5-HT levels are elevated in bronchoalveolar lavage fluid of allergen-sensitized mice and in asthmatic patients after allergen inhalation provocation (Durk et al, 2013). 5-HT is known to exert multiple pathogenic effects in the airway such as bronchoconstriction (Buckner et al, 1993; Martin et al, 1994), increases microvascular permeability (Arreola-Ramirez et al, 2015), and airway edema (Sumita et al, 1989; Lima et al, 2007). Taken together, the involvement of 5-HT in the pathophysiological changes in airway function in allergic airway inflammatory diseases may be mediated, at least in part, through its stimulatory effect on CSLV neurons.…”

Section: Discussionmentioning

confidence: 99%

Stimulatory Effect of 5-Hydroxytryptamine (5-HT) on Rat Capsaicin-Sensitive Lung Vagal Sensory Neurons via Activation of 5-HT3 Receptors

et al. 2019

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5-hydroxytryptamine (5-HT) is an inflammatory mediator known to be released in lung. Capsaicin-sensitive lung vagal (CSLV) afferents function as a primary sensor for detecting chemical stimuli and produce consequent reflexes during lung inflammation. To characterize the effect of 5-HT on CSLV afferents, responses of cardiorespiratory reflexes and single-unit C-fiber afferents to right-atrial injections of 5-HT were investigated in anesthetized Sprague-Dawley rats. Bolus injection of 5-HT (8 μg/kg) caused an immediate augmented breath and apnea, accompanied by hypotension and bradycardia. These initial responses were then followed by a brief pressor response and a more sustained depressor response. After a perineural treatment of both cervical vagi with capsaicin to block the conduction of C fibers, 5-HT still triggered the augmented breath, but no longer evoked the apnea, bradycardia and hypotension, indicating an involvement of C-fiber activation. The remaining augmented breath induced by 5-HT after perineural capsaicin treatment was totally eliminated by vagotomy. To further study the effect of 5-HT on CSLV afferents, activities arising from these afferents were determined using the single-fiber recording technique. Right-atrial injection of 5-HT evoked an intense discharge in CSLV afferents in a dose-dependent manner. The highest dose of 5-HT (16 μg/kg) activated 79% (19/24) of CSLV afferents which were also sensitive to capsaicin (0.8 μg/kg). The pretreatment of tropisetron, a selective antagonist of the 5-HT 3 receptor, completely blocked CSLV-afferents stimulation induced by 5-HT but did not affect that by capsaicin. Furthermore, a similar afferent response of CSLV afferents was mimicked by phenylbiguanide, a selective agonist of the 5-HT 3 receptor. In isolated rat lung vagal C neurons, 5-HT induced intense calcium transients in a dose-dependent manner. The highest concentration (3 μM) of 5-HT activated 67% (18/27) of the CSLV neurons. The 5-HT-induced response was totally abolished by pretreatment of tropisetron. In conclusion, 5-HT exerts an intense stimulatory effect on lung C-fiber terminals mediated through an activation of the 5-HT 3 receptor, which may contribute to the airway hypersensitivity under lung inflammation.

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Section: Discussionmentioning

confidence: 99%

Stimulatory Effect of 5-Hydroxytryptamine (5-HT) on Rat Capsaicin-Sensitive Lung Vagal Sensory Neurons via Activation of 5-HT3 Receptors

et al. 2019

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“…Basic studies have shown that 5-HT receptor antagonists can protect the lungs. For example, they attenuated ischemia-reperfusion injury after lung preservation in a rabbit model ( 10 ), and also reduced myofibroblast differentiation and connective tissue deposits in fibrosing interstitial lung diseases ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Association between ondansetron use and mortality of patients on mechanical ventilation in the intensive care unit: a retrospective cohort study

Tao¹,

Chen²,

Chang³

et al. 2023

Ann Transl Med

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Background Basic studies show that selective 5-hydroxytryptamine type 3 (5-HT 3 ) serotonin-receptor antagonists can protect organs from inflammatory injury and have shown lung protection. Whether 5-HT 3 receptor antagonists ondansetron benefits patients with mechanical ventilation is unclear in the intensive care unit (ICU). Methods The Medical Information Mart for Intensive Care-IV (MIMIC-IV) database was reviewed to identify patients on mechanical ventilation (aged >16 years) in the ICU, which was divided into two groups according to whether ondansetron is used. Demographic characteristics, medical history data, clinical parameters, diagnosis and treatment measures were included as covariates. Ondansetron use was defined as any kind of ondansetron administration regardless of the dose before the induction of mechanical ventilation. The primary outcome was in-hospital death. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by multivariable Cox regression. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to further adjust for confounding factors. Kaplan-Meier (KM) curves with log-rank test were also performed. Results A total of 18,566 patients on mechanical ventilation were included (5,735 with ondansetron use). The overall in-hospital mortality rate of patients on mechanical ventilation was 18.9% (3,512/18,566). Approximately 13.0% (746/5,735) and 21.6% (2,766/12,831) in-hospital mortality rates occurred in the ondansetron and non-ondansetron use groups, respectively. Multivariable regression indicated that ondansetron usage was associated with a 33% and 32% lower risk of in-hospital and 60-day death (HR =0.77, 95% CI: 0.70–0.85, P<0.001; HR =0.68, 95% CI: 0.62–0.75, P<0.001) in the whole sample. Multivariable regression post-PSM indicated that ondansetron usage was associated with a 38% and 31% lower risk of in-hospital and 60-day death (HR =0.62, 95% CI: 0.56–0.68, P<0.001; HR =0.69, 95% CI: 0.62–0.77, P<0.001). Log-rank test for the KM curve of ondansetron and 60-day death was statistically significant (P<0.001). The duration of ventilator use pre- and post-PSM was statistically different (P<0.001 and P=0.007) in the two groups. Conclusions Ondansetron usage was significantly associated with a lower mortality risk of ventilated patients in the ICU. The 5-HT3 receptor antagonist use is may be new potential adjunctive therapeutic strategy for patients on mechanical ventilation in the ICU.

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“…The mortality of mechanically ventilated patients is high at 30% 1,2 . It has been suggested that 5‐hydroxytryptamine (5‐HT) plays a role in the pathophysiology of a wide range of diseases and conditions, including chronic obstructive pulmonary disease (COPD), 3,4 myocardial infarction, 5 adult respiratory distress syndrome, 6 sepsis, 7 lung ischemia–reperfusion injury, 8 pulmonary arterial hypertension, 9–12 interstitial lung diseases, 13 non‐small‐cell lung cancer and lung adenocarcinoma 14–16 . 5‐HT is an inflammatory mediator released in the lung 17 .…”

Section: Introductionmentioning

confidence: 99%

Mediators of neutrophil–lymphocyte ratio in the relationship between ondansetron pre‐treatment and the mortality of ICU patients on mechanical ventilation: Causal mediation analysis from the MIMIC‐IV database

Zhou

Tao

Zhang

et al. 2022

Brit J Clinical Pharma

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Aims The mortality of critically ill patients undergoing mechanical ventilation (MV) is high and few strategies are available. We explored the relationship between ondansetron pre‐treatment, the neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR), and mortality of ventilated patients in the intensive care unit. Methods We developed a retrospective cohort study that involved patients undergoing MV in the Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC‐IV) database. Causal mediation analysis was conducted to assess the relationship of ondansetron use and mortality and to explore the potential causal pathway mediated by the NLR or PLR. The primary outcome was 28‐day mortality. Results A total of 17 927 eligible patients took part in the study (5665 had taken ondansetron before MV initiation and 12 262 patients had not). The odds ratio (OR) for 28‐day mortality for ondansetron use uncorrelated with the mediator (NLR, PLR) was 0.72 (95% confidence interval [CI] = 0.64–0.81, P < .001). Ondansetron was also associated with a reduction in 28‐day mortality after controlling for the mediator of NLR (OR = 0.98, 95% CI = 0.97–0.99, P < .01). For the indirect effect, the NLR could explain 13.47% (95% CI = 8.59–20.54%, P < .01) of the impact of ondansetron use on 28‐day mortality. The proportion mediated increased to 21.50% (95% CI = 12.36–47.44%, P < .01) for 90‐day mortality. Adjusted mediation analysis revealed no suggestion of a causal mediation pathway for this effect by the PLR (P = .12). Conclusions NLR may play substantial roles in the relationship between ondansetron pre‐treatment before initiation of mechanical ventilation and the reduction of death risk in ventilated patients.

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5-HT Receptor Antagonism Attenuates the Ischemia-Reperfusion Injury After Rabbit Lung Preservation

Cited by 5 publications

References 17 publications

Stimulatory Effect of 5-Hydroxytryptamine (5-HT) on Rat Capsaicin-Sensitive Lung Vagal Sensory Neurons via Activation of 5-HT3 Receptors

Stimulatory Effect of 5-Hydroxytryptamine (5-HT) on Rat Capsaicin-Sensitive Lung Vagal Sensory Neurons via Activation of 5-HT3 Receptors

Association between ondansetron use and mortality of patients on mechanical ventilation in the intensive care unit: a retrospective cohort study

Mediators of neutrophil–lymphocyte ratio in the relationship between ondansetron pre‐treatment and the mortality of ICU patients on mechanical ventilation: Causal mediation analysis from the MIMIC‐IV database

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