Ventilatory responses to intravenous and airway CO2 administration in anesthetized dogs

The ventilatory responses to steady-state venous CO2 loading (iv CO2) and CO2 inhalation have been observed in chloralose-urethan-anesthetized dogs. Intravenous CO2 was administered by increasing the CO2 fraction of gas ventilating a membrane gas exchanger in an arteriovenous bypass; blood flow rate was fixed at 30 ml/min. During the study, we identified a time-dependent hyperventilation in all 14 experimentally treated dogs and in 4 additional sham-treated dogs. When we tested 8 of these animals with a protocol having small progressive increments in iv CO2 loading rate, we observed a response approaching isocapnia during iv CO2 and a large hypocapnia when we returned to control conditions. The use of a randomized protocol in 6 animals demonstrated the necessity of accounting for this systematic base-line shift, because before doing so the response depended more on the passage of time than on the nature of the CO2 load. After this analytical adjustment was made, there was no significant difference between the respiratory controller gains (delta nu E/delta Paco2) for inhaled and iv CO2.     

Ventilatory responses to lung inflation and arterial CO2 in halothane-anesthetized dogs

Hypercapnia attenuates the effects of static airway pressure (Paw) on phrenic burst frequency (f) and the expiratory duration (TE) in chloralose-urethan-anesthetized dogs. Surgical removal of the carotid bodies abolishes this interaction. Since halothane anesthesia in hyperoxia greatly impairs peripheral chemoreflexes, experiments were conducted to determine whether hypercapnia would attenuate the effects of Paw on f and TE in halothane-anesthetized dogs (approximately 1.5 minimum alveolar concentration). Integrated activity of the phrenic nerve was monitored as a function of Paw (2-12 cmH2O) in a vascularly isolated left lung at varied levels of arterial PCO2 (PaCO2; 38-80 Torr) controlled by inspired gas concentrations ventilating the denervated but perfused right lung. Halothane was administered only to the right lung. The results were as follows: 1) integrated phrenic amplitude increased with PaCO2 but was unaffected by Paw; 2) f decreased as Paw increased but was not affected by PaCO2; 3) the inspiratory duration (TI) increased as PaCO2 increased but was unaffected by Paw; 4) TE increased as Paw increased but was unaffected by PaCO2; and 5) there was no phrenic response to intravenous sodium cyanide (50-100 micrograms/kg). Thus, unlike chloralose-urethan-anesthetized dogs, hypercapnia does not attenuate the effect of lung inflation on f or TE in halothane-anesthetized dogs. Furthermore, hypercapnia increases TI during halothane anesthesia, an effect found after carotid denervation but not found in intact chloralose-urethan-anesthetized dogs. It is suggested that these differences between chloralose-urethan- and halothane-anesthetized dogs may be due to functional carotid chemoreceptor denervation by halothane.     

Ventilatory responses to partial cardiopulmonary bypass at rest and exercise in dogs

We determined the role of blood flow-induced changes in CO2 load to the lungs on ventilatory control, at rest and in the steady-state of electrically induced exercise, in the anesthetized dog. A portion of the vena caval blood was diverted to the descending aorta following "arterialization" through an extracorporeal gas exchanger. Ventilation typically decreased, both at rest and during exercise (i.e., at 2 different levels of mixed venous CO2), in proportion to the CO2 loss; arterial PCO2 was consequently regulated. There were concomitant increases of the pulmonary and peripheral vascular resistance. Bilateral cervical vagosympathectomy markedly attenuated the ventilatory response at rest, thus disrupting arterial PCO2 homeostasis, but not so during exercise. The results therefore provide evidence for and support the suggestion of CO2 flow-related hyperpnea both at rest and during muscular exercise.     

Ventilatory and metabolic responses to ambient hypoxia or hypercapnia in rats exposed to CO hypoxia

Gautier, Henry, Cristina Murariu, and Monique Bonora.Ventilatory and metabolic responses to ambient hypoxia orhypercapnia in rats exposed to CO hypoxia. J. Appl. Physiol.83(1): 253-261, 1997.We have investigated at ambienttemperatures (T_am) of 25 and5°C the effects of ambient hypoxia(Hx_am; fractional inspired O₂ = 0.14) and hypercapnia(fractional inspiredCO₂ = 0.04) on ventilation (),O₂ uptake(O₂), andcolonic temperature (T_c) in 12 conscious rats before and after carotid body denervation (CBD). Therats were concomitantly exposed to CO hypoxia (Hx_CO; fractional inspired CO = 0.03-0.05%), which decreases arterial O₂ saturation by ~25-40%.The results demonstrate the following. 1) AtT_am of 5°C, in both intact andCBD rats,/O₂ islarger when Hx_am orCO₂ is associated withHx_CO than with normoxia. At T_am of 25°C, this is also thecase except for CO₂ in CBD rats. 2) AtT_am of 5°C, the changes inO₂ andT_c seem to result from additiveeffects of the separate changes induced byHx_am,CO₂, andHx_CO. It is concluded that, inconscious rats, central hypoxia does not depress respiratory activity.On the contrary, particularly whenO₂ is augmented during acold stress, both/O₂during Hx_CO and the ventilatoryresponses to Hx_am andCO₂ are increased. The mechanismsinvolved in this relative hyperventilation are likely to involvediencephalic integrative structures.

     

Ventilatory responses to specific CNS hypoxia in sleeping dogs.

Our study was concerned with the effect of brain hypoxia on cardiorespiratory control in the sleeping dog. Eleven unanesthetized dogs were studied; seven were prepared for vascular isolation and extracorporeal perfusion of the carotid body to assess the effects of systemic [and, therefore, central nervous system (CNS)] hypoxia (arterial PO(2) = 52, 45, and 38 Torr) in the presence of a normocapnic, normoxic, and normohydric carotid body during non-rapid eye movement sleep. A lack of ventilatory response to systemic boluses of sodium cyanide during carotid body perfusion demonstrated isolation of the perfused carotid body and lack of other significant peripheral chemosensitivity. Four additional dogs were carotid body denervated and exposed to whole body hypoxia for comparison. In the sleeping dog with an intact and perfused carotid body exposed to specific CNS hypoxia, we found the following. 1) CNS hypoxia for 5-25 min resulted in modest but significant hyperventilation and hypocapnia (minute ventilation increased 29 +/- 7% at arterial PO(2) = 38 Torr); carotid body-denervated dogs showed no ventilatory response to hypoxia. 2) The hyperventilation was caused by increased breathing frequency. 3) The hyperventilatory response developed rapidly (<30 s). 4) Most dogs maintained hyperventilation for up to 25 min of hypoxic exposure. 5) There were no significant changes in blood pressure or heart rate. We conclude that specific CNS hypoxia, in the presence of an intact carotid body maintained normoxic and normocapnic, does not depress and usually stimulates breathing during non-rapid eye movement sleep. The rapidity of the response suggests a chemoreflex meditated by hypoxia-sensitive respiratory-related neurons in the CNS.     

Respiratory responses to intravenous and intrapulmonary CO2 in awake dogs

Ventilatory responses to CO2 inhalation and CO2 infusion were compared in the awake dog. The CO2 was introduced directly into the systemic venous blood via a membrane gas exchanger in a femoral arteriovenous shunt circuit, and the extracorporeal blood flow, QX, was maintained constant at one of two rates: low, 0.5 l/min; or high, 2.0 l/min. A total of 13 experiments was performed in four dogs comprising 50 control and 25 inhalation and infusion observations at each of the two flow rates. Comparison of CO2-response curve slopes, S = delta V E/delta PaCO2, between CO2 inhalation and infusion showed no significant difference either within or between flow rates. The mean value of S for all conditions was 1.88 l/min per Torr with a 95% confidence interval of 1.66 -2.14. An independent additive ventilatory drive amounting to 28% of low-flow control VE was found at the highflow rate. We conclude that at constant blood flow the responses to both CO2 inhalation and infusion are hypercapnic and not significantly different.