EFFECTS ON THE HEART 211 



EFFECTS ON THE HEART 



It was natural that the interest aroused by the report of Lundsgaard on 

 voluntary muscle, the dissociation of contraction and rigor from lactate 

 formation, would stimulate similar studies on other tissues. Cardiac muscle 

 was one of the first investigated and remains perhaps the most thoroughly 

 studied tissue.* One may say that in general the myocardium resembles 

 voluntary muscle in its response to iodoacetate; i.e., its metabolism is altered 

 similarly, its function is depressed, and eventually a state of rigor occurs. 

 However, there are important differences and much to be learned from the 

 reports on the heart, especially in an analysis of the functional changes. 

 One may ask if there is an obvious difference in the sensitivities of the two 

 tissues to iodoacetate. Ever since the work of Pohl (1888) showing that the 

 heart beats for a short time after a frog is completely paralyzed and in a 

 generalized state of rigor, it has been the impression that the heart is some- 

 what less sensitive, and most work on isolated preparations tends to con- 

 firm this. Nevertheless, administration of iodoacetate to animals invariably 

 results in definite and often marked cardiac changes, as is well shown by the 

 electrocardiographic deviations (page 218); these may be briefly summarized 

 as depressions of contractility and rate, slowing of the conduction, appear- 

 ance of various dysrhythmias (occasionally terminating in ventricular fi- 

 brillation), and systolic arrest. 



Effects on the Heart Similar to Those on Skeletal Muscle 



Certain changes brought about by iodoacetate in the heart can be con- 

 veniently related to the previously discussed results in muscle and repeti- 

 tion of treatment reduced to a minimum. 



(A) Potentiation of the effects by anoxia and other inhibitors. The myocar- 

 dium will continue to function rather well at certain concentrations of iodo- 

 acetate if oxygen is present, but will fail rapidly if anoxia is imposed. This 

 is true in all cardiac preparations studied: frog heart (Clark et al., 1932; 

 Gaddie and Stewart, 1933; Kingisepp, 1935), rabbit atria (Chang, 1938 a), 

 dog heart (Bogue et al., 1938), and cat papillary muscle (Lee, 1954). The 

 frog heart can beat for several hours aerobically in 0.27 mM iodoacetate, 



* It is interesting, as a sidelight on the pattern of development of inhibitor studies, 

 that work Mith iodoacetate on the heart has waxed and waned in a very definite way. 

 Two peaks of activity are evident: 1931-1934 and 1953-1955. The rate of such pub- 

 lications by decades reflect., llie trends clearly: in the thirties there were 4.5/year, 

 in the forties 0.4/year, in the fifties 2.8/year, and so far in the sixties a fall to 1.0/year. 

 The various factors responsible for this undulant development are many and illustrate 

 one important aspect of the interrelationship of the various fields of science and 

 medicine, but are beyond the purpose of this treatise to describe. 



