Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 5, May, p. 587–595

doi: 10.17219/acem/121932

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Efficacy of intra-arterial lidocaine infusion in the treatment of cerulein-induced acute pancreatitis

Ryszard Antkowiak1,A,B,C,D,E,F, Łukasz Antkowiak2,A,B,C,D,E,F, Sławomir Grzegorczyn3,B,C,D, Klaudia Nalik-Iwaniak4,B,D, Natalia Kabała5,B,D, Zbigniew Arent4,B, Edyta Warmusz-Reichman6,B, Katarzyna Stęplewska7,C, Paweł Domosławski8,E,F

1 Department of General and Multiorgan Surgery, 3rd Provincial Hospital, Rybnik, Poland

2 Department of Pediatric Neurosurgery, Medical University of Silesia, Katowice, Poland

3 Department of Biophysics, Medical University of Silesia, Zabrze, Poland

4 Experimental and Innovative Medicine Centre, University of Agriculture, Kraków, Poland

5 University Centre of Veterinary Medicine, University of Agriculture, Kraków, Poland

6 Department of Histology and Embryology, Medical University of Silesia, Zabrze, Poland

7 Department of Pathology, Institute of Medical Sciences, University of Opole, Poland

8 Department of General, Gastroenterological and Endocrine Surgery, Wroclaw Medical University, Poland

Abstract

Background. Disturbances in pancreatic microcirculation, beginning with vasoconstriction, are crucial in early pancreatitis and progression to necrotizing pancreatitis. Thus, vascular-targeted treatment aiming to restore a sufficient level of microcirculation through vasodilation would possibly reduce the severity of pancreatitis. Lidocaine is an anti-arrhythmic and local anesthetic drug, which also acts as a vasodilator at higher concentrations.
Objectives. To evaluate the efficacy of intra-arterial infusion of lidocaine into the celiac trunk in treatment of cerulein-induced acute pancreatitis.
Material and Methods. Wistar rats (n = 20) were randomly divided into 2 equal groups: the control group (NaCl group, n = 10) and the study group (lidocaine group, n = 10). All subjects underwent surgical intervention with intra-arterial infusion of 0.9% NaCl (control group) or 1% lidocaine hydrochloride (study group) into the celiac trunk. Blood samples were collected 5 times at regular intervals from each rat for amylase and lipase measurements. Histopathological analysis of the pancreas was performed.
Results. A total number of 16 rats (control group n = 7, study group n = 9) were included. In the postoperative course, the study group (lidocaine group) revealed lower values of serum amylase and lipase levels compared to the control group (NaCl group), except the values at the 1st treatment point, which appeared 1 h after intraoperative drug injection. Significantly lower treatment endpoint levels of pancreatic enzymes were seen in the lidocaine group. Moreover, no differences were observed between the 1st and the last treatment point in the control group; however, these differences were significant for both enzymes in the study group. Histopathology revealed reduced pancreatitis severity in the study group compared to the controls.
Conclusion. Intra-arterial lidocaine infusion into the celiac trunk decreases pancreatitis severity. What is more, this study demonstrates the relevance of early vasodilation in the therapy of acute pancreatitis.

Key words

acute pancreatitis, lidocaine, regional arterial infusion, microcirculation

References (40)

  1. Goodchild G, Chouhan M, Johnson GJ. Practical guide to the management of acute pancreatitis. Frontline Gastroenterol. 2019;10(3):292–299. doi:10.1136/flgastro-2018-101102
  2. Machicado JD, Papachristou GI. Pharmacologic management and prevention of acute pancreatitis. Curr Opin Gastroenterol. 2019;35(5):460–467. doi:10.1097/MOG.0000000000000563
  3. Garg PK, Singh VP. Organ failure due to systemic injury in acute pancreatitis. Gastroenterology. 2019;156(7):2008–2023. doi:10.1053/j.gastro.2018.12.041
  4. Chatila AT, Bilal M, Guturu P. Evaluation and management of acute pancreatitis. World J Clin Cases. 2019;7(9):1006–1020. doi:10.12998/wjcc.v7.i9.1006
  5. Sah RP, Garg P, Saluja AK. Pathogenic mechanisms of acute pancreatitis. Curr Opin Gastroenterol. 2012;28(5):507–515. doi:10.1097/MOG.0b013e3283567f52
  6. Cuthbertson CM, Christophi C. Disturbances of the microcirculation in acute pancreatitis. Br J Surg. 2006;93(5):518–530. doi:10.1002/bjs.5316
  7. Bhatia M, Wong FL, Cao Y, et al. Pathophysiology of acute pancreatitis. Pancreatology. 2005;5(2–3):132–144. doi:10.1159/000085265
  8. Menger MD, Plusczyk T, Vollmar B. Microcirculatory derangements in acute pancreatitis. J Hepatobiliary Pancreat Surg. 2001;8(3):187–194. doi:10.1007/s005340170015
  9. Warshaw AL, O’Hara PJ. Susceptibility of the pancreas to ischemic injury in shock. Ann Surg. 1978;188(2):197–201. doi:10.1097/00000658-197808000-00012
  10. Kinnala PJ, Kuttila KT, Grönroos JM, Havia TV, Nevalainen TJ, Niinikoski JH. Pancreatic tissue perfusion in experimental acute pancreatitis. Eur J Surg. 2001;167(9):689–694. doi:10.1080/11024150152619345
  11. Klar E, Messmer K, Warshaw AL, Herfarth C. Pancreatic ischaemia in experimental acute pancreatitis: Mechanism, significance and therapy. Br J Surg. 1990;77(11):1205–1210. doi:10.1002/bjs.1800771104
  12. Vollmar B, Menger MD. Microcirculatory dysfunction in acute pancreatitis. A new concept of pathogenesis involving vasomotion-associated arteriolar constriction and dilation. Pancreatology. 2003;3(3):181–190. doi:10.1159/000070727
  13. Foitzik T, Eibl G, Hotz B, et al. Persistent multiple organ microcirculatory disorders in severe acute pancreatitis: Experimental findings and clinical implications. Dig Dis Sci. 2002;47(1):130–138. doi:10.1023/a:1013284008219
  14. Johns RA, DiFazio CA, Longnecker DE. Lidocaine constricts or dilates rat arterioles in a dose-dependent manner. Anesthesiology. 1985;62(2):141–144. doi:10.1097/00000542-198502000-00008
  15. Kim KH, Lee MG, Kim DG. The cholecystokinin receptor antagonist L-364,718 reduces taurocholate-induced pancreatitis in rats. Int J Pancreatol. 1996;20(3):205–211. doi:10.1007/BF02803770
  16. Satoh K, Kamada S, Kumagai M, Sato M, Kuji A, Joh S. Effect of lidocaine on swine lingual and pulmonary arteries. J Anesth. 2015;29(4):529–534. doi:10.1007/s00540-014-1965-9
  17. Newton DJ, McLeod GA, Khan F, Belch JJ. Mechanisms influencing the vasoactive effects of lidocaine in human skin. Anaesthesia. 2007;62(2):146–150. doi:10.1111/j.1365-2044.2006.04901.x
  18. de Klaver MJ, Buckingham MG, Rich GF. Lidocaine attenuates cytokine-induced cell injury in endothelial and vascular smooth muscle cells. Anesth Analg. 2003;97(2):465–470. doi:10.1213/01.ane.0000073162.27208.e9
  19. Piaścik M, Rydzewska G, Milewski J, et al. The results of severe acute pancreatitis treatment with continuous regional arterial infusion of protease inhibitor and antibiotic: A randomized controlled study. Pancreas. 2010;39(6):863–867. doi:10.1097/MPA.0b013e3181d37239
  20. Mikami Y, Takeda K, Matsuda K, et al. Rat experimental model of continuous regional arterial infusion of protease inhibitor and its effects on severe acute pancreatitis. Pancreas. 2005;30(3):248–253. doi:10.1097/01.mpa.0000153328.54569.28
  21. Manohar M, Verma AK, Venkateshaiah SU, Sanders NL, Mishra A. Pathogenic mechanisms of pancreatitis. World J Gastrointest Pharma­col Ther. 2017;8(1):10–25. doi:10.4292/wjgpt.v8.i1.10
  22. Sunamura M, Yamauchi J, Shibuya K, et al. Pancreatic microcirculation in acute pancreatitis. J Hepatobiliary Pancreat Surg. 1998;5(1):62–68. doi:10.1007/pl00009952
  23. Rakonczay Z Jr, Hegyi P, Takács T, McCarroll J, Saluja AK. The role of NF-kappaB activation in the pathogenesis of acute pancreatitis. Gut. 2008;57(2):259–267. doi:10.1136/gut.2007.124115
  24. Dawra R, Sah RP, Dudeja V, et al. Intra-acinar trypsinogen activation mediates early stages of pancreatic injury but not inflammation in mice with acute pancreatitis. Gastroenterology. 2011;141(6):2210–2217.e2. doi:10.1053/j.gastro.2011.08.033
  25. Plusczyk T, Witzel B, Menger MD, Schilling M. ETA and ETB receptor function in pancreatitis-associated microcirculatory failure, inflammation, and parenchymal injury. Am J Physiol Gastrointest Liver Physiol. 2003;285(1):G145–G153. doi:10.1152/ajpgi.00181.2002
  26. Laude K, Beauchamp P, Thuillez C, Richard V. Endothelial protective effects of preconditioning. Cardiovasc Res. 2002;55(3):466–473. doi:10.1016/s0008-6363(02)00277-8
  27. Kusterer K, Poschmann T, Friedemann A, Enghofer M, Zendler S, Usadel KH. Arterial constriction, ischemia–reperfusion, and leukocyte adherence in acute pancreatitis. Am J Physiol. 1993;265(1 Pt 1):G165–G171. doi:10.1152/ajpgi.1993.265.1.G165
  28. Plusczyk T, Westermann S, Rathgeb D, Feifel G. Acute pancreatitis in rats: Effects of sodium taurocholate, CCK-8, and Sec on pancreatic microcirculation. Am J Physiol. 1997;272(2 Pt 1):G310–G320. doi:10.1152/ajpgi.1997.272.2.G310
  29. Zhou ZG, Chen YD, Sun W, Chen Z. Pancreatic microcirculatory impairment in experimental acute pancreatitis in rats. World J Gastroenterol. 2002;8(5):933–936. doi:10.3748/wjg.v8.i5.933
  30. Ghimire K, Altmann HM, Straub AC, Isenberg JS. Nitric oxide: What’s new to NO? Am J Physiol Cell Physiol. 2017;312(3):C254–C262. doi:10.1152/ajpcell.00315.2016
  31. Anderson MC, Schoenfeld FB, Iams WB, Suwa M. Circulatory changes in acute pancreatitis. Surg Clin North Am. 1967;47(1):127–140. doi:10.1016/s0039-6109(16)38138-5
  32. Eibl G, Buhr HJ, Foitzik T. Therapy of microcirculatory disorders in severe acute pancreatitis: What mediators should we block? Intensive Care Med. 2002;28(2):139–146. doi:10.1007/s00134-001-1194-1
  33. Foitzik T, Eibl G, Hotz HG, Faulhaber J, Kirchengast M, Buhr HJ. Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates. Surgery. 2000;128(3):399–407. doi:10.1067/msy.2000.107104
  34. Aggarwal A, Manrai M, Kochhar R. Fluid resuscitation in acute pancreatitis. World J Gastroenterol. 2014;20(48):18092–18103. doi:10.3748/wjg.v20.i48.18092
  35. Ranson JH, Lackner H, Berman IR, Schinella R. The relationship of coagulation factors to clinical complications of acute pancreatitis. Surgery. 1977;81(5):502–511.
  36. Ke L, Ni HB, Tong ZH, Li WQ, Li N, Li JS. Efficacy of continuous regional arterial infusion with low-molecular-weight heparin for severe acute pancreatitis in a porcine model. Shock. 2014;41(5):443–448. doi:10.1097/SHK.0000000000000129
  37. Eibl G, Hotz HG, Faulhaber J, Kirchengast M, Buhr HJ, Foitzik T. Effect of endothelin and endothelin receptor blockade on capillary permeability in experimental pancreatitis. Gut. 2000;46(3):390–394. doi:10.1136/gut.46.3.390
  38. Zhou ZG, Chen YD. Influencing factors of pancreatic microcirculatory impairment in acute pancreatitis. World J Gastroenterol. 2002;8(3):406–412. doi:10.3748/wjg.v8.i3.406
  39. Inoue K, Hirota M, Kimura Y, Kuwata K, Ohmuraya M, Ogawa M. Further evidence for endothelin as an important mediator of pancreatic and intestinal ischemia in severe acute pancreatitis. Pancreas. 2003;26(3):218–223. doi:10.1097/00006676-200304000-00002
  40. Singh VK, Gardner TB, Papachristou GI, et al. An international multicenter study of early intravenous fluid administration and outcome in acute pancreatitis. United European Gastroenterol J. 2017;5(4):491–498. doi:10.1177/2050640616671077