Assessment of efficacy of bothropic antivenom therapy on microcirculatory effects induced by Bothrops jararaca snake venom

• Published in: Toxicon (Oxford) Vol. 41; no. 5; pp. 583 - 593
• Main Authors: Battellino, Carolina, Piazza, Roxane, da Silva, Ana M.M, Cury, Yara, Farsky, Sandra H.P
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.04.2003; Elsevier Science
• Subjects: Administration, Topical; Animal poisons toxicology. Antivenoms; Animals; Antivenins - administration & dosage; Antivenins - pharmacology; Biological and medical sciences; Bothropic antivenom; Bothrops; Bothrops jararaca venom; Capillaries - drug effects; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Hemorrhage - chemically induced; Injections, Intravenous; Intravital microscopy; Local effects; Male; Medical sciences; Microcirculation; Microcirculation - drug effects; Rats; Rats, Wistar; Snake Venoms - administration & dosage; Snake Venoms - toxicity; Spermatic Cord - blood supply; Spermatic Cord - drug effects; Toxicology; Intravital microscopy; Microcirculation; Bothropic antivenom; Bothrops jararaca venom; Local effects; Intravenous administration; Rat; Leukocyte; Toxicity; Treatment efficiency; Rodentia; Animal origin; Cardiovascular disease; Permeability; Hemorrhage; Endothelium; Ophidia; Prevention; Toxin; Vertebrata; Mammalia; Treatment; Antivenom; Animal; Venom; Reptilia; Circulatory system
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/S0041-0101(02)00389-6

Intravenous administration of antibothropic antivenom (BAv) neutralises the systemic effects, but does not efficiently reverse the local symptoms elicited by the Bothrops jararaca venom (BjV). The mechanisms involved in this poor protection have not been clarified. In this work, intravital microscopy studies were carried out to determine the efficacy of different schedules of BAv treatment on local effects evoked by topical application of BjV in the microcirculatory network of the internal spermatic fascia of Wistar rats. Results demonstrated that BAv administration 15 min before, simultaneously with, or 15 min after BjV application did not totally reverse the local symptoms, represented by disturbances of coagulation, development of haemorrhage lesions, vascular permeability increase and increment on leukocyte–endothelium interactions. This lack of effectiveness neither reflects an inadequate amount of specific antibodies in the antivenom against toxins responsible for local effects nor an insufficient dose of circulating BAv during the assays. Administration of fluorescein isothiocyanate (FITC) labelled-BAv showed the dynamics of distribution of the antivenom in the microcirculatory network. Images obtained from prior and simultaneously treated animals showed that the antivenom remains at luminal side of vessels before venom application, and the latency time to antivenom leakage is coincidental to that for local effects evoked by the venom. In addition, images from posterior treatment demonstrated that the intense alterations in the microcirculatory network impair antivenom distribution at the site of injection. Together, our data show that the lack of effectiveness of antivenom therapy is due to impaired and delayed venom and antivenom interaction at the site of injury.