Lomonte B, Lundgren J, Johansson B, Bagge U
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Toxicon. 1994 Jan;32(1):41-55. doi: 10.1016/0041-0101(94)90020-5.
The acute tissue damaging effects of Bothrops asper snake venom and a myotoxic Lys-49 phospholipase A2 (myotoxin II) on the mouse cremaster muscle were studied by intravital and electron microscopy. Both venom and myotoxin induced local contractions of the muscle fibres within 10-60 sec after exposure, which disappeared after 1-2 min. This observation is consistent with the hypothesis that Bothrops myotoxins act initially at the sarcolemma by affecting its permeability and allowing an influx of calcium. The venom also induced an early but transient vasoconstriction of arterioles. The development of edema was monitored using i.v. FITC-dextran as a marker. Plasma leakage started after about 2 min of exposure to venom or myotoxin, was extensive by 4-5 min, and originated from small venules and their adjoining capillary segments. The venom induced formation of thrombi and emboli in venules, but not in arterioles. Haemorrhage appeared after 4-6 min of exposure, the bleedings always originating from capillaries and small venules. The microbleedings were explosive, appearing as rapid bursts of erythrocytes into the extravascular space, and suggesting a per rhexis type of haemorrhage. This was confirmed by electron microscopy evaluation of the same microvessels observed intravitally, which showed erythrocyte extravasation through gaps in damaged endothelial cells. Other phenomena in the microcirculation included blood-flow disturbances, crenation and sphering of erythrocytes, and stasis with dense packing of cells in capillary networks. Muscle necrosis, caused by either venom or myotoxin, started 3-4 min after application. The first sign of damage in the fibres was the development of a narrow, transverse band with local loss of striation. This was followed by slow retraction of myofibrils until there was a complete transverse rupture of the fibre. This process was often repeated along the same fibre, leaving a row of fragments separated by spaces apparently devoid of myofibrillar material. The results confirm the rapid tissue damaging effects of B. asper venom, implying that potentially useful blocking agents must be administered early and have the ability to diffuse rapidly into the tissues.
通过活体显微镜和电子显微镜研究了矛头蝮蛇毒和一种具有肌毒性的Lys-49磷脂酶A2（肌毒素II）对小鼠提睾肌的急性组织损伤作用。毒液和肌毒素在暴露后10 - 60秒内均可诱导肌纤维局部收缩，1 - 2分钟后消失。这一观察结果与矛头蝮肌毒素最初通过影响肌膜通透性并允许钙内流而作用于肌膜的假说一致。毒液还可诱导小动脉早期但短暂的血管收缩。使用静脉注射异硫氰酸荧光素标记的葡聚糖作为标志物监测水肿的发展。暴露于毒液或肌毒素约2分钟后开始出现血浆渗漏，4 - 5分钟时渗漏广泛，且起源于小静脉及其相邻的毛细血管段。毒液可诱导小静脉内血栓和栓子形成，但小动脉内不会形成。暴露4 - 6分钟后出现出血，出血总是起源于毛细血管和小静脉。微出血具有突发性，表现为红细胞迅速大量涌入血管外间隙，提示为撕裂性出血。通过对活体观察的相同微血管进行电子显微镜评估证实了这一点，该评估显示红细胞通过受损内皮细胞的间隙外渗。微循环中的其他现象包括血流紊乱、红细胞皱缩和球形化以及毛细血管网中细胞密集堆积导致的血流停滞。由毒液或肌毒素引起的肌肉坏死在应用后3 - 4分钟开始。纤维损伤的第一个迹象是出现一条狭窄的横向带，局部横纹消失。随后肌原纤维缓慢回缩，直至纤维完全横向断裂。这个过程经常在同一根纤维上重复，留下一排由明显没有肌原纤维物质的间隙隔开的碎片。结果证实了矛头蝮蛇毒具有快速的组织损伤作用，这意味着必须尽早给予潜在有用的阻断剂，且其必须能够迅速扩散到组织中。
