MECHANISM OF COCAINE-INDUCED MYOCARDIAL DEPRESSION IN DOGS
MECHANISM OF COCAINE-INDUCED MYOCARDIAL DEPRESSION IN DOGS
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DOI：
10.1161/01.cir.81.3.1012
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发表时间：
1990-03-01
期刊：
影响因子：
37.8
通讯作者：
WILKERSON, RD
中科院分区：
文献类型：
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作者：
FRAKER, TD;TEMESYARMOS, PN;WILKERSON, RD
在静脉注射可卡因后，清醒的狗会立即出现明显的左心室功能下降。为了研究这种影响，14只杂种狗被戊巴比妥钠（32 mg/kg）麻醉，并在左旋冠状动脉上插入动脉和静脉导管和多普勒血流传感器。两周后，在动物完全清醒的情况下，在可卡因（4 mg/kg静脉注射）前、1、2、5和10分钟，测量心率、血压、冠状动脉血流量和局部左心室射血分数（通过二维超声心动图）。每次服用可卡因后，心率、血压和冠状动脉血流量均显著增加。然而，局部射血分数下降了50。7% +- 35。4%和21。4%，分别在可卡因治疗后1、2和5分钟。可卡因治疗10分钟后，区域射血分数恢复到与基线无显著差异的水平。由于观察到的可卡因后心肌抑郁伴随着心率压积的大幅增加，并且可能是心肌耗氧量的增加，这种抑郁可能是继发于心肌耗氧量的增加，而冠状动脉血流量的增加没有适当地匹配。为了尽量减少可卡因对心肌需氧量的影响，一组6只狗接受可卡因（4毫克/公斤静脉注射），同时用戊巴比妥镇静（25毫克/公斤）。在这些狗身上，可卡因没有显著改变心率或血压；然而，局部射血分数明显降低44。5% +- 36。可卡因治疗后1分钟和2分钟分别为6%。在心肌耗氧量的主要决定因素没有改变的情况下，犬左心室功能的显著抑制与可卡因的直接心肌抑制作用是一致的。
Cocaine causes pronounced depression of left ventricular function in conscious dogs immediately after intravenous administration. To examine this effect, 14 mongrel dogs were anesthetized with pentobarbital sodium (32 mg/kg) and instrumented with arterial and venous catheters and a Doppler blood flow transducer on the left circumflex coronary artery. Two weeks later, heart rate, blood pressure, coronary blood flow, and regional left ventricular ejection fraction (by two-dimensional echocardiography) were measured before and 1, 2, 5, and 10 minutes after cocaine (4 mg/kg i.v.), while the animals were fully conscious. Heart rate, blood pressure, and coronary blood flow were increased significantly at each time after cocaine. Regional ejection fraction, however, was depressed by 50 .+-. 7%, 35 .+-. 4%, and 21 .+-. 4%, at 1, 2, and 5 minutes after cocaine treatment, respectively. Ten minutes after cocaine treatment, regional ejection fraction had recovered to a level not significantly different from baseline. Because the observed myocardial depression after cocaine was accompanied by a large increase in the rate-pressure product, and presumably, myocardial oxygen consumption, this depression could have been secondary to increased myocardial oxygen demand not appropriately matched by an increase in coronary blood flow. To minimize the effects of cocaine on myocardial oxygen demand, a subset of six dogs received cocaine (4 mg/kg i.v.) while sedated with pentobarbital (25 mg/kg). In these dogs, cocaine did not significantly alter heart rate or blood pressure; however, regional ejection fraction was significantly depressed by 44 .+-. 5% and 36 .+-. 6% at 1 and 2 minutes after cocaine treatment, respectively. Significant depression of canine left ventricular function, in the absence of changes in major determinants of myocardial oxygen consumption, is consistent with a direct myocardial depressant action of cocaine.