Cardiac glycosides in the treatment of experimental overdose with calcium-blocking agents

Abstract

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)

Dose-dependent Hemodynamic Effect of Digoxin Therapy in Severe Verapamil Toxicity

“…A similar result was found in a model of mild-to-moderate verapamil toxicity (4 mg/kg over 30 minutes) treated with calcium (7.5 mg/kg) plus digoxin (0.009 mg/kg). 4 In the present study, we demonstrated that there is a dose-dependent effect of digoxin on systolic blood pressure and maximal ventricular pressure. The dosedependent effect of digoxin on systolic blood pressure was first detected at 3 hours, 15 minutes after the administration of digoxin and lasted until 5 hours or the end of the protocol.…”

“…We performed a controlled, unblinded laboratory investigation using eight adult male mongrel dogs (19.4-25.3 kg). The dog model was chosen because it previously was used to study verapamil and digoxin [3][4][5] toxicity. The animal care and use committee of the institution approved this protocol, and the care and handling of the animals were in accordance with National Institutes of Health guidelines.…”

“…Recently, digoxin was evaluated as a therapy that would increase the efficacy of calcium in large calcium channel antagonist overdoses. 3,4 In these two previous animal models of verapamil toxicity, digoxin improved hemodynamic parameters compared with calcium alone. These studies used only a single dose of digoxin.…”

Calcium and Digoxin vs Calcium Alone for Severe Verapamil Toxicity

“…17 In a dog model of mild to moderate verapamil poisoning (4 mg/kg over 30 minutes), calcium (7.5 mg/kg) plus digoxin (0.009 mg/kg) increased myocardial contractile force and increased peripheral vascular resistance when compared with calcium alone. Our animal model is different in many ways and more consistent with clinical presentation and current treatment.…”

“…We suspect the improvement in systolic blood pressure was from increases in both cardiac output and vas-cular resistance because this was shown previously. 17 We evaluated only the effect of digoxin plus calcium, and not digoxin only. Our result could be attributed to digoxin alone.…”