Cardiovascular Toxicology

, Volume 19, Issue 1, pp 56–61 | Cite as

Predictive Role of the Cervical Sympathetic Trunk Ischemia on Lower Heart Rates in an Experimentally Induced Stenoocclusive Carotid Artery Model by Bilateral Common Carotid Artery Ligation

  • Yavuzer KozaEmail author
  • Ednan Bayram
  • Mehmet Dumlu Aydin
  • Canan Atalay
  • Mehmet Resit Onen
  • Cengiz Ozturk
  • Sare Sipal
  • Elif Demirci
  • Akin Levent


Bilateral common carotid artery ligation (BCCAL) leads to acute craniocervicocerebral ischemia, retrograde blood flow, increased blood pressure, and significant hemodynamic and histomorphological changes at the posterior cerebral vasculature. We examined the potential relationship between denervation injury following BCCAL-induced cervical sympathetic trunk (CST) ischemia and heart rate after permanent BCCAL. Rabbits (n = 25) were randomly divided into three groups: an unoperated control group (GI, n = 6); a sham-operated control group (GII, n = 6), and an experimental group subjected to BCCAL (GIII, n = 13); and then followed for one month. All animals were then sacrificed and the stellate ganglia (STGs) were examined histologically using stereological methods. The densities of degenerated neurons in the STGs were compared with heart rates and the results were analyzed with the Mann–Whitney U test. The mean normal neuron density in STGs was 10.340 ± 954/mm3 and the degenerated neuron density was 12 ± 3/mm3 in the GI group (p > 0.5). The mean heart rates and degenerated neuron densities of STGs were recorded as 267 ± 19/min and 237 ± 45/mm3 in GII (p < 0.005 for GII vs. GI); and 190 ± 11/min 1421 ± 230/mm3 in GIII (p < 0.0001 for GIII vs. GI and p < 0.005 for GIII vs. GII). An inverse and meaningful association was observed between the heart rate and degenerated neuronal density in the STGs. BCCAL may lead to hazardous histomorphological changes in the CST. A high density of degenerated neurons in the STG may provoke excessive sympathetic hypoactivity-related cardiac damage and bradyarrhythmias after stenoocclusive carotid artery diseases.


Cervical sympathetic trunk ischemia Common carotid artery Heart rate 


Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.


  1. 1.
    Oldendorf, W. H. (1989). Trophic changes in the arteries at the base of the rat brain in response to bilateral common carotid ligation. Journal of Neuropathology & Experimental Neurology, 48, 534–547.CrossRefGoogle Scholar
  2. 2.
    Onen, M. R., Yilmaz, I., Ramazanoglu, L., Tanrıverdi, O., Aydin, M. D., Kanat, A., et al. (2016). Rational roots of sympathetic overactivity by neurogenic pulmonary edema modeling arising from sympathyco-vagal imbalance in subarachnoid hemorrhage: An experimental study. World Neurosurgery, 92, 463–470.CrossRefPubMedGoogle Scholar
  3. 3.
    Yilmaz, I., Eseoglu, M., Onen, M. R., Tanrıverdi, O., Kilic, M., Yilmaz, A., et al. (2017). Inverse association between basilar artery volume and neuron density in the stellate ganglion following bilateral common carotid artery ligation: An experimental study. World Neurosurgery, 100, 138–143.CrossRefPubMedGoogle Scholar
  4. 4.
    Huang, B., Yu, L., Scherlag, B. J., Wang, S., He, B., Yang, K., et al. (2014). Left renal nerves stimulation facilitates ischemia-induced ventricular arrhythmia by increasing nerve activity of left stellate ganglion. Journal of Cardiovascular Electrophysiology, 25, 1249–1256.CrossRefPubMedGoogle Scholar
  5. 5.
    Lujan, H. L., Palani, G., Zhang, L., & DiCarlo, S. E. (2010). Targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-inducedsustained ventricular tachycardia in conscious rats. American Journal of Physiology-Heart and Circulatory Physiology, 298, H1330–H1339.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Sterio, D. C. (1984). The unbiased estimation of number and sizes of arbitrary particles using the disector. Journal of Microscopy, 134, 127–136.CrossRefPubMedGoogle Scholar
  7. 7.
    Aydin, M. D., Ozkan, U., Gündoğdu, C., & Onder, A. (2002). Protective effect of posterior cerebral circulation on carotid body ischemia. Acta Neurochirurgica, 144, 369–372.CrossRefPubMedGoogle Scholar
  8. 8.
    Eseoglu, M., Yilmaz, I., Karalar, M., Aydin, M. D., Kayaci, S., Gundogdu, C., et al. (2014). The role of sympathectomy on the regulation of basilar artery volume changes in stenoocclusive carotid artery modeling after bilateral common carotid artery ligation: An animal model. Acta Neurochirurgica (Wien), 156, 963–969.CrossRefGoogle Scholar
  9. 9.
    Aygul, R., Aydin, M. D., Kotan, D., Demir, R., Ulvi, H., Karalar, M., et al. (2013). Role of the trigeminal system on posterior communicating artery remodelization after bilateral common carotid artery ligation. Analytical and Quantitative Cytopathology and Histopathology 35, 217–225.PubMedGoogle Scholar
  10. 10.
    Jago, R., Heath, D., & Smith, P. (1982). Structure of the glomic arteries. The Journal of Pathology, 138, 205–218.CrossRefPubMedGoogle Scholar
  11. 11.
    Milei, J., Lavezzi, A. M., Bruni, B., Grana, D. R., Azzato, F., & Matturri, L. (2009). Carotid barochemoreceptor pathological findings regarding carotid plaque status and aging. Canadian Journal of Cardiology, 25, e6–e12.CrossRefPubMedGoogle Scholar
  12. 12.
    Chao, A. C., Chern, C. M., Kuo, T. B., Chou, C. H., Chuang, Y. M., Wong, W. J., et al. (2003). Noninvasive assessment of spontaneous baroreflex sensitivity and heart rate variability in patients with carotid stenosis. Cerebrovascular Diseases, 16, 151–157.CrossRefPubMedGoogle Scholar
  13. 13.
    Nasr, N., Pavy-Le Traon, A., & Larrue, V. (2005). Baroreflex sensitivity is impaired in bilateral carotid atherosclerosis. Stroke, 36, 1891–1895.CrossRefGoogle Scholar
  14. 14.
    Tubbs, R. S., Salter, G., Wellons, J. C. 3rd, & Oakes, W. J. (2002). Blood supply of the human cervical sympathetic chain and ganglia. European Journal of Morphology, 40, 283–288.CrossRefPubMedGoogle Scholar
  15. 15.
    Moskowitz, M. A., Renhard, J. F., Romero, J., Melamed, E., & Pettibone, D. J. (1979). Neurotransmitters and the fifth cranial nerve: Is there a relation to the headache phase of migraine? Lancet, 2, 883–885.CrossRefPubMedGoogle Scholar
  16. 16.
    Aydin, M. D., Bayram, E., Atalay, C., Aydin, N., Erdogan, A. R., Gundogdu, C., et al. (2006). The role of neuron numbers of the petrozal ganglion in the determination of blood pressure. An experimental study. Minimally Invasive Neurosurgery, 49, 328–330.CrossRefPubMedGoogle Scholar
  17. 17.
    Bharati, S., & Lev, M. (1992). The pathologic changes in the conduction system beyond the age of ninety. American Heart Journal, 124, 486–496.CrossRefPubMedGoogle Scholar
  18. 18.
    Song, Y., Laaksonen, H., Saukko, P., Toivonen, S., & Zhu, J. (2001). Histopathological findings of cardiac conduction system of 150 finns. Forensic Science International, 119, 310–317.CrossRefPubMedGoogle Scholar
  19. 19.
    Chow, L. T., Chow, S. S., Anderson, R. H., & Gosling, J. A. (2001). Autonomic innervation of the human cardiac conduction system: changes from infancy to senility-an immunohistochemical and histochemical analysis. The Anatomical Record, 264, 169–182.CrossRefPubMedGoogle Scholar
  20. 20.
    Polydorou, A., Megalooikonomos, P., Portinos, A., Prapa, E., Kara, P., Tsiga, A., et al. (2010). Persistent bradycardia in a patient with coronary artery disease and concomitant carotid artery disease. Hospital Chronicles, 5(1 Sup), 101–104.Google Scholar
  21. 21.
    Kirby, D. A., & Vatner, F. (1987). Enhanced responsiveness to carotid baroreceptor unloading in conscious dogs during development of perinephritic hypertension. Circulation Research, 61, 678–686.CrossRefPubMedGoogle Scholar
  22. 22.
    Vatner, S. F., & Manders W. T. (1979). Depressed responsiveness of the carotid sinüs reflex in conscious newborn animals. American Journal of Physiology-Heart and Circulatory Physiology, 237, H40–H43.CrossRefGoogle Scholar
  23. 23.
    Kumagai, K., & Reid, I. A. (1994). Losartan inhibits sympathetic and cardiovascular responses to carotid occlusion. Hypertension, 23, 827–831.CrossRefPubMedGoogle Scholar
  24. 24.
    Schröder, H. J., Rybakowski, C., Eisermann, K., Tchirikov, M., & Ostermann, S. (2000). Unloading of baroreceptors by carotid occlusion does not increase heart rate in fetal sheep. European Journal of Obstetrics & Gynecology and Reproductive Biology, 92, 265–272.CrossRefGoogle Scholar
  25. 25.
    Fujiki, A., Masuda, A., & Inoue, H. (1999). Effects of unilateral stellate ganglion block on the spectral characteristics of heart rate variability. Japanese Circulation Journal, 63, 854–858.CrossRefPubMedGoogle Scholar
  26. 26.
    Rogers, M. C., Abildskov, J. A., & Preston, J. B. (1973). Cardiac effects of stimulation and block of the stellate ganglion. Anesthesiology, 39, 525–533.CrossRefPubMedGoogle Scholar
  27. 27.
    Schwartz, P. J. (1984). The rationale and the role of left stellectomy for the prevention of malignant arrhythmias. Annals of the New York Academy of Sciences, 427, 199–221.CrossRefPubMedGoogle Scholar
  28. 28.
    Song, J. G., Hwang, G. S., Lee, E. H., Leem, J. G., Lee, C., Park, P. H., et al. (2009). Effects of bilateral stellate ganglion block on autonomic cardiovascular regulation. Circulation Journal, 73, 1909–1913.CrossRefPubMedGoogle Scholar
  29. 29.
    Vaseghi, M., Zhou, W., Shi, J., Ajijola, O. A., Hadaya, J., Shivkumar, K., et al. (2012). Sympathetic innervation of the anterior left ventricularwall by the right and left stellate ganglia. Heart Rhythm, 9, 1303–1309.CrossRefPubMedGoogle Scholar
  30. 30.
    Kawashima, T. (2011). Anatomy of the cardiac nervous system with clinical and comparative morphological implications. Anatomical Science International, 86, 30–49.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yavuzer Koza
    • 1
    Email author
  • Ednan Bayram
    • 1
  • Mehmet Dumlu Aydin
    • 2
  • Canan Atalay
    • 3
  • Mehmet Resit Onen
    • 4
  • Cengiz Ozturk
    • 5
  • Sare Sipal
    • 6
  • Elif Demirci
    • 6
  • Akin Levent
    • 7
  1. 1.Department of Cardiology, Medical FacultyAtaturk UniversityErzurumTurkey
  2. 2.Department of Neurosurgery, Medical FacultyAtaturk UniversityErzurumTurkey
  3. 3.Department of Anesthesiology, Medical FacultyAtaturk UniversityErzurumTurkey
  4. 4.Neurosurgery ClinicUmraniye Education and Research HospitalIstanbulTurkey
  5. 5.Family MedicineOsman Gazi Family Health Medicine CenterErzurumTurkey
  6. 6.Department of Pathology, Medical FacultyAtaturk UniversityErzurumTurkey
  7. 7.Department of Radiology, Medical FacultyAtaturk UniversityErzurumTurkey

Personalised recommendations