We tested the hypothesis that activation of P2X receptors associated with vagal afferent nerves can evoke a Bezold‐Jarisch (B‐J) depressor reflex in anaesthetized rats. Injection of αβ‐methylene ATP (αβ‐MeATP; 0.6‐600 nmol i.v.) evoked a dose‐dependent B‐J reflex comprising bradycardia, hypotension and apnoea in rats anaesthetized with pentobarbitone. Apnoea was commonly preceded by hyperventilation. Bilateral vagotomy significantly reduced the bradycardia and most of the apnoeic response without affecting hyperventilation, and unmasked a vasopressor response. Hypotension and apnoea were subject to desensitization, and ATP was about 100 times less potent than αβ‐MeATP in evoking the B‐J reflex. ED50 values for responses to αβ‐MeATP were: bradycardia 14.6 ± 3.8 nmol; apnoea 47.1 ± 8.5 nmol; hyperventilation 23.3 ± 6.0 nmol, n= 14. The ED50 for apnoea was significantly greater than that for bradycardia or hyperventilation (P < 0.05). Atropine (2.8 μmol (kg body wt)−1 i.v.) antagonized the reflex bradycardia and hypotension. The P2 antagonists suramin (14 μmol (kg body wt)−1 i.v.) and PPADS (17 μmol (kg body wt)−1 i.v.) antagonized the bradycardic and apnoeic components of the reflex response to αβ‐MeATP, without reducing the vasopressor or hyperventilatory responses to the agonist. Recordings from vagal afferents showed that pulmonary inflation receptors were activated by αβ‐MeATP in 62 % of units recorded (ED50 22 ± 5 nmol) and this was blocked by PPADS (17 μmol (kg body wt)−1 i.v.); unidentified vagal afferents were also activated. αβ‐MeATP activated carotid chemoreceptor afferents (ED50 23 ± 9 nmol), an action that was unaffected by PPADS or suramin. The results support the hypothesis that P2X receptor subtypes for ATP are associated with specific sensory nerves that form part of the homeostatic mechanism for cardiovascular and respiratory regulation and these receptors therefore have physiological, pathological and therapeutic significance.

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Introduction The field of medicine is experiencing a crisis as high levels of physician and trainee burnout threaten the pipeline of future physicians. Grit, or passion and perseverance for long-term goals, has been studied in high-performing and elite military units and found to be predictive of successful completion of training in adverse conditions. The Uniformed Services University of the Health Sciences (USU) graduates military medical leaders who make up a significant portion of the Military Health System physician workforce. Taken together, an improved understanding of the relationships between burnout, well-being, grit, and retention among USU graduates is critical to the success of the Military Health System. Materials and Methods The current study was approved by the Institutional Review Board at USU and explored these relations among 519 medical students across three graduating classes. These students participated in two surveys approximately one year apart from October 2018 until November 2019. Participants completed measures on grit, burnout, and likelihood of leaving the military. These data were then merged with demographic and academic data (e.g., Medical College Admission Test scores) from the USU Long Term Career Outcome Study. These variables were then analyzed simultaneously using structural equation modeling to examine the relationships among variables in a single model. Results Results reaffirmed the 2-factor model of grit as both passion and perseverance (or interest consistency). No significant relationships emerged between burnout and other study variables. Sustained and focused interest was predictive of less likelihood of staying in the military. Conclusion This study offers important insights into the relationship among well-being factors, grit, and long-term career planning in the military. The limitations of using a single-item measure of burnout and measuring behavioral intentions in a short time frame during undergraduate medical education highlight the importance of future longitudinal studies that can examine actual behaviors across a career lifespan. However, this study offers some key insights into potential impacts on the retention of military physicians. The findings suggest that military physicians who are most likely to stay in the military tend to embrace a more fluid and flexible medical specialty path. This is critical in expectation setting for the military to train and retain military physicians across a wide range of critical wartime specialties.