Snakebite is a common occurrence in many parts of the world, paticularly in tropical ares. The venoms of certan snakes, especially the Crotalid family, which includes rattlesnakes, cooperheads, and water mocassins in the United States, causes extensive tissue damage, which in many cases leads to dysfunction or complete loss of extremity. Our objective is to determine the chemical and pharmavological properties of the toxins responsible for hemorrhage and necrosis and the mechanisms of tissue damage on envenomation. Different hemorrhagic toxins and myotoxins will be isolated from snake venoms and their effects on artificial membranes, platelet aggregation, isolated endothelial cells, and sarcoplasmic reticulum will be investigated. In order to establish structure- function relationships of myotoxin a, the toxin wll be modified using several methods and its effect on myonecrotic activity and SR calcium-ATPase activity will be investigated. For the long-term goal, we hope that our research will contribute to the long-range objective of better snakebite treatment, especially n the prevention of tissue damage. Also, by developing the experimental model for this research, we predict their applicability to the study of myodegenerating afflictions and hemorrhagic disorders of man.
