Arrhythmias induced by changing the medium of cultured rat heart muscle cells: A model for assessment of antiarrhythmic agents

Abstract

Neonatal rat atrial, ventricle, and whole heart muscle cells dissociated with collagenase and exposed to a medium without serum or glucose developed arrhythmias which progressed at a uniform rate and lasted for up to 16 hr. This effect was not obtained with cells dissociated with or exposed to trypsin. The suitability of the method for testing antiarrhythmic drugs was assessed with quinidine, procainamide, lidocaine, propranolol, and diphenylhydantoin (10 -10-10 -4 M). Arrhythmias were reversed by quinidine (10 -6 M) for 16 hr, and were partially and temporarily reversed by procainamide (10 -5 M) and lidocaine (10 -7 M). Higher concentrations were either less effective or were toxic. Neither propranolol nor diphenylhydantoin demonstrated antiarrhythmic activity. Their lack of effect at the cell level suggests the central or autonomic nervous system as possible sites of action.