Effect of pulmonary C-fibre afferent stimulation on cardiac vagal neurones in the nucleus ambiguus in anaesthetized cats

It has been demonstrated previously that the vagal bradycardia evoked by activation of pulmonary C-fibres is not respiratory modulated. Experiments were carried out in α-chloralose anaesthetized cats to determine if these cardiac vagal preganglionic neurones (CVPNs) in the nucleus ambiguus (NA), which have respiratory modulated activity, can be activated when pulmonary C-fibre afferents are stimulated by right atrial injections of phenylbiguanide (PBG).Eleven CVPNs with B-fibre axons in the right cardiac vagal branches were identified and found to be localized within or ventrolateral to the nucleus ambiguus. Ionophoretic application of a high current of dl-homocysteic acid (DLH) induced a vagally mediated bradycardia and hypotension in six of eight sites from which CVPNs were recorded.The activity of B-fibre CVPNs, whether spontaneous (n = 4) or induced by ionophoresis of DLH (n = 7) was respiratory modulated, firing perferentially during post-inspiration and stage 2 expiration. This activity also correlated with the rising phase of the arterial blood pressure wave consistent with these CVPNs receiving an arterial baroreceptor input.Right atrial injections of PBG excited nine of eleven CVPNs tested. In eight of these activated neurones the onset latency of the excitation was within the pulmonary circulation time, consistent with being activated only by pulmonary C-fibre afferents. In two neurones the PBG-evoked excitation still occurred when central inspiratory drive was inhibited, as indicated by the disappearance of phrenic nerve activity.In conclusion, B-fibre respiratory modulated CVPNs can be activated following stimulation of pulmonary C-fibre afferents

Cardiorespiratory and neural consequences of rats brought past their aerobic dive limit

The mammalian diving response is a dramatic autonomic adjustment to underwater submersion affecting heart rate, arterial blood pressure, and ventilation. The bradycardia is known to be modulated by the parasympathetic nervous system, arterial blood pressure is modulated via the sympathetic system, and still other circuits modulate the respiratory changes. In the present study, we investigate the submergence of rats brought past their aerobic dive limit, defined as the diving duration beyond which blood lactate concentration increases above resting levels. Hemodynamic measurements were made during underwater submergence with biotelemetric transmitters, and blood was drawn from cannulas previously implanted in the rats' carotid arteries. Such prolonged submersion induces radical changes in blood chemistry; mean arterial Pco2 rose to 62.4 Torr, while mean arterial Po2 and pH reached nadirs of 21.8 Torr and 7.18, respectively. Despite these radical changes in blood chemistry, the rats neither attempted to gasp nor breathe while underwater. Immunohistochemistry for Fos protein done on their brains revealed numerous Fos-positive profiles. Especially noteworthy were the large number of immunopositive profiles in loci where presumptive chemoreceptors are found. Despite the activation of these presumptive chemoreceptors, the rats did not attempt to breathe. Injections of biotinylated dextran amine were made into ventral parts of the medullary dorsal horn, where central fibers of the anterior ethmoidal nerve terminate. Labeled fibers coursed caudal, ventral, and medial from the injection to neurons on the ventral surface of the medulla, where numerous Fos-labeled profiles were seen in the rats brought past their aerobic dive limit. We propose that this projection inhibits the homeostatic chemoreceptor reflex, despite the gross activation of chemoreceptors

The rat: a laboratory model for studies of the diving response

Underwater submersion in mammals induces apnea, parasympathetically mediated bradycardia, and sympathetically mediated peripheral vasoconstriction. These effects are collectively termed the diving response, potentially the most powerful autonomic reflex known. Although these physiological responses are directed by neurons in the brain, study of neural control of the diving response has been hampered since 1) it is difficult to study the brains of animals while they are underwater, 2) feral marine mammals are usually large and have brains of variable size, and 3) there are but few references on the brains of naturally diving species. Similar responses are elicited in anesthetized rodents after stimulation of their nasal mucosa, but this nasopharyngeal reflex has not been compared directly with natural diving behavior in the rat. In the present study, we compared hemodynamic responses elicited in awake rats during volitional underwater submersion with those of rats swimming on the water's surface, rats involuntarily submerged, and rats either anesthetized or decerebrate and stimulated nasally with ammonia vapors. We show that the hemodynamic changes to voluntary diving in the rat are similar to those of naturally diving marine mammals. We also show that the responses of voluntary diving rats are 1) significantly different from those seen during swimming, 2) generally similar to those elicited in trained rats involuntarily “dunked” underwater, and 3) generally different from those seen from dunking naive rats underwater. Nasal stimulation of anesthetized rats differed most from the hemodynamic variables of rats trained to dive voluntarily. We propose that the rat trained to dive underwater is an excellent laboratory model to study neural control of the mammalian diving response, and also suggest that some investigations may be done with nasal stimulation of decerebrate preparations to decipher such control