Rate of onset of cardiotonic steroid-induced inotropism: influence of temperature and beat interval.
Isolated rabbit atria were employed to examine the rate of onset of inotropism of two glycosides (strophanthin and ouabain) and aglycones (acetylstrophanthidin and ouabagenin) under a variety of conditions of temperature and beat interval. The rate of onset of glycoside-induced inotropism was found to be highly and directly dependent on temperature between 27 and 37 degrees C at a beat interval of 10 seconds. At a beat interval of 1 second the rate of onset of glycoside effect was faster than at a beat interval of 10 seconds and was not dependent on temperature. At 32 degrees C the rate of onset of glycoside-induced inotropism was inversely related to beat interval (the faster the stimulation rate, the faster the onset). The rate of onset of aglycone-induced inotropism was not dependent on temperature at a beat interval of 1 or 10 seconds. At 32 degrees C the rate of onset of aglycone effect was not dependent on beat interval except at beat intervals of less than 1 second. Depending on experimental conditions, increased temperature and/or myocardial activity increases the rate-limiting step for the onset of effect of cardiac glycosides. Rapid myocardial activity increased, but neither moderate myocardial activity nor increased temperature increase the rate-limiting step for the rate of onset of effect of aglycones under our experimental conditions. The results are interpreted by postulating that the digitalis inotropic receptor is located in a membrane-limited compartment to which aglycones may gain access via passive diffusion but to which glycosides gain access mainly via a carrier mechanism.
D000818:Animals; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000031:analogs & derivatives / Q000494:pharmacology*; D011817:Rabbits; D013327:Strophanthidin / Q000031:analogs & derivatives; D013328:Strophanthins / Q000494:pharmacology*; D013696:Temperature; D013997:Time Factors
D013328:Strophanthins; D010042:Ouabain; D013327:Strophanthidin