A Respiratory Drive in Addition to the Increase in Co₂ Production at Raised Body Temperature in Rats

Abstract

Mammals that use the ventilatory system as the principal means of increasing heat loss, i.e. that pant, show two fundamental changes in the control of breathing at raised temperatures. First, alveolar ventilation increases by more than, rather than in proportion to, the increase in CO2 production. Second, hypocapnia no longer causes apnoea. Rats do not use the ventilatory system as the principal means of increasing heat loss, so we have investigated whether rats also show these two changes at raised temperatures. Breathing was detected from diaphragmatic electromyogram (EMG) activity. Anaesthesia and hyperoxia were used to minimise behavioural and hypoxic drives to ventilation and arterial PCO2 (Pa,CO2) was controlled using mechanical ventilation. At 36.6 ± 0.1 °C, breathing was absent as long as Pa,CO2 was held below a threshold level of 32.9 ± 0.7 mm Hg (n= 14) under steady‐state conditions. When body temperature in rats was raised above 37 °C, both fundamental changes in the control of breathing became apparent. First, at 39 °C the mean Pa,CO2 level during spontaneous breathing (39.6 ± 5.4 mm Hg, n= 4) fell by 3.9 ± 1.4 mm Hg (P < 0.05, Student's paired t test). Second, at 39.9 ± 0.1 °C breathing was present when mean Pa,CO2 levels were only 18.2 ± 1.5 mm Hg (n= 14), the lowest mean Pa,CO2 level we could achieve with mechanical ventilation. We calculate, however, that at 39.9 °C, the drive to breathe from the increased CO2 production alone would not sustain breathing below a Pa,CO2 level of 27.8 ± 1.4 mm Hg (n= 13). In rats at raised body temperatures therefore a respiratory drive exists that is in addition to that related to the increase in CO2 production.

The preoptic area in the hypothalamus is the source of the additional respiratory drive at raised body temperature in anaesthetised rats

“…We have also shown that the reappearance of breathing during hypocapnia at 39.9°C is not caused by the increase in COµ production at such raised temperature, or through any effect of hypocapnia on blood pressure, or through the increased affinity of haemoglobin for Oµ during hypocapnia (Boden et al 2000).…”

“…Blood pressure and ECG were recorded for 1 min periods and instantaneous heart rate and systolic, diastolic and mean blood pressures were subsequently measured over this period to calculate the overall mean blood pressure and heart rate. After 4 min of hypocapnic apnoea, Pa,COµ was increased by increasing the flow of COµ to the ventilator, at constant inflation frequency and volume, until rhythmic breathing was just detected (Boden et al 1998(Boden et al , 2000. A blood sample was taken to measure the Pa,COµ level of the apnoeic threshold, after allowing adequate time for the diaphragm to establish a stable level of EMG activity at threshold and for steady state equilibration.…”

“…Body temperature was first raised to 39°C using radiation from a 150 W infrared lamp (Boden et al 2000). Body temperature was raised only once in each rat because repeated raising and lowering of body temperature were not well tolerated.…”

“…All gas and pH measurements were made on samples of arterial blood and were corrected for the prevailing rectal temperature. Wire electrodes of stainless steel were sewn into the main body of the diaphragm and subcutaneously over the chest as described previously (Boden et al 1998(Boden et al , 2000, to measure electrical activity (EMG) of the diaphragm muscle and electrocardiogram (ECG) activity.…”

“…There is therefore no obvious requirement in rats for the existence of an additional respiratory drive from the thermoregulatory system. Nevertheless we have shown (Boden et al 2000) that, in anaesthetised rats during hyperoxia, raising body temperature to 39.9°C causes the reappearance of breathing during hypocapnia (18 ± 2 mmHg).…”