Stephen G Reid

Cardiovascular and respiratory reflexes in the tropical fish, traira (Hoplias malabaricus): CO2/pH chemoresponses

To examine the distribution and physiological role of CO2/pH-sensitive chemoreceptors in the gills of the tropical fish, traira (Hoplias malabaricus), fish were exposed to acute environmental hypercarbia (1.25, 2.5 and 5.0% CO2 in air) and subjected to injections of HCl into the ventral aorta and buccal cavity. This was done before and after selective denervation of branchial branches of the IXth and Xth cranial nerves to various gills arches. Hypercarbia produced a significant decrease in heart rate, a mild hypotension as well as increases in both ventilation rate and ventilation amplitude. The data suggest that the hypercarbic bradycardia and increase in ventilation frequency arise from receptors exclusively within the gills but present on more than the first gill arch, while extra-branchial receptors may also be involved in controlling the increase in ventilation amplitude. With the exception of a decrease in heart rate in response to HCl injected into the ventral aorta, the acid injections (internal and external) did not mimic the cardiorespiratory responses observed during hypercarbia suggesting that changes in CO2 are more important than changes in pH in producing cardiorespiratory responses. Finally, the data indicate that chemoreceptors sensitive to CO2/pH and to O2 in the gills of this species involved in producing ventilatory responses are distributed in a similar fashion, but that those involved in producing the bradycardia are not.

Respiratory pattern formation in the isolated bullfrog (Rana catesbeiana) brainstem-spinal cord

This study characterizes various patterns of motor output obtained from cranial nerves V, VII, X, and XII of in vitro, saline-perfused, brainstem-spinal cord preparations of the American bullfrog (Rana catesbeiana). Motor output indicative of fictive breathing was present in all preparations. In 17 of 26 preparations, fictive breaths were either evenly spaced or randomly distributed, while in the remaining nine preparations fictive breaths occurred in episodes separated by relatively long periods of quiescence. With the exception of fictive breath duration in the non-episodic preparations and the instantaneous frequency of fictive breaths within episodes, all variables associated with fictive breathing were insensitive to changes in perfusion saline pH. In addition to fictive breathing, a large number of other forms of motor output were observed arising from these nerves. While the data suggest that the in vitro preparation is capable of producing a wide repertoire of motor patterns, similar to those seen in vivo, it was difficult, with the current protocol, to reliably produce any single pattern in spite of carefully regulated conditions.

Do descending influences alternate to produce episodic breathing

This study examines the episodic breathing patterns of three disparate groups of vertebrates. In an in vitro bullfrog brainstem-spinal cord preparation, episodic breathing was replaced by uniformly spaced breaths following transection caudal to the optic chiasma. The same effect was produced in hibernating squirrels by inhalation of mild anesthesia. Preliminary data suggest that a similar conversion is also produced in hibernating squirrels by vagotomy, in conjunction with blockade of central NMDA-type glutamate receptors. In all cases, even though overall breathing frequency increased, due to elimination of periods of apnea, instantaneous breathing frequency slowed. Seals breathe episodically in sleep and when these animals awaken after the start of a breathing episode, breathing also immediately slows. The data presented here are consistent with the suggestion that in all vertebrates, higher centres can modulate the central rhythm generator for breathing, in both a positive and a negative fashion. During episodic breathing, in the species studied here, these modulating influences alternate in a fashion that produces periods of apnea alternating with periods of relatively high frequency ventilation.

Central respiratory pattern generation in the bullfrog, Rana catesbeiana☆

There are two components to breathing pattern generation the production of the pattern of neural discharge associated with individual breaths, and the pattern in which breaths are produced to effect ventilation. Bullfrogs typically breathe with randomly distributed breaths. When respiratory drive is elevated, breathing becomes more regular and often episodic. Studies on in vitro brainstem-spinal cord preparations of the adult bullfrog and in situ preparations of decerebrate, paralyzed, unidirectionally ventilated animals suggest that output from the central rhythm generator in frogs is conditional on receiving some input and that a host of central inputs remain even in the most reduced preparations. There appear to be descending inputs from sites in the dorsal brainstem just caudal to the optic chiasma that cluster breaths into episodes, a strong excitatory input caudal to this site but rostral to the origin of the Vth cranial nerve and, possibly, segmental rhythm generators throughout the medulla that are normally entrained to produce the normal breathing pattern. The data also suggest that the shape of the discharge pattern (augmenting, decrementing) and timing of outputs (alternating vs synchronous) associated with motor outflow during each breath are also dependent on the interconnections between these various sites.

The influence of descending inputs on breathing pattern formation in the isolated bullfrog brainstem-spinal cord

This study used in vitro brainstem-spinal cord preparations from the American bullfrog, Rana catesbeiana, to examine the influence of central descending inputs on breathing pattern formation. In preparations with an episodic pattern of fictive breathing, a transection slightly caudal to the optic chiasma produced a continuous breathing pattern and increased the overall frequency of fictive breathing. Following a transection to isolate the medulla, the frequency of fictive breathing decreased and the incidence of other forms of motor output increased. Further transections between the trigeminal and vagus nerve roots resulted in variable and asynchronous discharge from each nerve. These results suggest that a primary respiratory rhythm is produced within the medulla but descending influences stimulate breathing and promote episodic breathing. It would appear that multiple elements of the respiratory control system, including tegmental and medullary sites, play a role in shaping the burst pattern of motor output associated with each breath and that slower rhythms of longer burst duration are generated by more caudal hindbrain sites.

Interactive effects of mechano- and chemo-receptor inputs on cardiorespiratory outputs in the toad

Arterial blood pressure (P(b)), pulmocutaneous blood flow (Q(pc)), heart rate (f(H)), and fictive ventilation (motor activity in the Vth cranial nerve, V(int)), were recorded from decerebrated, paralysed toads receiving unidirectional ventilation with experimental gas mixtures over a range of lung inflation. At the onset of spontaneous bouts of fictive ventilation, (Q(pc)) and P(b) increased immediately, often with changes in heart rate, implying central cardiorespiratory interactions. Inflation of the lungs with different gas mixtures revealed that the effect of hypercarbia on V(int) was reduced by lung inflation and that feedback from pulmonary stretch receptors may summate with central feedforward control of f(H) and (Q(pc)) in an interactive fashion. The results of bolus injections of cyanide into the carotid or the pulmonary circulations suggest there are oxygen sensitive receptors in both circuits that affect the cardiovascular system directly and respiratory activity by complex central interactions with inputs from central chemoreceptors and pulmonary stretch receptors.

Pulmonary vagal modulation of ventilation in toads (Bufo marinus)

This study examined the role of pulmonary vagal feedback on hypercapnic chemosensitivity and breathing pattern formation in cane toads (Bufo marinus). Decerebrate, paralysed toads were uni-directionally ventilated with air, 2.5% CO(2) or 5.0% CO(2) with the lungs inflated or deflated, before and after pulmonary vagotomy. Motor output from the mandibular branch of the trigeminal nerve served as an index of fictive breathing. As respiratory drive was increased, breathing frequency increased and breaths were clustered into discrete episodes separated by periods of apnea. Lung deflation tended to enhance episodic breathing while inflation biased the system towards apnea at low levels of respiratory drive and a pattern of continuous, small breaths at higher levels of respiratory drive. Following bilateral pulmonary vagotomy there was no increase in ventilation during hypercapnia and lung inflation/deflation had no effect on breathing pattern. In isolated brainstem-spinal cord preparations from the same animals, all variables associated with fictive breathing were unaffected by changes in superfusate pH from 8.0 to 7.6. The breathing pattern from the in vitro preparations was highly variable. This study demonstrates a crucial role for vagal feedback in modulating respiration and the respiratory responses to hypercapnia in B. marinus.