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.     

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.     

Laryngeal-receptor responses to phasic CO2 in anesthetized cats

We compared the effects ofCO₂ applied continuously andduring expiration on laryngeal-receptor activity in paralyzed,artificially ventilated and nonparalyzed, spontaneously breathing catsby using an isolated larynx, artificially ventilated to approximate anormal respiratory cycle. The majority of quiescent negative-pressure and all cold receptors were excited by 5 and 9%CO₂ applied both continuously andduring expiration. In general, quiescent positive-pressure, tonicnegative-pressure, and tonic positive-pressure receptors were inhibitedby 5 and 9% CO₂ appliedcontinuously and during expiration. There were no significantdifferences between responses to 5 and 9%CO₂ or to continuous and expiredCO₂ or between paralyzed andnonparalyzed preparations. In conclusion, laryngeal receptors respondto changes in CO₂ concentrationoccurring during a normal respiratory cycle. Because laryngeal-receptorstimulation exerts reflex effects on ventilation and upper airwaymuscle activity, these results suggest that airwayCO₂ plays a role in reflexregulation of breathing and upper airway patency.

     

Cardiovascular effects of intravenous and intracoronary administration of atrial natriuretic peptide in halothane anesthetized dogs

Cardiovascular actions of synthetic 1-28 human natriuretic peptides (hANP) were examined in dogs anesthetized with halothane. In seven closed-chest dogs a Swan-Ganz catheter was inserted for measurement of cardiac output. Intravenous infusion of increasing doses of hANP (0.1, 0.3, 0.9 microgram/kg/min) lowered mean aortic pressure without affecting heart rate significantly. Cardiac output and pulmonary wedge pressure were markedly decreased while total peripheral resistance was increased significantly. All these parameters returned to control levels after 1 hr of recovery with an 100-150ml of saline infusion to increase pulmonary capillary wedge pressure to the preinfusion value. Intracoronary infusion of hANP (0.05 and 0.1 microgram/kg/min) did not cause any significant changes in coronary flow and regional contraction. These results indicate that the hypotensive action of hANP is due to a decrease in cardiac output mediated by reduced preload but not by negative inotropic action.     

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.     

Ventilatory response during CO2 inhalation after airway anesthesia with lidocaine

Airway anesthesia with inhaled aerosolized lidocaine has been associated with increases in minute ventilation (VE) and mean inspiratory flow rate (VT/TI) during CO2 inhalation. However, it is unclear whether these increases are local effects of the anesthesia or systemic effects of absorbed and circulating lidocaine. To evaluate this 20 normal subjects were treated on separate days with aerosolized lidocaine, intravenous lidocaine, aerosolized control solution, or intravenous control solution, and the effects of each treatment on VE and VT/TI were determined and compared during room-air breathing and inhalation of 5% CO2-95% O2. None of the treatments altered VE or VT/TI during room-air breathing. Aerosolized lidocaine produced small (5.9-6.0%) increases in VE and VT/TI during CO2 inhalation, but these effects were not present after intravenous lidocaine despite equivalent lidocaine blood levels. We concluded that the increases in VE and VT/TI after aerosolized lidocaine were local effects of airway anesthesia rather than systemic effects of absorbed and circulating lidocaine.     

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.     

Pressor and tachycardic responses to intravenous substance P in anesthetized rats

Intravenous injection of 3–33 nmol/kg of substance P (SP) caused pressor and tachycardic responses in anesthetized rats. The responses were not blocked by a ganglion nicotinic receptor antagonist or by pithing. Pretreatment with reserpine blocked both responses. β-Adrenoceptor blockade attenuated only the tachycardic response, and -adrenoceptor blockade attenuated only the pressor response. These findings indicated that the effects of SP to increase blood pressure and heart rate are due to sympathetic ganglion stimulation. Studies with adrenalectomized rats showed that stimulation of the adrenals by SP contributes to both responses but makes a greater contribution to the tachycardic response. These observations raise the possibility that the tachykinin innervation of sympathetic ganglia and the adrenal medulla may be involved in the local regulation of blood pressure and heart rate.