Histopathological Effects of Nimodipine and Pentoxifylline on the Vessel Wall in End-to-End Anastomoses in Rat Carotid Arteries

When reperfusion following ischemia occurs, oxygen returns to the ischemic tissue, increasing free oxygen radicals and inducing paradox secondary damage. Before infarction, revascularization may influence the morbidity rate. Successful revascularization is not always achieved due to stenosis incidence, proliferation of smooth muscle cells, and intimal hyperplasia. This study compares the effects of nimodipine that prevents vasospasm and pentoxifylline, which stimulates growth factors and reduces collagen synthesis on intimal hyperplasia. Eighteen randomly selected Sprague-Dawley rats were divided into three groups: Group 1, the control group; Group 2, intraperitoneally administered nimodipine; Group 3, orally administered pentoxifylline. Their right-sided carotid arteries were used for anastomosis and the left-sided ones for the control. After a 7-day treatment, both the right and left carotid arteries were removed. In the biopsy, the lumen’s area and diameter, thickness of tunica media thickness, thrombus, edema, intimal hyperplasia, vessel wall injury, and inflammation were analyzed. Pentoxifylline was effective in preventing intimal hyperplasia and tunica intima was similar to that in untreated carotid arteries. However, nimodipine inhibited intimal hyperplasia, but it was not as effective as pentoxifylline. The effects of pentoxifylline after anastomosis should be further assessed in vasoprotective treatment taking into account its efficacy against intimal hyperplasia.

___

  • 1. Brouns R, De Deyn PP. The complexity of neurobiological processes in acute ischemic stroke. Clin Neurol Neurosurg. 2009; 111: 483–495. https://doi.org/10.1016/j.clineuro.2009.04.001.
  • 2. Masters BS. Nitric oxide synthases: why so complex? Annu Rev Nutr. 1994; 14: 131–145. https://doi.org/10.1146/annurev.nu.14.070194.001023.
  • 3. Pauleto P, Sartore S, Pessina AC. Smooth muscle proliferation and differentiation in neointima formation and vascular restenosis. Clin Sci. 1994; 87: 467–479. https://doi.org/10.1042/cs0870467.
  • 4. Gartner LP, Hiatt JL. Circulatory system. Color Textbook of Histology, 2nd ed. Elsevier, Saunders; 2001: 251–70.
  • 5. British Pharmacopoeia, Vol. II, Nimodipine. London: 2005; 1409–10.
  • 6. Clowes AW, Reidy MA, Clowes MM. Mechanisms of stenosis after arterial injury. Lab Invest. 1983; 49: 208–215.
  • 7. Chen YM, Wu KD, Tsai TJ, Hsieh BR. Pentoxifyline inhibits PDGF-induced proliferation of and TGF-beta stimulated collagen synthesis by vascular smooth muscle cells. J Mol Cell Cardiol. 1999; 31: 773–783. https://doi.org/10.1006/jmcc.1998.0910.
  • 8. Schampel A, Volovitch O, Koeniger T, Scholz CJ, Jörg S, Linker RA, et al. Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis. Proc Natl Acad Sci. 2017; 114: E3295–E3304. https://doi.org/10.1073/pnas.1620052114.
  • 9. Shirazi M, Soltani MZ, Jahanabadi Z, Abdollahifar MA, Tanideh N, Noorafshan A. Stereological comparison of the effects of pentoxifylline, captopril, simvastatin, and tamoxifen on kidney and bladder structure after partial urethral obstruction in rats. Korean J Urol. 2014; 55: 756–763. https://doi.org/10.4111/kju.2014.55.11.75.
  • 10. Esclamado RM, Carroll WR. The pathogenesis of vascular thrombosis and its its impact in microvascular surgery. Head Neck. 1999; 21: 355–362. https://doi.org/10.1002/(sici)10970347(199907)21:4<355::aidhed10>3.0.co;2-y.
  • 11. Aydin Ozturk P, Yilmaz T, Ozturk U. Effects of bemiparin sodium versus dabigatran etexilate after anastomosis in rat carotid arteries on the development of neointima and thrombolytic efficacy. World Neurosurg. 2019; 126: e731–e735. https://doi.org/10.1016/j.wneu.2019.02.139. 12. Ohman J, Heiskanen O. Effect of nimodipine on the outcome of patients after aneurysmal subarachnoid hemorrhage and surgery. J Neurosurg. 1988; 69: 683–686. https://doi.org/10.3171/jns.1988.69.5.0683.
  • 13. Kadioglu HH, Barlas E, Kayaoglu CR, Tuzun Y, Aydin IH. The effect of nimodipine on vascular injury after temporary clipping in a rabbit model. AUTD. 1996; 28: 331–336. Turkish.
  • 14. Hammerman C, Goldschmidt D, Caplan MS, Kaplan M, Schimmel MS, Eidelman AI, et al. Amelioration of ischemia-reperfusion injury in rat pentoxifyline-mediated inhibition of xanthine oxidase. J Pediatr Gastroenteral Nutr. 1999; 29: 69–74. https://doi.org/10.1097/00005176-199907000-00017.
  • 15. Busk M, Mertz H, Espersen GT, Rasmussen K, Maeng M. Effects of pentoxifylineon the vascular responseto injury after angioplasty in rabbit iliac arteries. Basic Res Cardiol. 2008; 1003: 257–264. https://doi.org/10.1007/s00395-007-0694-8.
  • 16. Takahashi A, Taniguchi T, Ishikawa Y, Yokoyama M. Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction of p21waf1/cip1/sdi and p53. Circ Res. 1999; 84: 54350. https://doi.org/10.1161/01.res.84.5.543.
  • 17. Ustunsoy H, Sivrikoz C, Topal M. Protective Role of Pentoxifylline on Peripheral System During Extracorporeal Circulation. Turk J Cardiovasc Surg. 2000; 8: 687–689. Turkish.