216 



1. lODOACETATE AND lODOACETAMIDE 



cles resulting in dissociation, and eventually to serious impairment in con- 

 duction over the ventricles. De Boer and Spanhoff (1933) believed that sino- 

 atrial block occurs in the frog heart before atrio-ventricular block, but Gol- 

 denberg and Rothberger (1934) felt that the electrocardiogram obtained by 

 the former workers was abnormal, perhaps due to apical damage, and that 

 sino-atrial block is not particularly important. It seems from later work that 



I 2 3 



STIMULATION FREQUENCY (SEC"') 



Fig. 1-21. Effects of various inhibitors on the fre- 

 quency-force relationship in rabbit atria following 

 60-70 min exposure. F = 7.2 mM; iodoacetate = 

 0.05 mM; DNP = 0.03 mM; CN = 0.4 mM; and 

 fluoroacetate = 0.0 mil/. (From Katzung et al., 1957.) 



atrio-ventricular conduction is the most sensitive, but this may depend on 

 the species and many other factors. Anoxia of the frog heart causes slowing 

 of conduction and iodoacetate partially prevents this, which Kingisepp 

 (1935) attributes to the failure of the pH to decrease in the presence of 

 iodoacetate. Studies on isolated atria have confirmed the slowing of conduc- 

 tion. The conduction in rabbit atria is not altered by 0.04 mM iodoacetate 

 for 3 hr but then falls precipitously, following closely the change in refrac- 

 tory period (Fig. 1-22) (Gardner et al., 1954), both of these parameters 

 possibly being related to the depolarization rate. Higher concentrations of 

 iodoacetate and iodoacetamide (0.8-1 mM) produce moderate slowing of 

 conduction in rat atria in a shorter time, but conduction is not as sensitive 

 as the contractility (Webb and Hollander, 1959). 



The electrical excitability of rabbit atria decreases fairly rapidly to around 



