抗疟药物的心脏毒性

虽然长期应用抗疟药物诱发心脏毒性者罕见,但后果严重。临床主要表现为心脏传导阻滞、充血性心力衰竭、心律失常及心肌病。确诊需行心肌心内膜活检。光学显微镜下组织病理学改变为心肌细胞内大量空泡形成,电子显微镜下见髓样体及特征性的曲线体。抗疟药物被溶酶体选择性摄取后使溶酶体pH值升高,从而干扰溶酶体中酶类活性,导致糖原及磷脂积聚。

Cardiac Toxicity Related to Antimalarial Therapy

Cardiac toxic effects related to the antimalarial agents in long term treatment are rare, but severe. These side effects include heart conduction disturbances, arrhythmia, congestive heart failure, and cardiomyopathies. Histological findings from heart biopsies are essential to diagnose antimalarial toxicity. Light microscopy revealed swollen myocytes with severely vacuolated cytoplasm. Electron microscopy showed the cytoplasm of the myocytes contained numerous curvilinear bodies, and myeloid bodies. Antimalarial agents are regarded as lysosomotropic substances, that is, one that is selectively taken up into lysosomes. Lysosomal accumulation of antimalarial agents induces a rise in intralysosomal pH, which inhibits lysosomal enzymes, leading to accumulation of glycogen and phospholipids, thus forming myelmosos and curvilinear bodies.