402 2. ANALOGS OF ENZYME REACTION COMPONENTS 



Effects of 2-DG on the Heart * 



The contractile tension of rat atria is progressively depressed by 10 mM 

 2-DG when glucose is present at its usual concentration of 5.5 mM; the inhi- 

 bition is 25% at 20 min, 50% at 40 min, and 70% at 90 min (A. Gimeno and 

 M. Gimeno). If pyruvate is present, the rate of depression is slower and the 

 inhibition is 30% at 90 min; if pyruvate is added at 30 min when the depres- 

 sion by 2-DG is around 40-45%, there is partial recovery to the — 30% 

 level; if glucose and pyruvate are present and 2-DG is added at 30 min, 

 there is a depression to the — 30% level at 90 min. The atria in the absence 

 of glucose progressively fail so that at 30 min the contractile tension is 

 50% depressed (actually the course is quite similar to that when glucose 

 and 2-DG are present), but with 2-DG the rate of fall is much faster, in- 

 dicating that 2-DG can effect the endogenous metabolism. Addition of 

 glucose at 30 min when the depression is 80% or more results in partial 

 recovery, pyruvate is less effective, and both allow return to near the 

 — 30% level. The rapid cessation of the 2-DG depression brought about 

 by either glucose or pyruvate is noteworthy. The contractile levels reached 

 in 90 min may be summarized in the following tabulation. The failure of 



(I) Glucose-free and glucose added at 30 min — 0% 



(II) Glucose-free and pyruvate added at 30 min —15% 



(III) Glucose + pyruvate + 2-DG (in any order) —30% 

 (IV^ Glucose + 2-DG (in any order) -70% 



(V) 2-DG alone -90% to -100% 



pyruvate to maintain normal contractions might indicate that some 25-30% 

 of the tension is dependent on glycolysis, but it is also possible that 2-DG is 

 interfering in some way with the utilization of pyruvate. The ability of 

 glucose to stimulate 30 min after depression by 2-DG at 10 mM shows 

 that the block of glycolysis is only partial or that glucose is acting by some 

 other mechanism. The atrial depression by anoxia (— 85% at 10 min) is 

 accelerated by 2-DG (— 93% at 5 min and — 100% at 10 min), and re- 

 covery upon readmission of Og is much less when 2-DG is present (J. La- 

 cuara). Rat ventricle strip contractility is not affected over 160 min by 

 0.5-2 milf 2-DG, but 4 mM causes a slow depression and partially prevents 

 the positive inotropic effect of ouabain (E. Majeski). 



* Inasmuch as so little is known of the effects of 2-DG on tissue functions and 

 nothing has been reported relative to the heart, this section summarizes briefly some 

 of the recent work done in our department and not yet published at the time of sub- 

 mission of the manuscript. 



