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Vasodilating Effects of Antispasmodic Agents and Their Cytotoxicity in Vascular Smooth Muscle Cells and Endothelial Cells—Potential Application in Microsurgery

Ueda, Misato Hirayama, Yasuki Ogawa, Haruo Nomura, Tadashi Terashi, Hiroto Sakakibara, Shunsuke 神戸大学

2023.07

概要

This study aimed to elucidate the vasodilatory effects and cytotoxicity of various vasodilators used as antispasmodic agents during microsurgical anastomosis. Rat smooth muscle cells (RSMCs) and human coronary artery endothelial cells (HCAECs) were used to investigate the physiological concentrations and cytotoxicity of various vasodilators (lidocaine, papaverine, nitroglycerin, phentolamine, and orciprenaline). Using a wire myograph system, we determined the vasodilatory effects of each drug in rat abdominal aortic sections at the concentration resulting in maximal vasodilation as well as at the surrounding concentrations 10 min after administration. Maximal vasodilation effect 10 min after administration was achieved at the following concentrations: lidocaine, 35 mM; papaverine, 0.18 mM; nitroglycerin, 0.022 mM; phentolamine, 0.11 mM; olprinone, 0.004 mM. The IC₅₀ for lidocaine, papaverine, and nitroglycerin was measured in rat abdominal aortic sections, as well as in RSMCs after 30 min and in HCAECs after 10 min. Phentolamine and olprinone showed no cytotoxicity towards RSMCs or HCAECs. The concentrations of the various drugs required to achieve vasodilation were lower than the reported clinical concentrations. Lidocaine, papaverine, and nitroglycerin showed cytotoxicity, even at lower concentrations than those reported clinically. Phentolamine and olprinone show antispasmodic effects without cytotoxicity, making them useful candidates for local administration as antispasmodics.

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参考文献

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

Bigdeli, A.K.; Gazyakan, E.; Schmidt, V.J.; Bauer, C.; Germann, G.; Radu, C.A.; Kneser, U.; Hirche, C. Long-Term Outcome after

Successful Lower Extremity Free Flap Salvage. J. Reconstr. Microsurg. 2019, 35, 263–269. [CrossRef]

Bui, D.T.; Cordeiro, P.G.; Hu, Q.Y.; Disa, J.J.; Pusic, A.; Mehrara, B.J. Free flap reexploration: Indications, treatment, and outcomes

in 1193 free flaps. Plast. Reconstr. Surg. 2007, 119, 2092–2100. [CrossRef] [PubMed]

Brown, J.S.; Devine, J.C.; Magennis, P.; Sillifant, P.; Rogers, S.N.; Vaughan, E.D. Factors that influence the outcome of salvage in

free tissue transfer. Br. J. Oral Maxillofac. Surg. 2003, 41, 16–20. [CrossRef] [PubMed]

Yii, N.W.; Evans, G.R.; Miller, M.J.; Reece, G.P.; Langstein, H.; Chang, D.; Kroll, S.S.; Wang, B.; Robb, G.L. Thrombolytic therapy:

What is its role in free flap salvage? Ann. Plast. Surg. 2001, 46, 601–604. [CrossRef] [PubMed]

Vargas, C.R.; Iorio, M.L.; Lee, B.T. A Systematic Review of Topical Vasodilators for the Treatment of Intraoperative Vasospasm in

Reconstructive Microsurgery. Plast. Reconstr. Surg. 2015, 136, 411–422. [CrossRef]

Ueda, K.; Harii, K. Comparative study of topical use of vasodilating solutions. Scand. J. Plast. Reconstr. Surg. Hand Surg. 2003, 37,

201–207. [CrossRef]

Ricci, J.A.; Koolen, P.G.; Shah, J.; Tobias, A.M.; Lee, B.T.; Lin, S.J. Comparing the Outcomes of Different Agents to Treat Vasospasm

at Microsurgical Anastomosis during the Papaverine Shortage. Plast. Reconstr. Surg. 2016, 138, 401e–408e. [CrossRef]

Rinkinen, J.; Halvorson, E.G. Topical Vasodilators in Microsurgery: What Is the Evidence? J. Reconstr. Microsurg. 2017, 33, 1–7.

[CrossRef]

Gutterman, D.D. Adventitia-dependent influences on vascular function. Am. J. Physiol. 1999, 277, H1265–H1272. [CrossRef]

Schwartz, B.G.; Economides, C.; Mayeda, G.S.; Burstein, S.; Kloner, R.A. The endothelial cell in health and disease: Its function,

dysfunction, measurement and therapy. Int. J. Impot. Res. 2010, 22, 77–90. [CrossRef]

Wang, D.; Wang, Z.; Zhang, L.; Wang, Y. Roles of Cells from the Arterial Vessel Wall in Atherosclerosis. Mediat. Inflamm. 2017,

2017, 8135934. [CrossRef]

Rensen, S.S.; Doevendans, P.A.; van Eys, G.J. Regulation and characteristics of vascular smooth muscle cell phenotypic diversity.

Neth. Heart J. 2007, 15, 100–108. [CrossRef]

Le Brocq, M.; Leslie, S.J.; Milliken, P.; Megson, I.L. Endothelial dysfunction: From molecular mechanisms to measurement, clinical

implications, and therapeutic opportunities. Antioxid. Redox Signal. 2008, 10, 1631–1674. [CrossRef]

Ogawa, H.; Kusumoto, J.; Nomura, T.; Hashikawa, K.; Terashi, H.; Sakakibara, S. Wire Myography for Continuous Estimation

of the Optimal Concentration of Topical Lidocaine as a Vasodilator in Microsurgery. J. Reconstr. Microsurg. 2021, 37, 541–550.

[CrossRef]

Afridi, N.S.; Paletz, J.; Morris, S. Free Flap Failures: What to Do Next? Can. J. Plast. Surg. 2000, 8, 30–32. [CrossRef]

Yu, J.T.; Patel, A.J.; Malata, C.M. The use of topical vasodilators in microvascular surgery. J. Plast. Reconstr. Aesthet. Surg. 2011, 64,

226–228. [CrossRef]

Hyza, P.; Streit, L.; Schwarz, D.; Kubek, T.; Vesely, J. Vasospasm of the flap pedicle: The effect of 11 of the most often used

vasodilating drugs. Comparative study in a rat model. Plast. Reconstr. Surg. 2014, 134, 574e–584e. [CrossRef]

Zhang, J.; Lipa, J.E.; Black, C.E.; Huang, N.; Neligan, P.C.; Ling, F.T.; Levine, R.H.; Semple, J.L.; Pang, C.Y. Pharmacological

characterization of vasomotor activity of human musculocutaneous perforator artery and vein. J. Appl. Physiol. 2000, 89,

2268–2275. [CrossRef]

Demaria, R.G.; Vernhet, H.; Aya, G.; Oliva-Lauraire, M.C.; Juan, J.M.; Dauzat, M.M. Experimental model for comparative

evaluation of pharmacologically induced vasodilation of arterial wall mechanical properties. J. Cardiovasc. Pharmacol. 2003, 42,

389–394. [CrossRef]

Hou, S.M.; Seaber, A.V.; Urbaniak, J.R. Relief of blood-induced arterial vasospasm by pharmacologic solutions. J. Reconstr.

Microsurg. 1987, 3, 147–151. [CrossRef]

Beekman, W.H.; Sluimers, J.E.; Kort, W.J.; van der Meulen, J.C. Resolution of experimental microvascular vasoconstriction in

rats by topical application of lidocaine hydrochloride in varying concentrations. Ann. Plast. Surg. 1988, 21, 570–575. [CrossRef]

[PubMed]

Wolfe, J.W.; Butterworth, J.F. Local anesthetic systemic toxicity: Update on mechanisms and treatment. Curr. Opin. Anaesthesiol.

2011, 24, 561–566. [CrossRef] [PubMed]

Jernbeck, J.; Samuelson, U.E. Effects of lidocaine and calcitonin gene-related peptide (CGRP) on isolated human radial arteries. J.

Reconstr. Microsurg. 1993, 9, 361–365. [CrossRef] [PubMed]

Gherardini, G.; Samuelson, U.; Jernbeck, J.; Aberg, B.; Sjöstrand, N. Comparison of vascular effects of ropivacaine and lidocaine

on isolated rings of human arteries. Acta Anaesthesiol. Scand. 1995, 39, 765–768. [CrossRef] [PubMed]

Beekman, W.H.; Dammeijer, P.F.; Sluimers, J.E.; Kort, W.J.; van der Meulen, J.H. Improvement in blood flow and diameter of the

postanastomotic rat tail artery by topical application of lidocaine in varying concentrations. Ann. Plast. Surg. 1990, 24, 248–251.

[CrossRef] [PubMed]

Ichioka, S.; Nakatsuka, T.; Ohura, N.; Sato, Y.; Harii, K. Topical application of amrinone (a selective phosphodiesterase III

inhibitor) for relief of vasospasm. J. Surg. Res. 2000, 93, 149–155. [CrossRef]

Ohta, I.; Kawai, H.; Kawabata, H.; Masada, K.; Ono, K. Topical use of Xylocaine for relieving vasospasm: Effect of concentration.

J. Reconstr. Microsurg. 1991, 7, 205–208. [CrossRef]

Int. J. Mol. Sci. 2023, 24, 10850

28.

29.

30.

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42.

43.

44.

45.

46.

47.

16 of 16

Johnstone, R.E.; Wax, M.K.; Bishop, D.J.; Chafin, J.B. Large doses of topical lidocaine during microvascular surgery are not

associated with toxic blood concentrations. Anesthesiology 1995, 82, 593–596. [CrossRef]

Hou, S.M.; Liu, T.K.; Yu, H.Y. Absorption of lidocaine following topical application in microvascular procedures on rabbits. J.

Orthop. Res. 1991, 9, 545–549. [CrossRef]

Kerschner, J.E.; Futran, N.D. The effect of topical vasodilating agents on microvascular vessel diameter in the rat model.

Laryngoscope 1996, 106, 1429–1433. [CrossRef]

Swartz, W.M.; Brink, R.R.; Buncke, H.J. Prevention of thrombosis in arterial and venous microanastomoses by using topical

agents. Plast. Reconstr. Surg. 1976, 58, 478–481. [CrossRef]

Evans, G.R.; Gherardini, G.; Gürlek, A.; Langstein, H.; Joly, G.A.; Cromeens, D.M.; Sukumaran, A.V.; Williams, J.; Kilbourn, R.G.;

Wang, B.; et al. Drug-induced vasodilation in an in vitro and in vivo study: The effects of nicardipine, papaverine, and lidocaine

on the rabbit carotid artery. Plast. Reconstr. Surg. 1997, 100, 1475–1481. [CrossRef]

Gherardini, G.; Gürlek, A.; Cromeens, D.; Joly, G.A.; Wang, B.G.; Evans, G.R. Drug-induced vasodilation: In vitro and in vivo

study on the effects of lidocaine and papaverine on rabbit carotid artery. Microsurgery 1998, 18, 90–96. [CrossRef]

Huang, G.K.; Li, H.Q. Relief of vasospasm by drugs: An experimental study. Eur. J. Plast. Surg. 1991, 14, 10–14. [CrossRef]

Cooper, G.J.; Gillot, T.; Parry, E.A.; Kennedy, A.; Wilkinson, G.A. Papaverine injures the endothelium of the internal mammary

artery. Cardiovasc. Surg. 1995, 3, 553–555. [CrossRef]

Gao, Y.J.; Stead, S.; Lee, R.M. Papaverine induces apoptosis in vascular endothelial and smooth muscle cells. Life Sci. 2002, 70,

2675–2685. [CrossRef]

Ricci, J.A.; Singhal, D.; Fukudome, E.Y.; Tobias, A.M.; Lin, S.J.; Lee, B.T. Topical nitroglycerin for the treatment of intraoperative

microsurgical vasospasm. Microsurgery 2018, 38, 524–529. [CrossRef]

Ding, R.; Feng, W.; Li, H.; Wang, L.; Li, D.; Cheng, Z.; Guo, J.; Hu, D. A comparative study on in vitro and in vivo effects of topical

vasodilators in human internal mammary, radial artery and great saphenous vein. Eur. J. Cardiothorac. Surg. 2008, 34, 536–541.

[CrossRef]

Sasson, L.; Cohen, A.J.; Hauptman, E.; Schachner, A. Effect of topical vasodilators on internal mammary arteries. Ann. Thorac.

Surg. 1995, 59, 494–496. [CrossRef]

Taylor, S.H.; Sutherland, G.R.; Mackenzie, G.J.; Staunton, H.P.; Donald, K.W. The Circulatory Effects of Intravenous Phentolamine

in Man. Circulation 1965, 31, 741–754. [CrossRef]

Ma, Q.; Liu, D.; Gong, R.; Chen, S.; Fang, F.; Zhuang, Y. Mechanically Induced Vasospasm-Evaluation of Spasmolytic Efficacy of

10 Pharmaceutical Agents Using Laser Speckle Contrast Imaging. Lasers Surg. Med. 2021, 53, 684–694. [CrossRef] [PubMed]

Ruiz-Salmerón, R.J.; Mora, R.; Masotti, M.; Betriu, A. Assessment of the efficacy of phentolamine to prevent radial artery spasm

during cardiac catheterization procedures: A randomized study comparing phentolamine vs. verapamil. Catheter. Cardiovasc.

Interv. 2005, 66, 192–198. [CrossRef] [PubMed]

Mizushige, K.; Ueda, T.; Yukiiri, K.; Suzuki, H. Olprinone: A phosphodiesterase III inhibitor with positive inotropic and

vasodilator effects. Cardiovasc. Drug. Rev. 2002, 20, 163–174. [CrossRef] [PubMed]

Itoh, H.; Kusagawa, M.; Shimomura, A.; Suga, T.; Ito, M.; Konishi, T.; Nakano, T. Ca2+(-)dependent and Ca2+(-)independent

vasorelaxation induced by cardiotonic phosphodiesterase inhibitors. Eur. J. Pharmacol. 1993, 240, 57–66. [CrossRef]

Adachi, H.; Kamata, S.; Kodama, K.; Nagakura, T. Vasorelaxant effect of a phosphodiesterase 3 inhibitor, olprinone, on isolated

human radial artery. Eur. J. Pharmacol. 2000, 396, 43–47. [CrossRef]

Sasaki, H. The right gastroepiploic artery in coronary artery bypass grafting. J. Card. Surg. 2008, 23, 398–407. [CrossRef]

Sakakibara, S.; Ishida, Y.; Hashikawa, K.; Yamaoka, T.; Terashi, H. Intima/medulla reconstruction and vascular contractionrelaxation recovery for acellular small diameter vessels prepared by hyperosmotic electrolyte solution treatment. J. Artif. Organs

2014, 17, 169–177. [CrossRef]

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