Mathematical analysis of tissueP_{O_2 } distribution in the cat carotid body

The PO2 histogram of the carotid body tissue was calculated on the basis of a microscopical serial reconstruction, published physiological data, and a mathematical model. The calculation was made for glomoid as the subunit of the carotid body and the total organ by varying the following parameters: arterial PO2, oxygen consumption, hematocrit, diameter of the vessels, perfusion pressure, and capillary length. The results provide explanations for differences in the literature about the tissue PO2 distribution in the cat carotid body. Differences in the capillary length of the carotid bodies seem to be the main reason for different PO2 histograms. Furthermore, it is shown that the local flow velocities in the carotid body are in the range of local flow velocities known from other organs.     

The relation between carotid body chemoreceptor discharge, carotid sinus pressure and carotid body venous flow

1. Activity in forty-two single chemoreceptor afferent fibres from the carotid body in thirty-nine cats was measured when the carotid body was naturally and artificially perfused. In nine of these cats, carotid body venous flow was also measured.     

Observations on carotid body chemoreceptor activity and cervical sympathetic discharge in the cat

1. Parallel recordings have been made of the cervical sympathetic and carotid body chemoreceptor activity in the anaesthetized cat.

2. The sympathetic activity remains remarkably constant while the chemoreceptor activity is varied by changes in the blood gas tensions of relatively short duration.

3. Changes in intrathoracic pressure by obstruction to the airway or thoracic compression were associated with changes in the activity of both nerves.

4. It is likely that, under normal conditions, the sympathetic nervous activity provides a stable vasomotor tone within the carotid body.

     

A theoretical analysis of the carotid body chemoreceptor response to O2 and CO2 pressure changes

A simple mathematical model of the carotid body chemoreceptor response is presented. The model assumes that the static chemoreceptor characteristic depends on oxygen saturation in the arterial blood and on CO2 arterial concentration. The values of O2 saturation and of CO2 concentration are computed, from pressure, using blood dissociation curves, which include both the Bohr and Haldane effects. Moreover, the O2-CO2 static responses interact via a multiplicative term followed by an upper saturation. The dynamic response includes a term depending on the time derivative of CO2 concentration and a low-pass filter, which accounts for the time required to reach the steady state level. With a suitable choice of its parameters, the model reproduces the carotid chemoreceptor response under a variety of combined O2 and CO2 stimuli, both in steady state conditions and in the transient period following acute CO2 or O2 pressure changes. In particular, simulations show that if two hypercapnic stimuli are given in rapid succession, the response to the second stimulus is weaker than the first. Moreover, during transient conditions the effect of CO2 pressure changes prevail over the effect of O2 changes, due to the intrinsic derivative component of the response to CO2. In conclusion, the model allows present knowledge about chemoreceptor activity to be summarized in a single theoretical framework. In perspective, it may be used as an afferent block within large-scale models of the overall cardio-respiratory control system.     

The effects of blood osmolality changes on cat carotid body chemoreceptors in vivo

The possibility that carotid chemoreceptors respond to changes in plasma osmolality was investigated in the cat, perfusing the carotid artery with blood made hyper- or hypo-osmotic and recording chemoreceptor activity from carotid nerve fibers. Blood made hyperosmotic with sucrose or NaCl reduced the chemoreceptor discharge, while hypoosmotic blood increased chemoreceptor activity. The minimal osmolality variation necessary to obtain a detectable frequency change was 3–8% of the control. Frequency changes of 30% of the control were obtained with a 20% variation in osmolality. The frequency variations produced by the osmotic changes lasted as long as the infusion was maintained (up to 15 min). In some instances a rebound was observed when iso-osmotic saline was perfused again. A transient change in frequency and a clear rebound were obtained when blood made hyperosmotic with glycerol was perfused. These effects probably reflect a rapid change in intracellular osmolality due to the free passage of glycerol across cellular membranes.The modifications in chemoreceptor activity consecutive to osmolality variations are the opposite of those observed in isolated and superfused carotid bodies. As it is known that osmolality values affect the smooth muscle of the blood vessels, we conclude that our results are mainly produced by changes in carotid body blood flow due to a direct effect of hyper- and hypo-osmotic solutions on vascular muscle tone. Chemoreceptor excitation during a decrease in blood osmolality may contribute reflexly to the increased vascular resistance observed during acute osmolality reductions in man.     

Respiratory oscillations of the arterialP_{{\text{O}}_{\text{2}} } and their effects on the ventilatory controlling system in the cat

The respiratory oscillations of the arterial were measured in paralyzed, artificially ventilated cats by a small (1.2 mm) fast-responding catheter oxygen electrode. The amplitude of these oscillations could be changed independently of the mean by a specially designed respirator circuit. was shown to increase with increasing tidal volume or decreasing frequency of the respirator, and with increasing mean . The amplitude of the oscillations was attenuated considerably from the left atrium to the aorta. No attenuation occurred from the aorta to the carotid artery, provided that the blood flow in the carotid artery was not impeded. The measured attenuation of the oscillations was compared to that calculated by Yokota and Kreuzer (1973) and found to be quite different.The output of the ventilatory controlling system of the cat was measured from the quantified phrenic nerve activity. When only was changed at a constant level mean , the quantified phrenic nerve activity did not change, indicating that the amplitude of the oscillations does not influence the ventilatory controlling system.In vagotomized animals, the periodicities of the oscillations and the phrenic nerve activity were completely dissociated. From the fact that no Cheyne-Stokes type of breathing occurred, it was concluded that the effect of timing is negligible.     

Observations on the rhythmic variation in the cat carotid body chemoreceptor activity which has the same period as respiration

1. The activity in carotid body chemoreceptor afferent fibres in the cat has been recorded and found to have a rhythm with the same period as respiration.

2. This rhythm is not an artifact; it is not due to arterial pressure changes with respiration nor to cyclical changes in pulmonary venous admixture. It is caused by changes in blood gas tensions during each respiratory cycle.

3. The amplitude of the rhythm is modified by transient and long-term changes in inspired oxygen or CO₂ so that a rise or fall in O₂ or CO₂ tensions of arterial blood (P_a,O2, P_a,CO2) from the physiological range reduces it. The ratio of the rhythm amplitude to the mean rate of chemoreceptor discharge increases with P_a,O2 over the range 40-240 mm Hg.

4. The rhythm is modified by changes in respiratory frequency and volume.

5. The fluctuations of arterial oxygen tension which have the same period as respiration are shown to be conducted up the vertebral artery at least as far as the vertebro-occipital anastomosis.

6. It is proposed that the chemoreceptor rhythm reflects the moment to moment changes in blood gas tensions.

     

Kinetics of pulmonary \dot{V} \hbox{O}_{2} and femoral artery blood flow and their relationship during repeated bouts of heavy exercise

The mechanism that alters the pulmonary response to heavy-intensity exercise following prior heavy exercise has been frequently ascribed to an improvement in pre-exercise blood flow (BF) or O₂ delivery. Interventions to improve O₂ delivery have rarely resulted in a similar enhancement of However, the actual limb blood flow and dynamics in the second bout of repeated exercise remain equivocal. Seven healthy female subjects (21–32 years) performed consecutive 6-min (separated by 6 min of 10 W exercise) bilateral knee extension (KE) exercise in a semisupine position at a work rate halfway between the lactate threshold (LT) and peak. Femoral artery blood flow (FBF) was measured by Doppler ultrasound simultaneously with breath-by-breath each protocol being repeated at least four times for precise kinetic characterization. The effective time-constant (τ′) of the response was reduced following prior exercise (bout 1: 61.0 ±10.5 vs. bout 2: 51.6±9.0 s; mean ± SD; P<0.05), which was a result of a reduced slow component (bout 1: 16.0±8.0 vs. bout 2: 12.5±6.7 %; P<0.05) and an unchanged ‘primary’ τ. FBF was consistently faster than However, there was no bout-effect on τ′ FBF (bout 1: 28.2±12.0 vs. bout 2: 34.2±8.5 s). The relationship between the exercise-associated (i.e., ) and Δ FBF was similar between bouts, with a tendency (N.S: P>0.05) for to be increased during the transition to bout 2 rather than decreased, as hypothesized. The return of kinetics toward first order, therefore, was associated with an ‘appropriate’, not enhanced, BF to the working muscles. Whether a relative prior-hyperemia in bout 2 enables a more homogeneous intramuscular distribution of BF and/or metabolic response is unclear, however, these data are consistent with events more proximal to the exercise muscle in mediating the response during repeated heavy-intensity KE exercise.     

Respiratory response to arterial H+ at different levels of arterialP_{{\text{CO}}_{\text{2}} } during hyperoxia or hypoxia

Summary Experiments were carried out in 12 dogs anesthetized with halothane of constant alveolar concentration (mean: 0.89%). The ventilatory response to arterial with hyperoxia was determined in metabolic acidosis (by infusion of 0.5 N HCl solution). The ventilatory response to arterial with constant hypoxia (about 50 mm Hg arterial ) was determined in both metabolic acidosis and alkalosis (by infusion of 1 M NaHCO₃ solution).The arterial H⁺-ventilation response curve was obtained at different constant levels of by simultaneous analysis of the -H⁺ diagram and the -ventilation response curve. Ventilation in hyperoxia was largely dependent on if acid-base balance was near normal, but became independent of and dependent on arterial H⁺ as this increased. It was postulated that this was partly due to the negative interaction between and H⁺. The H⁺-ventilation response curves showed the same pattern in hypoxia, but only on the alkalotic side. However, with hypoxia in the range of normal to acidotic condition, control of ventilation was mainly dependent on H⁺ and independent of ; this implies an interaction between hypoxia and H⁺ at the peripheral chemoreceptors.