'52 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



frequently made contributions of more than parochial 

 interest which opened important avenues of approach 

 in other fields. We might mention the work of Ringer 

 on the importance of the composition of the bathing 

 fluid for muscle function, that of Loewi on the 

 chemical mediation of nerve impulses, and the recent 

 discovery that digitalis is an inhibitor of active trans- 

 port processes in many kinds of tissues. By the same 

 token the cardiac physiologist must borrow from work 

 on noncardiac tissues, and so when the reader of this 

 chapter on the heart discovers that veratrine causes 

 increased potassium loss from stimulated crab nerve 

 or that the calcium concentration of rabbit blasto- 

 cvtes is 0.5 mM per kg he should not conclude that the 

 authors have a particularly whimsical or perverse 

 turn of mind. 



As for the specific sections, the first is a discussion of 

 contractility along lines which have been so fruitful 

 in the study of skeletal muscle, but which are more 

 difficult to apply to heart and ha\e therefore only 

 recently begun to be explored. The second section is 

 about sodium and potassium which are of great im- 

 portance in cardiac muscle, not only because of their 

 relationship to the electrical properties of the cell 

 membrane, but also (and in this respect heart is quali- 

 tatively different from skeletal muscle) because of 

 their influence on contractile force. These ions are 

 discussed in section 11, but they also form the central 

 topic of section vi on stimulation frequency and 

 contractile force as well as the section on digitalis. 

 The alkali metals, rubidium and lithium, reviewed in 

 section iir, are of interest mainly because as chemical 

 congeners of sodium and potassium their fate provides 

 insight into certain aspects of cell membrane permea- 

 bility and function. Calcium, discussed at length in 

 section iv, was known by Ringer to have remarkable 

 effects on the contraction of cardiac muscle. Although 

 it is now appreciated that calcium influences many 

 structures and systems of muscle (membrane, 

 actomyosin, ATPase, relaxing factor), one may still 

 ask how alterations in external calcium concentra- 

 tion influence cardiac contractility and whether 

 calcium plays a critical role at some point in excitation- 

 contraction coupling. Barium and magnesium, re- 

 viewed briefly in section v, provide little insight at the 

 present time into the normal function of cardiac 

 muscle. A chapter on the physiology of cardiac muscle 

 would be incomplete without a discussion of quinidine, 

 veratrum, and the cardiac glycosides, each of which 

 has interesting effects on the cell membrane. Acetyl 

 choline and adrenaline are not included, since they 



are reviewed in another chapter of this Handbook. No 

 extended discussion of hydrogen ion or the anions 

 will be found in this chapter. 



The bibliography is not exhaustive, nor is it in- 

 tended to be a guide for the establishment of priority 

 for discoveries in the field. Rather an attempt has 

 been made to select the best references for providing 

 further background in areas the reader may wish to 

 pursue. 



I. CONTRACTILITY 



Since this chapter of the Handbook is concerned with 

 the effects of various interventions on the mechanical 

 performance of heart muscle, it will be appropriate to 

 begin with a discussion of the definition and measure- 

 ment of muscular contractility. The term "contrac- 

 tility" does not have a very precise meaning, and 

 Bayliss, for example, in his textbook of general 

 physiology has a carefully written chapter on muscle 

 in which the word is not used at all (12). The rest of 

 the physiological literature is not so eclectic however, 

 and "contractility" abounds, having various meanings 

 for various investigators. Isometric tension, isotonic 

 shortening, velocity of shortening, cardiac output, 

 stroke work, efficiency, all have been measured in the 

 name of contractility. The discussion of this subject 

 that follows has been drawn largely from the work of 

 Hill, Fenn, and others who have worked in their 

 tradition (75, 87, 136-139, 326) mostly on skeletal 

 muscle. Although much of this work is now well 

 known, it deserves emphasis as background for a 

 chapter on a type of muscle for which a rigorous bio- 

 physical experimental approach has been difficult to 

 make. 



Work Capacity and Length-Tension Curves 



We may begin by considering the measurement of 

 the work capacity of a muscle. Hill, noting that Fick 

 had failed to devise an adequate means of measuring 

 this capacity, made the following point (136): "In 

 order to obtain the full tale of work out of the potential 

 energy of a stretched elastic body as, e.g., in excited 

 muscle, the conditions of loading must be arranged so 

 as to be what is known in thermodynamics as 're- 

 versible': i.e., the load at every length, during the 

 course of the shortening, must be exactly equal to the 

 maximum tension the muscle can exert at that 

 length." In the simple ca.se of a mu.scle lifting a weight, 

 such conditions do not obtain, since at the onset of 



