Effects on breathing of carotid body denervation in neonatal piglets.

The purpose of these studies was to test the hypothesis that carotid chemoreceptor activity is necessary for postnatal maturation of the ventilatory control system. By using a lateral surgical access, 17 piglets were carotid body denervated (CBD) and 14 were sham denervated at 3-25 days of age. After surgery, there was no irregular breathing in any group. There was no significant hypoventilation when CBD was performed at less than 5 days of age (n = 5) and only a mild (arterial PCO(2) 5 Torr; P < 0.05) to moderate, transient (arterial PCO(2) 8 Torr; P < 0.5) hypoventilation in piglets denervated at 10-15 (n = 6) and 20-25 (n = 6) days of age, respectively. Three weeks after surgery, both breathing of a hypoxic gas mixture and jugular venous NaCN injections elicited a hyperpnea in the CBD piglets that was attenuated compared with that in sham CBD piglets. In the CBD piglets, there was no response to injections of NaCN in the carotid arteries, but there was a response to NaCN injected into the proximal descending aorta, suggesting the residual peripheral chemosensitivity was of aortic origin. Carotid chemoreceptor-intact piglets had carotid and aortic NaCN chemosensitivity by 2 days of age. The carotid response persisted for the 40 days of the study, but the aortic reflex persisted only until approximately 8 days of age. We conclude that 1) the major effect of CBD per se in neonatal piglets is age-dependent hypoventilation and 2) there is a high degree of plasticity in peripheral chemosensitivity in neonates that may contribute to minimizing the changes in breathing after CBD.     

Hypoventilation in ponies after carotid body denervation.

Seven ponies were subjected to carotid body denervation (CD) and two ponies were sham operated (S). Measurement of arterial blood gases and arterial blood and cerebrospinal fluid (CSF) acid-base balance were made prior to and 1,2,4,9, and 17 wks after surgery in unanesthetized animals. Resting ventilation and ventilatory responsiveness to hypoxia and NaCN infusion were assessed prior to and 2,9, and 17 wks after surgery. Alveolar hypoventilation in the CD ponies was marked 1-2 wk after surgery when VE and VA were reduced 40% and 10%, respectively, from control and PaCO2 was 12-15 mmHg above control. However, the effect was not nearly as great 4, 9, and 17 wk after surgery when the PaCO2 stabilized at approximately 6 mmHg above control PaCO2. Arterial blood pH was normal in the hypercapnic CD ponies, but CSF pH remained acid relative to normal throughout the 17-wk period. Changes in ventilatory responsiveness to hypoxia and NaCN tended to parallel changes in resting ventilation. These findings suggest: 1) the carotid bodies are essential in ponies to maintain normal ventilation: 2) in CD ponies peripheral chemosensitivity is partially regained at some unestablished locus; and 3) pH compensating mechanisms in chronically hypercapnic ponies function relatively better in blood than in CSF.     

Mortality after carotid body denervation in rats.

Carotid body denervation (CBD) in neonatal goats and piglets results in minimal irregular breathing and no fatalities. Redundancy and/or plasticity of peripheral chemosensitivity and a relatively mature ventilatory control system at birth may contribute to the paucity of CBD effects in these species. In the present study, we tested the hypothesis that CBD mortality would be greater in neonates of a less mature species such as the rat. We found that the mortality in rats denervated at 2-3 and 7-8 days of age was significantly higher (P < 0.05) than in sham-CBD rats. In all surviving rats, pulmonary ventilation during hypoxia was lower in CBD than in sham operated rats 2 days after denervation. In surviving rats denervated during the 7th and 8th postnatal days, there was also reduced weight gain and pulmonary ventilation during eupnea, including apneas up to 20 s in duration. However, the effects of CBD were compensated within 3 wk after denervation. Local injections of NaCN indicated that aortic chemoreceptors might have been one of the sites of recovery of peripheral chemosensitivity. We concluded that CBD has higher mortality in newborn rats than in other mammals, possibly because of the relative immaturity of these animals at birth. Nonetheless, in survivors there was enough redundancy and plasticity in the control of breathing to eventually compensate for the consequences of CBD.     

Effect of cardiac denervation on cardiorespiratory responses to exercise in goats

The purpose of this study was to determine whether intact cardiac innervation and a normal cardiovascular (CV) response are required for a normal ventilatory (VE) response to mild and moderate treadmill exercise in awake goats. Accordingly, we measured CV and respiratory responses to two levels of exercise in seven normal (N) and six cardiac-denervated (CD) goats. Evidence of surgical CD included 1) absence of a cardiac response during surgery when the left thoracic cardiac nerves, thoracic vagi, and right and left stellate ganglia were electrically stimulated, 2) total and 80% attenuation of baroreflex changes in heart rate (HR) when arterial blood pressure was raised or lowered, respectively, by infusion of vasoactive agents in awake goats, and 3) attenuation of the CV responses to exercise. At each level of exercise in the CD goats, the HR response was significantly reduced relative to the response observed before CD (P less than 0.05) and the recovery HR response was delayed. Cardiac index increased in a work rate-dependent manner in N and CD goats but was significantly lower in the CD animals (P less than 0.05). Hypotension was consistently observed during exercise following CD. There was no effect of CD on steady-state VE at any metabolic rate or on the VE-O2 uptake relationship (P greater than 0.05). The rest-to-work and work-to-work transition responses of arterial PCO2 were similar between N and CD goats, but there was a tendency toward greater hypocapnia at the exercise onset in CD goats at the highest work rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of spontaneous swallows on breathing in awake goats.

The effects of spontaneous swallows on breathing before, during, and after solitary swallows were investigated in 13 awake goats. Inspiratory (TI) and expiratory (TE) time and respiratory output were determined from inspiratory airflow [tidal volume (VT)] and peak diaphragmatic activity (Dia(peak)). The onset time for 1,128 swallows was determined from pharyngeal muscle electrical activity. During inspiration, the later the swallowing onset, the greater increase in TI and VT, whereas there was no significant effect on TE and Dia(peak). Swallows in early expiration increased the preceding TI and reduced TE, whereas later in expiration swallows increased TE. After expiratory swallows, TI and VT were reduced whereas minimal changes in Dia(peak) were observed. Phase response analysis revealed a within-breath, phase-dependent effect of swallowing on breathing, resulting in a resetting of the respiratory oscillator. However, the shift in timing in the breaths after a swallow was not parallel, further demonstrating a respiratory phase-dependent effect on breathing. We conclude that, in the awake state, within- and multiple-breath effects on respiratory timing and output are induced and/or required in the coordination of breathing and swallowing.     

Effect of body size on breathing pattern and fine-particle deposition in children.

Interchild variability in breathing patterns may contribute to variability in fine particle lung deposition and morbidity in children associated with those particles. Fractional deposition (DF) of fine particles (2-microm monodisperse, carnauba wax particles) was measured in healthy children, age 6-13 yr (n = 36), while they followed a resting breathing pattern previously determined by respiratory inductance plethysmography. Interchild variation in DF, measured by photometry at the mouth, was most strongly predicted by their tidal volume (Vt) (r =0.79, P < 0.001). Multiple regression analysis further showed that, for any given height and age, Vt increased with increasing body mass index (BMI) (P < 0.001). The overweight children (> or =95th percentile BMI) (n = 8) had twice the DF of those in the lowest BMI quartile (<25th percentile) (n = 9; 0.28 +/- 0.13 vs. 0.15 +/- 0.06, respectively; P < 0.02). In the same groups, resting minute ventilation was also significantly higher in the overweight children (8.5 +/- 2.2 vs. 5.9 +/- 1.1 l/min; P < 0.01). Consequently, the rate of deposition (i.e., particles depositing/time) in the overweight children was 2.8 times that of the leanest children (P < 0.02). Among all children, the rate of deposition was significantly correlated with BMI (r = 0.46, P = 0.004). These results suggest that increased weight in children may be associated with increased risk from inhalation of pollutant particles in ambient air.     

Effect of chronic hypoxia on cholinergic chemotransmission in rat carotid body.

Current views suggest that oxygen sensing in the carotid body occurs in chemosensory type I cells, which excite synaptically apposed chemoafferent nerve terminals in the carotid sinus nerve (CSN). Prolonged exposure in a low-oxygen environment [i.e., chronic hypoxia (CH)] elicits an elevated stimulus-evoked discharge in chemoreceptor CSN fibers (i.e., increased chemosensitivity). In the present study, we evaluated cholinergic chemotransmission in the rat carotid body in an effort to test the hypothesis that CH enhances ACh-mediated synaptic activity between type I cells and chemoafferent nerve terminals. Animals were exposed in a hypobaric chamber (barometric pressure = 380 Torr) for 9-22 days before evaluation of chemoreceptor activity using an in vitro carotid body/CSN preparation. Nerve activity evoked by ACh was significantly larger (P < 0.01) after CH, suggesting increased expression of cholinergic receptors. Approximately 80% of the CSN impulse activity elicited by ACh (100- or 1,000-microg bolus) in both normal and CH preparations was blocked by the specific nicotinic receptor antagonist mecamylamine (100 microM). CSN activity elicited by acute hypoxia or hypercapnia in normal preparations was likewise blocked (> or =80%) in the presence of 100 muM mecamylamine, but after CH the enhanced CSN activity elicited by acute hypoxia or hypercapnia was not reduced in the presence of 100 or 500 microM mecamylamine. A muscarinic receptor antagonist, atropine (10 microM), and a specific nicotinic receptor alpha7 subunit antagonist, methyllycaconatine (50 nM), blocked approximately 50% of the hypoxia-evoked activity in normal preparations but were ineffective after CH. Prolonged exposure to hypoxia appears to dramatically alter chemotransmission in the carotid body, and may induce alternative neurotransmitter mechanisms and/or electrical coupling between type I cells and chemoafferent nerve terminals.