Classical heart rate variability and nonlinear heart rate analysis in mice under Napentobarbital and ketamine/xylazine anesthesia

Classical heart rate variability and nonlinear heart rate analysis in mice under Napentobarbital and ketamine/xylazine anesthesia

Background/aim: Anesthetics are often used in animal experiments to achieve immobilization and relieve pain. However, many anesthetics can alter the dynamics of cardiovascular systems. We aimed to compare the effects of two frequently used anesthetics agents on heart rate variability (HRV) parameters in mice. Materials and methods: This observational study was performed between May and June 2014 in 21 male BALB/c mice aged 16–20 weeks. The animals were divided into three groups: pentobarbital (P), (n = 7); pentobarbital+fentanyl (P+F), (n = 7); and ketamine+xylazine (K+X), (n = 7). Surface electrocardiography (ECG) electrodes were placed in lead II configuration. The tachogram of RR intervals was obtained after R waves were detected using the Pan-Tompkins real-time QRS recognition algorithm. Frequency-domain, time-domain, and nonlinear HRV analyses were performed. Results: The bradycardia effect was higher in the K+X group (p < 0.01). Time-domain indices were higher in group K+X compared to group P (p < 0.01) and group P+F (p < 0.001). Very low frequency (VLF) power was significantly lower in group K+X compared to group P and group P+F (p < 0.01). Low frequency (LF) power, low frequency/high frequency (LF/HF) ratio, and total power (TP) were higher in group K+X compared to group P (p < 0.01) and group P+F (p < 0.001). The detrended fluctuation analysis short-term parameter $(DFAα_1 )$ was significantly higher in group K+X compared to group P+F (p < 0.05) and the long-term parameter $(DFAα_2 )$ was lower in group K+X compared to group P (p < 0.05). Standard deviations SD1 and SD2 were higher in group K+X compared to group P (p < 0.001) and group P+F (p < 0.001), SD2/SD1 ratio was lower in group K+X compared to group P (p < 0.05) and group P+F (p < 0.05). Entropy measures did not differ between groups. Conclusion: HRV analyses, including nonlinear methods, indicated that a K+X combination reduces imbalance and disorder in the regulation of the autonomic nervous system (ANS) in comparison to both P and the P+F combination.

___

  • 1. McCraty R, Shaffer F. Heart rate variability: new perspectives on physiological mechanisms, assessment of self-regulatory capacity, and health risk. Global Advances in Health And Medicine 2015; 4 (1): 46-66. doi: 10.7453/gahmj.2014.073
  • 2. Uchino BN, Uno D, Holt-Lunstad J, Flinders JB. Age-related differences in cardiovascular reactivity during acute psychological stress in men and women. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences 1999; 54 (6): 339–346.
  • 3. Gargiulo S, Greco A, Gramanzini M, Esposito S, Affuso A, Brunetti A et al. Mice anesthesia, analgesia, and care, Part I: anesthetic considerations in preclinical research. Institute for Laboratory Animal Research 2012; 53 (1): 55-69.
  • 4. Goldmann C, Ghofrani A, Hafemann B, Fuchs P, KhorramSeffat R, Afify M et al. Combination anesthesia with ketamine and pentobarbital: a long-term porcine model. Research in Experimental Medicine 1999; 199 (1): 35-50.
  • 5. Chiba S, Tsuboi M. Dominant anti-vagal effect of pentobarbital on cardiac responses to intracardiac autonomic nerve stimulation in the dog. Japanese Journal of Pharmacology 2001; 86 (2): 248–250. doi: 10.1254/jjp.86.248
  • 6. Johnstone M. The cardiovascular effects of ketamine in man. Anaesthesia 1976; 31 (7): 873-882. doi: 10.1111/j.1365- 2044.1976.tb11898.x
  • 7. Kuo TB, Lai CJ, Huang YT, Yang CC. Regression analysis between heart rate variability and baroreflex-related vagus nerve activity in rats. Journal of Cardiovascular Electrophysiology 2005; 16 (8): 864-869. doi: 10.1111/j.1540-8167.2005.40656.x
  • 8. Bauer JA, Fung HL. Concurrent hydralazine administration prevents nitroglycerin-induced hemodynamic tolerance in experimental heart failure. Circulation 1991; 84 (1): 35-39. doi: 10.1161/01.cir.84.1.35
  • 9. Baum D, Halter JB, Taborsky GJ Jr, Porte D Jr. Pentobarbital effects on plasma catecholamines: temperature, heart rate, and blood pressure. American Journal of Physiology 1985; 248 (1): 95- 100. doi: 10.1152/ajpendo.1985.248.1.E95
  • 10. Hosomi H, Sagawa K. Effect of pentobarbital anesthesia on hypotension after 10% hemorrhage in the dog. American Journal of Physiology 1979; 236 (4): 607-612. doi: 10.1152/ ajpheart.1979.236.4.H607
  • 11. Shekarforoush S, Fatahi Z, Safari F. The effects of pentobarbital, ketamine-pentobarbital and ketamine-xylazine anesthesia in a rat myocardial ischemic reperfusion injury model. Lab Anim 2016; 50 (3): 179-184. doi: 10.1177/0023677215597136
  • 12. Watkins L, Maixner W. The effect of pentobarbital anesthesia on the autonomic nervous system control of heart rate during baroreceptor activation. Journal of Autonomic Nervous System 1991; 36 (2): 107-114. doi: 10.1016/0165-1838(91)90106-d
  • 13. Moore KA, Ripple MG, Sakinedzad S, Levine B, Fowler DR. Tissue distribution of xylazine in a suicide by hanging. Journal of Analytical Toxicology 2003; 27 (2): 110-112. doi: 10.1093/ jat/27.2.110
  • 14. Jiang X, Gao L, Zhang Y, Wang G, Liu Y, Yan C et al. Comparison of the effects of ketamine, chloral hydrate and pentobarbital sodium anesthesia on isolated rat hearts and cardiomyocytes. Journal of Cardiovascular Medicine 2011; 12 (10):732-735. doi: 10.2459/JCM.0b013e32834a6697
  • 15. Liu D, Shao Y, Luan X, Zhang M, Shui C, Wu Q. Comparison of Ketamine-Pentobarbital anesthesia and Fentanyl-Pentobarbital anesthesia for open-heart surgery in minipigs. Lab Animal 2009; 38 (7):234-340. doi: 10.1038/laban0709-234
  • 16. Becker LD, Paulson BA, Miller RD, Severinghaus JW, Eger EI 2nd. Biphasic respiratory depression after fentanyldroperidol or fentanyl alone used to supplement nitrous oxide anesthesia. Anesthesiology 1976; 44 (4): 291-296. doi: 10.1097/00000542- 197604000-00003
  • 17. Murphy MR, Olson WA, Hug CC Jr. Pharmacokinetics of 3H-fentanyl in the dog anesthetized with enflurane. Anesthesiology 1979; 50 (1): 13-19. doi: 10.1097/00000542- 197901000-00004
  • 18. Hug CC Jr, Murphy MR. Fentanyl disposition in cerebrospinal fluid and plasma and its relationship to ventilatory depression in the dog. Anesthesiology 1979; 50 (4): 342-349. doi: 10.1097/00000542-197904000-00011
  • 19. Sato N, Miyake S, Akatsu J, Kumashiro M. Power spectral analysis of heart rate variability in healthy young women during the normal menstrual cycle. Psychosomatic Medicine 1995; 57 (4): 331-335. doi: 10.1097/00006842-199507000-00004
  • 20. Gaertner DJ, Hallman TM, Hankenson FC, Batchelder MA. Anesthesia and Analgesia for Laboratory Rodents. In: Fish RE, Brown MJ, Danneman PJ, Karas AZ (editors). American College of Laboratory Animal Medicine, Anesthesia and Analgesia in Laboratory Animals. 2nd Ed. Academic Press 2008, pp. 239-297. doi:10.1016/B978-012373898-1.50014-0
  • 21. Ha TW, Oh B, Kang JO. Electrocardiogram recordings in anesthetized mice using Lead II. Journal of Visualized Experiments 2020; (160). doi: 10.3791/61583
  • 22. Singh S. Pattern analysis of different ECG signal using PanTompkin’s algorithm. 1st International Journal on Computer Science and Engineering 2010; 2 (7): 2502–2505.
  • 23. Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. Journal of the American College of Cardiology 1998; 31 (3): 593-601. doi: 10.1016/ s0735-1097(97)00554-8
  • 24. Shaffer F, Ginsberg JP. An overview of heart rate variability metrics and norms. Front Public Health 2017; 5 (258). doi: 10.3389/fpubh.2017.00258
  • 25. Bigger JT Jr, Albrecht P, Steinman RC, Rolnitzky LM, Fleiss JL, Cohen RJ. Comparison of time- and frequency domainbased measures of cardiac parasympathetic activity in Holter recordings after myocardial infarction. American Journal of Cardiology 1989; 64 (8): 536-538. doi: 10.1016/0002- 9149(89)90436-0
  • 26. Huikuri HV, Mäkikallio TH, Perkiömäki J. Measurement of heart rate variability by methods based on nonlinear dynamics. Journal of Electrocardiology 2003; (36): 95-99.
  • 27. Kleiger RE, Stein PK, Bigger JT Jr. Heart rate variability: measurement and clinical utility. Annals of Noninvasive Electrocardiology 2005; 10 (1): 88-101. doi: 10.1111/j.1542- 474X.2005.10101.x
  • 28. Tarvainen MP, Niskanen JP, Lipponen JA, Ranta-Aho PO, Karjalainen PA. Kubios HRV-heart rate variability analysis software. Computer Methods and Programs in Biomedicine 2014; 113 (1): 210-220. doi: 10.1016/j.cmpb.2013.07.024
  • 29. Thireau J, Zhang BL, Poisson D, Babuty D. Heart rate variability in mice: a theoretical and practical guide. Experimental Physiology 2008; 93 (1): 83-94. doi: 10.1113/expphysiol.2007.040733
  • 30. Peng CK, Havlin S, Stanley HE, Goldberger AL. Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series. Chaos 1995; 5 (1): 82-87. doi: 10.1063/1.166141
  • 31. Lin TT, Sung YL, Wu CE, Zhang H, Liu YB, Lin SF. Proarrhythmic risk and determinants of cardiac autonomic dysfunction in collagen-induced arthritis rats. BMC BMC Musculoskeletal Disorders 2016; 17 (1): 491. doi: 10.1186/s12891-016-1347-6
  • 32. Tayel NB, AlSaba EI. Poincaré plot for heart rate variability. International Journal of Biomedical and Biological Engineering 2015; 9 (9): 708-711. doi: 10.5281/zenodo.1109321
  • 33. Roy S, Goswami DP, Sengupta A. Geometry of the Poincaré plot can segregate the two arms of autonomic nervous system - A hypothesis. Medical Hypotheses 2020; 138 (109574). doi: 10.1016/j.mehy.2020.109574
  • 34. Zerr CL, Bartochowski Z, Shrestha R, Moessner A, Shaffer F. Does Inhalation-to-Exhalation Ratio Matter in Heart Rate Variability Biofeedback? In: Proceedings of the 28th Annual Student Research Conference; Kirksville, MO, USA. Doi: 10.1007/s10484-015-9282-0
  • 35. Brennan M, Palaniswami M, Kamen P. Poincaré plot interpretation using a physiological model of HRV based on a network of oscillators. American Journal of PhysiologyHeart and Circulatory 2002; 283 (5): 1873-1886. doi: 10.1152/ ajpheart.00405.2000
  • 36. Motie-Nasrabadi A, Behbahani S, Dabanloo NJ. Ictal heart rate variability assessment with focus on secondary generalized and complex partial epileptic seizures. Advances in Bioresearch 2013; 4 (1): 50-58.
  • 37. Sassi R, Cerutti S, Lombardi F, Malik M, Huikuri HV, Peng CK, Schmidt G, Yamamoto Y. Advances in heart rate variability signal analysis: joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society. Europace 2015; 17 (9): 1341-1353. doi: 10.1093/ europace/euv015
  • 38. Grund F, Tjomsland O, Sjaastad I, Ilebekk A, Kirkebøen KA. Pentobarbital versus medetomidine-ketamine-fentanyl anaesthesia: effects on haemodynamics and the incidence of ischaemia-induced ventricular fibrillation in swine. Lab Animal 2004; 38 (1):70-78. doi: 10.1258/00236770460734425
  • 39. Murthy VS, Zagar ME, Vollmer RR, Schmidt DH. Pentobarbitalinduced changes in vagal tone and reflex vagal activity in rabbits. European Journal of Pharmacology 1982; 84 (1-2): 41- 50. doi: 10.1016/0014-2999(82)90155-8
  • 40. Ma X, Abboud FM, Chapleau MW. Analysis of afferent, central, and efferent components of the baroreceptor reflex in mice. American Journal of Physiology Regulatory, Integrative and Comparative Physiology 2002; 283 (5): 1033-1140. doi: 10.1152/ajpregu.00768.2001
  • 41. Yan B, Li L, Harden SW, Epstein PN, Wurster RD, Cheng ZJ. Diabetes induces neural degeneration in nucleus ambiguus (NA) and attenuates heart rate control in OVE26 mice. Experimental Neurology 2009; 220 (1): 34-43. doi: 10.1016/j. expneurol.2009.07.006
  • 42. Nash CB, Floyd D, Woodbury RA. Cardiovascular effects of anesthetic doses of pentobarbital sodium. American Journal of Physiology-Legacy Content 1956; 185 (1): 107-112.
  • 43. Sawyer DC, Lumb WV, Stone HL. Cardiovascular effects of halothane, methoxyflurane, pentobarbital, and thiamylal. Journal of Applied Physiology 1971; 30 (1): 36-43. doi: 10.1152/ jappl.1971.30.1.36
  • 44. Atalan G, Demirkan I, Güneş V, Cihan M, Celebi F, Citil M. Comparison of xylazine+ ketamine-HCI anaesthetic agents with acepromazine+ butorphanol+ ketamine combinations for their clinical and cardiorespiratory effects in dogs. Veteriner Cerrahi Dergisi 2002; 8 (3-4):35–40.
  • 45. Flacke JW, Davis LJ, Flacke WE, Bloor BC, Van Etten AP. Effects of fentanyl and diazepam in dogs deprived of autonomic tone. Anesthesia & Analgesia 1985; 64 (11): 1053-1059.
  • 46. Ozbek M, Domack U, Barnikol WK. Eine erweiterte Evaluation der Neurolept-Anästhesie für Meerschweinchen mit einer Analyse gemischt-exspiratorischer Gase während Spontanatmung. Wirkung des Fastens auf das kardiorespiratorische System und den Metabolismus [An extended evaluation of a neuroleptanesthesia for the guinea pig with analysis of mixed expiratory gases during spontaneous breathing. Effects of fasting on the cardiorespiratory system and metabolism]. (Article in German with an abstract in English). Journal of Animal Physiology and Animal Nutrition 2004; 88 (1-2): 20- 29. 10.1111/j.1439-0396.2004.00450.x
  • 47. Haney MF, Wiklund U. Can heart rate variability become a screening tool for anesthesia-related hypotension? Acta Anaesthesiologica Scandinavica 2007; 51 (10): 1289-1291. doi: 10.1111/j.1399-6576.2007.01517.x
  • 48. Vettorello M, Colombo R, De Grandis CE, Costantini E, Raimondi F. Effect of fentanyl on heart rate variability during spontaneous and paced breathing in healthy volunteers. Acta Anaesthesiologica Scandinavica 2008; 52 (8): 1064-1070. doi: 10.1111/j.1399-6576.2008.01713.x
  • 49. Parati G, Mancia M, Di Rienzo M, Castiglioni P, Taylor JA et al. Cardiovascular variability is/is not an index of autonomic control of circulation. Journal of Applied Physiology 2006; 101 (2): 690–691. doi:10.1152/japplphysiol.00584.2006
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

The effect of COVID-19 pandemic in a large series of patients with Takayasu arteritis

Fatoş ÖNEN, İsmail SARI, Tuba YÜCE İNEL, Ali KARAKAŞ

Determination of miRNA expression profile in patients with prostate cancer and benign prostate hyperplasia

Murat DEMİR, Osman ERGÜN, Alim KOŞAR, Muhammet Yusuf TEPEBAŞI, Pınar ASLAN KOŞAR, Okan SANCER

Reflux, dysphonia, and dysphagia symptoms in patients with diabetes and their association with diabetic complications

Güzide ATALIK, Yusuf Kemal KEMALOĞLU, Metin YILMAZ, Hakan GÖLAÇ

Investigation of miRNA and cytokine expressions in latent tuberculosis infection and active tuberculosis

Cumhur GÜNDÜZ, Fethiye Ferda YILMAZ, Can BİÇMEN, Onur KARAMAN, Tülay AKARCA, Şevket DERELİ, Haluk AKIN, Zehra CENGİSİZ, Asude DURMAZ, Hasan TAŞLIDERE, Cengiz ÇAVUŞOĞLU, Mehmet Sezai TAŞBAKAN, Özgür ÇOĞULU, Meltem TAŞBAKAN

Assessment of Tp–e interval, Tp–e/QT, and Tp-e/QTc ratios in patients with acromegaly

Uğur BOZKURT, Mikail YARLIOĞLU, İbrahim Etem ÇELİK, Mustafa DURAN, Sani Namık MURAT, Sevde Nur FIRAT

Does memantine show chemopreventive effect against mice 4T1 breast tumor model?

Elif Burcu BAL, Gülşah ALBAYRAK, Funda DEMİRTAŞ KORKMAZ, Emin Ümit BAĞRIAÇIK

Mortality related factors on hypoxic ischemic encephalopathic patients treated with therapeutic hypothermia: an 11-year single-center experience.

Hüseyin KAYA, Meral ALAGÖZ, Ramazan ÖZDEMİR, İsmail Kürşad GÖKÇE, Mehmet Fatih DEVECİ, Hatice TURGUT

The clinical follow-up and management of COVID-19 in children and adolescents with an immunocompromised state or a malignancy

Özlem TÜFEKÇİ, Dilek İNCE, Şefika AKYOL, Meral TORUN BAYRAM, Refik Emre ÇEÇEN, Ayşe ÇAKIL GÜZİN, Hatice KARAOĞLU ASRAK, İrem Ceren ERBAŞ, Şilem ÖZDEM ALATAŞ, Nurşen BELET

Oncometabolites in urine – a new opportunity for detection and prognosis of the clinical progress of verified prostate cancer-a pilot study

Rumyana STOYANOVA, Desislav TOMOV, Dimitar DELKOV, Lyubka YOANIDU, Ivan DECHEV, Yordanka UZUNOVA

Hydroxychloroquine induces endothelium-dependent and endothelium-independent relaxation of rat aorta

Ali PARLAR, Saliha Ayşenur ÇAM, Ahmet Cenk ANDAÇ, Ibraheem Akram OMAR, Fatma UYSAL, Seyfullah Oktay ARSLAN, Muhammed Fatih DOĞAN, Oğuzhan YILDIZ