Microcystin-LR decreases hepatic and renal perfusion, and causes circulatory shock, severe hypoglycemia, and terminal hyperkalemia in intravascularlydosed swine

Cross-bred, anesthetized female swine were given intravascularly a lethal ( 72 mug/kg; n = 6) or toxic-sublethal (25 mug/kg; n = 6) dose of microcystin -LR (MCLR), from Microcystis aeruginosa, or the vehicle (n = 4). At the hig h dose, from 12 to 18 min after administration , central venous pressure an d hepatic perfusion were significantly lower, and shortly thereafter, porta l venous pressure was significantly higher and aortic mean pressure was sig nificantly lower than controls. By 45 min postdosing, serum bile acids, lac tate, potassium , and total bilirubin, as well as blood pO(2),were signific antly higher, while hematocrit, platelet count, and blood bicarbonate, pCO( 2), and base excess were significantly lower than controls. By 90 min, seru m arginase, urea nitrogen, inorganic phosphorus, and creatinine were signif icantly higher, while glucose and blood pH were significantly lower than in controls. By 150 min, serum alanine and aspartate aminotransferases, alkal ine phosphatase, lactate dehydrogenase, and creatinine phosphokinase activi ties were significantly higher than controls. At the low dose, significant differences from controls occurred in hemodynamic, organ perfusion, and ser um chemistry parameters, but such changes generally took longer to occur an d 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% o f the total blood volume was lost into the liver. Terminally, all high-dose swine experienced hyperkalemia, and most had severe hypoglycemia. Death du e to acute MCLR toxicosis in intravascularly dosed swine appears to result from severe intrahepatic hemorrhage, partial obstruction of blood flow thro ugh the liver, circulatory shock, severe hypoglycemia, and/or terminal hype rkalemia.