RESPIRATORY AND CIRCULATORY EFFECTS OF SAXITOXIN IN THE CEREBROSPINAL FLUID
Open Access
- 1 December 1977
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 61 (4) , 679-689
- https://doi.org/10.1111/j.1476-5381.1977.tb07561.x
Abstract
1 In cats anaesthetized with pentobarbitone, saxitoxin and, on a few occasions, tetrodotoxin were injected into a lateral cerebral ventricle or into the subarachnoid space of the lower brain stem. Observations were made on frequency and tidal volume of breathing, on CO2 responsiveness and on electrical responsiveness of the respiratory centre. Effects on the blood pressure were observed simultaneously. 2 A single large dose of toxin, e.g., 250 ng, produced within minutes apneustic breathing and a rise in blood pressure which were converted rapidly to respiratory failure and hypotension. In contrast, repeated small doses, e.g., 25 ng, yielded only progressive slowing of the respiration together with circulatory hypotension. Bulbar depression was produced as effectively by subarachnoid injection as by intraventricular injection of the toxins. Onset of action was detectable within seconds. 3 Slowing of the respiration occurred independently of change in tidal volume and whether or not the vagus nerves were cut. The reduction in breathing frequency is attributed to direct toxin-induced depression of the central respiratory oscillator. 4 Steady-state measurements of tidal volume at controlled levels of alveolar CO2 pressure in intermediate stages of respiratory depression showed that the toxins produced an increase in CO2 stimulation threshold as well as a reduction in gain of CO2 responsiveness, whether or not the vagus nerves were cut. Carotid arterial chemoreceptor reactivity to O2 was demonstrable when central sensitivity to CO2 was depressed. These effects are attributed to a direct influence of the toxins upon the brainstem CO2-tidal volume controller. 5 Responsiveness of the medullary inspiratory centre to electrical stimulation persisted after the failure of spontaneous breathing was caused by the toxins. Conversely, restitution of electrical responsiveness preceded the reappearance of spontaneous respiratory activity in the recovery phase of toxic depression. Circulatory effects paralleled the changes in respiratory behaviour. 6 On the basis of the relatively prompt and discrete alterations in the central respiratory and circulatory control mechanisms produced by saxitoxin and tetrodotoxin placed in the cerebrospinal fluid, it is concluded that the agents rapidly penetrated to deep target loci in the lower brain stem.Keywords
This publication has 25 references indexed in Scilit:
- Administration of tetrodotoxin and saxitoxin into the lateral cerebral ventricle of the rabbitNeuropharmacology, 1975
- Influence of hypoxia on tidal volume response to CO2 in decerebrate catsRespiration Physiology, 1974
- Rate versus depth of breathing independent of alveolar oxygen in decerebrate catsRespiration Physiology, 1973
- Effects of central depressant drugs on respiratory regulation in the decerebrate catRespiration Physiology, 1969
- Volumetric compartmentalization of the cranial cerebrospinal fluid system determined radiographically in the catThe Anatomical Record, 1966
- Separation of Transducer and Impulse-Generating Processes in Sensory ReceptorsScience, 1963
- Action of Puffer Fish PoisonNature, 1963
- Vomiting, hypothermia, and respiratory paralysis due to tetrodotoxin (puffer fish poison) in the catToxicology and Applied Pharmacology, 1963
- THE ACTION OF MUSSEL POISON ON THE NERVOUS SYSTEMImmunology & Cell Biology, 1935