Proceedings of The Physiological Society

University College Cork (2004) J Physiol 560P, PC5



Bin-Jaliah,Ismaeel ; Maskell,P D; Kumar,P ;

1. Physiology, University of Birmingham, Birmingham, United Kingdom.

Insulin-induced hypoglycaemia increases ventilation in a carotid body-dependent manner due to the associated increase in metabolic rate (Bin-Jaliah et al. 2004). As an augmentation of peripheral chemoreceptor gain may underlie exercise hyperpnoea (e.g. Weil et al. 1972), in this study we evaluated chemoreceptor sensitivity to Pa,CO2 during elevated metabolism in anaesthetized rats. Phrenic nerve activity was recorded in adult Wistar rats (300-350g) which were vagotomized, neuromuscularly blocked (pancuronium bromide; 3 mg kg-1, I.V.) and artificially ventilated (O2-enriched air); adequacy of anaesthesia was continuously monitored (Bin-Jaliah et al. 2004). The level of pulmonary ventilation (VE) was measured from integrated tracheal airflow which was varied to alter the Pa,CO2. Thus, both metabolic hyperbolae (the effect of ΔVE upon Pa,CO2) and CO2 chemosensitivity (the effect of Pa,CO2 upon phrenic nerve activity ) were assessed simultaneously. All animals were humanely killed at the end of the experiment. Data are expressed as means ± S.E.M. Insulin (0.4 U min-1 kg-1) lowered blood glucose from 8.96 ± 0.34 mmol L-1 to 3.37 ± 0.12 mmol L-1 (P < 0.0001, ANOVA; n = 8). Hypoglycaemia induced an increase in metabolism, as demonstrated by a significant elevation of the Pa,CO2 by 4.6 ± 1.2 mmHg (P < 0.01, paired t test) at a fixed (euglycaemic, eucapnic) level of VE. The CO2 chemosensitivity, measured by linear regression, was increased by more than two-fold (from 1.33 ± 0.13 V min-1 kg-1 mmHg-1 to 3.31 ± 0.28 V min-1 kg-1 mmHg-1; P < 0.0001, paired t test) by hypoglycaemia. This elevation was mediated via an increase in the inspiratory drive (VT / TI) component of each breath (from 0.030 ± 0.009 V s-1 mmHg-1 to 0.073 ± 0.021 V s-1 mmHg-1; P < 0.02, paired t test). The normalized mean metabolic hyperbolae and linear CO2 sensitivities showed that Pa,CO2 remained unchanged (37.3 ± 2.6 mmHg) during hypoglycaemia from the basal setting of 40 mmHg (P > 0.21, paired t test). Thus hypermetabolism during insulin-induced hypoglycaemia is associated with an increase of CO2 chemosensitivity which is important for the maintenance of eucapnia during hypermetabolism.

Where applicable, experiments conform with Society ethical requirements