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Effect of lidocaine with and without epinephrine on lymphatic contractile activity in mice in vivo

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Abstract

A local anesthetic, lidocaine, is known to affect cutaneous blood flow when injected into the skin. However, it is unknown if dermal lymphatic function can also be affected. Therefore, we characterized lymphatic function in response to administration of lidocaine with and without epinephrine. Non-invasive near-infrared fluorescence imaging (NIRFI) with intradermal injection of indocyanine green (ICG) was used to characterize the lymphatic “pumping” function in mice after subcutaneous injection of 2 % lidocaine with and without 1:100,000 epinephrine or saline. NIRFI was performed for 10–20 min immediately after and 1, 3, and 5 h after these interventions. Lymphatic contraction frequencies significantly decreased 10 min after subcutaneous injection of lidocaine and remained plateaued for another 5 min, before returning to baseline. However, addition of 1:100,000 epinephrine to 2 % lidocaine rapidly increased lymphatic contraction frequencies at 5 min post-injection, which returned to baseline levels 15 min later. Injection of saline also increased lymphatic contraction frequency 5 min after injection, which returned to baseline 10 min post-injection. Although lidocaine administration showed a decrease in lymphatic function, the combination of epinephrine with lidocaine resulted in a predominant net effect of increased contractile activity.

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References

  1. Achar S, Kundu S. Principles of office anesthesia: part I. Infiltrative anesthesia. Am Fam Physician. 2002;66:91–4.

    PubMed  Google Scholar 

  2. Cummins TR. Setting up for the block: the mechanism underlying lidocaine’s use-dependent inhibition of sodium channels. J Physiol. 2007;582:11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Aps C, Reynolds F. The effect of concentration on vasoactivity of bupivacaine and lignocaine. Br J Anaesth. 1976;48:1171–4.

    Article  CAS  PubMed  Google Scholar 

  4. Guinard JP, Carpenter RL, Morell RC. Effect of local anesthetic concentration on capillary blood flow in human skin. Reg Anesth. 1992;17:317–21.

    CAS  PubMed  Google Scholar 

  5. Cederholm I, Evers H, Lofstrom JB. Effect of intradermal injection of saline or a local anaesthetic agent on skin blood flow—a methodological study in man. Acta Anaesthesiol Scand. 1991;35:208–15.

    Article  CAS  PubMed  Google Scholar 

  6. Swerdlow M, Jones R. The duration of action of bupivacaine, prilocaine and lignocaine. Br J Anaesth. 1970;42:335–9.

    Article  CAS  PubMed  Google Scholar 

  7. Liu S, Carpenter RL, Chiu AA, McGill TJ, Mantell SA. Epinephrine prolongs duration of subcutaneous infiltration of local anesthesia in a dose-related manner. Correlation with magnitude of vasoconstriction. Reg Anesth. 1995;20:378–84.

    CAS  PubMed  Google Scholar 

  8. Larrabee WF Jr, Lanier BJ, Miekle D. Effect of epinephrine on local cutaneous blood flow. Head Neck Surg. 1987;9:287–9.

    Article  PubMed  Google Scholar 

  9. Ghali S, Knox KR, Verbesey J, Scarpidis U, Izadi K, Ganchi PA. Effects of lidocaine and epinephrine on cutaneous blood flow. J Plast Reconstr Aesthet Surg. 2008;61:1226–31.

    Article  CAS  PubMed  Google Scholar 

  10. Kwon S, Agollah GD, Wu G, Chan W, Sevick-Muraca EM. Direct visualization of changes of lymphatic function and drainage pathways in lymph node metastasis of B16F10 melanoma using near-infrared fluorescence imaging. Biomed Opt Express. 2013;4:967–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kwon S, Sevick-Muraca EM. Mouse phenotyping with near-infrared fluorescence lymphatic imaging. Biomed Opt Express. 2011;2:1403–11.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wang GY, Zhong SZ. Experimental study of lymphatic contractility and its clinical importance. Ann Plast Surg. 1985;15:278–84.

    Article  CAS  PubMed  Google Scholar 

  13. Smith RO. Lymphatic contractility; a possible intrinsic mechanism of lymphatic vessels for the transport of lymph. J Exp Med. 1949;90:497–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. McHale NG, Roddie IC. The effect of intravenous adrenaline and noradrenaline infusion of peripheral lymph flow in the sheep. J Physiol. 1983;341:517–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hall JG, Morris B, Woolley G. Intrinsic rhythmic propulsion of lymph in the unanaesthetized sheep. J Physiol. 1965;180:336–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Takahashi N, Kawai Y, Ohhashi T. Effects of vasoconstrictive and vasodilative agents on lymphatic smooth muscles in isolated canine thoracic ducts. J Pharmacol Exp Ther. 1990;254:165–70.

    CAS  PubMed  Google Scholar 

  17. McHale NG, Roddie IC. The effects of catecholamines on pumping activity in isolated bovine mesenteric lymphatics. J Physiol. 1983;338:527–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. McHale NG, Thornbury KD. The effect of anesthetics on lymphatic contractility. Microvasc Res. 1989;37:70–6.

    Article  CAS  PubMed  Google Scholar 

  19. van Helden DF, Thomas PA, Dosen PJ, Imtiaz MS, Laver DR, Isbister GK. Pharmacological approaches that slow lymphatic flow as a snakebite first aid. PLoS Negl Trop Dis. 2014;8:e2722.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Telinius N, Majgaard J, Kim S, Katballe N, Pahle E, Nielsen J, Hjortdal V, Aalkjaer C, Boedtkjer DB. Voltage-gated sodium channels contribute to action potentials and spontaneous contractility in isolated human lymphatic vessels. J Physiol. 2015;593:3109–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hattori J, Yamakage M, Seki S, Okazaki K, Namiki A. Inhibitory effects of the anesthetics propofol and sevoflurane on spontaneous lymphatic vessel activity in rats. Anesthesiology. 2004;101:687–94.

    Article  CAS  PubMed  Google Scholar 

  22. Newton DJ, Burke D, Khan F, McLeod GA, Belch JJ, McKenzie M, Bannister J. Skin blood flow changes in response to intradermal injection of bupivacaine and levobupivacaine, assessed by laser Doppler imaging. Reg Anesth Pain Med. 2000;25:626–31.

    Article  CAS  PubMed  Google Scholar 

  23. Newton DJ, McLeod GA, Khan F, Belch JJ. Vasoactive characteristics of bupivacaine and levobupivacaine with and without adjuvant epinephrine in peripheral human skin. Br J Anaesth. 2005;94:662–7.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank veterinarian Dr. Christopher Janssen for the comments on the anesthesia method used in these experiments. This work was supported in part by the National Institutes of Health R21 CA159193 (SK).

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Correspondence to Sunkuk Kwon.

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Fig. 1

Whole body white light (A) and fluorescence (B) images 10 min after injection of ICG showing lymphatic drainage of ICG from the paw to the PLN. Arrowhead, ICG injection site. Double arrow, PLN. Arrow, injection site of local anesthetics or saline. (C) Magnified fluorescence image of the white rectangle in (B) showing afferent popliteal lymphatic vessels draining to the PLN (arrow) in mice. The same size ROI (circle) was selected on the same area on the fluorescence images for lymphatic pumping activity. Scale bar, 1 mm. (JPEG 172 kb)

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Kwon, S., Sevick-Muraca, E.M. Effect of lidocaine with and without epinephrine on lymphatic contractile activity in mice in vivo. J Anesth 30, 1091–1094 (2016). https://doi.org/10.1007/s00540-016-2260-8

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  • DOI: https://doi.org/10.1007/s00540-016-2260-8

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