Antiarrhythmic effect of antibodies to digoxin in acute myocardial ischemia in rats

Characterization of a Urinary Bufodienolide Na + ,K + -ATPase Inhibitor in Patients After Acute Myocardial Infarction

“…21,22 Based on these observations, we hypothesized that ischemia-induced inhibition of myocardial Na ϩ ,K ϩ -ATPase may be due at least in part to the action of DLF. In support of this hypothesis, it has been demonstrated that in coronary-ligated rats and in patients with AMI, plasma levels of digoxin-like immunoreactivity were increased and Na ϩ ,K ϩ -ATPase levels in erythrocytes [23][24][25] and in myocardium 26 were inhibited. Pretreatment of the coronary-ligated rats with digoxin antibody prevented inhibition of erythrocyte and myocardial Na ϩ ,K ϩ -ATPase and was associated with an antiarrhythmic effect.…”

“…It is believed that inhibition of the Na ϩ -K ϩ pump in cardiomyocytes plays an important role in the genesis of ischemia-induced arrhythmias. 46 Previously we showed that this inhibition is due at least in part to the action of increased plasma digoxin-like immunoreactive factor 23 and that pretreatment of the coronary-ligated rats with digoxin antibody prevents both inhibition of myocardial Na ϩ -K ϩ pump and ventricular arrhythmias. 23,26 Delva et al 47 have observed an increase in plasma Na ϩ ,K ϩ -ATPase inhibitory activity in the course of a period of myocardial ischemia during transcutaneous coronary angioplasty in a group of patients with ischemic heart disease.…”

“…Pretreatment of the coronary-ligated rats with digoxin antibody prevented inhibition of erythrocyte and myocardial Na ϩ ,K ϩ -ATPase and was associated with an antiarrhythmic effect. 23,26 When the antiarrhythmic potency of several antibodies was compared in coronary-ligated rats, antibody against the mixture of bufodienolides possessed greater effect than rabbit and ovine (DIGIBIND) digoxin antibody. 27 Considering the sensitivity of endogenous marinobufagenin-like immunoreactive factor to plasma volume expansion 16 and the vasoconstrictor properties of marinobufagenin, 13,14 we decided to further characterize the human marinobufageninlike substance.…”

“…27 Considering the sensitivity of endogenous marinobufagenin-like immunoreactive factor to plasma volume expansion 16 and the vasoconstrictor properties of marinobufagenin, 13,14 we decided to further characterize the human marinobufageninlike substance. Since increased DLF has been shown to be involved in the genesis of sodium pump inhibition in acute myocardial ischemia [23][24][25][26][27] and increased urinary excretion of endogenous digoxin-like material has been observed in patients with AMI, 28 we chose this source to examine the urine of these patients for material with chromatographic properties similar to that of marinobufagenin.…”

Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

“…Maixent and Lelièvre (1987) demonstrated that acute myocardial ischemia is associated with a loss in the number of high-affinity ouabain binding sites and with inhibition of the Na + /K + -ATPase in canine LV myocardium. Bagrov et al (1989) hypothesized that endogenous CTS may be responsible for myocardial ischemia-induced inhibition of LV Na + /K + -ATPase and that heightened CTS levels may contribute to ischemia-induced ventricular arrhythmias. In agreement with this notion, Delva et al (1990) observed a rapid increase in plasma Na + /K + -ATPase inhibitory activity in patients with coronary artery disease associated with decreased cardiac output during a transient period of myocardial ischemia while undergoing percutaneous coronary angioplasty.…”