Digoxin-specific antibody fragments and a calcium antagonist for reversal of digoxin-induced mesenteric vasoconstriction.
The effect of digoxin-specific antibody fragments on glycoside-induced mesenteric vasoconstriction were investigated. Digoxin caused a sustained contraction of strips of isolated feline mesenteric artery lasting for several hours, while in anaesthetized cats it produced a significant decrease in blood flow and increase in resistance in the mesenteric artery. In-vitro, digoxin's contractile effect was inhibited by 'prophylactic' addition of antibody to the organ bath, but the clinical use for prophylaxis is not a practical proposition. When the antibodies were added with the contraction of the arterial strip in response to digoxin already established, the tone of the preparation decreased significantly over 3 h, but the effect of the glycoside was not fully reversible. In-vivo, control animals not treated with antibodies developed arrhythmias, mesenteric blood flow fell by more than 50% and resistance increased by more than 80% relative to the initial values. These animals died of ventricular fibrillation before the end of the experiment. Animals treated with digoxin-specific antibody fragments after receiving digoxin injections showed no further decrease in mesenteric blood flow and 90 min after the last dose of digoxin, the flow was recovering and mesenteric resistance decreasing. Furthermore, all the animals that had received antibodies remained in sinus rhythm to the end of the experiment. In view of the latent period to onset of action of the antibodies, valuable time may be lost in impaired mesenteric blood flow. To bridge the gap or, indeed, as primary treatment, calcium antagonists merit consideration; in our experiments mesenteric vasoconstriction was abolished within a few minutes by application of the dihydropyridine calcium antagonist 4-(2,1,3-benzo-oxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic aid, diethyl ester (PY 108-068).
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002415:Cats; D004077:Digoxin / Q000037:antagonists & inhibitors / Q000276:immunology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007140:Immunoglobulin Fab Fragments; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D007140:Immunoglobulin Fab Fragments; D004077:Digoxin; D009543:Nifedipine; C034600:darodipine