Far-field recordings of short latency auditory responses in the White Leghorn chick.

Far-field recordings of short latency auditory responses were characterized in the White Leghorn chick (Gallus domesticus, 2-3 weeks post hatch). Six to twelve positive peaks were normally present within the first 8 ms following the onset of a click stimulus (stimulus intensity = 99.0 +/- 6.3 dB pe SPL, 44.3 +/- 1.2 dB SL). Both cochlear microphonic (CM) and neural response components were distinguished based on functional criteria. Neural responses (P1a-P6b) were readily masked by white noise. CM responses were resistant to masking and inverted when click polarity was reversed. Systemic cooling produced shifts in neural response latencies such that later peaks (e.g. latencies greater than or equal to P3) were delayed to a greater extent than early peaks (P1a and P2a). The latencies of CM components were relatively unaffected by cooling. The mean latencies and amplitudes were described quantitatively for dominant positive peaks. The mean auditory response threshold for 18 animals was 54.5 +/- 7 dB pe SPL. Dominant later components (P3a and the P3b/P4a complex) were the first to disappear after lethal injection of anesthetic. These were followed immediately by earlier neural peaks. CM components were the last to disappear. A working hypothesis is advanced regarding the distinction between central (P3a, P3b and P4a) and peripheral (P1a, P2a) neural components.

Simulation of sensory neuronal discharge characteristics: the effects of multiple receptor sites and sources of variability.

There is conflict in the literature concerning the effect of multiple receptive endings on sensory afferent discharge. We simulated the discharge of intrapulmonary chemoreceptors of ducks and studied the effect of numbers of receptive endings, membrane 'noise' and changes in receptor threshold and gain. We found increasing membrane noise could not account for variability in spontaneously discharging intrapulmonary chemoreceptors and that, over a wide range of amplitude of various sources of noise, increasing the number of receptive endings increased discharge frequency and precision of transduction of the stimulus by reducing variability.

Respiratory gas exchange and control in the chicken.

Gas exchange in parabronchial lungs can be described by: 1) representing the entire lung as one parabronchus, 2) solving iteratively a series of equations relating CO2 and O2 levels to the partial pressures of the gases, blood pH, and flows of gas and blood at thin sections of the parabronchus to give changes of gas pressures, and 3) integrating the changes over the parabronchus. At rest, diffusion resistance to exchange between gas and blood is a relatively small effect while ventilation/perfusion inequalities between parabronchi are responsible for most of the disequilibrium between gas and blood. Ventilation is altered to control body temperature and intrapulmonary and arterial PCO2. Chickens pant at a relatively lower respiratory frequency than mammals of comparable body weight. The respiratory time constant of hyperthermic chickens predicts maximal parabronchial ventilation at usual panting frequencies. Above this frequency, CO2 would increase from the minimum in hyperthermia, decreasing frequency of respiration. Inhaling CO2-enriched air in hyperthermia slows frequency but increases ventilation, protecting against lethally hot climates. Intrapulmonary chemoreceptors reduce ventilation if intrapulmonary PCO2 falls. Left ventricular CO2-sensitive mechanoreceptors also inhibit ventilation if PaCO2 falls or blood pressure increases. Both sensory systems may buffer respiratory gas and acid-base changes at the tissue. No known system can explain ventilation during exercise.

Intrapulmonary chemoreceptor control of ventilatory movements in the self-ventilating chicken.

The importance of intrapulmonary chemoreceptors (IPC), sensitive to PCO2 in the lung, in the control of ventilatory movements is yet to be demonstrated in the self-ventilating bird. We distinguished between the effects of PCO2 on IPC and on extrapulmonary CO2-sensitive receptors (EPC) in anaesthetized cockerels by denervating IPC in the right lung, ligating the left pulmonary artery and changing PICO2. Left IPC were thus exposed to a combination of PCO2 from inspired gas and dead space, while EPC were exposed to greatly increased arterial PCO2 resulting from the ventilation-perfusion inequality. At 0 Torr PICO2, steady state ventilatory depth and frequency did not change (P greater than 0.5) after the ligation, although PaCO2 rose by 12.2 +/- 1.7 Torr. After the ligation, ventilatory movements were more sensitive to increasing PICO2. Tracheostomy, which results in a greater decrease in PCO2 in the innervated lung after ligation, produced greater effects. We conclude that these responses were due to the strong controlling influence of IPC on ventilatory movements in the self-ventilating cockerel.

Sodium bicarbonate infusion increases discharge frequency of intrapulmonary chemoreceptors only at high CO2.

We felt that earlier determinations of independent effects of extracellular pH and PCO2 on intrapulmonary chemoreceptors (IPC) discharge frequency were difficult to analyze because they used perfused lungs, and ventilation-perfusion changes among parabronchi could not be controlled. We decided to repeat these studies in non-perfused lungs. We cannulated both extrapulmonary bronchi of 10 thoracotomized Pekin ducks anesthetized with sodium pentobarbital (25-35 mg/kg) and unidirectionally ventilated each lung. The perfused right lung maintained gas exchange while the non-perfused left lung received 0.6 L/min of CO2 mixed in air. We recorded the discharge frequency of one IPC per duck at various PCO2, re-established circulation, and infused 3.0 mmol/kg of sodium bicarbonate intravenously. After 15 min, discharge frequencies were again measured from the same IPC in the nonperfused lung. The slopes and intercepts of discharge frequencies vs ln PCO2 relationship were depressed in six IPC, increased in two IPC and not significantly affected in two IPC. Arterial pH was increased significantly (0.11 unit) at 38 Torr arterial PCO2. We conclude that acutely increased extracellular sodium bicarbonate affects IPC discharge only by depressing sensitivity of most IPC to PCO2 and does not have an independent effect through pH.

Comparison of intrapulmonary chemoreceptor response to PCO2 in the duck and chicken.

Intrapulmonary chemoreceptors (IPC) in the burrowing owl are reported to be much less sensitive to PCO2 than IPC in the chicken. This blunted IPC sensitivity has been suggested to be a physiological adaptation to hypercapnic subterranean environments. To investigate the natural variation IPC responses in non-burrowing species, stimulus-response characteristics of 87 IPC in 22 anesthetized Pekin ducks were recorded and compared to those from 54 previously reported chicken IPC. Average logarithmic stimulus response curves were described by slopes of - 11.2 and - 10.7 imp X (sec X InPCO2)-1 for duck and chicken, respectively. Each had slopes steeper than the - 6.87 imp X (sec X InPCO2)-1 slope reported for the burrowing owl. As with chicken IPC, slopes and intercepts of the individual curves were highly correlated in the duck. It appears that a general mechanism of receptor transduction exists in birds, with some quantitative interspecies variation.

Response of avian intrapulmonary chemoreceptors to venous CO2 and ventilatory gas flow.

Avian intrapulmonary chemoreceptor activity is reduced by increasing airway PCO2 from 0 to 60 torr. Using extracellular electrodes, we recorded discharge of individual intrapulmonary chemoreceptor cell bodies in the left nodose ganglion of the rooster (Gallus domesticus) during unidirectional ventilation of the lungs. All receptors recorded were in the left lung. To vary pulmonary arterial PCO2 independently of ventilation, we ventilated the two lungs separately and supplied the left pulmonary circulation with systemic arterial blood. When the PCO2 in the pulmonary arterial blood was increased, discharge frequency decreased in all 21 receptors studied. Sensitivity to pulmonary arterial PCO2 was similar to sensitivity to airway PCO2. When PCO2 of ventilatory gas was lower than that of pulmonary arterial blood, discharge frequency of the receptor increased when pulmonary blood flow was stopped. Discharge frequency also increased when PCO2 at the receptor site was lowered by increased ventilatory gas flow. We conclude that intrapulmonary chemoreceptors respond to the delivery and removal of CO2 by blood and ventilatory gas. This suggests that the receptors are located within the respiratory gas exchange region of the lung. Because these receptors have a strong inhibitory effect on ventilation, they may serve to (1) adjust minute ventilation to the rate of metabolic CO2 production and (2) to regulate individual breath size.

Pulmonary circulation--vertebral venous interconnections in the chickens.

Injections of India ink colored blood, latex, and plastic followed by study of corrosion casts and dissections were used to determine the interconnections of the vertebral venous system and pulmonary circulation in the chicken. Multiple, minute connections are found to the intercostal veins, small mesenteric veins and others connected to the vertebral venous system. Thus, blood can flow in quantities between the vertebral venous system and the pulmonary circulation depending upon pressure gradients.

Interaction of temperature with extra- and intrapulmonary chemoreceptor control of ventilatory movements in the awake chicken.

Several studies in artificially ventilated, anesthetized birds with opened thoracoabdominal cavities have shown that intrapulmonary chemoreceptors (IPC) sensitive to CO2 contribute to the control of ventilatory movements. Increasing colonic temperature (Tc) has been shown to increase depth and decrease frequency of ventilatory movements if PaCO2 is held constant at less than 35 torr in awake and anesthetized, artificially ventilated cockerels. The relative importances, though, of IPC and of extrapulmonary CO2-sensitive chemoreceptors (EPC) in controlling ventilation in the awake or hyperthermic bird is unknown. We dissociated the PCO2 affecting IPC and EPC in awake cockerels by ligating the left pulmonary artery, denervating the IPC in the right lung and artificially ventilating each lung separately. We found, that at constant PaCO2, ventilatory movements increased in depth and decreased in frequency with: (1) increasing PICO2 to the innervated, non-perfused lung (PipcCO2); and (2) increasing Tc. Similar responses were observed with increasing PaCO2 or Tc during constant PipcCO2. Multiple regression analyses show that IPC and EPC have about equal controlling influences on ventilatory movements in the awake and hyperthermic cockerel.

The alteration of CO2 respiratory sensitivity in chickens by thoracic visceral denervation.

We measured respiratory movements in nine groups of six cockerels, 20-24 weeks of age. We opened the thorax and all air sacs, and unidirectionally ventilated each lung separately. The right lung received constant P(CO2), while the P(CO2) was altered to the left lung. There were only small differences in response to P(CO2) alterations whether both pulmonary circulations were intact, the left pulmonary circulation was blocked, or the left lung was denervated and the right pulmonary circulation blocked, suggesting (1) that the extrapulonary and pulmonary P(CO2) -sensitive afferents (in one lung) have equivalent influence, and (2) the influences of the two afferent systems are not additive. Respiratory sensitivity after bilateral vagotomy is small despite pulmonary innervation by CO2 -sensitive spinal afferents, perhaps one reason for abnormal respiration after vagotomy. The respiratory influences of pulmonary vagal and spinal CO2-sensitive afferents are also non-additive, suggesting that non-additive interactions among afferents controlling respiration may be common in the chicken. Rates of response to altered intrapulmonary P(CO2) are determined by central mechanisms and not the time for CO2 distribution or receptor response.

Chicken intrapulmonary chemoreceptors: discharge at static levels of intrapulmonary carbon dioxide and their location.

We studied 54 intrapulmonary chemoreceptors in the unidirectionally ventilated left lungs of 12 thoracotomized cockerels. We ligated the left pulmonary artery to eliminate CO2 contributed by mixed venous blood. At zero PCO2 many units discharge irregularly, and some cease discharging after several seconds. Discharge frequencies at 13.7 torr PCO2 and above are described by logarithmic regressions. The slopes and intercepts of the logarithmic regressions are correlated so that the average response can be written: frequency = 3.86 -B . 1n (24.5 PCO2-1). Afferent activity above 6.8 torr PCO2 is described by 0.073 + 78.6 exp (-0.11 PCO2) -63.3 exp (-0.15 PCO2). For each unit, receptive site PCO2 in a perfused lung was assumed to be the PCO2 in the unperfused lung which gave the same discharge frequency. Location of the receptor was determined as the fraction of ventilation-perfusion region which had the same PCO2 as receptive site PCO2. Two major concentrations of receptors accounted for 85% of the total, one near the entering gas and one near the middle of the gas-exchange region. Sensitivity of individual receptors did not vary systematically with location.

Receptive fields of intrapulmonary chemoreceptors in the Pekin duck.

Reflex experiments indicate a uniform distribution of CO2 chemosensitivity in avian lungs, but neural recording experiments suggest a non-uniform distribution of intrapulmonary chemoreceptor (IPC) endings. To reconcile these observations, blood gases and PECO2 were measured while recording discharge frequencies of 32 IPC innervating the unidirectionally ventilated lungs of 14 Pekin ducks. IPC discharge frequencies, recorded from the left vagus, were determined while ventilating the perfused left lung with caudocranial and craniocaudal flows of 1% CO2 in air, and then while ventilating the unperfused left lung with known levels of CO2 in air. Lung PCO2 profiles were predicted using an eight-compartment computer model of cross-current gas exchange with log-normal ventilation-perfusion inequality and shunt. The PCO2 profiles and IPC discharge frequencies were used to calculate receptor location. At the 99% confidence limit, estimates of IPC location changed significantly in all but 7 IPC when the direction of ventilation was reversed, indicating many IPC have multiple endings. Eighteen of 32 IPC had receptive fields extending at least 50% of the parabronchial length, which may explain the uniform reflex chemosensitivity to intrapulmonary CO2 noted by others.

Ventilatory response to the PCO2 profile in chicken lungs.

We investigated the influence of intrapulmonary chemoreceptors (IPC) on ventilatory movements in anesthetized chickens when PCO2 profiles along the parabronchi were changed. In all experiments the right lung was denervated, both lungs unidirectionally ventilated, and PaCO2 kept constant. In series 1 (7 birds), gas flow and the PCO2 profile in the left lung were reversed. PaCO2, PECO2 and ventilatory movements did not change. In Series 2 (4 birds), PCO2 in caudal regions of the innervated lung was elevated by increasing gas flow and P1CO2 from 0 to 21 Torr. Ventilatory movements did not change. In Series 3 (4 birds), either lung was over-ventilated with 7 or 49 Torr P1CO2, alternating the gases between lungs every 100 sec. Ventilatory movements changes with P1CO2 but much less than predicted from P1CO2 effects in the non-perfused, innervated lung. From the longitudinal distribution of IPC and PCO2 profiles in the lung we predicted moderate to large changes in ventilatory movements in all series. The discrepancy between predicted and observed results in Series 1 and 2 indicates that IPC in caudal regions of the lung have little effect on ventilation under the conditions examined. In Series 3, observed ventilatory movements were less sensitive to P1CO2 than predicted, indicating that IPC sense a different PCO2 than the PCO2 profile in the parabronchial lumen and that IPC have a significant sensitivity to pulmonary blood PCO2.