Fct. Chang et al., CENTRAL AND PERIPHERAL CARDIORESPIRATORY EFFECTS OF SAXITOXIN (STX) IN URETHANE-ANESTHETIZED GUINEA-PIGS, Toxicon, 31(5), 1993, pp. 645-664
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.