Action of Acetylcholine on Heart and Skeletal Muscle. ∗

Hall, Ettinger and Banting 1 found that long-continued administration of acetylcholine produced myocardial and coronary artery damage, the effects being more severe and extensive in old than in young animals. In pursuing our interests in the problem of myocardial and skeletal muscle disease in relation to the creatine reserve, we attempted to study the effects in the rat. As in the experiments reported from the Banting Institute, acetylcholine bromide (Eastman-Kodak) and acetylcholine iodide (Hoffmann-La Roche) were used. The dose was 10 mg. of acetylcholine daily, administered in a single dose or in 2 divided doses. The rats were 5–6 months old at the beginning of the experiments and the average weight exceeded 300 gm. Fourteen of the 17 rats on which the present report is based received the drug for a period of 85–90 clays, at which time they were sacrificed.

Within a few seconds after each injection, the characteristic effects of the drug referable to autonomic activity, i. e., profuse salivation and lacrimation, accelerated respiration and heart rate, were manifested. These symptoms gradually subsided during the succeeding 10 minutes.

Heart. The changes in the heart were somewhat variable, but in most animals there was present some degree of myocardial degeneration, hyaline change and beginning fibrosis. A striking feature was the patchy distribution of the small areas of degeneration, often verging on necrosis. Infiltration of these areas with inflammatory cells, vacuolization, hydropic change, thickening of the vessel walls due mainly to endothelial proliferation, and scattered small hemorrhages into the myocardium were likewise in evidence. Despite these changes it was remarkable to discover that the creatine concentration was essentially unaffected (159–237 mg., average 206 mg.) in all the animals that survived the period of experimentation (15 out of 17).