EFFECTS ON" THE HEART 215 



(1) the pacemaker cells may be more permeable to pyruvate, (2) the ener- 

 getic basis for impulse discharge may reside in the cycle more exclusively, 

 (3) the pacemaker cells may be less permeable to iodoacetate, which thus 

 acts less on the cycle, allowing pyruvate to be more effective, and (4) the 

 pacemaker cells may possess a lower energy requirement than the rest of 

 the cells (here one must assume that they do not contract) and hence re- 

 tain a higher level of ATP and creatine-P, so that secondary changes, inter- 

 fering with the utilization of pyruvate, do not occur. The dependence of the 

 pacemaker cells on the operation of the cycle is also suggested by the fact 

 that fluoroacetate depresses rate and amplitude equally in contrast to the 

 action of iodoacetate (Webb, 1950). 



All the cardiac responses to iodoacetate discussed in the preceding sec- 

 tion are fundamentally like those of skeletal muscle, except where there is 

 obvious functional difference between the two types of muscle (e.g., the 

 spontaneous discharge in the heart), and there is no doubt that the basic 

 actions of iodoacetate are the same in both. 



Effects on Specific Cardiac Functions and Behavior 



Iodoacetate reduces both the rate of heating and the contractile afnplitude, 

 but usually affectes the latter earlier and more strongly (Neuss, 1931; 

 Kleinfeld et al., 1955; Webb, 1950 a). At certain times during the action of 

 iodoacetate, the contractility may be quite depressed and the rate remain 

 normal, or even be greater, as in the perfused frog heart where 0.05 mM 

 iodoacetate slowly increases the rate to some 15% above normal while the 

 cardiac output and stroke volume are depressed 70-80% (Kleinfeld et al., 

 1955). Gardner et al. (1954) reported that the depression of rate by iodo- 

 acetate is always less than the depression of amplitude in rabbit atria at 

 37-380, whereas at 30° the opposite is the case, but my work was done at 

 30° and the rate was much less sensitive. No explanation for this discrep- 

 ancy can be offered. The frequency-force relationship in rabbit atria is 

 altered by iodoacetate (Fig. 1-21) (Katzung et al., 1957). However, at all 

 rates there is a depression of the basal contraction by iodoacetate, although 

 the degree of inhibition varies somewhat. Iodoacetate also reduces post- 

 stimulation potentiation to the same degree as the basal contraction. 



There has been some argument about the relative effects of iodoacetate 

 on the rate of conduction in different regions of the heart, but there is no 

 disagreement that conduction is generally slowed, although it may occur 

 relatively late in the sequence of actions. Electrocardiographic studies have 

 shown a progressive lengthening of the p-r interval (slowing of conduction 

 between atria and ventricles) and a broadening of the qrst complex (slow- 

 ing of intraventricular conduction) (Siegel and Unna, 1931 a; Goldenberg 

 and Rothberger, 1931; De Boer and Spanhoff, 1933; Lenzi and Caniggia, 

 1953). This may lead to a complete block between the atria and the ventri- 



