Hypoglycaemia Modulates The Patterns Of Ventilatory Responses Evoked By Chemoreceptor Stimulation

Abstract

Hypoglycaemia (HG) evokes a counter‐regulatory response to restore arterial blood glucose levels. Additionally, HG has also been shown to evoke an increase in ventilation whilst maintaining normocapnia suggesting the ventilation remained matched to metabolism. Whilst it has been shown that HG induces an increase in CO2 sensitivity, there is a lack of data on how HG may modulate the pattern of breathing in normoxia as well as during chemoreceptor‐mediated responses. Whole body plethysmography (WBP) allows the measurement of respiratory variables in conscious unanesthetised animals under baseline conditions as well as during hypercpanic or hypoxic challenges.WBP was used to measure the ventilatory responses to air breathing (21% O2), acute hypoxia (10% O2) and hypercapnia (8% CO2) in male Wistar rats that had free access to food, were fasted overnight or were made hypoglycaemic by insulin injection. Blood glucose levels tended to be lower after fasting but not significantly (8±0.8mM vs 6.8±0.5mM), however, insulin injection did induce a significant HG (3.8±0.5mM). HG induced an increase in response to hypercapnia primarily by increasing tidal volume changes. Further, HG induced an increase in expiratory time (Te) that was abolished during hypercapnia but remained present during hypoxia with no changes in inspiratory time (TI). The TI:TE ratio increased in both hypercapnia and hypoxia, however, the magnitude of increase was only dependent on glycaemic state with hypercapnia.HG induces changes in baseline ventilation but also interacts with the response to a hypercapnic stimulus but not a hypoxic stimulus. The dependency on blood glucose levels of the TI:TE increase during hypercapnia may reflect the coordinated neuroendocrine responses seen during the counter‐regulatory response to HG and matching ventilation to an increased metabolic rate.Support or Funding InformationA. Mobley carried out this work in support of his MRes degree