北美珊瑚蛇抗蛇毒血清在小鼠模型中对非本土眼镜蛇科毒液的中和作用。

North American coral snake antivenin for the neutralization of non-native elapid venoms in a murine model.

作者信息

Richardson William H, Tanen David A, Tong Tri C, Betten David P, Carstairs Shaun D, Williams Saralyn R, Cantrell Frank L, Clark Richard F

机构信息

Palmetto Richland Memorial Hospital, Department of Emergency Medicine, Palmetto Poison Center, South Carolina College of Pharmacy, Columbia, SC, USA.

出版信息

Acad Emerg Med. 2006 Feb;13(2):121-6. doi: 10.1197/j.aem.2005.07.033. Epub 2006 Jan 25.

DOI:10.1197/j.aem.2005.07.033

PMID:16436788

Abstract

OBJECTIVES

North American coral snake antivenin (CSAV; Wyeth Antivenin [Micrurus fulvius], equine origin) is approved for the treatment of coral snake envenomations in the United States. The coral snake is the only elapid that is native to North America, but envenomations from non-native elapids are occurring more commonly in this country. This study was designed to evaluate the efficacy of CSAV in the neutralization of two exotic elapid envenomations: Naja naja (Indian cobra) and Dendroaspis polylepsis (black mamba).

METHODS

A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was employed. Venom potency was determined in preliminary dosing studies. Study animals then were divided into five groups: 1) N. naja venom + CSAV, 2) N. naja venom + 0.9% normal saline (NS), 3) D. polylepsis venom + CSAV, 4) D. polylepsis venom + NS, and 5) CSAV + NS. The venom dose was chosen to be twice the estimated LD50. The amount of CSAV injected was ten times the amount necessary for neutralization of a 2 x LD50 dose of M. f. fulvius venom in a murine model. Statistical analysis included Fisher's exact and log-rank testing to compare survival rates and times.

RESULTS

Preliminary studies estimated the venom LD50 to be 2.58 mg/kg and 0.45 mg/kg, respectively, for the N. naja and D. polylepsis. A significant difference was shown in comparison of survival times between CSAV-venom groups and normal saline-venom groups despite all animals in both treatment and control arms dying. Animals receiving CSAV and N. naja venom survived (mean +/- SD) 24.4 +/- 3.0 minutes, versus 17.8 +/- 1.3 minutes in the control group (p < 0.001), whereas those receiving CSAV and D. polylepsis venom survived 203.8 +/- 37.0 minutes versus 130.0 +/- 42.6 minutes in the control group (p < 0.001). All animals in the CSAV + NS group survived to the conclusion of the study.

CONCLUSIONS

When premixed with venom, CSAV increased survival time in a murine model of intraperitoneal N. naja and D. polylepsis venom injection. The clinical implications of this are unclear, given unchanged mortality rates.

摘要

目的

北美珊瑚蛇抗蛇毒血清（CSAV；惠氏抗蛇毒血清[佛罗里达珊瑚蛇]，马源）已获美国批准用于治疗珊瑚蛇咬伤。珊瑚蛇是北美本土唯一的眼镜蛇科动物，但该国非本土眼镜蛇科动物咬伤事件正变得越来越常见。本研究旨在评估CSAV对两种外来眼镜蛇科动物咬伤的中和效果：印度眼镜蛇（Naja naja）和黑曼巴蛇（Dendroaspis polylepsis）。

方法

采用随机、双盲、安慰剂对照的小鼠腹腔注射毒液模型。在初步剂量研究中测定毒液效力。然后将研究动物分为五组：1）印度眼镜蛇毒液+CSAV，2）印度眼镜蛇毒液+0.9%生理盐水（NS），3）黑曼巴蛇毒液+CSAV，4）黑曼巴蛇毒液+NS，5）CSAV+NS。毒液剂量选择为估计半数致死量（LD50）的两倍。注射的CSAV量是小鼠模型中中和2倍LD50剂量的佛罗里达珊瑚蛇毒液所需量的10倍。统计分析包括Fisher精确检验和对数秩检验，以比较生存率和生存时间。

结果

初步研究估计印度眼镜蛇和黑曼巴蛇的毒液LD50分别为2.58mg/kg和0.45mg/kg。尽管治疗组和对照组的所有动物均死亡，但CSAV - 毒液组和生理盐水 - 毒液组的生存时间比较显示出显著差异。接受CSAV和印度眼镜蛇毒液的动物存活（均值±标准差）24.4±3.0分钟，而对照组为17.8±1.3分钟（p<0.001）；接受CSAV和黑曼巴蛇毒液的动物存活203.8±37.0分钟，而对照组为130.0±42.6分钟（p<0.001）。CSAV + NS组的所有动物均存活至研究结束。