Reversal of Saxitoxin (STX) and Tetrodotoxin (TTX) Induced Cardio-Respiratory Failure with 4-Aminopyridine (4-AP).
Abstract
Reversal of STX and TTX induced cardio-respiratory failure with 4-AP was studied in urethane-anesthetized guinea pigs instrumented for the recordings of medullary respiratory activities, diaphragm EMG, ECoG, ECG, blood pressure, end-tidal CO(2), and arterial O(2)/CO2/pH. The toxin (STX or TTX) was infused at a dose rate of 0.3 ug/kg/min (i.v.) to produce a state of cardio-respiratory depression. Animals were maintained with artificial ventilation when the magnitude of diaphragm activity was reduced by 50%. Seconds after the disappearance of the diaphragm activity, the toxin infusion was terminated, and 4-AP (2 mg/kg; i.v.) was administered. The therapeutic effect of 4-AP was striking in that the toxin-induced functional blockade of the diaphragm, vascular hypotension and bradycardia could all be promptly returned to a level comparable to, and in many cases surpassing, that of control condition. The animals were typically able to breathe spontaneously within minutes after 4-AP. Despite an auspicious return of ventilatory function and cardiovascular performance, a variety of other 4-AP induced central and peripheral effects were also observed. The most notable ones are (1) a cortical excitant/arousal effect as indicated by the emergence of an 8-30 Hz EEG power spectral complex, (2) an increase in the magnitude of skeletal muscle (neck) background activities, and (3) a cardio-respiratory performance decrement noted in some animals attributable to an acid-base homeostatic imbalance which was readily reversible by sodium bicarbonate solution. Side effects at higher intravenous dose levels (viz., 4, 6, and 8 mg/kg) are of some concern in that 4-AP not only can cause muscle fasciculations, but also becomes seizurogenic and proconvulsant.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008879
Entities
People
- B. J. Benton
- E. L. Moore
- F. C. Chang
- R. M. Bauer
Organizations
- United States Army Medical Research Institute of Chemical Defense