Effect of 3,4 Diaminopyridine on Saxitoxin- and Tetrodotoxin-Induced Cardiorespiratory Depression.
Abstract
The effect of 3,4 diaminopyridine (3,4 DAP) on saxitoxin (STX) - and tetrodotoxin (TTX)-induced cardiorespiratory depression was examined in anesthetized guinea pigs which were instrumented to record medullary respiratory neuronal activity, arterial pressure, ECG, ECoG, diaphragm EMG (DEMG), end-tidal CO(2) and arterial pH, Co(2) and O(2). Infusion of STX or TTX (0.3 ug/kg/min, IV) elicited progressive vascular hypotension, bradycardia and bradypnea leading to complete inhibition of DEMG activity. Artificial ventilation was introduced when DEMG activity was reduced by 50% due to STX or TTX. Toxin infusion was stopped upon the inhibition of DEMG activity and 3,4 DAP (8 Mg/kg, IV) was given subsequently. Arterial pressure and heart rate returned to pretoxin levels and DEMG activity reappeared rapidly following 3,4 DAP infusion. In most cases, animals resumed spontaneous breathing within minutes after 3,4 DAP. Spontaneous breathing was often sustained for several hours after a single infusion of 3,4 DAP. Uncompensated arterial acidosis was typically observed during spontaneous breathing after 3,4 DAP treatment; however, this could be corrected with sodium bicarbonate (7.5%, IV). Despite the therapeutic actions of 3,4 DAP, some side effects were identified. Adverse side effects of 3,4 DAP administration included aberrant patterns of medullary discharge. Current investigations address strategies to minimize these medullary neuronal side effects of 3,4 DAP and to potentiate its therapeutic actions.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008882
Entities
People
- B. J. Benton
- E. L. Moore
- F. C. Chang
- R. M. Bauer
Organizations
- United States Army Medical Research Institute of Chemical Defense