CARDIAC MUSCLE CONTRACTILITY I 73 



associated with prolongation of the plateau; whereas 

 terminal repolarization, when it begins, proceeds at a 

 normal rate. (See section iv.) 



It is well established that barium chloride can 

 cause contracture of the isolated frog heart when 

 added to the Ringer's solution (175, 321) or serum 

 (321) bathing the tissue. If rather low concentrations 

 of barium chloride are given (10-100 /umoles/liter) 

 no effect is observed if the calcium concentration is 

 normal, but contracture occurs with barium in the 

 complete absence of calcium ion (unpublished 

 observations). This brings to mind the findings of 

 Thomas (295) that the addition of strontium to an 

 isolated frog heart in the absence of calcium increases 

 the isometric tension almost to the point of contrac- 

 ture. The addition of calcium reverses the strontium 

 action. These results might be formulated according 

 to the following scheme. There is a chemical site in 

 the excitation-contraction process for which barium, 

 strontium, and calcium all can compete. This site 

 has a stronger affinity for calcium than for either of 

 the other two cations. However, once attached to the 

 site, the order of increasing potency for enhancing 

 contractile force is calcium, strontium, barium. 

 Therefore, barium or strontium in the presence of 

 comparable concentrations of calcium has no effect 

 because, according to this scheme, the site prefer- 

 entially binds calcium. In the absence of calcium, 

 barium or strontium is free to reach the site, 

 where they are more effective than calciiun in 

 increasing contractility. 



VI. EFFECT OF STIMULATION FREQ^UENCY 

 ON CONTRACTILE FORCE 



Historical Xote and Definitions 



The twitch tension developed by cardiac muscle is 

 affected in large measure by variations in the fre- 

 quency and regularity of stimulation. Comparable 

 effects have been observed in smooth (60, 186) and 

 striated muscle (243), but are much less obvious in 

 the latter tissue. In the case of heart muscle the 

 variations in contractile force with frequency are 

 probably due to either pure examples or mixtures of 

 two basic phenomena, the so-called Bowditch 

 staircase and the reverse staircase. Postextrasystolic 

 potentiation may represent yet a third phenomenon 

 responsible for tension changes, or may be closely 

 related to the Bowditch staircase as will be discussed 

 below. The term staircase has recently been applied 



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FIG. 12. Schematic diagrams of frequency-tension relation- 

 ships. Continuous tracings of contractions. (See text for details.; 

 A: Bowditch staircase. Following a rest period the first con- 

 tractile response is small, but rises progressively with each 

 stimulus until a plateau is reached. B: Bowditch staircase. The 

 higher the stimulus frequency, the higher the tension. C: post- 

 stimulation potentiation, a mixture of Bowditch and reverse 

 staircase. The first contraction after shifting from a high to low 

 frequency is greater than before (reverse staircase). Then there 

 is progressive drop to a new plateau characteristic of the slow 

 stimulus frequency (Bowditch staircase). D: reverse staircase. 

 The higher the stimulus frequency the lower the tension. E: 

 rest contraction, an example of reverse staircase. Stimulation 

 rate before and after the rest is the same. The first few contrac- 

 tions after the rest are greater than before. F: postextrasystolic 

 potentiation. The first few contractions after the extrasystole are 

 greater than before. [From Hajdu & Leonard (i 13).] 



by Rosenblueth and co-workers to a frequency- 

 independent stepwise change in contractile force of 

 the heart which occurs under certain conditions 

 following changes in inffow or output pressure (250). 

 This is referred to in the section on contractility and 

 will not be discussed further here. 



The first correlation between stimulation frequency 

 and contractile force was reported by Bowditch (24) 

 in 1 87 1. Working with an isolated frog heart, he 

 noted that following a long period of asystole the 

 amplitude of contractions which occurred when the 

 heart was subsequently stimulated at a regular 

 frequency began at a low level and increased progres- 

 sively to a maximum which was then maintained at 

 a plateau (fig. 12.4). Later workers confirmed this 

 observation, not only for amphibian but also for 

 some mammalian hearts, and also made the generali- 

 zation that for any regular stimulation rate a charac- 

 teristic level of twitch tension was achieved (61, 114), 

 being low at low frequency and higher at increased 

 frequencies over a certain range (fig. 12B). It was 

 clear, however, especially in the case of mammalian 



