Cardiotoxic Effect of Primaquine in Mammals:Histological and Ultrastructural Investigation

It has been known that the antimalarial drugs of aminoquinolinesincluding 8-aminoquinolines may cause inhibition of heart conduction or evenAdams-Stokes syndrome,but their morphologic bases were obscure.The purposeof the present study is to define the histological and ultrastructural features ofprimaquine in mammals including dogs,monkeys and rats in the subacute toxicexperiments with the stress on the morphological alteration of the heart.In most(11/16)of the intoxicated dogs,granular degeneration,eosinophilic degeneration,coagulation necrosis,vacuolar degeneration and colliquative myocytolysis werefound in the myocardium and conduction systems.Under electron microscopicstudy,the myocardial cells of intoxicated dogs showed swelling of mitochondria,dilatation of transverse tubules and sarcoplasmic reticulum,fusion or dissolutionof myofibrils,deformity of nuclei,clumping of chromatin,and eventually cellnecrosis.The severities of lesions were dose dependent.These lesions weresupposed to be the morphologic evidence of the toxic symptoms and signs caused byprimaquine.A few rats also revealed myocardial eosinophilic degeneration.Noimportant cardiac lesions were found in the monkeys,but the pathologic changesin the liver were obvious.Different species of laboratory animals showed differentorgan sensitivities to primaquine,but the heart lesions should be considered as animportant toxic effect of primaquine.

Cardiotoxic Effect of Primaquine in Mammals:Histological and Ultrastructural Investigation

It has been known that the antimalarial drugs of aminoquinolines including 8-aminoquinolines may cause inhibition of heart conduction or even Adams-Stokes syndrome,but their morphologic bases were obscure.The purpose of the present study is to define the histological and ultrastructural features of primaquine in mammals including dogs,monkeys and rats in the subacute toxic experiments with the stress on the morphological alteration of the heart.In most (11/16)of the intoxicated dogs,granular degeneration,eosinophilic degeneration, coagulation necrosis,vacuolar degeneration and colliquative myocytolysis were found in the myocardium and conduction systems.Under electron microscopic study,the myocardial cells of intoxicated dogs showed swelling of mitochondria, dilatation of transverse tubules and sarcoplasmic reticulum,fusion or dissolution of myofibrils,deformity of nuclei,clumping of chromatin,and eventually cell necrosis.The severities of lesions were dose dependent.These lesions were supposed to be the morphologic evidence of the toxic symptoms and signs caused by primaquine.A few rats also revealed myocardial eosinophilic degeneration.No important cardiac lesions were found in the monkeys,but the pathologic changes in the liver were obvious.Different species of laboratory animals showed different organ sensitivities to primaquine,but the heart lesions should be considered as an important toxic effect of primaquine.