Richardson William H, Tanen David A, Tong Tri C, Betten David P, Carstairs Shaun D, Williams Saralyn R, Cantrell Frank L, Clark Richard F
Department of Emergency Medicine, Palmetto Richland Memorial Hospital, Palmetto Poison Center, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
Ann Emerg Med. 2005 Jun;45(6):595-602. doi: 10.1016/j.annemergmed.2004.08.038.
Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) is used in the treatment of symptomatic crotaline envenomations in North America. Unlike Antivenin (Crotalidae) Polyvalent, which is approved for treatment of crotaline envenomation in North and South America, FabAV is manufactured using only venoms from crotaline snakes native to the United States. This study was designed to evaluate the efficacy of FabAV in the neutralization of venom from 2 South American crotaline snakes: Crotalus durissus terrificus (tropical rattlesnake) and Bothrops atrox (fer-de-lance).
A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was used. Venom potency was determined in preliminary median lethal dose (LD 50) dosing studies. Study animals were then divided into 7 groups: (1) C durissus terrificus venom (Sigma-Aldrich Co.)+FabAV, (2) C durissus terrificus venom (Sigma-Aldrich Co.)+0.9% normal saline solution, (3) C durissus terrificus venom (Biotoxins Inc.)+FabAV, (4) C durissus terrificus venom (Biotoxins Inc.)+normal saline solution, (5) B atrox venom+FabAV, (6) B atrox venom+normal saline solution, and (7) FabAV+normal saline solution. Twice the estimated LD 50 was the chosen venom dose, and the amount of FabAV injected was 10 times the amount needed for venom neutralization. Statistical analysis included Fisher's exact test and log-rank testing to compare survival rates and times.
The venom LD 50 was found in preliminary studies to be 0.9 mg/kg and 1.35 mg/kg for the C durissus terrificus venom obtained from Sigma-Aldrich Co. and Biotoxins Inc., respectively. The LD 50 for B atrox venom was 5.0 mg/kg. All animals receiving venom only and saline solution died. Animals receiving FabAV together with either venom survived to the end of the 24-hour observation period ( P <.001). Comparison of survival times between groups demonstrated a significant difference in time to death between venom-only control groups and the FabAV+venom groups (P <.001). All animals in the FabAV+normal saline solution group survived to the conclusion of the study.
FabAV, when premixed with venom, decreases lethality in a murine model of intraperitoneal venom injection of the South American pit vipers, C durissus terrificus and B atrox .
响尾蛇科多价免疫Fab(羊源)(CroFab;FabAV)用于治疗北美洲有症状的响尾蛇咬伤。与批准用于治疗北美洲和南美洲响尾蛇咬伤的抗蛇毒血清(响尾蛇科)多价不同,FabAV仅使用原产于美国的响尾蛇蛇毒制造。本研究旨在评估FabAV对两种南美响尾蛇蛇毒的中和效果:杜氏响尾蛇(热带响尾蛇)和矛头蝮(矛头蛇)。
采用随机、盲法、安慰剂对照的小鼠腹腔注射蛇毒模型。在初步的半数致死剂量(LD50)给药研究中确定蛇毒效力。然后将研究动物分为7组:(1)杜氏响尾蛇蛇毒(西格玛-奥德里奇公司)+FabAV,(2)杜氏响尾蛇蛇毒(西格玛-奥德里奇公司)+0.9%生理盐水溶液,(3)杜氏响尾蛇蛇毒(生物毒素公司)+FabAV,(4)杜氏响尾蛇蛇毒(生物毒素公司)+生理盐水溶液,(5)矛头蝮蛇毒+FabAV,(6)矛头蝮蛇毒+生理盐水溶液,(7)FabAV+生理盐水溶液。选定的蛇毒剂量为估计LD50的两倍,注射的FabAV量为中和蛇毒所需量的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。
在初步研究中,从西格玛-奥德里奇公司和生物毒素公司获得的杜氏响尾蛇蛇毒的LD50分别为0.9mg/kg和1.35mg/kg。矛头蝮蛇毒的LD50为5.0mg/kg。所有仅接受蛇毒和生理盐水溶液的动物均死亡。接受FabAV与任何一种蛇毒的动物均存活至24小时观察期结束(P<.001)。各组生存时间的比较表明,仅蛇毒对照组与FabAV+蛇毒组之间的死亡时间存在显著差异(P<.001)。FabAV+生理盐水溶液组的所有动物均存活至研究结束。
在南美蝰蛇杜氏响尾蛇和矛头蝮的小鼠腹腔注射蛇毒模型中,FabAV与蛇毒预混时可降低致死率。