Acute and subacute toxicity of 7.5% hypertonic saline/6% dextran‐70 (hsd) in dogs 1. serum immunoglobulin and complement responses

Abstract

Clinical use of modern dextran solutions has been limited by concerns of anaphylactoid reactions. To assess the short-term antigenic response to 7.5% hypertonic saline in 6% Dextran-70 (HSD), sera were obtained from dogs involved in the acute and subacute toxicology testing of HSD and its individual components, and analyzed for IgG, IgM and C3 complement. In separate studies, beagles were infused i.v. with a single dose of HSD or its components at 20 ml kg-1 (the maximum tolerated dose; MTD), or the MTD daily for 14 days, and serum was obtained prior to and at various times after infusion up to 14 days. In both studies, despite serum dextran concentrations exceeding 2000 mg dl-1, no induction of IgG, IgM or C3 complement concentrations were observed. In addition, serum IgG immunoelectrophoretic patterns were of normal curvature, position and intensity; the immunoprecipitin bands were not displaced, bowed, inhibited or thicker than the normal preinfusion immunoelectrophoretograms. The data suggest that single or multiple HSD i.v. injections, as much as five times the proposed therapeutic level for the treatment of hypovolemia, evoked no increase in antibody titers in dogs. Therefore, therapeutic use of HSD in the treatment of hemorrhagic shock should not be associated with widespread concomitant allergic complications.

Lessons learned from the porcine CARPA model: constant and variable responses to different nanomedicines and administration protocols

“…Accordingly, there is a great number of reports in the literature on C activation and its consequences in various animals, Brought to you by | University of Michigan Authenticated Download Date | 6/16/15 10:59 PM including rats (9,(29)(30)(31)(32)(33), mice (33), dogs (34)(35)(36)(37), rabbits (38,39) nonhuman primates (40)(41)(42)(43)(44)(45)(46)(47)(48)(49) and pigs (50)(51)(52)(53)(54)(55). Among these experimental systems, it is the pigs' response to C activator liposomes that best mimics the human infusion reactions to liposomes in terms of kinetics and spectrum of symptoms and the conditions of reaction induction (Table 1).…”

Acute and Subacute Toxicity of 7.5% Hypertonic Saline/6% Dextran-70 (HSD) in Dogs

“…However, since hematocrit and serum protein concentrations were not affected 6 hours after HSD infusion, 25 this effect on serum K cannot be readily explained by simple hemodilution and may be related to increased renal excretion of Na and K following HSD infusion. However, urine was not collected in this study to confirm this hypothesis.…”

Eficácia da solução de cloreto de sódio a 7,5% com e sem dextran 70 a 6% na preservação da função renal de cães hipovolêmicos submetidos à isquemia-reperfusão

“…Média e Desvio Padrão em Cada Momento nos 3 Grupos Comentário: Após a hemorragia (30% da volemia) e posterior reposição (M1), O volume urinário teve relevância estatística (p<0,05) em G3*, com valores elevados, comparando-se aos dos demais grupos, no decorrer do experimento A associação de dextran 70 a 6% permitiu prolongar os efeitos hemodinâmicos da SH por mais de 30 minutos 11 . Na dose de 4 ml.kg -1 e utilizada uma única vez, a SHD é eficiente e virtualmente isenta de efeitos adversos 12,13 .…”

“…The association of 6% dextran 70 has prolonged HS hemodynamic effects for more than 30 minutes 11 . In a single dose of 4 ml.kg -1 , HSD is effective and virtually free of adverse effects 12,13 . In post-hemorrhagic situations, HSD restores blood flow to several organs, including the kidney 14 .…”