Reversal of saxitoxin-induced cardiorespiratory failure by a burro-raised alpha-STX antibody and oxygen therapy.
Reversal of saxitoxin (STX; 10 micrograms/kg, ip) induced cardiorespiratory effects by oxygen ventilation and burro-raised alpha-STX antitoxin (60 mg/kg, i.v.) was studied in urethane-anesthetized guinea pigs acutely instrumented for concurrent monitoring of medullary respiratory-related single units, diaphragm EMG, Lead II electrocardiogram, arterial blood pressure (BP), arterial pH, and O2/CO2 tensions, electrocorticogram (ECoG), and end-tidal CO2. STX-induced cardiorespiratory effects included (1) a state of progressive bradypnea and hypercapnia; (2) a functional blockade of the diaphragm; (3) a prolongation of respiratory cycle duration; (4) an aberrant bulbar respiratory-related neuronal activity pattern; and (5) a decline in BP and heart rate. The therapeutic effect of artificial ventilation following STX-induced apnea was equivocal in that the cardiorespiratory activities, be they of central or peripheral nature, remained dysfunctional despite continued oxygen ventilation. Spontaneous breathing and cardiovascular performance following STX-induced apnea could all be promptly restored (typically in less than a minute) by combined oxygen/antitoxin therapy. Notable also was a state of uncompensated acidemia (as revealed by changes in arterial pH and CO2 tension) which persisted throughout the course of therapeutic intervention. Notwithstanding, the ventilatory frequency continued to be low, the central respiratory activity pattern remained aberrant, and the ECoG amplitudes were still depressed. In consideration of these findings, and of the large molecular weight of alpha-STX antitoxin (> 150,000 Da) which limits its entry into the CNS, we are of the opinion that the therapeutic effects of antitoxin are probably confined primarily to the periphery.
Benton
B J
BJ
Neurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Rivera
V R
VR
Hewetson
J F
JF
Chang
F C
FC
D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000992:Antitoxins / Q000276:immunology* / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000139:chemically induced* / Q000503:physiopathology / Q000628:therapy*; D002319:Cardiovascular System / Q000187:drug effects; D004562:Electrocardiography; D004594:Electrophysiology; D006168:Guinea Pigs; D010102:Oxygen Inhalation Therapy; D010527:Perissodactyla; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000503:physiopathology / Q000628:therapy*; D012530:Saxitoxin / Q000276:immunology* / Q000633:toxicity*
D000906:Antibodies; D000992:Antitoxins; D012530:Saxitoxin