Involvement of ventral medullary surface in respiratory responses induced by 2,4-dinitrophenol

We examined the contribution of the neural elements near the ventral medullary surface (VMS) to the respiratory response caused by 2,4-dinitrophenol (DNP). Two series of experiments were performed on 12 vagotomized and sinoaortic denervated cats. The first series examined the effect of focal cooling of the VMS on the respiratory response to DNP in four spontaneously breathing, anesthetized cats. When the VMS temperature was 37 degrees C, systemic administration of DNP increased minute ventilation under nearly isocapnic conditions, and focal cooling of the intermediate area of VMS to 20 degrees C attenuated the ventilatory augmentation caused by DNP. To eliminate the influence of anesthetics, a second group of experiments was performed on eight decerebrate, artificially ventilated cats while phrenic nerve activity was monitored as an index of respiration. AgNO3 (10%) was topically applied to the VMS until the respiratory response to inhaled CO2 was abolished. Apnea occurred in seven of eight cats after AgNO3, whereas in the remaining one animal, tidal phrenic activity decreased substantially. Systemic administration of DNP produced no respiratory excitation in any of the animals. On the other hand, rhythmic respiratory activity could be provoked by electrical stimulation of the mesencephalic locomotor area and carotid sinus nerve and by excitation of somatic afferents. Histological examination of the brain stem showed that the AgNO3 had penetrated no more than 350 microns from the ventral medullary surface. These results indicate superficial structures of the VMS are of potential importance in mediating the respiratory responses to hypermetabolism.     

Effect of N-methyl-D-aspartate applied to the ventral surface of the medulla on the trachea

Structures located near the ventral surface of the medulla (VMS) affect both cardiovascular tone and respiratory activity. In addition cooling the intermediate area of the VMS blocks the increases in parasympathetic activity and tracheal tone resulting from ventilation with hypercapnic or hypoxic gas mixtures, or due to stimulation of mechanoreceptors within the lung. Since cooling the surface of the VMS may affect fibers of passage as well as cell bodies, we performed studies in which pledgets containing N-methyl-D-aspartic acid (NMDA), a synthetic excitatory amino acid, were applied to intermediate area of the VMS. The studies were performed in chloralose-anesthetized, artificially ventilated cats. Application of pledgets containing NMDA (10(-7) mol at 10(-3) M) caused increases in tracheal pressure and the onset of phasic phrenic activity, but application of 10(-8) mol at 10(-4) M of NMDA could produce tracheal constriction without the appearance of phasic phrenic activity. Applying to the entire VMS either 2-amino-5-phosphonovalerate (2-APV, 10(-6) M), a specific antagonist to NMDA, or lidocaine (2%), a local anesthetic, 60 s before the application of pledgets containing NMDA, prevented the increase in tracheal tone and phasic phrenic activity. Intravenous administration of atropine methyl nitrate 0.5 mg/kg, a cholinergic antagonist, blocked tracheal responses to local application of pledgets containing NMDA but did not affect the increase in phasic phrenic nerve activity. These findings suggest that when stimulated, neurons near the surface of the VMS in the vicinity of the intermediate area increase the activity of parasympathetic fibers to the airway.     

State influences on ventral medullary surface and physiological responses to sodium cyanide challenges.

Intravenous sodium cyanide (NaCN) administration lowers ventral medullary surface (VMS) activity in anesthetized cats. Sleep states modify spontaneous and blood pressure-evoked VMS activity and may alter VMS responses to chemoreceptor input. We studied VMS activation during peripheral chemoreceptor stimulation by intravenous NaCN using optical procedures in six cats instrumented for recording sleep physiology during sham saline and control site trials. Images of scattered 660-nm light were collected at 50 frames/s with an optical device after 80-100 microg total bolus intravenous NaCN delivery during waking and sleep states. Cyanide elicited an initial ventilatory decline, followed by large inspiratory efforts and an increase in respiratory rate, except in rapid eye movement sleep, in which an initial breathing increase occurred. NaCN evoked a pronounced decrease in VMS activity in all states; control sites and sham injections showed little effect. The activity decline was faster in rapid eye movement sleep, and the activity nadir occurred later in waking. Sleep states alter the time course but not the extent of decline in VMS activity.     

Age differences in responsiveness of brainstem chemosensitive neurons to extracellular pH changes

The sensitivity of neurons in the caudal chemosensitive area on the ventrolateral surface of the medulla oblongata (VMS) to extracellular pH changes was examined in newborn and young developing kittens and compared to that of adult cats. The pH was varied by superfusion of the VMS with mock cerebrospinal fluid (CSF) of pH 7.4 (control), 7.0 (acid) and 7.8 (alkaline). A total of 97 neuronal units in the three age groups changed their firing rates inversely in response to extracellular fluid (ECF) pH changes. The greatest sensitivity was found in the adult group where acid superfusion caused an increase in neuronal activity. The least sensitivity was observed in the newborn group (1-6 days old), whereas the young kitten group (4-6 weeks old) exhibited an intermediate sensitivity. Neurons of kittens older than 7 weeks of age demonstrated a response pattern characteristic of the adult group. Neurons of neonates older than seven days, exhibited a response pattern characteristic of the young kitten group.     

Naloxone-induced enhancement of carbon dioxide stimulated respiration

In unanesthetized rats, naloxone (5 mg/kg, s.c.) produced an increase in both respiratory frequency and tidal volume as compared to saline administered animals. Maximal respiratory stimulation was observed within 5 minutes after naloxone injection and duration of the response was greater than 30 minutes. Exposure to different atmospheres of carbon dioxide potentiated the increase in ventilation in a step-wise manner as the carbon dioxide concentration was increased. Pretreatment with low doses of morphine sulfate (2 mg/kg daily for 2 days) or naloxone HCl (5 mg/kg daily for 5 days) enhanced respiratory stimulation induced by naloxone. It was concluded that naloxone increases the sensitivity of central ventilatory response to carbon dioxide as a result of displacement of endogenous endorphins from central opioid receptors.     

Ventilatory effects of impaired glial function in a brain stem chemoreceptor region in the conscious rat.

Glia are thought to regulate ion homeostasis, including extracellular pH; however, their role in modulating central CO2 chemosensitivity is unclear. Using a push-pull cannula in chronically instrumented and conscious rats, we administered a glial toxin, fluorocitrate (FC; 1 mM) into the retrotrapezoid nucleus (RTN), a putative chemosensitive site, during normocapnia and hypercapnia. FC exposure significantly increased expired minute ventilation (VE) to a value 38% above the control level during normocapnia. During hypercapnia, FC also significantly increased both breathing frequency and expired VE. During FC administration, maximal ventilation was achieved at approximately 4% CO2, compared with 8-10% CO2 during control hypercapnic trials. RTN perfusion of control solutions had little effect on any ventilatory measures (VE, tidal volume, or breathing frequency) during normocapnic or hypercapnic conditions. We conclude that unilateral impairment of glial function in the RTN of the conscious rat results in stimulation of respiratory output.     

Spinal cord injury-induced changes in breathing are not due to supraspinal plasticity in turtles (Pseudemys scripta)

After occurrence of spinal cord injury, it is not known whether the respiratory rhythm generator undergoes plasticity to compensate for respiratory insufficiency. To test this hypothesis, respiratory variables were measured in adult semiaquatic turtles using a pneumotachograph attached to a breathing chamber on a water-filled tank. Turtles breathed room air (2 h) before being challenged with two consecutive 2-h bouts of hypercapnia (2 and 6% CO2 or 4 and 8% CO2). Turtles were spinalized at dorsal segments D8-D10 so that only pectoral girdle movement was used for breathing. Measurements were repeated at 4 and 8 wk postinjury. For turtles breathing room air, breathing frequency, tidal volume, and ventilation were not altered by spinalization; single-breath (singlet) frequency increased sevenfold. Spinalized turtles breathing 6-8% CO2 had lower ventilation due to decreased frequency and tidal volume, episodic breathing (breaths/episode) was reduced, and singlet breathing was increased sevenfold. Respiratory variables in sham-operated turtles were unaltered by surgery. Isolated brain stems from control, spinalized, and sham turtles produced similar respiratory motor output and responded the same to increased bath pH. Thus spinalized turtles compensated for pelvic girdle loss while breathing room air but were unable to compensate during hypercapnic challenges. Because isolated brain stems from control and spinalized turtles had similar respiratory motor output and chemosensitivity, breathing changes in spinalized turtles in vivo were probably not due to plasticity within the respiratory rhythm generator. Instead, caudal spinal cord damage probably disrupts spinobulbar pathways that are necessary for normal breathing.     

Decreased CSF pH at ventral brain stem induces widespread c-Fos immunoreactivity in rat brain neurons.

Physiological evidence has indicated that central respiratory chemosensitivity may be ascribed to neurons located at the ventral medullary surface (VMS); however, in recent years, multiple sites have been proposed. Because c-Fos immunoreactivity is presumed to identify primary cells as well as second- and third-order cells that are activated by a particular stimulus, we hypothesized that activation of VMS cells using a known adequate respiratory stimulus, H(+), would induce production of c-Fos in cells that participate in the central pH-sensitive respiratory chemoreflex loop. In this study, stimulation of rostral and caudal VMS respiratory chemosensitive sites in chloralose-urethane-anesthetized rats with acidic (pH 7.2) mock cerebrospinal fluid induced c-Fos protein immunoreactivity in widespread brain sites, such as VMS, ventral pontine surface, retrotrapezoid, medial and lateral parabrachial, lateral reticular nuclei, cranial nerves VII and X nuclei, A(1) and C(1) areas, area postrema, locus coeruleus, and paragigantocellular nuclei. At the hypothalamus, the c-Fos reaction product was seen in the dorsomedial, lateral hypothalamic, supraoptic, and periventricular nuclei. These results suggest that 1) multiple c-Fos-positive brain stem and hypothalamic structures may represent part of a neuronal network responsive to cerebrospinal fluid pH changes at the VMS, and 2) VMS pH-sensitive neurons project to widespread regions in the brain stem and hypothalamus that include respiratory and cardiovascular control sites.     

Breathing hypoxic gas affects the physiology as well as the diving behaviour of tufted ducks

We measured the effects of exposure to hypoxia (15% and 11% oxygen) and hypercapnia (up to 4.5% carbon dioxide) on rates of respiratory gas exchange both between and during dives in tufted ducks, Aythya fuligula, to investigate to what extent these may explain changes in diving behaviour. As found in previous studies, the ducks decreased dive duration (t(d)) and increased surface duration when diving from a hypoxic or hypercapnic gas mix. In the hypercapnic conditions, oxygen consumption during the dive cycle was not affected. Oxygen uptake between dives was reduced by only 17% when breathing a hypoxic gas mix of 11% oxygen. However, estimates of the rate of oxygen metabolism during the foraging periods of dives decreased nearly threefold in 11% oxygen. Given that tufted ducks normally dive well within their aerobic dive limits and that they significantly reduced their t(d) during hypoxia, it is not at all clear why they make this physiological adjustment.     

Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats

Spinal cord hemisection at C2 (C2HS) severs bulbospinal inputs to ipsilateral phrenic motoneurons causing transient hemidiaphragm paralysis. The spontaneous crossed-phrenic phenomenon (sCPP) describes the spontaneous recovery of ipsilateral phrenic bursting following C2HS. We reasoned that the immediate (next breath) changes in tidal volume (V(T)) induced by ipsilateral phrenicotomy during spontaneous breathing would provide a quantitative measure of the contribution of the sCPP to postinjury V(T). Using this approach, we tested the hypothesis that the sCPP makes more substantial contributions to V(T) when respiratory drive is increased. Pneumotachography was used to measure V(T) in anesthetized, spontaneously breathing adult male rats at intervals following C2HS. A progressive increase in V(T) (ml/breath) occurred over an 8 wk period following C2HS during both poikilocapnic baseline breathing and hypercapnic respiratory challenge (7% inspired CO(2)). The sCPP did not impact baseline breathing at 1-3 days postinjury since V(T) was unchanged after ipsilateral phrenicotomy. However, by 2 wk post-C2HS, baseline phrenicotomy caused a 16 ± 2% decline in V(T); a comparable 16 ± 4% decline occurred at 8 wk. Contrary to our hypothesis, the phrenicotomy-induced declines in V(T) (%) during hypercapnic respiratory stimulation did not differ from the baseline response at any postinjury time point (all P > 0.11). We conclude that by 2 wk post-C2HS the sCPP makes a meaningful contribution to V(T) that is similar across different levels of respiratory drive.     

Influence of the ventral surface of the medulla on tracheal responses to CO2

These studies investigated the role of the intermediate area of the ventral surface of the medulla (VMS) in the tracheal constriction produced by hypercapnia. Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. Airway responses were assessed from pressure changes in a bypassed segment of the rostral cervical trachea. Hyperoxic hypercapnia increased tracheal pressure and phrenic nerve activity. Intravenous atropine pretreatment or vagotomy abolished the changes in tracheal pressure without affecting phrenic nerve discharge. Rapid cooling of the intermediate area reversed the tracheal constriction produced by hypercapnia. Graded cooling produced a progressive reduction in the changes in maximal tracheal pressure and phrenic nerve discharge responses caused by hypercapnia. Cooling the intermediate area to 20 degrees C significantly elevated the CO2 thresholds of both responses. These findings demonstrate that structures near the intermediate area of the VMS play a role in the neural cholinergic responses of the tracheal segment to CO2. It is possible that neurons or fibers in intermediate area influence the motor nuclei innervating the trachea. Alternatively, airway tone may be linked to respiratory motor activity so that medullary interventions that influence respiratory motor activity also alter bronchomotor tone.     

Negative arterial-mixed expired PC02 gradient during acute and chronic hypercapnia.

In resting conscious dogs physiological dead space was calculated using the Bohr equation and measurements of arterial and mixed expired carbon dioxide tension. Whenever dogs inhaled carbon dioxide mixtures (5-10%) that had normal or low oxygen concentrations, the calculated dead space became negative. This paradox was based on the fact that the mixed expired carbon dioxide tension in resting hypercapnic dogs. Under these circumstances carbon dioxide was produced from the lung as measured by gas analyses and blood analyses. By the lung as measured by gas analyses and blood analyses. By reasoning this implies that "alveolar" carbon dioxide tension was higher than pulmonary venous carbon dioxide tension. The negative carbon dioxide gradient persisted at 14 days of chronic hypercapnia and reverted to normal within 10 min of breathing air after chronic hypercapnia. These findings suggest that the exchange of carbon dioxide in the lung cannot be explained solely on the basis of passive diffusion.     

Chronic hypoxia and chronic hypercapnia differentially regulate an NMDA-sensitive component of the acute hypercapnic ventilatory response in the cane toad (<Emphasis Type="Italic">Rhinella marina</Emphasis>)

This study addressed the hypotheses that exposure to chronic hypoxia (CH) and chronic hypercapnia (CHC) would modify the acute hypercapnic ventilatory response in the cane toad (Rhinella marina; formerly Bufo marinus or Chaunus marinus) and its regulation by NMDA-mediated processes. Cane toads were exposed to 10 days of CH (10% O₂) or CHC (3.5% CO₂) followed by acute in vivo hypercapnic breathing trials, conducted before and after an injection of the NMDA-receptor channel blocker, MK801 into the dorsal lymph sac. CH, CHC and MK801 did not alter ventilation under acute normoxic normocapnic conditions. CH blunted the increase in breathing frequency during acute hypercapnia while CHC had no effect. The effect of CH on breathing frequency was mediated by a decrease in the number of breaths per breathing episode. Neither CH nor CHC altered breath area (volume). MK801 augmented breathing frequency (via an increase in breaths per episode) and total ventilation during acute hypercapnia in control toads and toads exposed to CH; there was no effect of MK801 on the increase in breathing frequency or total ventilation, during acute hypercapnia in toads exposed to CHC. The results indicate that CH and CHC differentially alter breathing pattern. Furthermore, they indicate an absence of NMDA-mediated glutamatergic tone during normoxic normocapnia but that NMDA-mediated processes attenuate the increase in breathing frequency during acute hypercapnia under control conditions and following CH but not following CHC. Given that MK801 was administered systemically, the effects could be acting anywhere in the reflex pathway from CO₂-sensing to respiratory motor output.     

The influence of a respiratory acidosis on the exercise blood lactate response

The purpose of the present study was to examine the influence of a respiratory acidosis on the blood lactate (La) threshold and specific blood La concentrations measured during a progressive incremental exercise test. Seven males performed three step-incremental exercise tests (20 W.min-1) breathing the following gas mixtures; 21% O2 balance-nitrogen, and 21% O2, 4% CO2 balance-nitrogen or balance-helium. The log-log transformation of La oxygen consumption (VO2) relationship and a 1 mmol.l-1 increase above resting values were used to determine a La threshold. Also, the VO2 corresponding to a La value of 2 (La2) and 4 (La4) mmol.l-1 was determined. Breathing the hypercapnic gas mixtures significantly increased the resting partial pressure of carbon dioxide (PCO2) from 5.6 kPa (42 mm Hg) to 6.1 kPa (46 mm Hg) and decreased pH from 7.395 to 7.366. During the incremental exercise test, PCO2 increased significantly to 7.2 kPa (54 mm Hg) and 6.8 kPa (51 mm Hg) for the hypercapnic gas mixtures with nitrogen and helium, respectively, and pH decreased to 7.194 and 7.208. In contrast, blood PCO2 decreased to 4.9 kPa (37 mm Hg) at the end of the normocapnic exercise test and pH decreased to 7.291. A blood La threshold determined from a log-log transformation [1.20 (0.28) l.min-1] or as an increase of 1 mmol.l-1 [1.84 (0.46) l.min-1] was unaffected by the acid-base alterations. Similarly, the VO2 corresponding to La2 and La4 was not affected by breathing the hypercapnic gas mixtures [2.12 (0.46) l.min-1 and 2.81 (0.52) l.min-1, respectively].(ABSTRACT TRUNCATED AT 250 WORDS)     

Synergism between cocaine and atropine at the caudal ventrolateral medulla of cats

We have previously reported that the anticholinergic properties of cocaine may be important in cocaine induced apneusis. We have studied the effects of the cholinergic muscarinic antagonist atropine (ATR) on cocaine induced apneusis at the caudal chemosensitive areas of the ventrolateral medulla oblongata (CVLM). Experiments were performed in urethane anesthetized and tracheotomized cats with the CVLM surgically exposed. Topical application of ATR (44 mM ) to the CVLM produced significant decrements in minute ventilation (V(E)) and mean arterial blood pressure (MABP) (P<0.05) but the effects on tidal volume (V(T)), respiratory frequency (f) and heart rate (HR) were not significant. Administration of cocaine (37 mM) to ATR pretreated animals increased the incidence of cocaine induced respiratory arrest to more than twofold greater than when cocaine was administered in the absence of pretreatment. The ATR pretreated animals that did not experience inspiratory arrest after cocaine were shown to exhibit significant decrements in f and V(E) as a consequence of prolonged inspiratory pauses. The reduction in MABP after cocaine in ATR pretreated animals was also significant. These results suggest that ATR enhances the central respiratory toxicity of cocaine by acting synergistically at CVLM chemosensitive sites.     

D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

Opioids depress respiration and decrease chest wall compliance. A previous study in this laboratory showed that dopamine-D(1) receptor (D(1)R) agonists restored phrenic nerve activity after arrest by fentanyl in immobilized, mechanically ventilated cats. The reinstated phrenic nerve rhythm was slower than control, so it was not known whether D(1)R agonists can restore spontaneous breathing to levels that provide favorable alveolar gas exchange and blood oxygenation. It was also not known whether the agonists counteract opioid analgesia. In the present study, anesthetized, spontaneously breathing cats were given intravenous doses of fentanyl (18.0 +/- 3.4 microg/kg) that severely depressed depth and rate of respiration, lowered arterial hemoglobin oxygenation (HbO(2)), elevated end-tidal carbon dioxide (ETCO(2)), and abolished the nociceptive hind limb crossed-extensor reflex. Fentanyl (30 microg/kg) also evoked tonic discharges of caudal medullary expiratory neurons in paralyzed mechanically ventilated cats, which might explain decreased chest compliance. The selective D(1)R agonists 6-chloro APB (3 mg/kg) or dihydrexidine (DHD, 1 mg/kg) increased depth and rate of spontaneous breathing after opioid depression and returned HbO(2) and ETCO(2) to control levels. Opioid arrest of the nociceptive reflex remained intact. Pretreatment with DHD prevented significant depression of spontaneous breathing by fentanyl (17.5 +/- 4.3 microg/kg). Tonic firing evoked by fentanyl in expiratory neurons was converted to rhythmic respiratory discharges by DHD (1 mg/kg). The results suggest that D(1)R agonists might be therapeutically useful for the treatment of opioid disturbances of breathing without impeding analgesia.     

Topography of cat medullary ventral surface hypoxic acidification.

The topographic relationship between previously identified medullary ventral surface respiratory chemosensitive regions and brain surface extracellular fluid (ECF) acid production during acute hypoxia was explored in anesthetized, paralyzed, and artificially ventilated cats. Glass pH electrodes (0.8-mm diam, sheathed in stainless steel tubing) were mounted in mechanical contact with surfaces of medullary surface or adjacent pyramids, pons, spinal cord, or parietal cortex. Isocapnic hypoxia of 5 min [at arterial O2 saturation (SaO2) = 48 +/- 10%] reduced pH over rostral (Mitchell) and caudal (Loeschcke) areas by 0.12 +/- 0.09 and 0.07 +/- 0.04, respectively (n = 10, P < 0.05). Change in pH (delta pH) was proportional to desaturation with slopes 100 delta pH/delta SaO2 of 0.45 (rostral) and 0.20 (caudal) (R = 0.91 and 0.88, respectively). pH drop usually began within 3 min of hypoxia, became stable between 5 and 15 min, began to rise within 2 min of reoxygenation, and returned to control within 10 min. During equally hypoxic tests, intermediate area (Schl?fke), pons, and spinal cord surfaces showed no significant acid shift. Parietal cortex ECF pH dropped more slowly but steadily by 0.079 +/- 0.034 during 20 min at SaO2 = 50% after a small but significant initial alkaline shift, and acidification of cortical surface continued for > 5 min after reoxygenation. We conclude that medullary ventral chemosensitive regions produce more lactic acid during hypoxia than neighboring brain surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory impairment in a mouse model of amyotrophic lateral sclerosis.

Amyothrophic lateral sclerosis (ALS) is a progressive, lethal neuromuscular disease that is associated with the degeneration of cortical and spinal motoneurons, leading to atrophy of limb, axial, and respiratory muscles. Patients with ALS invariably develop respiratory muscle weakness and most die from pulmonary complications. Overexpression of superoxide dismutase 1 (SOD1) gene mutations in mice recapitulates several of the clinical and pathological characteristics of ALS and is therefore a valuable tool to study this disease. The present study is intended to evaluate an age-dependent progression of respiratory complications in SOD1(G93A) mutant mice. In each animal, baseline measurements of breathing pattern [i.e., breathing frequency and tidal volume (VT)], minute ventilation (VE), and metabolism (i.e., oxygen consumption and carbon dioxide production) were repeatedly sampled at variable time points between 10 and 20 wk of age with the use of whole-body plethysmographic chambers. To further characterize the neurodegeneration of breathing, VE was also measured during 5-min challenges of hypercapnia (5% CO(2)) and hypoxia (10% O(2)). At baseline, breathing characteristics and metabolism remained relatively unchanged from 10 to 14 wk of age. From 14 to 18 wk of age, there were significant (P < 0.05) increases in baseline VT, VE, and the ventilatory equivalent (VE/oxygen consumption). After 18 wk of age, there was a rapid decline in VE due to significant (P < 0.05) reductions in both breathing frequency and VT. Whereas little change in hypoxic VE responses occurred between 10 and 18 wk, hypercapnic VE responses were significantly (P < 0.05) elevated at 18 wk due to an augmented VT response. Like baseline breathing characteristics, hypercapnic VE responses also declined rapidly after 18 wk of age. The phenotypic profile of SOD1(G93A) mutant mice was apparently unique because similar changes in respiration and metabolism were not observed in SOD1 controls. The present results outline the magnitude and time course of respiratory complications in SOD1(G93A) mutant mice as the progression of disease occurs in this mouse model of ALS.     

Assessment of the reflex vagal origin of broncho-constrictor effects of hypercapnia in cats (author's transl)

Breath-by-breath measurements of pulmonary resistance (RL) were used to study the bronchomotor effects produced by the inhalation of a CO2-enriched gas mixture in anaesthetized, spontaneously breathing cats. A significant increase in RL occurred from the second inhalation of the hypercapnic gas mixture. This bronchoconstrictor effect lasted about 18 seconds, then a marked decrease in RL was observed. The secondary bronchodilatation persisted during the entire hypercapnic test (4 min). After surgical suppression of the sensory vagal component at the level of the nodose ganglion (bilateral sensory vagotomy), the early bronchoconstrictor effect of CO2 disappeared, but the secondary bronchodilatation was unchanged. In other experiments, after procaine block of the nervous conduction in non-myelinated vagal fibers, the bronchomotor effects of CO2 were the same as those observed after sensory vagotomy. In contrast, an electrotonic block of both vagus nerves, which abolished nervous conduction in myelinated fibers, did not suppress the bronchoconstrictor response to hypercapnia. Thus, the early increase in RL, which follows inhalation of a hypercapnic gas mixture, seems to be reflexly mediated by vagal afferents, especially by non-myelinated fibers.     

Sleep states alter ventral medullary surface responses to blood pressure challenges

Ventral medullary surface (VMS) activity declines during rapid eye movement (REM) sleep, suggesting a potential for reduced VMS responsiveness to blood pressure challenges during that state. We measured VMS neural activity, assessed as changes in reflected 660-nm wavelength light, during pressor and depressor challenges within sleep/waking states in five adult, unrestrained, unanesthetized cats and in two control cats. Phenylephrine elevated blood pressure and elicited an initial VMS activity decline and a subsequent rise in VMS activity in all states, although the initial decline during quiet sleep occurred only in rostral placements. Phasic REM periods elicited a momentary recovery from the evoked activity rise, and arousals diminished the overall elevation in activity. A sodium nitroprusside depressor challenge increased VMS activity more in REM sleep than in quiet sleep, with the increase being even less in waking. Enhanced responses to depressor challenges during REM sleep suggest a loss of dampening of evoked activity during that state; state-related differential baroreflex sensitivity may result from sleep-waking changes in VMS responses to blood pressure challenges.