Acute CO2 tolerance in fishes is associated with air breathing but not the Root effect, red cell ßNHE, or habitat.

High CO2 (hypercapnia) can impose significant physiological challenges associated with acid-base regulation in fishes, impairing whole animal performance and survival. Unlike other environmental conditions such as temperature and O2, the acute CO2 tolerance thresholds of fishes are not understood. While some fish species are highly tolerant, the extent of acute CO2 tolerance and the associated physiological and ecological traits remain largely unknown. To investigate this, we used a recently developed ramping assay, termed the Carbon Dioxide maximum (CDmax), that increases CO2 exposure until loss of equilibrium (LOE) is observed. We investigated if there was a relationship between CO2 tolerance and the Root effect, ß-adrenergic sodium proton exchanger (ßNHE), air-breathing, and fish habitat in 17 species. We hypothesized that CO2 tolerance would be higher in fishes that lack both a Root effect and ßNHE, breathe air, and reside in tropical habitats. Our results showed that CDmax ranged from 2.7 to 26.7 kPa, while LOE was never reached in four species at the maximum PCO2 we could measure (26.7 kPa); CO2 tolerance was only associated with air-breathing, but not the presence of a Root effect or a red blood cell (RBC) ßNHE, or fish habitat. This study demonstrates that the diverse group of fishes investigated here are incredibly tolerant of CO2 and that although this tolerance is associated with air-breathing, further investigations are required to understand the basis for CO2 tolerance.

Evolution of vertebrate respiratory central rhythm generators.

Tracing the evolution of the central rhythm generators associated with ventilation in vertebrates is hindered by a lack of information surrounding key transitions. To begin with, central rhythm generation has been studied in detail in only a few species from four vertebrate groups, lamprey, anuran amphibians, turtles, and mammals (primarily rodents). Secondly, there is a lack of information regarding the transition from water breathing fish to air breathing amniotes (reptiles, birds, and mammals). Specifically, the respiratory rhythm generators of fish appear to be single oscillators capable of generating both phases of the respiratory cycle (expansion and compression) and projecting to motoneurons in cranial nerves innervating bucco-pharyngeal muscles. In the amniotes we find oscillators capable of independently generating separate phases of the respiratory cycle (expiration and inspiration) and projecting to pre-motoneurons in the ventrolateral medulla that in turn project to spinal motoneurons innervating thoracic and abdominal muscles (reptiles, birds, and mammals). Studies of the one group of amphibians that lie at this transition (the anurans), raise intriguing possibilities but, for a variety of reasons that we explore, also raise unanswered questions. In this review we summarize what is known about the rhythm generating circuits associated with breathing that arise from the different rhombomeric segments in each of the different vertebrate classes. Assuming oscillating circuits form in every pair of rhombomeres in every vertebrate during development, we trace what appears to be the evolutionary fate of each and highlight the questions that remain to be answered to properly understand the evolutionary transitions in vertebrate central respiratory rhythm generation.

Defining comparative physiology: results from an online survey and systematic review.

August Krogh's 1929 principle is referenced as the cornerstone of comparative physiology (CP). However, there are diverse views as to what type of research falls under the CP approach. This study had three aims: 1) determine how CP is defined through an online survey (OS) of physiologists and a systematic review (SR), 2) put forth an updated definition of CP by summarizing OS and SR results, and 3) outline the numerous CP research approaches. Professional physiology societies (n = 54) were invited to share the OS with their members, and a SR was conducted, which yielded 197 and 70 definitions, respectively. The three most common words in descending order in the OS definitions were "different," "animals," and "species" and in the SR definitions, "animals," "species," and "organisms." The three most prevalent themes from the OS and SR definitions were comparing/differences/diversity across species (78% and 51%, respectively), response to the environment/ecology (28% and 43%, respectively), and included evolution or adaptation (24% and 60%, respectively). Ten research approaches were identified, which include broad comparison (i.e., many species generalization), specific comparison (e.g., 2 species; for traits that are different, exaggerated, extreme, missing, or not induced), or comparison while considering evolution (i.e., evolutionary physiology), ecology (i.e., ecophysiology), or human physiology/medicine. Only 5% and 33% of OS and SR definitions described or mentioned Krogh's principle. In conclusion, CP can best be defined as a compilation of research approaches that utilize different types of comparisons to elucidate physiological mechanisms and not simply comparing physiologies as the name implies.

Preferential intracellular pH regulation is a common trait amongst fishes exposed to high environmental CO2.

Acute (<96 h) exposure to elevated environmental CO2 (hypercarbia) induces a pH disturbance in fishes that is often compensated by concurrent recovery of intracellular and extracellular pH (pHi and pHe, respectively; coupled pH regulation). However, coupled pH regulation may be limited at CO2 partial pressure (PCO2 ) tensions far below levels that some fishes naturally encounter. Previously, four hypercarbia-tolerant fishes had been shown to completely and rapidly regulate heart, brain, liver and white muscle pHi during acute exposure to >4 kPa PCO2  (preferential pHi regulation) before pHe compensation was observed. Here, we test the hypothesis that preferential pHi regulation is a widespread strategy of acid-base regulation among fish by measuring pHi regulation in 10 different fish species that are broadly phylogenetically separated, spanning six orders, eight families and 10 genera. Contrary to previous views, we show that preferential pHi regulation is the most common strategy for acid-base regulation within these fishes during exposure to severe acute hypercarbia and that this strategy is associated with increased hypercarbia tolerance. This suggests that preferential pHi regulation may confer tolerance to the respiratory acidosis associated with hypercarbia, and we propose that it is an exaptation that facilitated key evolutionary transitions in vertebrate evolution, such as the evolution of air breathing.

Brainstem mechanisms controlling cardiovascular reflexes in channel catfish.

Microinjections of kynurenic acid and kainic acid into the general visceral nucleus (nGV), homologous to the mammalian nucleus tractus solitarius of the medulla, in anesthestized, spontaneously breathing catfish were used to identify central areas and mechanisms controlling resting normoxic heart rate and blood pressure and the cardiovascular responses to hypoxia. Kynurenic acid, an antagonist of ionotropic glutamate receptors, significantly reduced resting normoxic heart rate but did not block the bradycardia associated with aquatic hypoxia. Kainic acid (an excitotoxic glutamatergic receptor agonist) also significantly reduced normoxic heart rate, but blocked the hypoxia-induced bradycardia. Neither kynurenic acid nor kainic acid microinjections affected blood pressure in normoxia or hypoxia. The results of this study indicate that glutamatergic receptors in the nGV are involved in the maintenance of resting heart rate and the destruction of these neurons with kainic acid abolishes the bradycardia associated with aquatic hypoxia.

Comparative cardiovascular physiology: future trends, opportunities and challenges.

The inaugural Kjell Johansen Lecture in the Zoophysiology Department of Aarhus University (Aarhus, Denmark) afforded the opportunity for a focused workshop comprising comparative cardiovascular physiologists to ponder some of the key unanswered questions in the field. Discussions were centred around three themes. The first considered function of the vertebrate heart in its various forms in extant vertebrates, with particular focus on the role of intracardiac shunts, the trabecular ('spongy') nature of the ventricle in many vertebrates, coronary blood supply and the building plan of the heart as revealed by molecular approaches. The second theme involved the key unanswered questions in the control of the cardiovascular system, emphasizing autonomic control, hypoxic vasoconstriction and developmental plasticity in cardiovascular control. The final theme involved poorly understood aspects of the interaction of the cardiovascular system with the lymphatic, renal and digestive systems. Having posed key questions around these three themes, it is increasingly clear that an abundance of new analytical tools and approaches will allow us to learn much about vertebrate cardiovascular systems in the coming years.

Evolutionary and physiological variation in cardiac troponin C in relation to thermal strategies of fish.

Striated muscle contraction is initiated when troponin C (TnC) binds Ca(2+), which activates actinomyosin ATPase. We investigated (i) the variation between cardiac TnC (cTnC) primary structure within teleost fish and (ii) the pattern of TnC expression in response to temperature acclimation. There were few differences between rainbow trout (Oncorhynchus mykiss), yellowfin tuna (Thunnus albacares), yellow perch (Perca flavescens), goldfish (Carassius auratus), white sucker (Catostomus commersoni), and icefish (Chaenocephalus aceratus) in cTnC amino acid sequence. No variation existed in the regulatory Ca(2+)-binding site (site 2). The site 3 and 4 substitutions were limited to residues not directly involved in Ca(2+) coordination. Fish cTnC primary structure was highly conserved between species (93%-98%) and collectively divergent from the highly conserved sequence seen in birds and mammals. Northern blots and polymerase chain reaction showed that thermal acclimation of trout (3 degrees, 18 degrees C) did not alter the TnC isoform pattern. While cardiac and white muscle had the expected isoforms-cTnC and fast troponin C (fTnC), respectively-red muscle unexpectedly expressed primarily ftnC. Cold acclimation did not alter myofibrillar ATPase Ca(2+) sensitivity, but maximal velocity increased by 60%. We found no evidence that TnC variants, arising between species or in response to thermal acclimation, play a major role in mitigating the effects of temperature on contractility of the adult fish heart.

Effect of a single-channel wide dynamic range compression circuit on perception of stop consonant place of articulation.

Previous studies have shown that altering the amplitude of a consonant in a specific frequency region relative to an adjacent vowel's amplitude in the same frequency region will affect listeners' perception of the consonant place of articulation. Hearing aids with single-channel, fast-acting wide dynamic range compression (WDRC) alter the overall consonant-vowel (CV) intensity ratio by increasing consonant energy. Perhaps one reason WDRC has had limited success in improving speech recognition performance is that the natural amplitude balances between consonant and vowel are altered in crucial frequency regions, thus disturbing the aforementioned amplitude cue for determining place of articulation. The current study investigated the effect of a WDRC circuit on listeners' perception of place of articulation when the relative amplitude of consonant and vowel was manipulated. The stimuli were a continuum of synthetic CV syllables stripped of all place cues except relative consonant amplitudes. Acoustic analysis of the CVs before and after hearing aid processing showed a predictable increase in high-frequency energy, particularly for the burst of the consonant. Alveolar bursts had more high-frequency energy than labial bursts. Twenty-five listeners with normal hearing and 5 listeners with sensorineural hearing loss labeled the consonant sound of the CV syllables in unaided form and after the syllables were recorded through a hearing aid with single-channel WDRC. There were significantly more listeners who were unable to produce a category boundary when labeling the aided stimuli. Of those listeners who did yield a category boundary for both aided and unaided stimuli, there were significantly more alveolar responses for the aided condition. These results can be explained by the acoustic analyses of the aided stimuli.

Effects of temperature and physical activity on blood flow shunts and intracardiac mixing in the toad Bufo marinus.

Blood flow in systemic (.Qsys) and pulmocutaneous (.Qpul) arteries was measured as a function of body temperature (10 degrees, 20 degrees, and 30 degrees C) at rest and following enforced physical activity in conscious, adult cane toads (Bufo marinus). Arterial and mixed venous hemoglobin concentration (CHb) and total oxygen content (Co2, tot) were measured in a separate group under identical conditions. Heart rate (fH) and total flow (.Qtot) increased significantly (P<0.001) with elevated temperature and with activity, whereas stroke volume (VS) increased (P<0.001) only with activity. .Qtot ranged about 10-fold, from 10 degrees C (rest) to 30 degrees C (activity); increases in both fH and VS contributed to the increase in .Qtot. The overall distribution of blood to the pulmocutaneous circuit (net L-R shunt) increased with both temperature and activity and was significantly correlated with .Qtot. These data indicate that blood flow distribution in toads is a direct function of cardiac output, and this is linked to relative changes in resistance in the major outflow vessels. Arterial O2 saturation (Sa) was high (mean=93%) in all conditions except activity at 30 degrees C, when it decreased to 74% and contributed to a decrease in the arteriovenous O2 difference. Venous O2 saturation (Sv) was high at rest (76%) and dropped significantly during activity to about 30% at all temperatures. Intracardiac arterial-venous mixing (systemic mixing index) showed the strongest correlation with variation in fH with minimal mixing (17%) occurring at about 50 beats min-1. The most mixing occurred at the lowest fH (13 beats min-1) and at the highest fH (103 beats min-1). The results indicate that the heart of a 0.25-kg toad becomes more efficient from an oxygen transport perspective from low fH to 50 beats min-1 and then less efficient at higher fH, contributing to an uncoupling of blood flow and metabolic rates at these high rates.

Nitric oxide as a modulator of central respiratory rhythm in the isolated brainstem of the bullfrog (Rana catesbeiana).

Nitric oxide (NO) is a unique interneuronal neurotransmitter and/or neuromodulator that is involved in a variety of physiological functions within the central nervous system (CNS). In neural tissue, NO is generated from an oxygen-dependent, constitutive NO synthase (NOS) by glutamatergic stimulation of N-methyl-D-aspartate (NMDA) receptors. Recent studies indicate that NO has excitatory effects on breathing within the CNS and mediates a central component of the hypoxic ventilatory reflex in mammals. Because NMDA receptors are important in central respiratory rhythmogenesis, we hypothesized that NO would have significant effects on the central pattern generator (CPG) for breathing in the brainstem. To test this hypothesis, the effects of NO on respiratory-related neural activity were investigated using an in vitro brainstem preparation from North American bullfrogs (Rana catesbeiana). Extracellular recordings of respiratory-related burst activity were made from cranial nerves V, X and XII before and during superfusion of the brainstem with NO-generating compounds, or inhibitors of NO synthesis. Addition of the NO donor, sodium nitroprusside (SNP; 0.1-1.0 mM), or the amino acid precursor for NO synthesis, L-arginine (L-Arg; 0.01-1.0 mM), caused significant increases in respiratory-related burst frequency. Inhibition of NOS with N omega-nitro-L-arginine (L-NA; 5-10 mM), a non-selective NOS inhibitor, caused a significant reduction in burst frequency or reversibly abolished neural activity. Brainstem perfusion with the specific neuronal NOS (nNOS) inhibitor, 7-nitro indazole (7-NI), produced significant, dose-dependent reversible reductions in burst frequency at concentrations of 0.1, 0.5 and 1.0 mM. These results suggest that production of NO, probably via nNOS, provides an excitatory input to the respiratory CPG in the amphibian brainstem. Our results suggest that NO may be a necessary inter- or intracellular messenger for neurotransmission and/or neuromodulation of central respiratory drive to motor effectors in the bullfrog.

Control and interaction of the cardiovascular and respiratory systems in anuran amphibians.

In anuran amphibians, respiratory rhythm is generated within the central nervous system (CNS) and is modulated by chemo- and mechanoreceptors located in the vascular system and within the CNS. The site for central respiratory rhythmogenesis and the role of various neurotransmitters and neuromodulators is described. Ventilatory air flow is generated by a positive pressure, buccal force pump driven by efferent motor output from cranial nerves. The vagus (cranial nerve X) also controls heart rate and pulmocutaneous arterial resistance that, in turn, affect cardiac shunts within the undivided anuran ventricle; however, little is known about the control of central vagal motor outflow to the heart and pulmocutaneous artery. Anatomical evidence indicates a close proximity of the centers responsible for respiratory rhythmogenesis and the vagal motoneurons involved in cardiovascular regulation. Furthermore, anurans in which phasic feedback from chemo- and mechanoreceptors is prevented by artificial ventilation exhibit cardiorespiratory interactions that appear similar to those of conscious animals. These observations indicate interactions between respiratory and cardiovascular centers within the CNS. Thus, like mammals and other air-breathing vertebrates, the cardio-respiratory interactions in anurans result from both feedback and feed-forward mechanisms.

Nitric oxide modulates respiratory-related neural activity in the isolated brainstem of the bullfrog.

The effects of nitric oxide (NO) on respiratory-related neural activity were investigated using the isolated brainstem preparation from bullfrogs (Rana catesbeiana). Addition of the NO donor, sodium nitroprusside (SNP), or the amino acid precursor for NO synthesis, L-arginine (L-Arg), produced significant increases in respiratory-related burst frequency. Inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NA), a non-selective NOS inhibitor, 7-nitro indazole (7-NI), reversibly abolished burst activity. These results suggest that production of NO, probably via neuronal NOS (nNOS), provides a facilitatory input to the respiratory central pattern generator (CPG) in the amphibian brainstem. Endogenous production of NO may be a necessary inter- or intracellular messenger for neurotransmission and/or neuromodulation of central respiratory drive to motor effectors in the bullfrog.

Differential respiratory muscle recruitment induced by clonidine in awake goats.

The purpose of this study was to test the hypothesis that dysrhythmic breathing induced by the alpha2-agonist clonidine is accompanied by differential recruitment of respiratory muscles. In adult goats (n = 14) electromyographic (EMG) measurements were made from inspiratory muscles (diaphragm and parasternal intercostal) and expiratory muscles [triangularis sterni (TS) and transversus abdominis (Abd)]. EMG of the thyroarytenoid (TA) muscle was used as an index of upper airway (glottal) patency. Peak EMG activities of all spinal inspiratory and expiratory muscles were augmented by central and peripheral chemoreceptor stimuli. Phasic TA was apparent in the postinspiratory phase of the breathing cycle under normoxic conditions. During dysrhythmic breathing episodes induced by clonidine, TS and Abd activities were attenuated or abolished, whereas diaphragm and parasternal intercostal activities were unchanged. There was no tonic activation of TS or Abd EMG during apneas; however, TA activity became tonic throughout the apnea. We conclude that 1) alpha2-adrenoceptor stimulation results in differential recruitment of respiratory muscles during respiratory dysrhythmias and 2) apneas are accompanied by active glottic closure in the awake goat.

Effect of relative amplitude and formant transitions on perception of place of articulation by adult listeners with cochlear implants.

Previous studies have shown that manipulation of a particular frequency region of the consonantal portion of a syllable relative to the amplitude of the same frequency region in an adjacent vowel influences the perception of place of articulation. This manipulation has been called the relative amplitude cue. Earlier studies have examined the effect of relative amplitude and formant transition manipulations upon labeling place of articulation for fricatives and stop consonants in listeners with normal hearing. The current study sought to determine if (a) the relative amplitude cue is used by adult listeners wearing a cochlear implant to label place of articulation, and (b) adult listeners wearing a cochlear implant integrated the relative amplitude and formant transition information differently than listeners with normal hearing. Sixteen listeners participated in the study, 12 with normal hearing and 4 postlingually deafened adults wearing the Nucleus 22 electrode Mini Speech Processor implant with the multipeak processing strategy. The stimuli used were synthetic consonant-vowel (CV) syllables in which relative amplitude and formant transitions were manipulated. The two speech contrasts examined were the voiceless fricative contrast /s/-"sh" and the voiceless stop consonant contrast /p/-/t/. For each contrast, listeners were asked to label the consonant sound in the syllable from the two response alternatives. Results showed that (a) listeners wearing this implant could use relative amplitude to consistently label place of articulation, and (b) listeners with normal hearing integrated the relative amplitude and formant transition information more than listeners wearing a cochlear implant, who weighted the relative amplitude information as much as 13 times that of the transition information.

Effect of relative amplitude, presentation level, and vowel duration on perception of voiceless stop consonants by normal and hearing-impaired listeners.

Previous work on the influence of relative amplitude and presentation level in listeners with normal hearing and those with sensorineural hearing loss was extended to include (1) a comparison of relative amplitude manipulation in the presence of neutral formant transitions versus manipulation of both formant transition and relative amplitude and (2) the additional variable of vowel duration. Synthetic consonant-vowel (CV) stimuli were used, and the amplitude of the burst relative to the vowel in the F4-F5 frequency range was varied across a 20-dB range using a /p-t/ contrast. In experiment I, some stimuli had neutral formant transition values and relative amplitude manipulations; other stimuli had both formant transition and relative amplitude manipulations. For stimuli in experiment II, neutral formant transition values were used, relative amplitude was manipulated, and vowel duration ranged from 14 to 200 ms. Results from experiment I showed no significant difference between listener groups when only relative amplitude information was manipulated, but significant differences when both relative amplitude and formant transition information was present. These results suggest that the listeners with normal hearing weighted the two acoustic cues differently from listeners with sensorineural hearing loss. Results from experiment II indicated that increasing vowel duration generally increased the number of labial responses from listeners with normal hearing, but did not always increase the number of labial responses from listeners with sensorineural hearing loss.

Effect of relative and overall amplitude on perception of voiceless stop consonants by listeners with normal and impaired hearing.

Previous studies of the /p/-/t/ contrast for normal-hearing listeners have shown that both manipulation of the amplitude of the burst relative to the vowel in the F4-F5 frequency region and overall presentation level can influence the perception of place of articulation [R. N. Ohde and K. N. Stevens, J. Acoust. Soc. Am. 74, 706-714 (1983); Gravel and Ohde, Asha 25, 101 (1983)], such that greater burst amplitude in the high frequencies and higher presentation levels result in more alveolar responses. The influence of relative amplitude and presentation level was tested for both normal-hearing (NH) and hearing-impaired (HI) listeners in the present study. Synthetic CV stimuli were used, and the amplitude of the burst relative to vowel-onset amplitude in the F4-F5 frequency region was manipulated across a 20-dB range. In addition, overall presentation level was varied across a 45-dB range. The findings revealed that the hearing-impaired listeners selected more alveolar responses than listeners with normal hearing when tested at equivalent SPLs. A group of five normal-hearing listeners were then presented the synthetic stimuli in a background of broadband noise at a level that produced thresholds at 4 kHz equivalent to the thresholds of five hearing-impaired listeners. Results from the noise-masked normal-hearing listeners did not consistently show more alveolar responses as presentation level of the stimuli was increased, thus failing to mimic the responses from the hearing-impaired listeners in quiet.

Recurrent laryngeal nerve activation by alpha 2 adrenergic agonists in goats.

The purpose of this study was to test the hypothesis that respiratory and apneas induced by alpha 2 agonists in anesthetized goats are associated with an increase of upper airway expiratory-related activity, rather than a general depression of breathing. Activities of phrenic (Phr) and recurrent laryngeal nerves (RLN) were recorded in response to the alpha 2 agonists clonidine (0.5-3.0 microgram.kg-1 i.v.) or guanabenz (7.0-20.0 micrograms.kg-1 i.v.) in ten chloralose-anesthetized goats. Injection of either alpha 2 agonist resulted in respiratory arrhythmias with a greater than seven-fold increase in TE and a 30% reduction in TI. During apneas RLN expiratory-related activity remained tonic until the next Phr burst, consistent with our hypothesis. Cessation of Phr activity during hypocapnia also resulted in a tonic increase of RLN expiratory activity; and injection of NaCN (50 micrograms.kg-1 i.v.) increased Phr and RLN inspiratory activities, while attenuating RLN expiratory-related activity. Inspiratory and expiratory-related activity of RLN motoneurons appear to be reciprocally modulated by alpha 2 agonists or changes in central or peripheral chemoreceptor drive. The results indicate that central apneas and respiratory arrhythmias may be associated with alpha 2-adrenoceptor modulation of laryngeal expiratory-related activity.

Intracarotid substance P infusion inhibits ventilation in the goat.

Substance P (SP) has been proposed as an excitatory neuromodulator of the carotid body (CB) response to hypoxia based on data from the cat and rat. The role of SP as a CB neuromodulator in the goat is unknown. Awake (n = 14) and chloralose anesthetized goats (n = 6) were used to investigate the effects of intracarotid (IC) SP infusions (1-6 micrograms.kg-1.min-1) and bolus injections (6 micrograms kg-1) to the CB intact and denervated (CBX) sides (control) on mean ventilation (VE) and mean blood pressure (MBP). In awake goats VE was decreased by infusion or bolus SP injection at a dose of 6 micrograms.kg-1 (P < 0.05) and occurred with infusions to the intact or CBX sides. MBP was elevated with SP infusion to either the CB intact or CBX sides at all SP doses. The SP antagonist CP-96,345 (0.1 mg.kg-1, IV) blocked the decrease in VE induced by SP in normoxia and significantly increased the hypoxic ventilatory response (PaO2 = 40 torr). In anesthetized goats, IC injections of SP (1 to 6 micrograms.kg-1) reduced phrenic activity and MBP before and after CBX. In only one of five goats airway pressure was increased suggesting that bronchoconstriction was not a cause for the reduced ventilatory and phrenic activity induced by SP. Immunohistochemistry provided evidence of SP in CB nerve fibers and terminals, carotid sinus nerve axons and petrosal ganglion cells, but not in type I glomus cells. Our results do not support the view that SP is an excitatory neuromodulator of CB chemotransduction in the goat.

Effects of carotid body sympathetic denervation on ventilatory acclimatization to hypoxia in the goat.

Our objective was to test the hypothesis that diminishing sympathetic input to the carotid body (CB) during prolonged exposure to hypoxia results in increased CB afferent activity and increased ventilatory drive. Six awake goats were studied prior to and following sectioning of the efferent sympathetic input to the CB from the superior cervical ganglion. Ventilatory responses to acute and prolonged isocapnic hypoxia (PaO2 40 Torr) and drugs (norepinephrine and dopamine, 0.5, 1.0 and 5.0 micrograms.kg-1 min-1) were collected prior to the denervation. One week and 3-4 weeks following the sympathetic denervation, the animals were restudied following the above protocol. Ventilation was significantly lower following sympathetic denervation in normoxia and during the hypoxic exposure. However, the response to acute hypoxia and the time-course of ventilatory acclimatization to hypoxia was not altered by sympathetic denervation. All doses of norepinephrine and dopamine significantly inhibited VE in a dose-dependent manner. Sympathetic denervation did not significantly alter the response to the drug infusions. The sympathetic innervation to the CB does not appear to play a role in either the acute or prolonged ventilatory responses to hypoxia in the awake goat, but may affect overall ventilation.