A pharmacological approach to first aid treatment for snakebite

Saul, Megan; Thomas, Paul; Dosen, Peter J.; O’Leary, Margaret A.; Whyte, Ian M.; McFadden, Sally A; Helden, Dirk F. van

doi:10.1038/nm.2382

Cited by 43 publications

(49 citation statements)

References 16 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has recently been demonstrated that oxazolone-mediated inflammatory responses increase capillary permeability (9), spur inducible nitric oxide (NO) release (17), and reduce lymphatic flow (11). NO is a key molecular regulator of lymphatic contractility (1) that is known to slow lymphatic drainage by reducing lymphatic contraction (30,43). Reduced lymphatic pumping activity due to increased NO production may explain the appearance of edema in the ALND Ϫ oxazolone ϩ forelegs.…”

Section: Discussionmentioning

confidence: 99%

A chronic and latent lymphatic insufficiency follows recovery from acute lymphedema in the rat foreleg

Mendez

Stroup

Lynch

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Mendez U, Stroup EM, Lynch LL, Waller AB, Goldman J. A chronic and latent lymphatic insufficiency follows recovery from acute lymphedema in the rat foreleg. Am J Physiol Heart Circ Physiol 303: H1107-H1113, 2012. First published August 31, 2012; doi:10.1152/ajpheart.00522.2012.-Secondary lymphedema in humans is a common consequence of axillary lymph node dissection (ALND) to treat breast cancer. Remarkably, secondary lymphedema generally first appears following a delay of over a year and can be triggered suddenly by an inflammatory insult. However, it remains unclear why the apparently functional lymphatic system is unable to accommodate an inflammatory trigger. To provide mechanistic insight into the delayed and rapid secondary lymphedema initiation, we compared the ability of the ALND-recovered rat foreleg lymphatic system to prevent edema during an inflammatory challenge with that of the uninjured lymphatic system. At 73 days postsurgery, the forelegs of ALND Ϫ -and ALND ϩ -sensitized rats were exposed to the proinflammatory agent oxazolone, which was found to reduce fluid drainage and increase skin thickness in both ALND Ϫ and ALND ϩ forelegs (P Ͻ 0.05). However, drainage in the ALNDrecovered forelegs was more severely impaired than ALND Ϫ forelegs, as visualized by indocyanine green lymphography and quantified by interstitial transport of fluid marker (P Ͻ 0.05). Although both ALND ϩ and ALND Ϫ forelegs experienced significant inflammationinduced edema with the oxazolone exposure (P Ͻ 0.05), the peak tissue swelling in the ALND ϩ group was significantly greater than that of the ALND Ϫ forelegs (arm area peaked at ϳ13.4 vs. ϳ5.7% swelling, respectively, P Ͻ 0.005; wrist diameter peaked at 9.7 vs. 2.2% swelling, respectively, P Ͻ 0.005). The findings demonstrate that outward recovery from ALND in the rat foreleg masks an ensuing chronic and latent lymphatic insufficiency, which reduces the ability of the foreleg lymphatic system to prevent edema during an acute inflammatory process.

show abstract

Section: Discussionmentioning

confidence: 99%

A chronic and latent lymphatic insufficiency follows recovery from acute lymphedema in the rat foreleg

Mendez

Stroup

Lynch

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…The treatment group received a topical application of a glyceryl trinitrate ointment (GTNO) (0.2% wt∕wt, Rectogesic, Care Pharmaceuticals, commercially available), which is an ointment with an NO donor group that has previously been reported to slow lymphatic transport time. 35 Fig . 2 Tissue phantom schematic and operation.…”

Section: In Vivo Imagingmentioning

confidence: 99%

“…Our findings, that GTNO significantly reduces lymphatic transport, corroborates existing knowledge that NO has an inhibitory effect on lymphatic pump function. 29,31,35 We have shown that NIR lymphatic imaging can provide real-time in vivo measurements of lymphatic pump function in response to NO, which has never previously been available, and may help to further elucidate the relationship between NO and lymphatic contractile regulatory mechanisms. The ability to measure this response non-invasively would be particularly useful given recent findings that certain immune cells migrate to the lymphatics and release NO as a means of regulating local lymphatic draining.…”

Section: Quantifying Functional Effects Of No On Lymphatics In Vivomentioning

confidence: 99%

Sensitivity analysis of near-infrared functional lymphatic imaging

2012

View full text Add to dashboard Cite

Abstract. Near-infrared imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, yet the imaging capabilities of this approach have yet to be quantitatively characterized. We seek to quantify its capabilities as a diagnostic tool for lymphatic disease. Imaging is performed in a tissue phantom for sensitivity analysis and in hairless rats for in vivo testing. To demonstrate the efficacy of this imaging approach to quantifying immediate functional changes in lymphatics, we investigate the effects of a topically applied nitric oxide (NO) donor glyceryl trinitrate ointment. Premixing ICG with albumin induces greater fluorescence intensity, with the ideal concentration being 150 μg∕mL ICG and 60 g∕L albumin. ICG fluorescence can be detected at a concentration of 150 μg∕mL as deep as 6 mm with our system, but spatial resolution deteriorates below 3 mm, skewing measurements of vessel geometry. NO treatment slows lymphatic transport, which is reflected in increased transport time, reduced packet frequency, reduced packet velocity, and reduced effective contraction length. NIR imaging may be an alternative to invasive procedures measuring lymphatic function in vivo in real time.

show abstract

“…The application of pressure-immobilization, by applying a bandage and a splint to the entire bitten limb, has been used in Australia for delaying the systemic absorption of neurotoxic venoms (Sutherland et al, 1979;White, 2010). Recently, a pharmacological intervention, based on the application of an ointment containing a nitric oxide donor, aimed at reducing the lymphatic absorption of venom, has been proposed (Saul et al, 2011), and its testing in the clinical setting is pending.…”

Section: First Aid In Snakebite Envenomingmentioning

confidence: 99%

Snakebite Envenoming: A Public Health Perspective

Gutiérrez¹

2012

Public Health - Methodology, Environmental and Systems Issues

View full text Add to dashboard Cite

A pharmacological approach to first aid treatment for snakebite

Cited by 43 publications

References 16 publications

A chronic and latent lymphatic insufficiency follows recovery from acute lymphedema in the rat foreleg

A chronic and latent lymphatic insufficiency follows recovery from acute lymphedema in the rat foreleg

Sensitivity analysis of near-infrared functional lymphatic imaging

Snakebite Envenoming: A Public Health Perspective

Contact Info

Product

Resources

About