Abstract 3596: The Effect of Chiral Isolates of Digoxin on Systemic Vascular Resistance
Digoxin has been observed to cause a rise in systemic vascular resistance as well as coronary vascular resistance. In a study evaluating the effects of chiral isolates of digoxin on cardiac contractility and conduction in dogs anesthetized with isoflurance anesthesia, systemic vascular resistance (SVR) was calculated as aortic pressure less right atrial pressure divided by cardiac output times 80 and reported as dynes - sec1(cm−5). The chiral isolates of digoxin were obtained through HPLC techniques employing a cyclobond chiral column, separating digoxin into two distinct chromatographic peaks each with a different retention time. The optical rotation of the two isolates was +17 and +3 respectively with the same mass/charge ratio of 788, identical to racemate digoxin. The effects of the isolates and digoxin were determined in 15 catheterized dogs (n = 5 each group). Digoxin and the two isolates were infused at 1.5 μg/kg/min for 120 min. Digoxin caused a progressive increase in PR and AH intervals as well as LV and RV dp/dt. Chiral isolate 1 failed to decrease HR, or increase PR or AH intervals by 15%, while dp/dtr was increased by 50% at 15 min. Isolate 2 slowed HR and increased PR and AH intervals by 15% at 15 min while dp/dtr increased to a lesser extent (20% at 75 min and no 50% augmentation) than with chiral 1. SVR was increased by 29, 32 and 57% at 30, 90 and 120 min by racemate digoxin. Chiral isolate 1 caused a 101, 41, 105 and 50% increase in SVR 30, 60, 90 and 120 min while chiral isolate 2 decreased SVR by 28, 6, 20 and 79% at these times points. While these results represent a small sample, it appears that one chiral isolate causes a marked and consistent increase in SVR, while the other isolate that affects conduction to a greater extent causes a decline in SVR. Chiral separation of digoxin appears to provide two isolates with very different effects on SVR, and this may have important clinical implications.