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[一例由意外洋地黄中毒引起的“儿茶酚胺坏死”罕见病例]

[An unusual case of "catecholamine necrosis" caused by accidental digitalis poisoning].

作者信息

Piccone U, Saviotti M, Pala M, Caprari M

机构信息

Divisione di Cardiologia, Ospedale S. Carlo Borromeo, Milano.

出版信息

Minerva Cardioangiol. 1995 Sep;43(9):383-8.

PMID:8552267
Abstract

Toxic manifestations of digitalis are one of the most prevalent adverse drug reactions encountered in clinical practice. The estimated incidence is about 20% in hospitalized patients in the USA. The authors describe a rare case of myocardial "catecholamine necrosis" (anteroseptal myocardial infarction) during accidental digitalis intoxication. A male patient, 75 years old, suffering from cirrhosis and ascites, take on by mistake a tablet of digoxin 0.25 mg. four times at day for eleven days. He hadn't heart disease in the past. At the eleventh day the patient showed a deep tiredness and so he was submitted to a clinical examination and electrocardiogram. The ECG demonstrated an anteroseptal myocardial infarction in the second-third electrical stage. The patient was hospitalized. The successive examination revealed: very high plasma digitalis concentrations; an increase of the serum levels of CPK and LDH; a significant increase of plasmatic and urinary catecholamine levels which return to normal values after fifteen days; apical akinesia at the echocardiographic examination; no signs of residual myocardial ischemia to the echo-dypiridamole stress test; normal coronary artery to the coronary arteriography and absence of coronary artery spasm to the ergonovine test. Furthermore the abdominal echography and the abdominal computerized tomography didn't reveal surrenal disease but showed an important liver disease. The patient was free from other cardiac events in the follow-up. Generally, during the digitalis intoxication we observe various rhythm and conduction disturbances. Instead in this case no serious arrhythmias were registered and the main expression of the drug toxicity was an anteroseptal myocardial infarction with undamaged coronary artery. Also the usual extracardiac symptoms and signs of the digitalis intoxication were absent in this case. All these observations can be explained with the pathological increase of the cathecholamine levels, indirectly induced by digitalis; with the direct toxic effect of the drug at the myocardic level; with the contemporary absence of ionic disturbances; with the concomitant liver disease. The direct toxic effect of the digitalis produced an increase in calcium ions availability for the electromechanical coupling and an increase of the intramyocardial pressure; the increase of the adrenergic activity determined contemporary an increase in the oxygen consumption of the myocardial cells, a rise of vascular tone and coronary artery tone and a reduction of the duration of the diastole. All these factors provoked a "primary and secondary" ischemia which evolved toward a real "cathecholamine necrosis" and produced a myocardial infarction. This hypothesis explains the myocardial infarction in absence of injury at the coronary arteriography and without coronary spasm at the ergonovine test; moreover it explains the transient increase in cathecholamine plasma levels observed in the acute phases an normalized after fifteen days. The "cathecholamine necrosis" is an anatomical definition, nevertheless in our opinion it gives account of the rare clinical situation observed.

摘要

洋地黄的毒性表现是临床实践中最常见的药物不良反应之一。在美国,住院患者中的估计发病率约为20%。作者描述了一例意外洋地黄中毒期间发生心肌“儿茶酚胺坏死”(前间隔心肌梗死)的罕见病例。一名75岁男性患者,患有肝硬化和腹水,误服地高辛0.25mg片剂,每日4次,共11天。他既往无心脏病史。在第11天,患者出现极度疲劳,因此接受了临床检查和心电图检查。心电图显示在心电图第二至第三阶段出现前间隔心肌梗死。患者住院治疗。后续检查发现:血浆洋地黄浓度极高;肌酸磷酸激酶(CPK)和乳酸脱氢酶(LDH)血清水平升高;血浆和尿儿茶酚胺水平显著升高,15天后恢复正常;超声心动图检查显示心尖运动减弱;多巴酚丁胺负荷超声心动图试验未发现残余心肌缺血迹象;冠状动脉造影显示冠状动脉正常,麦角新碱试验未发现冠状动脉痉挛。此外,腹部超声和腹部计算机断层扫描未发现肾上腺疾病,但显示有严重肝脏疾病。在随访中患者未发生其他心脏事件。一般来说,在洋地黄中毒期间,我们会观察到各种节律和传导紊乱。而在该病例中,未记录到严重心律失常,药物毒性的主要表现是前间隔心肌梗死,冠状动脉未受损。此外,该病例中也没有洋地黄中毒常见的心脏外症状和体征。所有这些观察结果可以用洋地黄间接诱导的儿茶酚胺水平病理性升高、药物在心肌水平的直接毒性作用、同时不存在离子紊乱以及合并肝脏疾病来解释。洋地黄的直接毒性作用使钙离子可用于电机械耦联的量增加,心肌内压力升高;肾上腺素能活性增加同时导致心肌细胞耗氧量增加、血管张力和冠状动脉张力升高以及舒张期持续时间缩短。所有这些因素引发了“原发性和继发性”缺血,进而发展为真正的“儿茶酚胺坏死”并导致心肌梗死。这一假说解释了冠状动脉造影无损伤且麦角新碱试验无冠状动脉痉挛情况下的心肌梗死;此外,它还解释了急性期观察到的儿茶酚胺血浆水平短暂升高并在第15天后恢复正常的现象。“儿茶酚胺坏死”是一种解剖学定义,不过在我们看来,它解释了所观察到的这种罕见临床情况。

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