Research Article
BibTex RIS Cite

Evaluation of differential effects of CDP-choline and choline on parasympathetic activity and changes in choline levels with heart rate variability

Year 2024, Volume: 37 Issue: 1, 80 - 85, 28.01.2024

Hasan Kazdağlı Şüheda Alpay Hasan Fehmi Özel Elif Barış

https://doi.org/10.5472/marumj.1379856

Abstract

Objective: Heart rate variability (HRV) is used to evaluate the autonomic activity of heartbeat. This study aimed to investigate the
effects of cholinomimetic drugs cytidine diphosphate-choline (CDP-choline) and choline, on short-term HRV parameters.
Materials and Methods: Animals were randomized into three groups; control (0.9% NaCl), choline (100 mg/kg), CDP-choline (400
mg/kg). Electrocardiography recordings were obtained for 45-minutes after treatments with 15-minutes intervals. HRV analyses and
total choline level measurements in serum and heart tissues were performed.
Results: High frequency power and total power increased in treatment groups, while heart rates were decreased. Low frequency was
decreased with choline while very low frequency power decreased with CDP-choline. Choline affected most of the HRV parameters
in the first 15 minutes, while the effect of CDP-choline started within 30 minutes. Total choline levels were higher in both treatment
groups than in the control while the levels were also higher in the choline group compared to CDP-choline group.
Conclusion: This study showed that CDP-choline and choline treatments produced a rapid response to short-term HRV parameters,
while increasing tissue choline levels. Moreover, the differences in effects and onset time between the drugs on HRV might be related
to tissue choline concentration.

Keywords

Parasympathomimetics Autonomic nervous system Cytidine diphosphate choline Choline

References

  • Chovatiya R, Medzhitov R. Stress, inflammation, and defense of homeostasis. Mol Cell 2014; 54: 281-88. doi: 10.1016/j. molcel.2014.03.030.
  • Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation 1996; 93: 1043-65. doi: 10.1161/01.CIR.93.5.1043.
  • Brodal P. The central nervous system : structure and function. New York: Oxford University Press, 2004; 224-33.
  • Parrish W R, Rosas-Ballina M, Gallowitsch-Puerta M, et al. Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor-mediated signaling. Mol Med Camb Mass 2008; 14: 567-74. doi: 10.2119/2008-00079. Parrish.
  • Papke R, Bencherif M, Lippiello P. An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the α7 subtype. Neurosci Lett 1996; 213: 201-04. doi: 10.1016/0304-3940(96)12889-5.
  • Ulus I H, Millington W R, Buyukuysal R L, Kiran B K. Choline as an agonist: Determination of its agonistic potency on cholinergic receptors. Biochem Pharmacol 1988; 37: 2747-55. doi: 10.1016/0006-2952(88)90037-8.
  • Cornell R B, Ridgway N D. CTP: phosphocholine cytidylyltransferase: Function, Regulation, and Structure of an amphitropic enzyme required for membrane biogenesis. Prog Lipid Res 2015; 59: 147-71. doi: 10.1016/j.plipres.2015.07.001.
  • Köppen A, Klein J, Holler T, Löffelholz K. Synergistic effect of nicotinamide and choline administration on extracellular choline levels in the brain. J Pharmacol Exp Ther 1993; 266: 720-25.
  • Savci V, Goktalay G, Cansev M, Cavun S, Yilmaz M S, Ulus I H. Intravenously injected CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock: Effect is mediated by central cholinergic activation. Eur J Pharmacol 2003; 468: 129-39. doi: 10.1016/S0014-2999(03)01602-9.
  • Synoradzki K, Grieb P. Citicoline: A superior form of choline? Nutrients 2019; 11: 1569. doi: 10.3390/nu11071569.
  • Cheng M, Bhujwalla Z M, Glunde K. Targeting phospholipid metabolism in cancer. Front Oncol 2016; 6: 266. doi: 10.3389/ fonc.2016.00266.
  • Grieb P. Neuroprotective properties of citicoline: facts, doubts and unresolved issues. CNS Drugs 2014; 28: 185-93. doi: 10.1007/s40263.014.0144-8.
  • Ottobelli L, Manni G L, Centofanti M, Iester M, Allevena F, Rossetti L. Citicoline oral solution in glaucoma: is there a role in slowing disease progression? Ophthalmologica 2013; 229: 219-26. doi: 10.1159/000350496.
  • Skripuletz T, Manzel A, Gropengiesser K, et al. Pivotal role of choline metabolites in remyelination. Brain 2015; 138: 398-13 doi: 10.1093/brain/awu358.
  • Bagdas D, Sonat F A, Hamurtekin E, Sonal S, Gurun M S. The antihyperalgesic effect of cytidine-5′-diphosphate-choline in neuropathic and inflammatory pain models. Behav Pharmacol 2011; 22: 589-98. doi: 10.1097/FBP.0b013e32834a1efb.
  • Sato N, Miyake S, Akatsu J, Kumashiro M. Power spectral analysis of heart rate variability in healthy young women during the normal menstrual cycle. Psychosom Med 1995; 57: 331-35. doi: 10.1097/00006.842.199507000-00004.
  • Halliwill J R, Billman G E. Effect of general anesthesia on cardiac vagal tone. Am J Physiol 1992; 262: H1719-24. doi: 10.1152/ajpheart.1992.262.6.H1719.
  • Baris E, Simsek O, Efe H, et al. Effects of CDP-Choline and Choline on COX pathway in LPS-Induced Inflammatory Response in Rats. Int J Pharmacol 2021; 17: 84-96. doi: 10.3923/ijp.2021.84.96.
  • Dempsey R J, Raghavendra Rao V L. Cytidinediphosphocholine treatment to decrease traumatic brain injury—induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats. J Neurosurg 2003; 98: 867- 73. doi: 10.3171/jns.2003.98.4.0867.
  • Ha T H, Oh B, Kang J-O. Electrocardiogram recordings in anesthetized mice using lead II. J Vis Exp 2020; 20. doi: 10.3791/61583.
  • Shaffer F, Ginsberg J P. An Overview of heart rate variability metrics and norms. Front Public Health 2017; 5: 1-17. doi: 10.3389/fpubh.2017.00258.
  • Lin T-T, Sung Y-L, Wu C-E, Zhang H, Liu Y-B, Lin S-H. Proarrhythmic risk and determinants of cardiac autonomic dysfunction in collagen-induced arthritis rats. BMC Musculoskelet Disord 2016; 17: 1-8. doi: 10.1186/ s12891.016.1347-6.
  • Kamen P W, Krum H, Tonkin A M. Poincaré plot of heart rate variability allows quantitative display of parasympathetic nervous activity in humans. Clin Sci Lond Engl 1996; 91: 201- 8. doi: 10.1042/cs0910201.
  • Lippman N, Stein K M, Lerman B B. Comparison of methods for removal of ectopy in measurement of heart rate variability. Am J Physiol 1994; 267: H411-8. doi: 10.1152/ ajpheart.1994.267.1.H411.
  • Kazdağlı H, Özel H F, Özbek M, Alpay Ş, Alenbey M. Classical heart rate variability and nonlinear heart rate analysis in mice under napentobarbital and ketamine/xylazine anesthesia. Turk J Med Sci 2022; 52: 858-69. doi: 10.55730/1300-0144.5383.
  • Kocaturk M, Yilmaz Z, Cansev M, et al. Choline or CDPcholine restores hypotension and improves myocardial and respiratory functions in dogs with experimentally – Induced endotoxic shock. Res Vet Sci 2021; 141: 116-28. doi: 10.1016/j. rvsc.2021.10.010.
  • Adibhatla R M, Hatcher J F. Cytidine 5’-diphosphocholine (CDP-choline) in stroke and other CNS disorders. Neurochem Res 2005; 30: 15-23. doi: 10.1007/s11064.004.9681-8. [28] Scremin O U, Li M G, Roch M, Booth R, Jenden D J. Acetylcholine and choline dynamics provide early and late markers of traumatic brain injury. Brain Res 2006; 1124: 155- 66. doi: 10.1016/j.brainres.2006.09.062.
  • Başkaya M K, Dogan A, Rao A M, Dempsey R J. Neuroprotective effects of citicoline on brain edema and blood-brain barrier breakdown after traumatic brain injury. J Neurosurg 2000; 92: 448-52. doi: 10.3171/jns.2000.92.3.0448.
  • Javaid S, Farooq T, Rehman Z, et al. Dynamics of cholinecontaining phospholipids in traumatic brain injury and associated comorbidities. Int J Mol Sci 2021; 22: 11313. doi: 10.3390/ijms222111313.
  • Cansev M, Yilmaz M S, Ilcol Y O, Hamurtekin E, Ulus I H. Cardiovascular effects of CDP-choline and its metabolites: Involvement of peripheral autonomic nervous system. Eur J Pharmacol 2007; 577: 129-42. doi: https://doi.org/10.1016/j. ejphar.2007.08.029.
  • Ilcol Y O, Gurun M S, Taga Y, Ulus I H. Choline increases serum insulin in rat when injected intraperitoneally and augments basal and stimulated aceylcholine release from the rat minced pancreas in vitro. Eur J Biochem 2003; 270: 991-99. doi: 10.1046/j.1432-1033.2003.03472.x.

Year 2024, Volume: 37 Issue: 1, 80 - 85, 28.01.2024

Hasan Kazdağlı Şüheda Alpay Hasan Fehmi Özel Elif Barış

https://doi.org/10.5472/marumj.1379856

Abstract

References

  • Chovatiya R, Medzhitov R. Stress, inflammation, and defense of homeostasis. Mol Cell 2014; 54: 281-88. doi: 10.1016/j. molcel.2014.03.030.
  • Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation 1996; 93: 1043-65. doi: 10.1161/01.CIR.93.5.1043.
  • Brodal P. The central nervous system : structure and function. New York: Oxford University Press, 2004; 224-33.
  • Parrish W R, Rosas-Ballina M, Gallowitsch-Puerta M, et al. Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor-mediated signaling. Mol Med Camb Mass 2008; 14: 567-74. doi: 10.2119/2008-00079. Parrish.
  • Papke R, Bencherif M, Lippiello P. An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the α7 subtype. Neurosci Lett 1996; 213: 201-04. doi: 10.1016/0304-3940(96)12889-5.
  • Ulus I H, Millington W R, Buyukuysal R L, Kiran B K. Choline as an agonist: Determination of its agonistic potency on cholinergic receptors. Biochem Pharmacol 1988; 37: 2747-55. doi: 10.1016/0006-2952(88)90037-8.
  • Cornell R B, Ridgway N D. CTP: phosphocholine cytidylyltransferase: Function, Regulation, and Structure of an amphitropic enzyme required for membrane biogenesis. Prog Lipid Res 2015; 59: 147-71. doi: 10.1016/j.plipres.2015.07.001.
  • Köppen A, Klein J, Holler T, Löffelholz K. Synergistic effect of nicotinamide and choline administration on extracellular choline levels in the brain. J Pharmacol Exp Ther 1993; 266: 720-25.
  • Savci V, Goktalay G, Cansev M, Cavun S, Yilmaz M S, Ulus I H. Intravenously injected CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock: Effect is mediated by central cholinergic activation. Eur J Pharmacol 2003; 468: 129-39. doi: 10.1016/S0014-2999(03)01602-9.
  • Synoradzki K, Grieb P. Citicoline: A superior form of choline? Nutrients 2019; 11: 1569. doi: 10.3390/nu11071569.
  • Cheng M, Bhujwalla Z M, Glunde K. Targeting phospholipid metabolism in cancer. Front Oncol 2016; 6: 266. doi: 10.3389/ fonc.2016.00266.
  • Grieb P. Neuroprotective properties of citicoline: facts, doubts and unresolved issues. CNS Drugs 2014; 28: 185-93. doi: 10.1007/s40263.014.0144-8.
  • Ottobelli L, Manni G L, Centofanti M, Iester M, Allevena F, Rossetti L. Citicoline oral solution in glaucoma: is there a role in slowing disease progression? Ophthalmologica 2013; 229: 219-26. doi: 10.1159/000350496.
  • Skripuletz T, Manzel A, Gropengiesser K, et al. Pivotal role of choline metabolites in remyelination. Brain 2015; 138: 398-13 doi: 10.1093/brain/awu358.
  • Bagdas D, Sonat F A, Hamurtekin E, Sonal S, Gurun M S. The antihyperalgesic effect of cytidine-5′-diphosphate-choline in neuropathic and inflammatory pain models. Behav Pharmacol 2011; 22: 589-98. doi: 10.1097/FBP.0b013e32834a1efb.
  • Sato N, Miyake S, Akatsu J, Kumashiro M. Power spectral analysis of heart rate variability in healthy young women during the normal menstrual cycle. Psychosom Med 1995; 57: 331-35. doi: 10.1097/00006.842.199507000-00004.
  • Halliwill J R, Billman G E. Effect of general anesthesia on cardiac vagal tone. Am J Physiol 1992; 262: H1719-24. doi: 10.1152/ajpheart.1992.262.6.H1719.
  • Baris E, Simsek O, Efe H, et al. Effects of CDP-Choline and Choline on COX pathway in LPS-Induced Inflammatory Response in Rats. Int J Pharmacol 2021; 17: 84-96. doi: 10.3923/ijp.2021.84.96.
  • Dempsey R J, Raghavendra Rao V L. Cytidinediphosphocholine treatment to decrease traumatic brain injury—induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats. J Neurosurg 2003; 98: 867- 73. doi: 10.3171/jns.2003.98.4.0867.
  • Ha T H, Oh B, Kang J-O. Electrocardiogram recordings in anesthetized mice using lead II. J Vis Exp 2020; 20. doi: 10.3791/61583.
  • Shaffer F, Ginsberg J P. An Overview of heart rate variability metrics and norms. Front Public Health 2017; 5: 1-17. doi: 10.3389/fpubh.2017.00258.
  • Lin T-T, Sung Y-L, Wu C-E, Zhang H, Liu Y-B, Lin S-H. Proarrhythmic risk and determinants of cardiac autonomic dysfunction in collagen-induced arthritis rats. BMC Musculoskelet Disord 2016; 17: 1-8. doi: 10.1186/ s12891.016.1347-6.
  • Kamen P W, Krum H, Tonkin A M. Poincaré plot of heart rate variability allows quantitative display of parasympathetic nervous activity in humans. Clin Sci Lond Engl 1996; 91: 201- 8. doi: 10.1042/cs0910201.
  • Lippman N, Stein K M, Lerman B B. Comparison of methods for removal of ectopy in measurement of heart rate variability. Am J Physiol 1994; 267: H411-8. doi: 10.1152/ ajpheart.1994.267.1.H411.
  • Kazdağlı H, Özel H F, Özbek M, Alpay Ş, Alenbey M. Classical heart rate variability and nonlinear heart rate analysis in mice under napentobarbital and ketamine/xylazine anesthesia. Turk J Med Sci 2022; 52: 858-69. doi: 10.55730/1300-0144.5383.
  • Kocaturk M, Yilmaz Z, Cansev M, et al. Choline or CDPcholine restores hypotension and improves myocardial and respiratory functions in dogs with experimentally – Induced endotoxic shock. Res Vet Sci 2021; 141: 116-28. doi: 10.1016/j. rvsc.2021.10.010.
  • Adibhatla R M, Hatcher J F. Cytidine 5’-diphosphocholine (CDP-choline) in stroke and other CNS disorders. Neurochem Res 2005; 30: 15-23. doi: 10.1007/s11064.004.9681-8. [28] Scremin O U, Li M G, Roch M, Booth R, Jenden D J. Acetylcholine and choline dynamics provide early and late markers of traumatic brain injury. Brain Res 2006; 1124: 155- 66. doi: 10.1016/j.brainres.2006.09.062.
  • Başkaya M K, Dogan A, Rao A M, Dempsey R J. Neuroprotective effects of citicoline on brain edema and blood-brain barrier breakdown after traumatic brain injury. J Neurosurg 2000; 92: 448-52. doi: 10.3171/jns.2000.92.3.0448.
  • Javaid S, Farooq T, Rehman Z, et al. Dynamics of cholinecontaining phospholipids in traumatic brain injury and associated comorbidities. Int J Mol Sci 2021; 22: 11313. doi: 10.3390/ijms222111313.
  • Cansev M, Yilmaz M S, Ilcol Y O, Hamurtekin E, Ulus I H. Cardiovascular effects of CDP-choline and its metabolites: Involvement of peripheral autonomic nervous system. Eur J Pharmacol 2007; 577: 129-42. doi: https://doi.org/10.1016/j. ejphar.2007.08.029.
  • Ilcol Y O, Gurun M S, Taga Y, Ulus I H. Choline increases serum insulin in rat when injected intraperitoneally and augments basal and stimulated aceylcholine release from the rat minced pancreas in vitro. Eur J Biochem 2003; 270: 991-99. doi: 10.1046/j.1432-1033.2003.03472.x.
There are 31 citations in total.

Details

Primary Language English
Subjects Surgery (Other)
Journal Section Original Research
Authors

Hasan Kazdağlı 0000-0001-6617-604X

Şüheda Alpay 0000-0003-3775-8491

Hasan Fehmi Özel 0000-0003-1676-0648

Elif Barış 0000-0001-6838-7932

Publication Date January 28, 2024
Published in Issue Year 2024 Volume: 37 Issue: 1

Cite

APA Kazdağlı, H., Alpay, Ş., Özel, H. F., Barış, E. (2024). Evaluation of differential effects of CDP-choline and choline on parasympathetic activity and changes in choline levels with heart rate variability. Marmara Medical Journal, 37(1), 80-85. https://doi.org/10.5472/marumj.1379856
AMA Kazdağlı H, Alpay Ş, Özel HF, Barış E. Evaluation of differential effects of CDP-choline and choline on parasympathetic activity and changes in choline levels with heart rate variability. Marmara Med J. January 2024;37(1):80-85. doi:10.5472/marumj.1379856
Chicago Kazdağlı, Hasan, Şüheda Alpay, Hasan Fehmi Özel, and Elif Barış. “Evaluation of Differential Effects of CDP-Choline and Choline on Parasympathetic Activity and Changes in Choline Levels With Heart Rate Variability”. Marmara Medical Journal 37, no. 1 (January 2024): 80-85. https://doi.org/10.5472/marumj.1379856.
EndNote Kazdağlı H, Alpay Ş, Özel HF, Barış E (January 1, 2024) Evaluation of differential effects of CDP-choline and choline on parasympathetic activity and changes in choline levels with heart rate variability. Marmara Medical Journal 37 1 80–85.
IEEE H. Kazdağlı, Ş. Alpay, H. F. Özel, and E. Barış, “Evaluation of differential effects of CDP-choline and choline on parasympathetic activity and changes in choline levels with heart rate variability”, Marmara Med J, vol. 37, no. 1, pp. 80–85, 2024, doi: 10.5472/marumj.1379856.
ISNAD Kazdağlı, Hasan et al. “Evaluation of Differential Effects of CDP-Choline and Choline on Parasympathetic Activity and Changes in Choline Levels With Heart Rate Variability”. Marmara Medical Journal 37/1 (January 2024), 80-85. https://doi.org/10.5472/marumj.1379856.
JAMA Kazdağlı H, Alpay Ş, Özel HF, Barış E. Evaluation of differential effects of CDP-choline and choline on parasympathetic activity and changes in choline levels with heart rate variability. Marmara Med J. 2024;37:80–85.
MLA Kazdağlı, Hasan et al. “Evaluation of Differential Effects of CDP-Choline and Choline on Parasympathetic Activity and Changes in Choline Levels With Heart Rate Variability”. Marmara Medical Journal, vol. 37, no. 1, 2024, pp. 80-85, doi:10.5472/marumj.1379856.
Vancouver Kazdağlı H, Alpay Ş, Özel HF, Barış E. Evaluation of differential effects of CDP-choline and choline on parasympathetic activity and changes in choline levels with heart rate variability. Marmara Med J. 2024;37(1):80-5.
 Download Cover Image