CENTRAL AND PERIPHERAL CARDIORESPIRATORY EFFECTS OF SAXITOXIN (STX) IN URETHANE-ANESTHETIZED GUINEA-PIGS

Effects of saxitoxin (STX; 10 mug/kg; i.p.) on cardio-respiratory acti vities were evaluated in urethane-anesthetized guinea-pigs. Concurrent recordings were made of electrocorticogram (ECoG), bulbar respiratory -related unit activities, diaphragmatic electromyogram (DEMG), electro cardiogram (Lead II ECG), blood pressure, heart rate, end-tidal CO2, a rterial O2/CO2 tensions, and arterial pH. The average time to STX-indu ced respiratory failure was about 10 min. The most striking effect pri or 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 deg ree of diaphragm neuromuscular blockade; (iii) a state of combined hyp ercapnia 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 equ ivocal in that the cardio-respiratory activities, be they of central o f peripheral nature, remained conspicuously dysfunctional and precario us despite 100% oxygen ventilation. What can be inferred from this stu dy is two-fold. First, STX-induced ventilatory insufficiency can be at tributed to a loss of functional integrity of both central and periphe ral respiratory system components. That is, although diaphragm blockad e contributes significantly to STX-induced respiratory failure, analys es of single respiratory unit activity data revealed that the central respiratory rhythmogenic mechanism also appeared to play a pivotal rol e in the development of a bradypneic profile which promotes, and direc tly causes, a complete loss of respiratory drive. Second, a state of u nabating depression of central respiratory activities, which seemed to be refractory to the effect of O2, suggests STX has a direct and pers istent action on medullary rhythmogenic mechanisms. In conclusion, the se findings indicate that both central and peripheral cardio-respirato ry components are critically involved in STX-induced apnea, dysfunctio nal cardiovascular performance, and lethality.