Pharmacological Approaches That Slow Lymphatic Flow As a Snakebite First Aid

Abstract

BackgroundThis 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 FindingsThe 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/SignificanceThe 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.

Voltage‐gated sodium channels contribute to action potentials and spontaneous contractility in isolated human lymphatic vessels

“…Another study demonstrated a slowing of lymph flow in rats after the application of the local anaesthetic lignocaine, which was also attributed to an inhibition of nerves (van Helden et al . ). Such an observation can also partly result from a direct LSMC effect because isolated rat lymphatic vessels reduce the contraction frequency when VGSC are blocked, and lymphatic vessels from sheep, which are known to express VGSC in the LSMC, reduce the lymphatic pumping in the presence of VGSC blockade (Zawieja et al .…”

Research Gaps in Wilderness Medicine

“…One such study reported the use of rats as a proxy for humans to study a novel first aid treatment for snake envenomations. 37 2. This discrepancy may result from differences in the source and composition of ginkgo products.…”

Tumescent contravenom: murine model for prehospital treatment of Naja naja neurotoxic snake envenomation

“…Larger venom molecules reach the systemic circulation mainly by lymphatic transport. Lidocaine (1 g/l) and verapamil at safe dosages and concentrations are known to impair lymphatic smooth muscle function and slow lymphatic transport of large protein molecules toward the thoracic duct and the systemic circulation . Future studies are needed to investigate the efficacy of lidocaine and verapamil against lymphatic transport of larger snake venom molecules.…”