THE CIRCULATION AND CIRCULATION RESEARCH IN PERSPECTIVE 



clues for their betterment. Hence a brief historical 

 recall does not seem out of place in an introductory 

 chapter. 



Methods for Studying the Determinants 

 of Cardiac Performance 



The reactions of isolated ventricles of frogs, con- 

 tracting isotonically and isometrically under various 

 degrees of filling, had been studied by Frank (19) 

 in 1895. He found that within limits stepwise in- 

 increases in end-diastolic filling and pressure deter- 

 mine the magnitude of the all-or-none response. He 

 concluded that the magnitude of end-diastolic pressure 

 was the basic determinant. 



In 1905, it was my privilege to witness Y. Hender- 

 son's demonstration of a method for recording the 

 volume curves of the ventricles in dogs. This technique 

 appeared to be a definite advance, because it per- 

 mitted registration of the details of ventricular filling 

 and ejection as well as the magnitude of successive 

 stroke volumes. It therefore constituted a better way 

 for determining the principles underlying ventricular 

 performance. As reviewed by Henderson (29), he 

 and various associates concluded a) that atrial con- 

 traction contributes so little to ventricular filling 

 that it could be ignored and b) that the ventricles 

 contract in so uniform a manner that curves taken 

 at different heart rates can be superimposed like 

 triangles in geometry. Further analysis indicated 

 c) that stroke volume is not aff"ected by increases in 

 venous pressures above the normal, and d) that stroke 

 volumes change very little at ranges of heart rate 

 from 20 to 100 per min, but, e) that at higher heart 

 rates they decrease progressively, because contrac- 

 tions encroach more and more on the rapid inflow 

 during early diastole. The corollary followed that the 

 only way that cardiac output can be altered is through 

 changes in heart rate. Henderson's conclusions were 

 contested partly on the grounds of unreliability of 

 the procedure and failure to recognize the importance 

 of atrial systole, but chiefly because all his reports 

 were linked with the hypothesis that acapnia is the 

 cause of shock (30). In short, Henderson violated a 

 well-known principle in advertising, namely, that 

 favorable features of a product must not be associated 

 with unpopular notions. Physiologists have been 

 slow to learn that new viewpoints are more often 

 accepted on the basis of their psychological appeal 

 than on the validity of data and the conservatism 

 with which conclusions are drawn. 



During my visit to Starling's laboratory in 1923, 



he told me that his decision to develop a heart-lung 

 preparation was motivated by his impression that 

 opening of the chest of an anesthetized dog did some- 

 thing that weakened cardiac contractions. The prep- 

 aration developed with Jerusalem and Patterson 

 allowed heart rate, venous inflow, and arterial re- 

 sistance to be altered one at a time. It immediately 

 came into general favor for studying the principles of 

 ventricular behavior. On the basis of observations 

 made with various associates (56, 57), Starling con- 

 cluded, contrary to Henderson, that cardiac output is 

 not altered by changes in heart rate between 60 and 

 160 per min, and can be changed only by alteration 

 of filling and stroke volume. Starling (56) held that 

 changes in end-diastolic volume or stretch, rather 

 than pressure, were the basic determinants (Starling's 

 law of the heart). 



It is not uncommon in research that adversaries 

 are right in general but wrong in particulars. This 

 was the conclusion to which Katz and I came in 

 1922; we found elements of truth in both Henderson's 

 and Starling's interpretations. Since knowledge is 

 slow afoot, but wisdom limps far behind, it was not 

 until later that the present author (70, 71, 73) realized 

 that the concepts could be harmonized with each 

 other and also with the postulates of Englemann 

 [see also Katz (36, 37)]. It remained a question, 

 however, whether changes in end-diastolic pressure 

 and volume or alterations in contractility, produced 

 by humoral or nervous influences, constituted the 

 prepotent factor in stresses to which the body is 

 submitted under normal conditions. For instance, 

 when it seemed demonstrated that venous pressure 

 rises during moderate exercise [Eyster (15)], it seemed 

 a reasonable assumption that stroke volume increases 

 during exertion in accordance with Starling's law 

 despite cardiac acceleration. Katz, Opdyke, and 

 Bulkley and their respective co-workers have studied 

 the importance of varying impedance to ventricular 

 filling in heart preparations in which one ventricle 

 only performs work. 



It is not surprising that all the dynamic factors 

 capable of affecting ventricular performance were 

 not thought of by experimenters of past generations 

 and remained fertile fields for study in the present 

 era. Better apparatus was designed and new types of 

 special circulatory preparations were developed. 

 While the results of numerous studies still seem con- 

 tradictory in many respects, they will undoubtedly 

 be integrated in subsequent chapters. Here, it is only 

 possible to refer very briefly to a few of the many 

 notable contributions of recent vears: Katz and his 



