7-oxo PGI2 dramatically increases the safety margin of digitalis.
In our earlier experiments pretreatment with 7-oxo PGI2 was found to be effective against ouabain induced rhythm disturbances in guinea pigs. Maximal protection appeared 48 hours after a single dose of 50 micrograms/kg administered i.m. In the present study we wanted to clarify how cardiac glycoside induced positive inotropic responses as well as appearance of rhythm disturbances in higher doses were influenced by 7-oxo PGI2 pretreatment in dogs. The experiments were performed on anesthetized, artificially ventilated mongrel dogs weighing 9-11 kg. The ECG, left ventricular pressure, as well as +dP/dtmax and -dP/dtmax were continuously recorded. Ouabain was applied by intermittent infusion, i.e. an initial i.v. dose of 30 micrograms/kg was infused during 5 min followed by a 25 min interval, then 15 micrograms/kg was infused every 10 min for 2.5 min until cardiac arrest. Ouabain induced increasingly severe patterns of rhythm disturbances, ventricular extrasystoles (ES), ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrest (CA). In the case of 7-oxo PGI2 (50 micrograms/kg) pretreatment the dose of ouabain necessary to provoke ES was 62 +/- 5.0 micrograms/kg versus (v.s.) 53.3 +/- 3.4 micrograms/kg in the control group, VT: 97 +/- 5.0 micrograms/kg v.s. 80 +/- 6.2 micrograms/kg and CA: 100 +/- 4.2 micrograms/kg v.s. 87 +/- 7.7 micrograms/kg. In the pretreated group 25% of the maximal positive inotropic effect was produced by 14.2 +/- 3.6 micrograms/kg ouabain v.s. 31.7 +/- 3.6 micrograms/kg. According to the above results 7-oxo PGI2 increases the safety margin of ouabain.
Szilvássy
Z
Z
Department of Pharmacology, Szent-Györgyi Albert University Medical School, Szeged, Hungary.
Szekeres
L
L
Udvary
E
E
Karcsu
S
S
Végh
A
A
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004070:Digitalis; D004285:Dogs; D004562:Electrocardiography; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D010946:Plants, Medicinal; D010947:Plants, Toxic; D013268:Stimulation, Chemical
D010042:Ouabain; C033705:7-oxoprostaglandin I2; D011464:Epoprostenol