title: Acute and subacute toxicity of 7.5% hypertonic saline-6% dextran-70 (HSD) in dogs. 2. Biochemical and behavioral responses.
abstract: 7.5% Hypertonic saline-6% Dextran-70 (HSD) is currently being evaluated in our laboratory as a resuscitation solution for the treatment of hypovolemia at a dose of 4 ml kg-1 body weight. A few reports of dextran toxicity, particularly of the kidney, have been cited in the literature, so the present study evaluated the acute and subacute toxicity of HSD administered i.v. to beagle dogs. In the acute toxicity studies animals were infused with a single dose of HSD, or its components of hypertonic saline (HS) or Dextran-70 (D-70), at the maximum tolerated dose (MTD: 20 ml kg-1). Controls received Ringers lactate (RL). In the HSD-infused dogs, transient but significant increases in serum alanine (ala) aminotransferase (AT), aspartate (asp) AT and alkaline phosphatase (AP) were observed for the first 72 h. In most cases this increase was also observed in the HS group. In the subacute studies, dogs were infused daily with the MTD of the above test solutions. Serum ala AT activity was 2-3-fold higher in the HSD than the RL group for the first 3 days. Again, a similar effect was observed in the HS group. Slight, transient increases in asp AT and AP activity were also observed in the HSD group. Higher lactate dehydrogenase (LDH) activity was only observed at Day 14 in dogs infused with the MTD of HSD or HS. In both studies, no adverse effects on blood urea nitrogen (BUN) or serum creatinine were observed and other transient changes in serum parameters were attributable to hemodilution induced by HSD.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Military Trauma Research, Letterman Army Institute of Research, Presidio of San Francisco, CA 94129-6800.
authors.forename: M A
authors.initials: MA
authors.lastname: Dubick
authors.forename: G M
authors.initials: GM
authors.lastname: Zaucha
authors.forename: D W
authors.initials: DW
authors.lastname: Korte
authors.forename: C E
authors.initials: CE
authors.lastname: Wade
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003911:Dextrans / Q000633:toxicity*; D004285:Dogs; D004573:Electrolytes / Q000097:blood; D004798:Enzymes / Q000097:blood; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D012140:Respiratory Tract Diseases / Q000139:chemically induced; D012462:Saline Solution, Hypertonic / Q000633:toxicity*
chemical_list: D003911:Dextrans; D004573:Electrolytes; D004798:Enzymes; D012462:Saline Solution, Hypertonic; D003404:Creatinine