The effect of Ranolazine on random pattern skin flap survival in rats
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Abstract
Objective: Flap surgery is widely used in the field of plastic surgery for defect reconstruction. The most important problem of this surgery is ischemic necrosis which may occur in the distal of the flap. For this reason, studies have been conducted to develop many treatment methods to solve this problem. Our study aimed to investigate the effects of different doses of ranolazine, a selective late sodium current blocker, on the viability of skin flaps prepared from the back of the rat.
Material and Methods: A total of 32 rats, including 8 rats in each group, were included in the study. A random patterned caudal base 3x9 cm width : length modified McFarlane skin flap was elevated from the backs of all rats and adapted back to its place For 7 days postoperatively, 1 cc of saline was added to the control group (Group A), and 45 mg/kg, 90 mg/kg, and 180 mg/kg of ranolazine were added to the study groups (Group B, C, D), respectively, and administered daily with gastric lavage On the 7th postoperative day, photographs were taken to evaluate the viability of the flaps and scintigraphic evaluations were made. After the rats were sacrificed, the flaps were separated from their bases and evaluated histopathologically.
Results: As a result of the evaluations, the viable flap area was calculated as 12.7548 cm2 for Group A, 14.9533 cm2, 16.494 cm2 and 16.7599 cm2 for Groups B, C and D, respectively, and a statistically significant difference was found between the groups (P = 0.00 <0.05 ). The viable flap area percentages were calculated as 57.486% for Group A, 68.908% for Group B, 70.174% for Group C and 74.603% for Group D, and a statistically significant difference was found between the groups (P = 0.00 <0.05). As a result of scintigraphic evaluation, the viable flap area was found to be 61.57% for Group A, 71.04% for Group B, 70.21% for Group C and 73.85% for Group D, and a statistically significant difference was found between the groups (P = 0.03 <0.05). Histopathological evaluation revealed a decrease in the flaps' inflammation, edema and necrosis scores with the increasing drug dose.
Conclusion: As a result, although flap viability increased with increasing doses in the group given ranolazine, more detailed studies are needed before it can be used clinically.
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Accepted 2023-04-24
Published 2023-04-27
References
Simman R. Wound closure and the reconstructive ladder in plastic surgery. J Am Col Certif Wound Spec. 2009. 1(1): p. 6-11. doi: 10.1016/j.jcws.2008.10.003.
Rohrich RJ, Cherry GW, Spira M. Enhancement of skin-flap survival using nitroglycerin ointment. Plast Reconstr Surg. 1984. 73(6): p. 943-8. doi: 10.1097/00006534-198406000-00016.
Gürsoy K, Koca G, Alışık M, Yumuşak N, Korkmaz M, Koçer U. Effect of concentrated growth factor on random pattern skin flap viability: experimental study. J Health Sci Med. 2020; 3(2): p. 125-131. doi: 10.32322/jhsm.680345.
Fatemi M. Forootan KS, Jalali SZ, Mousavi SJ, Pedram S. The Effect of Enoxaparin and Clopidogrel on Survival of Random Skin Flap in Rat Animal Model. World J Plast Surg. 2012. 1: p. 64-70. pmcid: pmc4345431, pmid: 25734046.
Freedman AM, Hyde GL, Luce EA. Failure of Pentoxifylline to Enhance Skin Flap Survival in the Rat. Ann Plast Surg. 1989. 23(1): p. 31-34. doi: 10.1097/00000637-198907000-00006.
Huang N, Ashrafpour H, Levine RH, Forrest CR, Neligan PC, Lipa JE, Pang CY. Vasorelaxation Effect and Mechanism of Action of Vascular Endothelial Growth Factor-165 in Isolated Perfused Human Skin Flaps. J Surg Res. 2010. 172: p. 177-86. doi: 10.1016/j.jss.2010.08.016.
Nichter LS, Sobieski MW. Efficacy of Verapamil in the Salvage of Failing Random Skin Flaps. Ann Plast Surg. 1988. 21(3): p. 242-245. doi: 10.1097/00000637-198809000-00009.
Schein O, Westreich M, Shalom A. Effect of intradermal human recombinant copperzinc superoxide dismutase on random pattern flaps in rats. Head Neck. 2013. 35(9): p. 1265- 8. doi: 10.1002/hed.23114.
Cavallino C, Facchini M, Veia A, Bacchni S, Rosso R, Rognoni A, Rametta F, Lupi A, Bongo AS. New Anti-Anginal Drugs: Ranolazine. Cardiovasc Hematol Agents Med Chem. 2015. 13(1): p. 14-20. doi: 10.2174/1871525713666141219112841.
Özdemir M. Ranolazin: mechanism of antianginal effects. Archives of the Turkish Society of Cardiology, 2016. 44(0): p. 8-12. doi: 10.5543/tkda.2016.72626.
Amrani FB, Guerra S, Rueda DA, Mauricio MD, Marchio P, Vila JM, Valles SL, Fernandez F, Aldasoro M. Anti-inflammatory and antioxidant effects of ranolazine on primary cultured astrocytes. Crit Care. 2014. 18: p. P447-P447. doi:10.1186/cc13637.
Greiner L, Hurren K, Brenner M. Ranolazine and Its Effects on Hemoglobin A1C. Ann Pharmacother. 2016. 50(5): p. 410-5. doi: 10.1177/1060028016631757.
Lisi D, Andrews E, Parry C, Hill C, Ombengi D, Ling H. The Effect of Ranolazine on Glycemic Control: a Narrative Review to Define the Target Population. Cardiovasc Drugs Ther. 2019. 33(6): p. 755-761. doi: 10.1007/s10557-019-06917-6.
Naveena R, Hashilkar N, Davangeri R, Majagi SI. Effect of anti-inflammatory activity of ranolazine in rat model of inflammation. Indian J Med Res. 2018. 148(6): p. 743-747. doi:10.4103/ijmr.IJMR_1504_16.
Veronique R, Alan G, Donald M LJ, Robert J A, Jarret D B, Todd M B, Mercedes R C, Shifan D, Giovanni de S, Earl S F, Caroline S F, Heather J F, Cathleen G, Kurt J G, Susan M H, John A H, Michael H, Virginia J H, Brett M K, Steven J K, Daniel T L, Judith H L, Lynda D L, Diane M M, Gregory M M, Ariane M, David B M, Mary M M, James B M, Claudia S M, Dariush M, Michael E M, Graham N, Nina P P, Wayne D, R, Paul D S, Randall S S, Tanya N T, Melanie B T, Nathan D W, Judith WR. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011 Feb 1;123(4):e18-e209. doi: 10.1161/CIR.0b013e3182009701.
Sun ZH, Cao Y, Li HF. Multislice computed tomography angiography in the diagnosis of coronary artery disease. J Geriatr Cardiol. 2011 Jun;8(2):104-13. doi: 10.3724/SP.J.1263.2011.00104.
Mody P, Sidhu MS, Brikalis ES, Sacco JD, Banerjee S, Boden WE. Antianginal Agents for the Management of Stable Ischemic Heart Disease: A Review. Cardiol Rev. 2006 Jul-Aug;24(4):177-89. doi: 10.1097/CRD.0000000000000085.
Belardinelli L, Shryock J C, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart. 2006 Jul; 92(Suppl 4): iv6-iv14. doi: 10.1136/hrt.2005.078790.
Hasenfuss G, Maier L S. Mechanism of action of the new anti-ischemia drug ranolazine. Clin Res Cardiol. 2008 Apr;97(4):222-6. doi: 10.1007/s00392-007-0612-y.
Calderón-Sánchez EM, Rodriguez AD, Haldon JL, Navarro MFJ, Gomez AM, Smani T, Ordonez A. Cardioprotective Effect of Ranolazine in the Process of Ischemia-reperfusion in Adult Rat Cardiomyocytes. Rev Esp Cardiol (Engl Ed). 2016. 69(1): p. 45-53. doi: 10.1016/j.rec.2015.02.027.
Aldakkak M, Camara AKS, Heisner JS, Yang M, Stowe DF. Ranolazine reduces Ca2+ overload and oxidative stress and improves mitochondrial integrity to protect against ischemia reperfusion injury in isolated hearts. Pharmacol Res. 2011. 64(4): p. 381-92. doi: 10.1016/j.phrs.2011.06.018.
Dehina L, Descotes J, Chevalier P, Bui-Xuan B, Romestaing C, Dizerens N, Mamou Z, Timour Q. Protective effects of ranolazine and propranolol, alone or combined, on the structural and functional alterations of cardiomyocyte mitochondria in a pig model of ischemia/reperfusion. Fundam Clin Pharmacol. 2014. 28(3): p. 257-67. doi: 10.1111/fcp.12033.
Virsolvy A, Farah C, Pertuit N, Kong Lingyan, Lacampagne A, Reboul C, Aimond F, Richard S. Antagonism of Nav channels and α1-adrenergic receptors contributes to vascular smooth muscle effects of ranolazine. Sci Rep. 2015. 5: p. 17969. doi: 10.1038/srep17969.