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THE EFFECT OF ADRIAMYCIN ON MAMmaLIAN CARDIAC CELLS IN TISSUE CULTURE. M. R. Ross, B. C. Abbott. Department of Biological Sciences, University of Southern California, Los Angeles, California.

Adriamycin is an anticarcinogenic agent which produces cardiotoxicity as a side effect in a significant number of cancer patients with eventual congestive heart failure. The cause of the cardiotoxic effect is not known. To investigate the basis for the cardiotoxic effect a model sys- tem of mammalian cardiac cells in culture was used to study the effect o~ the rate of total protein synthesis and DNA synthesis. The cultures were derived from neonatal (2-4 days old) rat hearts. At 24 hours after plat- ing they were incubated with adriamycin (i ~g/ml growth medium) for 3 hours. The drug was removed and the cultures reincubated with control me- dium. Duplicate cultures were used as controls. At selected times (27 hrs., 48 hrs., 72 hrs., 96 hrs., and 120 hrs.) the cultures were pulsed with radioactively labelled substrates from 5 minutes to 210 minutes. The incorporation of t~.e ~T, ino acid L-leucine [4,5-3H] was used as th~ parameter for the rate of protein synthesis and incorporation of thymi- dine [methyl-14C] for the rate of DNA synthesis. The rates of incorpora- tion in treated and control cultures were not significantly different, suggesting that the rates of protein and DNA syntheses are not impaired. Work is now in progress to isolate the myocardial cells from the epithe- lial-fibroblast cells as homogeneous entities, and to investigate the sensitivity of each to adriamycin. [Supported by the American Heart Association Los Angeles Affiliate Grant 5181G2].

The ionic determinants of the membrane potential in the rabbit ventricle E. Ruiz-Ceretti and O.F . Schanne, Department of Biophysics, University of Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4

In order to interpret the mechanisms underlying the electrophyslological effects of total ischemia and ouabaln, the intracellular concentrations of Na, K, and CI were estimated under different experimental conditions: varying~K-]_ from 0.5 to

O . 18 raM, ouabalr., 0.5 isM, and arrest of perfusion. The resting potential (RP), action potential amplitude (APA), and maximum rate of rise (V ) were measured max . throughout. The upstroke of the ventrlcular action potential was mainly determined by the activation of a sodium current, as indicated by the dependence of APA, and V on the log /_NaJo/ [Na] i . On the other hand, the potassium gradient w a s

no~at~e only determinant of the resting potentlal, as suggested by the effects of ouabain and o tKJo of 0.5 raM. Under these conditions, the measured RP departed largely from the theoretical values calculated with the Goldman equation. These results suggest that on eiectrogenic pump contributes to determine the resting potential in rabbit.ventricular muscle. [n addition, the effects of ouabain and total ischemla on V can only be explained if it is assumed that these experimental challenges act on th~a~ynamlc conductance.