Central and peripheral cardio-respiratory effects of saxitoxin (STX) in urethane-anesthetized guinea-pigs

Abstract

F.-C. T. Chang, B. J. Benton, R. A. Lenz and B. R. Capacio. Central and peripheral cardio-respiratory effects of saxitoxin (STX) in urethane-anesthetized guinea-pigs. Toxicon 31, 645–664, 1993.—Effects of saxitoxin (STX; 10 μg/kg; i.p.) on cardio-respiratory activites were evaluated in urethane-anesthetized guinea-pigs. Concurrent recordings were made of electrocorticogram (ECoG), bulbar respiratory-related unit activities, diaphragmatic electromyogram (DEMG), electrocardiogram (Lead II ECG), blood pressure, heart rate, end-tidal CO 2, arterial O 2/CO 2 tensions, and arterial pH. The average time to STX-induced respiratory failure was about 10 min. The most striking effect prior to apnea was a state of progressive bradypnea which emerged 5–7 min after the toxin administration. Other noteworthy responses included (i) a time-dependent decrease in ECoG amplitudes which typically began before the development of a bradypneic profile; (ii) an increasing degree of diaphragm neuromuscular blockade; (iii) a state of combined hypercapnia and uncompensated acidemia; (iv) a declining blood pressure; (v) an incrementally dysfunctional myocardial performance; and (vi) an increasingly degenerative central respiratory activity profile which ultimately culminated in a complete loss of central respiratory drive. The therapeutic effect of intratracheally administered oxygen was equivocal in that the cardio-respiratory activities, be they of central of peripheral nature, remained conspicuously dysfunctional and precarious despite 100% oxygen ventilation. What can be inferred from this study is two-fold. First, STX-induced ventilatory insufficiency can be attributed to a loss of functional integrity of both central and peripheral respiratory system components. That is, although diaphragm blockade contributes significantly to STX-induced respiratory failure, analyses of single respiratory unit activity data reveale d that the central respiratory rhythmogenic mechanism also appeared to play a pivotal role in the development of a bradypneic profile which promotes, and directly causes, a complete loss of respiratory drive. Second, a state of unabating depression of central respiratory activities, which seemed to be refractory to the effect of O 2, suggests STX has a direct and persistent action on medullary rhythmogenic mechanisms. In conclusion, these findings indicate that both central and peripheral cardio-respiratory components are critically involved in STX-induced apnea, dysfunctional cardiovascular performance, and lethality.