Heartbeats entrain breathing via baroreceptor-mediated modulation of expiratory activity.

NEW FINDINGS: Cardio-ventilatory coupling refers to the onset of inspiration occurring at a preferential latency following the last heartbeat (HB) in expiration. According to the cardiac-trigger hypothesis, the pulse pressure initiates an inspiration via baroreceptor activation. However, the central neural substrate mediating this coupling remains undefined. Using a combination of animal data, human data and mathematical modelling, this study tests the hypothesis that the HB, by way of pulsatile baroreflex activation, controls the initiation of inspiration that occurs through a rapid neural activation loop from the carotid baroreceptors to Bötzinger complex expiratory neurons. ABSTRACT: Cardio-ventilatory coupling refers to a heartbeat (HB) occurring at a preferred latency prior to the next breath. We hypothesized that the pressure pulse generated by a HB activates baroreceptors that modulate brainstem expiratory neuronal activity and delay the initiation of inspiration. In supine male subjects, we recorded ventilation, electrocardiogram and blood pressure during 20-min epochs of baseline, slow-deep breathing and recovery. In in situ rodent preparations, we recorded brainstem activity in response to pulses of perfusion pressure. We applied a well-established respiratory network model to interpret these data. In humans, the latency between a HB and onset of inspiration was consistent across different breathing patterns. In in situ preparations, a transient pressure pulse during expiration activated a subpopulation of expiratory neurons normally active during post-inspiration, thus delaying the next inspiration. In the model, baroreceptor input to post-inspiratory neurons accounted for the effect. These studies are consistent with baroreflex activation modulating respiration through a pauci-synaptic circuit from baroreceptors to onset of inspiration.

Evaluation of core concepts of physiology in undergraduate physiology curricula: results from faculty and student surveys.

Unlike other STEM (Science, Technology, Engineering, Mathematics) disciplines, program guidelines for undergraduate physiology degree programs have yet to be firmly established. The purpose of this study was to examine the use of physiology core concepts within undergraduate physiology curricula to discern whether a common subset could be broadly recommended for inclusion in programmatic guidelines. A curricular survey tool was developed to evaluate the depth to which each core concept was included in physiology curricula. Seven self-selected physiology programs assessed core concept inclusion across all courses within the major (0 = not covered, 1 = minimally covered, and 2 = covered to a great extent). The top core concepts ranked by each institution varied considerably, but all were robustly represented across programs. The top five combined rankings for all institutions were as follows: 1) interdependence (1.47 ± 0.63); 2) structure/function (1.46 ± 0.72); 3) homeostasis (1.45 ± 0.71); 4) scientific reasoning (1.44 ± 0.70); and 5) cell-cell communication (1.38 ± 0.75). No common subset of specific core concepts was evident among the seven participating institutions. Next, results were compared with recent Physiology Majors Interest Group (P-MIG) faculty and student surveys that ascertained perceptions of the top five most important core concepts. Three core concepts (homeostasis, structure/function, cell-cell communication) appeared in the top five in more than one-half of survey questions included. We recommend that future programmatic guidelines focus on inclusion of the core concepts of physiology as general models to scaffold learning in physiology curricula, but the programmatic guidelines should allow flexibility in the core concepts emphasized based on program objectives.

Degree requirements of physiology undergraduate programs in the Physiology Majors Interest Group.

Physiology undergraduate degree programs operate in isolation relative to other biological science programs, with little to no understanding of how other institutions structure their course requirements and other degree requirements. The purpose of this report is to preliminarily describe the collective curriculum of physiology programs represented at the Physiology Majors Interest Group (P-MIG) annual meetings from 2018 to 2019. A short preconference survey was sent to attendees that inquired about degree requirements of their respective physiology programs. The requirement for Physiology I (69.2%) with laboratory (66.7%) and Anatomy I (57.1%) with laboratory (42.9%), or combined Anatomy and Physiology I (16.7%) and laboratory (18.2%), were common requirements, but many programs did not require Physiology II (27.3%) or Anatomy II (11.1%). There was nearly consensus on required prerequisites such as Biology (2 semesters with laboratories, 85.7%), Chemistry (2 semesters with laboratory, 88.9%), Physics (2 semesters with laboratory, 75%), Calculus I (61.1%), and Statistics (Biostatistics 42.9%; General Statistics 13.3%). There was less agreement among programs in regards to Calculus II (20.0%), Organic Chemistry (2 semesters, 55.6%), and Biochemistry I (47%), which may be reflective of individual department focus. There was considerable heterogeneity among physiology program course requirements for disciplinary core courses and upper division electives. This report is meant to generate discussion on physiology program curricula in efforts to improve physiology education for majors and assist P-MIG in determining minimal points of consensus as they write the first set of national curricular guidelines for degree programs.

From proposal to poster: course-based undergraduate research experience in a physiology laboratory course.

The laboratory course is an excellent venue to apply content, practice inquiry, improve critical thinking, practice key clinical skills, and work with data. The use of inquiry-based course projects allows for students to propose open ended questions, form a hypothesis, design an experiment, collect data, analyze data, draw conclusion, and present their findings. This comprehensive experience is ideal for a capstone (senior level) laboratory course that is the culmination of 4 yr of study in the degree. At Michigan State University, the capstone laboratory has incorporated a formal course-based research experience in human physiology. The rationale and logistics for running such an experience are described in this paper.

Physiology educators find community in the Physiology Majors Interest Group.

The Physiology Majors Interest Group (P-MIG) is a grass-roots consortium of physiology educators with the common interest of creating program-level guidelines for undergraduate physiology and related programs. A key component of the consortium's activities are the annual P-MIG conferences that have been held at different universities over the past 3 yr (Michigan State University, 2017; University of Arizona, 2018; and University of Minnesota, 2019). Postconference surveys indicate that the conferences are highly valued by the participants, as they have provided an opportunity to get to know others who are passionate about undergraduate education, to discuss best practices in program and course delivery, and to form working groups with the goal to develop national and international guidelines for physiology program delivery and assessment.

Role of the carotid body chemoreceptors in glucose homeostasis and thermoregulation in humans.

The carotid bodies (CBs) are multi-modal sensory organs located bilaterally at the bifurcation of the carotid artery and innervated by the carotid sinus nerve (Hering's nerve), a branch of the IX cranial nerve. While the CBs (or embryologically analogous structures) are well known as the dominant oxygen-sensing organ in vertebrates, in mammals there is evidence that the CBs may also sense glucose and temperature, and respond to circulating hormones and other factors. Additionally, the CBs likely participate in regulating baseline levels of sympathetic tone. In this brief review, we focus on the evolution of our efforts to understand 'what else' beyond oxygen sensing the CBs do in humans.

Organizing a large-scale Physiology Understanding (PhUn) Week event at a science center.

For the past 6 yr, the Department of Physiology at Michigan State University (MSU) has partnered with Impression 5 Science Center in Lansing, MI. Together, we host a day-long community engagement event on a Saturday each year in early November coinciding with the American Physiological Society's Physiology Understanding Week. The purpose was to provide a fun and memorable hands-on experience for children and families. This paper describes the detailed planning and logistics. The event takes place in the main exhibit space at the science center, generally has 15-17 physiology activities stations set up as booths run by volunteers, and the event runs as an open-house format. Three to five trained volunteers were needed per station for the full day. Since this was primarily based on undergraduate student volunteer involvement (a population already limited for time), morning, afternoon, and/or full-day shifts were offered to accommodate a variety of schedules. Additional set-up, clean-up, and general help was also recruited. Overall, ~100-150 MSU students, faculty, and staff members served as volunteers, alongside Impression 5 staff. Hosting the event at the science center generated a larger audience, aided in advertisement, and allowed for access to a large facility capable of handling the 600-1,000 attendees. The partnership facilitated the sharing of equipment and supplies for physiology demonstrations, allowed for activities on site in the chemistry laboratory space, and facilitated the growth of new community partnerships with local schools and groups who attended the event.

Physiology undergraduate degree requirements in the U.S.

Course-level learning objectives and core concepts for undergraduate physiology teaching exist. The next step is to consider how these resources fit into generalizable program-level guidelines for Bachelor of Science (BS) degrees in Physiology. In the absence of program-level guidelines for Physiology degree programs, we compiled a selective internal report to review degree requirements from 18 peer BS programs entitled "Physiology" in the United States (U.S.). There was a range of zero to three required semesters of math, physics, physics laboratory, general biology, biology laboratory, general chemistry, chemistry laboratory, organic chemistry, organic chemistry laboratory, biochemistry, biochemistry laboratory, anatomy, anatomy laboratory, core systems physiology, and physiology laboratory. Required upper division credits ranged from 11 to 31 and included system-specific, exercise and environmental, clinically relevant, pathology/disease-related, and basic science options. We hope that this information will be useful for all programs that consider themselves to be physiology, regardless of name. Reports such as this can serve as a starting point for collaboration among BS programs to improve physiology undergraduate education and best serve our students.

Effect of bilateral carotid body resection on the counterregulatory response to hypoglycaemia in humans.

NEW FINDINGS: What is the central question of this study? Hyperoxia blunts hypoglycaemia counterregulation in healthy adults. We hypothesized that this effect is mediated by the carotid bodies and that: (i) hyperoxia would have no effect on hypoglycaemia counterregulation in carotid body-resected patients; and (ii) carotid body-resected patients would exhibit an impaired counterregulatory response to hypoglycaemia. What is the main finding and its importance? Our data indicate that the effect of hyperoxia on hypoglycaemic counterregulation is mediated by the carotid bodies. However, a relatively normal counterregulatory response to hypoglycaemia in carotid body-resected patients highlights: (i) the potential for long-term adaptations after carotid body resection; and (ii) the importance of redundant mechanisms in mediating hypoglycaemia counterregulation. Hyperoxia reduces hypoglycaemia counterregulation in healthy adults. We hypothesized that this effect is mediated by the carotid bodies and that: (i) hyperoxia would have no effect on hypoglycaemia counterregulation in patients with bilateral carotid body resection; and (ii) carotid body-resected patients would exhibit an impaired counterregulatory response to hypoglycaemia. Five patients (three male and two female) with bilateral carotid body resection for glomus tumours underwent two 180 min hyperinsulinaemic, hypoglycaemic (∼ 3.3 mmol l(-1)) clamps separated by a minimum of 1 week and randomized to either normoxia (21% fractional inspired O2 ) or hyperoxia (100% fractional inspired O2). Ten healthy adults (seven male and three female) served as control subjects. Hypoglycaemia counterregulation in carotid body-resected patients was not significantly altered by hyperoxia (area under the curve expressed as a percentage of the normoxic response: glucose infusion rate, 111 ± 10%; cortisol, 94 ± 6%; glucagon, 107 ± 7%; growth hormone, 92 ± 10%; adrenaline, 89 ± 26%; noradrenaline, 79 ± 15%; main effect of condition, P > 0.05). This is in contrast to previously published results from healthy adults. However, the counterregulatory responses to hypoglycaemia during normoxia were not impaired in carotid body-resected patients when compared with control subjects (main effect of group, P > 0.05). Our data provide further corroborative evidence that the effect of hyperoxia on hypoglycaemic counterregulation is mediated by the carotid bodies. However, relatively normal counterregulatory responses to hypoglycaemia in carotid body-resected patients highlight the importance of redundant mechanisms in mediating hypoglycaemia counterregulation.

Role of the carotid body chemoreceptors in baroreflex control of blood pressure during hypoglycaemia in humans.

Activation of the carotid body chemoreceptors with hypoxia alters baroreceptor-mediated responses. We aimed to examine whether this relationship can be translated to other chemoreceptor stimuli (i.e. hypoglycaemia) by testing the following hypotheses: (i) activation of the carotid body chemoreceptors with hypoglycaemia would reduce spontaneous cardiac baroreflex sensitivity (sCBRS) in healthy humans; and (ii) desensitization of the carotid chemoreceptors with hyperoxia would restore sCBRS to baseline levels during hypoglycaemia. Ten young healthy adults completed two 180 min hyperinsulinaemic [2 mU (kg fat-free mass)(-1) min(-1)], hypoglycaemic (∼ 3.2 µmol ml(-1)) clamps, separated by at least 1 week and randomized to normoxia (arterial partial pressure of O2, 122 ± 10 mmHg) or hyperoxia (arterial partial pressure of O2, 424 ± 123 mmHg; to blunt activation of the carotid body glomus cells). Changes in heart rate, blood pressure, plasma catecholamines, heart rate variability (HRV) and sCBRS were assessed. During hypoglycaemia, HRV and sCBRS were reduced (P < 0.05) and the baroreflex working range was shifted to higher heart rates. When hyperoxia was superimposed on hypoglycaemia, there was a greater reduction in blood pressure and a blunted rise in heart rate when compared with normoxic conditions (P < 0.05); however, there was no detectable effect of hyperoxia on sCBRS or HRV during hypoglycaemia (P > 0.05). In summary, hypoglycaemia-mediated changes in HRV and sCBRS cannot be attributed exclusively to the carotid chemoreceptors; however, the chemoreceptors appear to play a role in resetting the baroreflex working range during hypoglycaemia.

Autonomic control during acute hypoglycemia in type 1 diabetes mellitus.

PURPOSE: We hypothesized that adults with type 1 diabetes mellitus (T1DM) would exhibit impaired heart rate variability (HRV), QT interval, T-wave amplitude, and baroreflex sensitivity (BRS) when compared with healthy controls. In addition, we hypothesized that acute hypoglycemia would result in further adverse changes in measures of autonomic and cardiovascular function. METHODS: A single 180-min hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic (~3.3 umol/mL) clamp was completed in 10 healthy adults and 13 adults with T1DM. Counterregulatory hormones were assessed and measures of heart rate (electrocardiogram) and blood pressure (intra-arterial catheter or finger photoplethysmography) were analyzed at baseline and during the hypoglycemic clamp for measures of HRV, QT interval, T-wave amplitude, and spontaneous cardiac BRS (sCBRS). RESULTS: Baseline measures of HRV, sCBRS, and T-wave amplitude were blunted in adults with T1DM when compared with healthy controls. Hypoglycemia resulted in significant reductions in HRV, sCBRS, and T-wave amplitude and prolonged QT intervals; these changes were not different between adults with T1DM and healthy controls. CONCLUSIONS: Results from the current study show that adults with T1DM exhibit impaired autonomic and cardiovascular function. Additionally, novel findings highlight an effect of acute hypoglycemia to further reduce measures of autonomic and cardiovascular function similarly between adults with T1DM and healthy controls. These results suggest that acute hypoglycemia may worsen impairments in autonomic and cardiovascular control in patients with T1DM, thus increasing the risk of ventricular arrhythmias and cardiovascular mortality.