EFFECTS ON THE HEART 221 



of the myocardium to tliis inhibitor. It is also clear that these actions are 

 mediated through alterations in the transmembrane ionic fluxes, but we 

 cannot at present say much more than that K+ movements are ])robably 

 modified. lodoacetate at 0.5 mM over a 30 min period causes a significant 

 net loss of atrial K+ (126.5 to 121.1 mM), K^^ efflux being increased 13% 

 and K^2 influx being decreased 11%, the contractile depression at 30 min 

 being 86% (Chin, 1963). 



Development of Rigor in Cardiac Muscle 



Cardiac preparations exposed to iodoacetate go into rigor terminally, 

 either during contraction failure or immediately after cessation of activity, 

 and the picture in general is very similar to that with skeletal muscle. 

 When iodoacetate is injected into an animal the skeletal muscles go into 

 rigor first, the heart continuing to beat for some time; then the ventricles 

 pass into rigor, and the atria may continue beating or be relaxed; and finally 

 atrial rigor occurs (Lowenbach, 1931; Goldenberg and Rothberger, 1931; 

 Wertheimer, 1931). The apparently greater tendency for the ventricles to 

 go into rigor compared to the atria may be due only to the greater amount 

 of work performed by the former and the faster depletion of high-energy 

 compounds. Clark et al. (1932) showed that ATP and creatine-P disappear 

 rapidly during rigor in the frog heart, but Dale (1937) felt that depletion 

 of these substances is not responsible for the rigor, since other inhibitors 

 such as urethane which deplete the cell of energy do not cause rigor. Dale 

 favored the accumulation of some substance. Druckrey and Loch (1943) 

 reported, rather surprisingly, that acetate not only can prevent or delay 

 rigor, but will actually cause some relaxation of a frog heart in rigor. Neither 

 acetate nor pyruvate, nor other substrate, was found to relax rabbit atria 

 in rigor (Webb, 1950 a). lodoacetate and iodoacetamide are the only in- 

 hibitors which regularly produce a marked rigor in rat atria, although 

 arsenite often produces a slowly developing rigor; p-chloromercuribenzoate 

 never produces rigor, even 2 hr after contractile failure (Webb and Hollan- 

 der, 1959). Pyruvate has no ability to relax rat atria in rigor, but it is likely, 

 that pyruvate oxidation is interfered with. A complete lack of correlation 

 between rigor and resting potential, or other membrane property, may be 

 noted; some inhibitors markedly reduce the resting potential without pro- 

 ducing rigor, while iodoacetate and arsenite lead to rigor which is initiated 

 at a time when the resting potential is definitely depressed (around 25- 

 35%) and contractions have failed, the potential continuing to fall during 

 rigor. Cardiac contractility is augmented by Ca++ and some relationship 

 to rigor might be imagined, but Thomas (1960) found that the presence of 

 EDTA in the medium neither prevents nor reverses the rigor of frog heart 

 induced by iodoacetate. Essentially nothing has been done on the mechan- 

 ical properties of the myocardium in rigor. We have never observed spon- 



