Preparation and evaluation of technetium-99m labeled cardiac glycoside derivatives as potential myocardial imaging agent.

Three cardiac glycosides, two natural, cymarin and convallotoxin and one synthetic, strophanthidin-beta-D-glucoside were converted to their thiosemicarbazone and subsequently radiolabeled with 99mTc by chelation. The resulting radioactive chelate complexes were evaluated in animals to determine the suitability of this class of compounds for myocardial imaging. It was observed from the animal biodistribution data of the three radioactive compounds, there was a considerable variation in the heart to non-target organ uptake ratio. A possible explanation of this variation was offered in the light of their lipophilic character, protein binding ability and affinity towards non-target receptors. It is anticipated that this study may help to develop a 99mTc-cardiac glycoside complex with better distribution characteristics, and such a compound may offer a suitable alternative to 201Tl, which is at present used for myocardial imaging.

The effects of acetylstrophanthidin on the response of the AV junction to adrenergic stimulation studied in dogs.

The response of the AV junction to adrenergic stimulation was studied in 35 anesthetized open-chest dogs before and after the injection of acetylstrophanthidin (5mug) directly into the AV node artery. An AV junctional rhythm was obtained under control conditions by injecting norepinephrine (n = 9) or isoproterenol (n = 8) into the AV node artery and by stimulation of the left stellate ganglion (n = 11) after selectively injecting propranolol into the sinus node artery. Acetylstrophanthidin brought about various degrees of conduction block from simple PR interval prolongation to complete heart block, and decreased the chronotropic response of the AV junction to adrenergic stimulation. In seven animals the appearance of a spontaneous second degree AV block did not reduce the AV junctional response to adrenergic stimulation. Acetylstrophanthidin also reduced the ventricular acceleration produced by adrenergic stimulation during atrial fibrillation. These results suggest that the anti-adrenergic effect of cardiac glycosides may not only be involved in the mechanism of AV conduction disturbances during digitalis intoxication, but may also play a role in slowing the ventricular rate during atrial fibrillation.

Neural mechanisms involved in acetylstrophanthidin-induced bradycardia.

The role of neural sites in the bradycardia produced by acetylstrophanthidin (14.1, 22.5 and 35.5 mug/kg) was studied in chloralose-anesthetized cats with efferent vagal tone blocked by atropine. The sites were: carotid sinus baroreceptors, aortic arch baroreceptors, cardiac sensory receptors, nodose ganglion receptors and central nervous system structures. The role of each site was determined by selective ablation of all sites except the one under study. Significant slowing in heart rate occurred when: 1) only carotid sinus baroreceptors were intact; 2) only aortic arch baroreceptors were intact and 3) only cardiac sensory receptors were intact. No cardiac slowing was observed when only nodose ganglion receptors, central sympathoinhibitory sites and beta adrenergic receptors were intact. These results indicate that in atropine-treated cats, the further slowing in heart rate produced by acetylstrophanthidin arises from activation of reflex sites located in the carotid sinus, aortic arch and myocardium.