Effects of Hyperthermia on Ventilation and Metabolism during Hypoxia in Conscious Mice

Abstract

It has been reported that hyperthermia associated with fever and heat stroke may lead to apnea and death [1], and that elevated body temperature (BT) is recorded after death in sudden infant death syndrome [2]. Thus hyperthermia is an important risk factor for cardiorespiratory disorders. Here we are concerned with hyperthermia in respect to the control of ventilation and metabolism.Thermal effects on breathing patterns have been examined by artificially increasing BT under anesthesia. The increased BT affects the rate-determining mechanism in the respiratory centers to increase the respiratory frequency ( f ), even in a range below the panting threshold in cats [3][4][5] and rabbits [6]; thus most mammals show an increase of f under elevated BT. We have also observed the BT-induced polypnea during hypercapnic conditions in mice [7]. However, the thermal effect on the ventilation under the breathing of room air or hypoxic gas is uncertain in mice.The effects of hyperthermia on ventilation under hypoxia remain misunderstood in comparison with the effects of hypothermia. In general, ventilation under acute hypoxia shows an initial augmentation and a subsequent decline, referred to as hypoxic depression, followed by hypometabolism [8,9]. Hypoxic depression lowers cellular activity by reducing cell metabolism and energy requirements, a survival mechanism for neurons and other cells. Furthermore, hypoxic hypometabolism affects the thermoregulatory set point Japanese Journal of Physiology, 54, 53-59, 2004 Key words: hyperthermia, hypoxia, ventilation, aerobic metabolism, mice.Abstract: Hyperthermia and hypoxia influence ventilation and metabolism; however, their synergistic effects remain unanswered. We hypothesized that an enhancement of ventilation induced by hyperthermia is competitive with hypoxic hypometabolism. We then examined the relationship of body temperature, hypoxia, and respiration in conscious mice, measuring minute ventilation (V E), aerobic metabolism, and arterial blood gases. All parameters were measured at two different body temperatures (BTs), approximately 37°C (normothermia) and 39°C (hyperthermia), under both normoxia (room air inhalation) and hypoxia (7% O 2 inhalation). Under normoxia, V E and O 2 consumption (V O 2 ) were lower at hyperthermia than at normothermia, and the V E-V O 2 ratio remained constant. PaCO 2 values were normal at both BTs under normoxia. Hypoxic gas inhalation increased V E, which reached a peak in 2 min, then decreased at both BTs. V E remained at a higher level during hyperthermia than during normothermia throughout the 10 min experiment. V O 2 decreased during hypoxia at both BTs. Hypoxia increased the V E-V O 2 ratio because of relatively high V E with respect to the decreased V O 2 , which means hyperventilation. At hypoxia under hyperthermia, serious hyperventilation occurred with a further increase in V E. The augmented ventilation may be due to the thermal stimulus and a lowered thermoregulatory set point for hypoxia. Thus hyperthermia reduces ventilation an...

The effects of hyperthermia and hypoxia on ventilation during low-intensity steady-state exercise

“…The response to hypoxia has also been shown to depend on the end-tidal partial pressure of carbon dioxide (PET CO 2 ) (27). Hyperthermia in resting mice elevates their HVR (14), but what has not been examined in humans is whether the concomitant increase in core temperature evident with exercise has an influence on the ventilatory response to hypoxia. To this end, we have implemented an underwater exercise method, similar to that by Park and colleagues (24) to prevent increases in core temperature during exercise.…”

Hypoxic ventilatory response during light and dark periods and the involvement of histamine H1 receptor in mice

“…In this condition, air was perfused for 30 min, and then hypoxic gas (7% O2 ϩ 3% CO2 balanced in N2) was perfused for 20 min. Hypoxic gas contained 3% CO2 to compensate for the reduction in arterial PO2 caused by "blowing off" of CO2 during elevated ventilation associated with hypoxia (16,33). Tests for hypoxic gas exposure were performed in light and dark periods.…”

Time-Dependent Ventilatory Response to Poikilocapnic Hypoxia during Light and Dark Periods and the Role of Histamine H1 Receptors in Mice

“…The HVD is most likely involved in hypocapnia following an initial increase in poikilocapnic hypoxia. Our previous study of blood gas analyses in mice revealed that PaCO 2 levels are strictly limited in poikilocapnic hypoxia [10] compared to normocapnic hypoxia [4,10] at 10 min after each hypoxic gas inhalation. Hypocapnia is more significant during the dark period than during the light because the initial increase is augmented during the dark period.…”

“…We added 3% CO 2 to the hypoxic gas to maintain a constant level of arterial PCO 2 (PaCO 2 ) [2,4,7]; this prevents hypocapnia induced by hypoxic hyperventilation [8]. Indeed, our previous blood gas analyses in mice showed PaCO 2 levels of 36-39 mmHg at 10 min after 7% O 2 inhalation adding 3% CO 2 [4, 9], but 19 mmHg at the same time after 7% O 2 inhalation [10]. However, hypoxic gas inhalation adding 3% CO 2 , augments the initial increase because of the activation of the chemoreceptor afferents responsible for changes in both PaO 2 and PaCO 2 [11].…”