Many inotropic maneuvers act by increasing the intracellular
calcium concentration [( Ca2+]i). The present report illustrates this with respect to the positive inotropic effects of
cardiac glycosides and
catecholamines. It is shown that the increased contractility produced by
cardiac glycosides is accompanied by an increase in intracellular Na concentration and, furthermore, that the relationship between contraction and Na is very steep. This steep dependence, which may result from a Na-Ca exchange which exchanges several Na
ions per Ca, means that maneuvers that have only small effects on Na will have significant effects on contraction.
Cardiac glycosides also produce abnormal pacemaker activity and
cardiac arrhythmias. These originate from a transient inward current activated by oscillations of [Ca2+]i, which result from spontaneous oscillatory release of Ca
ions from the sarcoplasmic reticulum. The
local anesthetic group of antiarrhythmic agents abolishes the transient inward current.
Catecholamines also increase systolic [Ca2+]i and, in high enough concentrations, can produce oscillations of [Ca2+]i. This tendency of
glycosides and
catecholamines to produce arrhythmogenic oscillations of [Ca2+]i is a major limitation to their use. Therefore, inotropic agents that act by means other than increasing [Ca2+]i may be of great efficacy.