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Hemodynamic Effects of The Fab Fragment of Digoxin Antibody (Digibind) in Corticotropin (ACTH) - Induced Hypertension
Hemodynamic Effects of The Fab Fragment of Digoxin Antibody (Digibind) in Corticotropin (ACTH) - Induced Hypertension
BRIEF COMMUNICATIONS
D
igitalis-like substances (DLS), which in- body to rats decreased blood pressure in DOCA-salt,3–5
hibit Na, K-ATPase, have been repeatedly 1 kidney, 1 clip,4 and aortic coarctate hypertension,6 but
demonstrated in vascular smooth muscle not in spontaneously hypertensive rats (SHR).4 How-
and myocardium of animals with various ever, Mann et al5 demonstrated that the Fab fragment
forms of ‘‘volume-expanded’’ experimental hyperten- of digoxin antibody (digibind, intravenously) did not
sion.1,2 The acute administration of antidigoxin anti- alter blood pressure in DOCA-salt hypertensive rats. In
Received June 20, 1994. Accepted August 5, 1996. Address correspondence and reprint requests to Judith A. Whit-
From the Department of Medicine, St. George Hospital, Kogarah, worth, Department of Medicine, St. George Hospital, Kogarah,
New South Wales, Australia. NSW 2217, Australia.
contrast, a recent study7 reported that digibind de- pressure transducer (World Precision Instruments, Inc.,
creased blood pressure in DOCA-salt hypertensive rats. Sarasota, FL) to pressure monitor BP-1 (World Precision
Corticotropin ( ACTH ) administration reproducibly Instruments, Inc., Sarasota, FL).
increases blood pressure in the rat, and this effect is Digibind, Digibind Vehicle (Sorbitol), Digibind
adrenally dependent.8 ACTH also increases plasma Control [Sheep IgG and Sheep IgG (Fab)2 Fragment]
immunoreactive DLS concentration in the rat, and Administration Digoxin immune Fab (ovine) digi-
there is a significant correlation between plasma DLS bind (The Wellcome Foundation Ltd., Beckenham,
and systolic blood pressure (SBP) (r Å 0.53, P õ.001, Kent, England) was reconstituted with sterile water for
n Å 44).9 Ludens et al10 suggested that the adrenal injection BP (Astra Pharmaceuticals Pty. Ltd., N. Ryde,
cortex may be a major contributor to circulating DLS NSW, Australia) and diluted to desired protein concen-
in the rat. These data led us to propose that DLS may tration (between 9 and 11 mg/mL) with sterile saline
play a role in ACTH-induced hypertension. 9 This (0.9% NaCl) for injection BP (Astra). Sorbitol was dis-
study examined the ability of digibind to antagonize solved in sterile saline for injection BP (1.8 mg/mL).
ACTH-induced hypertension in rats. Sigma’s (Sigma Chemical, St. Louis, MO) purified sheep
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