A humanized anti-cocaine mAb antagonizes the cardiovascular effects of cocaine in rats.
A humanized anti-cocaine mAb antagonizes the cardiovascular effects of cocaine in rats.
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DOI：
10.1002/prp2.1045
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发表时间：
2023-02
影响因子：
2.6
通讯作者：
中科院分区：
文献类型：
--
作者：
重组单克隆抗可卡因抗体h2E2在血浆中螯合可卡因，使浓度增加10倍以上。血浆中可卡因水平的增加可能会对外周产生有害影响，特别是对心血管系统。我们研究了可卡因对大鼠心脏的作用的持续时间和幅度，以及H2E2是否可以拮抗这种作用。使用超声心动图评价异氟烷麻醉下的心脏功能，同时使用尾袖测量血压。静脉内给予钴，连续监测大鼠共45分钟。每5分钟记录一次超声心动图测量值，并在整个实验期间使用30秒循环记录血压测量值。ECG记录与超声心动图测量同时进行。可卡因推注后，射血分数增加，最大变化发生在25分钟。在可卡因推注前1小时用h2E2治疗对心脏参数没有任何影响。随后的可卡因治疗对射血分数没有影响，表明抗体结合的可卡因不影响心脏。可卡因的这种拮抗作用在1周后大大降低，1个月后完全消失。可卡因在h2E2存在下是无活性的，并且h2E2可能具有逆转可卡因对心血管系统的作用的额外临床效用。可卡因推注后，射血分数增加，最大变化发生在25分钟。在可卡因推注前1小时用h2E2治疗对心脏参数没有任何影响。随后的可卡因治疗对射血分数没有影响，表明抗体结合的可卡因不影响心脏。可卡因在h2E2存在下是无活性的，并且h2E2可能具有逆转可卡因对心血管系统的作用的额外临床效用。
The recombinant monoclonal anti‐cocaine antibody, h2E2, sequesters cocaine in plasma increasing concentrations more than 10‐fold. The increased levels of cocaine in the plasma could have detrimental peripheral effects, particularly on the cardiovascular system. We investigated the duration and magnitude of the effect of cocaine on the rat heart, and if h2E2 could antagonize that effect. Echocardiography was used to evaluate cardiac function under isoflurane anesthesia, while a tail‐cuff was used to measure blood pressure. Cocaine was delivered intravenously and the rats were continuously monitored for a total of 45 min. Echocardiography measurements were recorded every 5 min and blood pressure measurements were recorded throughout the duration of the experiment using 30‐s cycles. ECG recordings were taken simultaneously with the echocardiography measurements. An increase in ejection fraction was seen after the cocaine push with the maximum change occurring at 25 min. Treatment with h2E2 1 h before the cocaine push did not have any effect on cardiac parameters. Subsequent cocaine treatment had no effect on the ejection fraction, indicating that the antibody‐bound cocaine does not affect the heart. This antagonism of cocaine's effects was greatly decreased after 1 week and entirely absent after 1 month. Cocaine in the presence of h2E2 is pharmacologically inert and h2E2 may have additional clinical utility for reversing cocaine effects on the cardiovascular system. An increase in ejection fraction was seen after the cocaine push with the maximum change occurring at 25 min. Treatment with h2E2 1 h before the cocaine push did not have any effect on cardiac parameters. Subsequent cocaine treatment had no effect on the ejection fraction, indicating that the antibody‐bound cocaine does not affect the heart. Cocaine in the presence of h2E2 is pharmacologically inert and h2E2 may have additional clinical utility for reversing cocaine effects on the cardiovascular system.
影响因子：
6.1
作者：
Wetzel HN;Zhang T;Norman AB
通讯作者：
Norman AB