Pharmacological approaches that slow lymphatic flow as a snakebite first aid

van Helden, Dirk F., Thomas, Paul A., Dosen, Peter J., Imtiaz, Mohammad S., Laver, Derek R. and Isbister, Geoffrey K. (2014) Pharmacological approaches that slow lymphatic flow as a snakebite first aid. PLoS Neglected Tropical Diseases, 8 2: e2722.1-e2722.7. doi:10.1371/journal.pntd.0002722

Author van Helden, Dirk F.
Thomas, Paul A.
Dosen, Peter J.
Imtiaz, Mohammad S.
Laver, Derek R.
Isbister, Geoffrey K.
Title Pharmacological approaches that slow lymphatic flow as a snakebite first aid
Journal name PLoS Neglected Tropical Diseases   Check publisher's open access policy
ISSN 1935-2735
Publication date 2014-02-01
Sub-type Article (original research)
DOI 10.1371/journal.pntd.0002722
Open Access Status DOI
Volume 8
Issue 2
Start page e2722.1
End page e2722.7
Total pages 7
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Background: This study examines the use of topical pharmacological agents as a snakebite first aid where slowing venom
reaching the circulation prevents systemic toxicity. It is based on the fact that toxin molecules in most snake venoms are
large molecules and generally first enter and traverse the lymphatic system before accessing the circulation. It follows on
from a previous study where it was shown that topical application of a nitric oxide donor slowed lymph flow to a similar
extent in humans and rats as well as increased the time to respiratory arrest for subcutaneous injection of an elapid venom
(Pseudonaja textilis, Ptx; Eastern brown snake) into the hind feet of anaesthetized rats.

Methodology/Principal Findings: The effects of topical application of the L-type Ca2+ channel antagonist nifedipine and
the local anesthetic lignocaine in inhibiting lymph flow and protecting against envenomation was examined in an
anaesthetized rat model. The agents significantly increased dye-measured lymph transit times by 500% and 390%
compared to controls and increased the time to respiratory arrest to foot injection of a lethal dose of Ptx venom by 60% and
40% respectively. The study also examined the effect of Ptx venom dose over the lethal range of 0.4 to 1.5 mg/kg finding a
negative linear relationship between increase in venom dose and time to respiratory arrest.

Conclusions/Significance: The findings suggest that a range of agents that inhibit lymphatic flow could potentially be used
as an adjunct treatment to pressure bandaging with immobilization (PBI) in snakebite first aid. This is important given that
PBI (a snakebite first aid recommended by the Australian National Health and Medical research Council) is often incorrectly
applied. The use of a local anesthetic would have the added advantage of reducing pain.
Keyword Guinea-Pig Mesentery
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
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