218 1. lODOACETATE AND lODOACET AMIDE 



acetate. This is probably related to the shortening of the action potential 

 duration (see page 219), as first suggested by Dale (1935). It is surprising 

 that Gardner et al. (1954) found little if any change in the refractory period 

 of rabbit atrium up to 3-4 hr and then only a sudden increase (i.e., de- 

 crease in maximal following rate) (Fig. 1-22); possibly the terminal changes 

 are more related to excitability than refractory period. The dysrhythmias 

 seen both in vivo and in vitro are perhaps to be mainly attributed to the 

 usually marked decrease in the refractory period, coupled with centers of 

 lowered membrane potential and heightened automaticity. Since anoxia 

 causes similar changes one would like to know if there is an effect of iodo- 

 acetate on coronary flow, but little work has been done. In the dog heart- 

 lung preparation, iodoacetate causes a marked increase in coronary flow 

 (Gottdenker and Rothberger, 1936), but it is not known if this occurs in 

 vivo. 



The alterations of the electrocardiogram observed with iodoacetate are 

 generally those associated with metabolic insufficiency of the myocardium. 

 The lengthening of the p-r and qrst intervals has been mentioned. In addi- 

 tion there is a decrease in the t wave amplitude, inversion, and eventual 

 disappearance in the frog (Lowenbach, 1931; Goldenberg and Rothberger, 

 1931, 1934; Kossmann, 1957), rabbit (Siegel, 1931; Siegel and Unna, 1931 a; 

 Maltesos, 1934), and dog (Andersen et al., 1955). The behavior of the t wave 

 during metabolic depression by various agents was much studied in the 

 attempt to relate it to myocardial metabolism or to particular pathways. 

 Siegel and Unna (1931 a, b) believed the t wave to be an expression of 

 glycolysis and lactate formation, whereas Lowenbach (1931) felt it to be 

 independent of lactate formation. These arguments are not now of much 

 relevance, since the magnitude and form of the t wave are known to be 

 dependent on the repolarization rate and the pattern of repolarization 

 throughout the ventricle, processes affected by essentially any metabolic 

 disturbance. The t wave inversion seen with iodoacetate is probably not 

 due to coronary constriction but to the direct metabolic deficiency of the 

 myocardium. 



Effects on Myocardial Transmembrane Potentials 



Cardiac function and many of the characteristics discussed in the pre- 

 vious sections depend primarily on the cellular potentials and their changes. 

 Iodoacetate produces alterations generally similar to those occurring during 

 metabolic depression, whether by inhibitors, anoxia, or substrate depletion. 

 Although the electrical changes in atria and ventricles are fundamentally 

 the same, we shall discuss them separately for convenience. 



The magnitude of the action potential of rabbit atrium is gradually re- 

 duced by 0.04 m.M iodoacetate in some cases, but in others there is an initial 

 depression of some 30% followed by a period of no change and then a sudden 



