Hemodynamic and calorimetric changes induced by microcystin-LR in the rat.
Microcystin-LR, a cyclic peptide from the cyanobacterium Microcystis aeruginosa, given at acutely toxic doses causes severe hepatic interstitial hemorrhage. Hemodynamic, calorimetric and acid-base balance changes after i.v. microcystin were measured. The effect of isoproterenol, dopamine, methylprednisolone and whole-blood volume expansion on the immediate hemodynamic effects after toxin administration were also evaluated. A dose of 100 micrograms kg-1 was invariably lethal for rats in all studies. Pathophysiological changes included: a sustained, rapid decline in cardiac output and stroke volume; an acute hypotension responsive to volume expansion with whole blood; a decreased heart rate, responsive to both isoproterenol and dopamine; an early decline in oxygen consumption, carbon dioxide production and metabolic rate accompanied by progressive hypothermia; and acid-base balance changes indicating partially compensated metabolic acidosis. The lethal effects of microcystin-LR were previously attributed to hypovolemic shock as a result of hepatic interstitial hemorrhage. These results indicate that, in addition, there may be a cardiogenic component that limits the physiological cardiac reserve, compromising a normal response to circulatory inadequacy.
LeClaire
R D
RD
Toxicology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
Parker
G W
GW
Franz
D R
DR
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D001481:Basal Metabolism / Q000187:drug effects*; D001810:Blood Volume; D001831:Body Temperature / Q000187:drug effects*; D002245:Carbon Dioxide / Q000378:metabolism; D000458:Cyanobacteria; D004298:Dopamine / Q000494:pharmacology; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D008387:Marine Toxins; D008775:Methylprednisolone / Q000494:pharmacology; D052998:Microcystins; D010101:Oxygen Consumption / Q000187:drug effects; D010456:Peptides, Cyclic / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D001427:Bacterial Toxins; D007773:Lactates; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D002245:Carbon Dioxide; D019344:Lactic Acid; C057862:cyanoginosin LR; D007545:Isoproterenol; D004298:Dopamine; D008775:Methylprednisolone