Cardiac glycosides in the treatment of experimental overdose with calcium-blocking agents.
The ability of digitalis compounds to counteract calcium antagonist overdose was studied in anesthetized dogs (n = 6, 13.5 +/- 0.7 kg) and isolated trabeculae from human hearts (n = 7). Digitalis caused by increasing intracellular cytosolic Ca2+ concentration through Na+/Ca(2+)-exchange across the cell membrane, was postulated to overcome the detrimental effects of excessive slow calcium-channel blockade. In anesthetized dogs, an infusion of verapamil (40 mg/30 min, i.v.) decreased mean arterial pressure from 88 +/- 6 to 66 +/- 6 mm Hg (P < 0.05), reduced systemic vascular resistance (SVR) from 3838 +/- 916 to 2200 +/- 669 dyne.s/cm5 (P < 0.05), and induced total atrio-ventricular (A-V) block in three animals. Stroke volume (SV) remained unchanged. Administration (i.v.) of NaCl (0.9%, 200 ml) and calcium gluconate (100 mg)--to increase the availability of Na+ and Ca(2+)--together with atropine (0.2 mg)--to block the parasympathetic effects of digoxin on A-V conduction--increased left ventricular contractility (15%) but had no significant effects on blood pressure, SV, or A-V block. Digoxin (0.125 mg) returned sinus rhythm in all dogs and, by increasing SVR (P < 0.05) and left ventricular contractility (P < 0.05), returned arterial pressures to baseline. Because of increased afterload, SV decreased slightly (15%) despite increased cardiac contractility. In experiments with isolated trabeculae from diseased human hearts, TA 3090 (Clentiazem) depressed contractile force and ouabain, another glycoside, restored contractile force within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Ramo
M P
MP
Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine.
Grupp
I
I
Pesola
M K
MK
Heikkila
J
J
Luomanmaki
K
K
Schroder
T
T
Grupp
G
G
D000818:Animals; D001285:Atropine / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000506:poisoning; D002125:Calcium Gluconate / Q000627:therapeutic use; D003864:Depression, Chemical; D004077:Digoxin / Q000627:therapeutic use*; D004110:Diltiazem / Q000031:analogs & derivatives / Q000506:poisoning; D004285:Dogs; D062787:Drug Overdose; D004562:Electrocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D014700:Verapamil / Q000506:poisoning*
D002121:Calcium Channel Blockers; C056595:clentiazem; D004077:Digoxin; D001285:Atropine; D014700:Verapamil; D004110:Diltiazem; D002125:Calcium Gluconate; D002118:Calcium