title: Microcystin-LR decreases hepatic and renal perfusion, and causes circulatory shock, severe hypoglycemia, and terminal hyperkalemia in intravascularly dosed swine.
abstract: Cross-bred, anesthetized female swine were given intravascularly a lethal (72 microg/kg; n = 6) or toxic-sublethal (25 microg/kg; n = 6) dose of microcystin-LR (MCLR), from Microcystis aeruginosa, or the vehicle (n = 4). At the high dose, from 12 to 18 min after administration, central venous pressure and hepatic perfusion were significantly lower, and shortly thereafter, portal venous pressure was significantly higher and aortic mean pressure was significantly lower than controls. By 45 min postdosing, serum bile acids, lactate, potassium, and total bilirubin, as well as blood pO2, were significantly higher, while hematocrit, platelet count, and blood bicarbonate, pCO2, and base excess were significantly lower than controls. By 90 min, serum arginase, urea nitrogen, inorganic phosphorus, and creatinine were significantly higher, while glucose and blood pH were significantly lower than in controls. By 150 min, serum alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase, and creatinine phosphokinase activities were significantly higher than controls. At the low dose, significant differences from controls occurred in hemodynamic, organ perfusion, and serum chemistry parameters, but such changes generally took longer to occur and were of a lesser magnitude than at the high dose. Livers of the high-dose swine were swollen and dark red-purple, and exuded excessive blood on the cut surface. Based on increases in liver weight and liver hemoglobin, 38% of the total blood volume was lost into the liver. Terminally, all high-dose swine experienced hyperkalemia, and most had severe hypoglycemia. Death due to acute MCLR toxicosis in intravascularly dosed swine appears to result from severe intrahepatic hemorrhage, partial obstruction of blood flow through the liver, circulatory shock, severe hypoglycemia, and/or terminal hyperkalemia.
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana 61802, USA. val@uiuc.edu
authors.forename: V R
authors.initials: VR
authors.lastname: Beasley
authors.forename: R A
authors.initials: RA
authors.lastname: Lovell
authors.forename: K R
authors.initials: KR
authors.lastname: Holmes
authors.forename: H E
authors.initials: HE
authors.lastname: Walcott
authors.forename: D J
authors.initials: DJ
authors.lastname: Schaeffer
authors.forename: W E
authors.initials: WE
authors.lastname: Hoffmann
authors.forename: W W
authors.initials: WW
authors.lastname: Carmichael
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis; D001784:Blood Gas Analysis; D000458:Cyanobacteria; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006403:Hematologic Tests; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced*; D007003:Hypoglycemia / Q000139:chemically induced*; D007275:Injections, Intravenous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008099:Liver / Q000098:blood supply / Q000187:drug effects*; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000633:toxicity*; D012769:Shock / Q000139:chemically induced*; D013047:Specific Pathogen-Free Organisms; D013552:Swine; D014871:Water Microbiology
chemical_list: D004791:Enzyme Inhibitors; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C057862:cyanoginosin LR