Cardio protective effect of glucose-insulin infusion on acute digoxin toxicity in rat.
We recently observed a case of digoxin and insulin self-poisoning without cardiac repercussion. We raised the hypothesis that insulin may have a cardio-protective effect in case of digoxin toxicity. We have therefore evaluated the effect of glucose-insulin infusion on mortality and ECG abnormalities during acute digoxin toxicity in rats. Before and after a hyperinsulinemia-euglycemia clamp, rats in glucose-insulin-digoxin (GID) group (n=10) received an intravenous infusion of 12ml/h or 2,5ml/h digoxin (0.25mg/ml) respectively until death occured. Animals receiving digoxin or saline solution intravenously served as control (n=10). ECG recording was performed in all animals over the entire period. Serum insulin and digoxin concentrations were measured by ELISA method after digoxin administration. When digoxin was administered after the clamp, all animals in GID group were alive, whereas 80% of animals in the digoxin group were dead (p<0.001) after 30min. The administration of Digoxin provoked rapid death of rats in the digoxin group in 15+/-12min whereas in GID group the survival period was significantly increased to 38+/-3min (p<0.001). Twenty minutes after digoxin administration, P waves disappeared for 78% of animals in digoxin group while they were present in all rats of GID group (p<0.001). Animal death occurred after a digoxin infusion volume of 7.7+/-0.6ml and 3.0+/-2.4ml in GID and digoxin group respectively (p<0.001). Five minutes after digoxin administration, potassium plasmatic level increased significantly in digoxin group as compared to GID group: 7.1+/-2mmol/l versus 4.4+/-0.4mmol/l (p<0.001). When digoxin was infused before the clamp, 40% of animals in GID group were alive after 180min and the other 60% died after 137+/-40min whereas death of rats in the digoxin group occurred within 80+/-10min (p<0.001). The death of animals was preceded by the P waves disappearing. Thirty minutes after digoxin administration, the potassium plasmatic level increased significantly in the digoxin group as compared to the GID group: 6.9+/-0.5mmol/l versus 4.9+/-0.3mmol/l (p<0.001). At the time of death, both volume of digoxin infusion and serum digoxin concentration were increased in GID group as compared to digoxin group: 5.7+/-1.6ml versus 3.3+/-0.4ml (p<0.001) and 10.7+/-8.3mg/l versus 8.5+/-4.6mg/l.


CONCLUSIONS
Glucose-insulin infusion delayed the abnormalities in cardiac conduction and improved rat survival after acute digoxin toxicity. These results suggest a cardioprotective effect of insulin in case of acute digoxin toxicity.
Oubaassine
R
R
Laboratory of Cellular and Genetic Therapy, European Centre of Diabetes Study, Strasbourg, France.
Bilbault
P
P
Roegel
J C
JC
Alexandre
E
E
Sigrist
S
S
Lavaux
T
T
Jaeger
A
A
Pinget
M
M
Kessler
L
L
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000401:mortality / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D013997:Time Factors; D023382:Toxicity Tests, Acute / Q000379:methods; D016896:Treatment Outcome
D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D004077:Digoxin; D005947:Glucose; D011188:Potassium