Myocardial uptake of ouabain in intact dog and man

The time corse of ouabain extraction from the coronary circulation was determined after single i.v. doses (3-H-labeled in the dogs). Plasma ouabain concentration ([O]) was measured in serial, paried arterial (A) and coronary sinus (CS) blood samples by radioimmunoassay in the patients and by 3-H-counting in the dogs. In both species, the difference in [O] between A and CS (A - CS [O]) narrowed rapidly during the initial 1 to 3 minutes and then at a slower rate in an exponential fashion the next 4 to 12 minutes, with a mean half-life of 2.6 plus or minus 0.4 (S.D.) minutes in the patient (n equals 6) and 1.4 plus or minus 0.5 minutes in the canine (n equals 10) studies. In four dogs, the A - CS concentration difference of sucrose (an extracellular fluid marker) was gone within 60 seconds after an i.v. bolus. In the canine studies, the exponential phase of ouabain removal from the coronary circulation accounted for 49 plus or minus 8% of that directly measured in left ventricular samples obtained shortly after ouabain uptake was complete (17.0 plus or minus 4.5 minutes after the i.v. dose). Left ventricular [O] in these samples was 11.6-fold higher than in simultaneously obtained plasma. Thus, the initial rapid efflux of ouabain, like sucrose, from the coronary circulation would appear toreflect movement into interstitial fluid, whereas the subsequent exponential removal of ouabain, occurring after equilibrium between plasma and intersitital fluid, reflects binding to myocardial cells.