Ascorbic acid: a nonradioactive extracellular space marker in canine heart

Abstract

The distribution pattern of ascorbic acid and L-[14C]ascorbic acid in myocardial tissue was compared with those of the classical radioactive extracellular space markers [3H]-inulin, [3H]sucrose, and Na82Br. A new polarographic technique was developed for analogue registration of ascorbic acid concentration in coronary venous blood. The kinetic data of the markers were studied in an open-chest canine heart preparation (n = 17 dogs) during a constant tracer infusion of up to 9 min. Distribution volumes were calculated based on the mean transit time method of Zierler (K. L. Zierler, Circ. Res. 10:393-407, 1962). The distribution volume of ascorbic acid (23.6 ml/100 g wet wt) as well as of L-[14C]ascorbic acid (24.5 ml/100 g wet wt) in myocardial tissue agreed closely with those of [3H]inulin (18.6 ml/100 g wet wt) and [3H]sucrose (22.0 ml/100 g wet wt), as well as 82Br- (27.3 ml/100 g wet wt). The obtained kinetic data confirmed that ascorbic acid exhibits the physicochemical properties of an extracellular space marker, though this compound was shown to leak slowly into myocardial cells. Favorable attributes of this indicator are its low molecular weight, high diffusibility in interstitial fluid, low binding affinity to macromolecules, and high transcapillary (1.8 X 10(-5) cm/s) as well as low transplasmalemmal penetration rate (3.7 X 10(-8) cm/s). Therefore, this nonradioactive marker can be applied in a safe and simple fashion, and without untoward side effects in experimental animals as well as in patients.