Michael Maskrey

Ventilatory and metabolic responses to cold and hypoxia in conscious rats with discrete hypothalamic lesions

We tested the hypothesis that hypothalamic nuclei involved in thermoregulatory control could represent a site of integration of the metabolic and ventilatory response to cold and hypoxia. Electrolytic lesions were performed bilaterally under stereotaxic guide, either within the anterior or posterior hypothalamic areas of adult rats. One week later, oxygen consumption (VO2) and ventilation (VE) were measured in the conscious animals during warm (27 degrees C) or cold (12 degrees C) conditions, in normoxia (21% O2) or hypoxia (10% O2), and compared to measurements obtained in control rats, which were either intact or sham-operated. VO2, VE, and body temperature did not differ between lesioned and control rats during warm normoxia. In cold and hypoxia, singly or combined, VE/VO2 was higher in the lesioned rats, because of higher VE. The differences in the cold were mostly confined to rats with anterior lesions, whereas differences in hypoxia were mostly in rats with posterior lesions. We conclude that the integrity of the anterior and posterior hypothalamic areas is important for the proper coupling of metabolism and ventilation during cold or hypoxic stimuli.

Ventilatory response to asphyxia in conscious rats: effect of ambient and body temperatures

In many mammals the ventilatory response to hypoxia depends on ambient temperature (Ta), largely because of the hypometabolic effects of hypoxia below thermoneutrality. We questioned whether the ventilatory response to asphyxia also depends upon Ta, and the role played by metabolism and body temperature (Tb). Oxygen consumption (VO2) and pulmonary ventilation (VE) were measured in conscious rats at Ta = 27 degrees C (warm) and 11 degrees C (cold), breathing air or two levels of asphyxic gases, moderate (10% O2-4% CO2), or severe (10% O2-8% CO2), for approximately 30 min each. In the cold, the pattern of the VE response to moderate asphyxia was qualitatively similar to that seen in hypoxia alone, i.e the attained VE/VO2 was similar in warm and cold conditions, with, in the latter, a major drop in VO2 and little or no hyperpnea. During severe asphyxia, however, the VE/VO2 attained in the cold was less than in the warm, and it was accompanied by a large drop in Tb (approximately 6 degrees C). Blood gases confirmed the lower asphyxic hyperventilation in the cold. By maintaining Tb at 38 degrees C with an implanted abdominal heat exchanger, the VE/VO2 levels attained during asphyxia were the same between cold and warm conditions. We conclude that (a) the VE response to asphyxia is Ta-dependent, largely because of the hypometabolic effect of the hypoxic component in the cold, (b) during moderate asphyxia the hypercapnic component is qualitatively unimportant, and (c) with severe asphyxia the hypercapnia becomes an important contributor to the Ta-sensitivity by aggravating the decrease in Tb in the cold and lowering VE sensitivity.

Respiratory responses to combined hypoxia and hypothermia in rats after posterior hypothalamic lesions

Urethane-anaesthetised rats were exposed to hypoxia (7% O2 in N2) for 5 min periods while body core temperature (Tbc) was maintained within the normal range (37–38° C) using an abdominal heat exchanger. Animals were exposed to hypoxia and after placement of electrolytic lesions in either the anterior (n=6) or posterior hypothalamus (n=6). Neither lesion altered respiration while rats breathed air at either Tbc. At normal Tbc, rats responded to hypoxia with increased ventilation throughout the exposure period. This response was unchanged by lesions in either location. At reduced Tbc rats responded to hypoxia with an initial increase in ventilation followed by depression to below air-breathing levels. This depressive response was unchanged after anterior hypothalamic lesions but eliminated after posterior hypothalamic lesions. It is concluded that neurons either originating in the posterior hypothalamus, or passing through it, play a role in the interaction between cold and hypoxia which leads to inhibition of respiration.

Metabolism, Temperature, and Ventilation

In mammals and birds, all oxygen used (VO2) must pass through the lungs; hence, some degree of coupling between VO2 and pulmonary ventilation (VE) is highly predictable. Nevertheless, VE is also involved with CO2 elimination, a task that is often in conflict with the convection of O2. In hot or cold conditions, the relationship between VE and VO2 includes the participation of the respiratory apparatus to the control of body temperature and water balance. Some compromise among these tasks is achieved through changes in breathing pattern, uncoupling changes in alveolar ventilation from VE. This article examines primarily the relationship between VE and VO2 under thermal stimuli. In the process, it considers how the relationship is influenced by hypoxia, hypercapnia or changes in metabolic level. The shuffling of tasks in emergency situations illustrates that the constraints on VE-VO2 for the protection of blood gases have ample room for flexibility. However, when other priorities do not interfere with the primary goal of gas exchange, VE follows metabolic rate quite closely. The fact that arterial CO2 remains stable when metabolism is changed by the most diverse circumstances (moderate exercise, cold, cold and exercise combined, variations in body size, caloric intake, age, time of the day, hormones, drugs, etc.) makes it unlikely that VE and metabolism are controlled in parallel by the condition responsible for the metabolic change. Rather, some observations support the view that the gaseous component of metabolic rate, probably CO2, may provide the link between the metabolic level and VE.

Effects of decortication and carotid sinus nerve section on ventilation of the rat

The effect on ventilation of exposure to hypoxic, hypercapnic and hypoxic/hypercapnic gas mixtures was studied before and after functional decortication of intact rats and rats in which the carotid chemoreceptors had been disconnected. Unanaesthetized rats responded to both hypoxia and hypercapnia with an increase in minute ventilation (V) through increases in both frequency (f) and tidal volume (VT). Decortication led to a greater V response to CO2. This was through an effect on f, rather than VT. Carotid sinus nerve section (CSNS) caused a lessening in the V response to gas mixtures, f and VT being equally affected. Decortication, following CSNS, increased the V response but this time through increased VT rather than f. This effect on VT was not specific to any particular gas mixture. It is concluded that the carotid body chemoreceptors, together with the bulbopontine rate controller, influence the response to CO2. It is further suggested that this integration takes place in the reticular formation and is normally under some degree of inhibition from the cerebral cortex.

THERMOREGULATION IN THE BROWN NODDY (ANOUS STOLIDUS)

Abstract 1. 1. Oxygen consumption ( V O 2 ), body temperature (Tb), respiratory frequency (f) and total evaporative water loss were measured in Brown Noddies exposed to air temperatures (Ta) between −0.2 and 41.9°C, in a climatic chamber. 2. 2. The thermoneutral zone of Ta was approx. 22–37°C and the V O 2 in the thermoneutral zone (1.031 ml/g h) was 77–80% of predicted values. 3. 3. The body temperature was characterized by its lability: even within the thermoneutral zone, there was a significant correlation with Ta. 4. 4. Exposure to low Ta resulted in shivering and a maximal increase in V O 2 of 129%. The minimal thermal conductance of the tissues and plumage below the lower critical Ta was 86% of the predicted value. 5. 5. At high Ta, thermal polypnea and open-beak panting were observed but the birds did not gular flutter. In some birds evaporative heat loss exceeded concurrent metabolic heat production. 6. 6. The features of thermoregulation in adult Brown Noddies are compared with those of the hatchling and also with thermoregulation in the related Sooty Tern.

INFLUENCE OF BODY TEMPERATURE ON RESPONSES TO HYPOXIA AND HYPERCAPNIA: IMPLICATIONS FOR SIDS

1. This paper reviews current knowledge regarding interactions between body temperature and the respiratory responses to hypoxia and/or hypercapnia, with special emphasis on how these interactions might predispose towards sudden infant death syndrome (SIDS).

Effect of changing body temperature on the ventilatory and metabolic responses of lean and obese Zucker rats

We measured body temperature (Tb) and ventilatory and metabolic variables in lean (n = 8) and obese (n = 8) Zucker rats. Measurements were made while rats breathed air, 4% CO2, and 10% O2. Under control conditions, Tb in obese rats was always less than that of their lean counterparts. Obese rats adopted a more rapid, shallow breathing pattern than lean rats in air and had a lower ventilation rate in 4% CO2. Respiration in 10% O2 was similar for the two groups. Metabolic variables did not differ between lean and obese rats whatever the gas breathed. When lean rats were cooled to match Tb in control obese rats with an implanted abdominal heat exchanger, they increased ventilation and metabolism in air; there was no effect of cooling on responses to 4% CO2; and ventilation increased while metabolism decreased in 10% O2. When obese rats were warmed to match Tb in control lean rats, trends in ventilation and metabolism resulted in a tendency toward hyperventilation in air and 4% CO2, but not in 10% O2. Taken overall, matching Tb in lean and obese rats accentuated differences in respiratory and metabolic variables between the two groups. We conclude that differences in respiration between lean and obese Zucker rats are not due to the difference in Tb.We measured body temperature (Tb) and ventilatory and metabolic variables in lean ( n = 8) and obese ( n = 8) Zucker rats. Measurements were made while rats breathed air, 4% CO2, and 10% O2. Under control conditions, Tb in obese rats was always less than that of their lean counterparts. Obese rats adopted a more rapid, shallow breathing pattern than lean rats in air and had a lower ventilation rate in 4% CO2. Respiration in 10% O2 was similar for the two groups. Metabolic variables did not differ between lean and obese rats whatever the gas breathed. When lean rats were cooled to match Tb in control obese rats with an implanted abdominal heat exchanger, they increased ventilation and metabolism in air; there was no effect of cooling on responses to 4% CO2; and ventilation increased while metabolism decreased in 10% O2. When obese rats were warmed to match Tb in control lean rats, trends in ventilation and metabolism resulted in a tendency toward hyperventilation in air and 4% CO2, but not in 10% O2. Taken overall, matching Tb in lean and obese rats accentuated differences in respiratory and metabolic variables between the two groups. We conclude that differences in respiration between lean and obese Zucker rats are not due to the difference in Tb.

Phrenicotomy in the rat: Acute changes in blood gases, pH and body temperature

Adult male rats were used to compare blood gases, pH and body temperature (Tb) before and after acute bilateral phrenicotomy. Under anaesthesia a femoral artery was catheterised and ties were placed round the phrenic nerves of seven rats (PNX group), while in five rats the ties were placed in the vicinity of the phrenic nerves (SHAM group). Twenty-four hours after surgery arterial blood samples were collected during quiet wakefulness (QW) and grooming (G), before and 1 h after the ties were pulled, and analysed for PO2, PCO2 and pH. No changes were detected in the SHAM samples taken before and after the ties were pulled. In the PNX group a significant decrease in Tb occurred (QW, 0.6 degrees C; G, 1.5 degrees C). Following PNX PaO2 decreased by 11.2 mmHg (QW) and 10.0 mmHg (G); PaCO2 increased by 2.6 mmHg (QW) and 2.4 mmHg (G) and pH fell by 0.04 (QW) and 0.03 (G). All changes except in PaCO2 (QW) were significant. It is concluded that the changes in Tb, blood gases and pH which follow phrenicotomy in the rat are due to an increase in dead space ventilation (VD) and a small reduction in alveolar ventilation (VA) associated with a faster, shallower pattern of breathing.

Alteration in breathing of the awake rat after laryngeal and diaphragmatic muscle paralysis

The respiratory rate (f), tidal volume (VT) and ventilation (V) were measured in 3 groups of rats: 10 rats before and after cutting both recurrent laryngeal nerves (RLNX), 10 rats before and after bilateral phrenicotomy (PNX) and 5 sham transected (SHAMX) rats. All rats were exposed to air and gas mixtures, deficient in O2 and/or enriched with CO2. The barometric method was used to measure ventilatory parameters. The sham operation did not affect breathing pattern or ventilation. In RLNX rats, breathing the various gas mixtures exhibited no changes in V because f uniformly increased as VT declined. Therefore, loss of the neural control of the respiratory functions of the larynx in awake rats exposed to selected gas mixtures has no untoward effects on alveolar ventilation. Changes in ventilation of PNX rats, compared with SHAMX rats, depends on the gas composition breathed. With increasing severity of hypoxia and/or hypercapnia, PNX rats show a marked reduction in alveolar ventilation over that of the SHAMX rats. Thus, when the diaphragm is no longer able to participate in ventilatory responses, gas exchange is likely to become deficient.