Neurophysiological concomitants of soman-induced respiratory depression in awake, behaving guinea pigs

Soman-induced respiratory failure was investigated in awake, behaving guinea pigs chronically instrumented to allow concurrent recordings of medullary respiratory-related unit (RRU) activity, diaphragm electromyogram (DEMG), and electrocorticogram. Responses to soman typically began with hyperpnea. Loss of consciousness, as indicated by the development of seizure activities, took place shortly after the onset of hyperpnea. This was followed by dyspnea, hypopnea, and finally, respiratory failure. The most profound respiratory dysfunctions were seen during the development of dyspnea characterized by a progressively degenerative RRU-DEMG phase relationship (phase anomalies) and mixed patterns of ataxic breathing. Electrophysiographic records indicated that the anomalous RRU-DEMG phase phenomenon is attributable to a state of functional dissociation in some brainstem mechanisms that are normally involved in the orchestration of a synchronous respiratory drive. The failure of bulbar rhythmogenic mechanisms to maintain an orderly and synchronous recruitment of respiratory drive, which led to untimely and chaotic activations of respiratory muscles, was apparently the underlying cause of various ataxic breathing patterns and a reduced ventilatory efficiency. Spectral analyses of DEMG activities showed that, despite episodic muscle fasciculations and signs of fatigue, the functional integrity of the diaphragm was not significantly compromised by soman at a dose sufficient to produce respiratory failure. These findings not only support the notion of a relatively more important involvement of central respiratory mechanisms in soman-induced respiratory failure, but also identify a state of functional dissociation of central respiratory timing mechanisms as being a significant component in soman intoxication.