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 mu g 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.