Biology:Trigeminocardiac reflex

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The Trigemino-Cardiac Reflex (TCR) consists of a reduction in heart rate associated with a marked decrease in mean arterial pressure following stimulation of the trigeminal nerve.[1]

In recent years, the TCR has emerged as the prototype for a family of physiological reflex reactions—not necessarily pathological—which includes the oculocardiac reflex and the diving reflex.[2] The renewed interest in the TCR and related reflexes is largely due to the research of the Swiss physician Bernard Schaller.[3]

Characteristics of the Reflex

The trigemino-cardiac reflex is usually defined as a 20% drop in mean arterial pressure associated with a heart rate lower than 60 beats per minute.[4] Another common consequence of the TCR is apnea, suggesting a close relationship with the diving reflex.[5] However, unlike the diving reflex, the TCR does not cause peripheral vasoconstriction. Gastric hypermotility is another typical consequence of the reflex.[1]

The reflex can be triggered by mechanical, electrical, or chemical stimulation of any of the trigeminal afferent sensory fibers, including proprioceptive ones.[6] Where the reflex is exteroceptive in origin, sensory afferents first reach the Gasserian ganglion before projecting centrally to the brainstem.[2] The spinal trigeminal nucleus, located in the medulla oblongata, serves as the primary relay station for the afferent arc of the reflex. Localized electrical stimulation has shown that the most sensitive sites for eliciting the TCR are located within the dorsal portion of the spinal tract and the pars caudalis of the spinal nucleus.[7]

Neurophysiological evidence suggests the existence of fibers that reach the nucleus ambiguus indirectly from the trigeminal nuclei.[8] This nucleus, situated within the medullary reticular formation, is one of the two neural centers—along with the dorsal motor nucleus of the vagus—that sends inhibitory projections to the heart. Other trigeminal fibers indirectly project to the sympathetic nuclei controlling arterial tone,[3] causing peripheral vasodilation and a subsequent reduction in arterial pressure. This effect appears to occur independently of bradycardia.[7]

Prevalence

The TCR is frequently reported in cranio-maxillofacial surgery, with a prevalence of reflex bradycardia ranging from 1 to 2%. In skull base surgery the prevalence increases significantly, reaching up to 18%.[9] These figures, however, appear modest in comparison to the prevalence of the oculocardiac reflex during strabismus surgery, which is reported to occur in over 32% of cases.[10]

TCR cases are also documented outside surgical settings.[11] Evidence suggests that mandibular stretching can induce the same reductions in heart rate and mean arterial pressure observed in the TCR.[12][6] A rare case of recurring TCR was reported in 2017 involving an elderly person whose symptoms persisted for several years post-surgery, only improving following the ablation of the fifth cranial nerve.[13]

Several predisposing have been identified, ranging from light anesthesia to elevated resting vagal tone.[14] Delayed-onset TCR has also been reported, with bradycardia occurring 48 hours after an intraorbital procedure.[15]

Health Risks

The TCR and its related reflexes can pose a serious hazard to patients undergoing medical procedures in the facial region. While the cardiovascular changes induced by the reflex are usually reversible upon cessation of the stimulus,[2] in some cases, arrhythmia, asystole, and even death may occur.[14] Furthermore, a rapid reduction in blood pressure below the lower limit of cerebral autoregulation can lead to central nervous system dysfunction, secondary to reflex-induced hypoperfusion.[16][17]

Preventive measures in medical practice include local anesthesia of the trigeminal nerve or the prophylactic administration of anticholinergic drugs; however, neither approach eliminates the risks associated with the TCR.[18]

It has been hypothesized that Sudden Infant Death Syndrome may be linked to the induction of the TCR.[19] Conversely, TCR induced via the proprioceptive pathway does not appear to trigger such extreme reactions; however, the body of evidence remains limited.[6][12][20]

Physiological Significance

The exact physiological significance of the TCR has yet to be defined, though several hypotheses have been put forward:

  • Neonatal protection: Some researchers emphasize its importance during the early months of life. During breastfeeding, a newborn's nasal passages may be partially obstructed, leading to hypoventilation.The metabolic changes induced by the reflex could potentially the developing brain from hypoxic damage.[21]
  • Compensatory Mechanism: The TCR has been proposed as a mechanism to counteract tachycardia tachycardia induced by nocturnal bruxism.[22]
  • Oxygen Conservation: Schaller and colleagues suggested that the TCR serves an oxygen-conserving role, similar to the diving reflex.[3] This is supported by evidence that trigeminal stimulation promotes pial vasodilation and an increase in cerebral blood flow.[23]

History of the Reflex

The term 'trigeminocardiac reflex' was coined in 1988 by British authors to encompass the extra-ocular sources of the oculocardiac reflex—specifically, a reduction in heart rate associated with manipulation of the ocular globe.[8]

Starting in the late 1990s, the work of Swiss neurosurgeon Bernard Schaller and his collaborators significantly advanced the understanding of this clinical phenomenon.[24][25] More recently, Italian neuroscientist Marcello Brunelli identified a proprioceptive mechanism within the TCR family, triggered by mechanical stretching of the jaw.[12] Additionally, concurrent vasodilation of pial arterioles was observed in rat models following mandibular extension.[26][27]

References

  1. ↑ 1.0 1.1 Chowdhury, Tumul; Rosemann, Thomas; Schaller, Bernhard (August 2018). "Trigeminocardiac reflex: an overview". Revista Argentina de Cardiologia 86 (4): 276–282. doi:10.7775/rac.v86.i4.105393415. http://ppct.caicyt.gov.ar/index.php/rac/article/view/13415/pdf. 
  2. ↑ 2.0 2.1 2.2 Meuwly, C.; Golanov, E.; Chowdhury, T.; Erne, P.; Schaller, B. (February 2015). "Trigeminal Cardiac Reflex: New Thinking Model About the Definition Based on a Literature Review" (in en). Medicine 94 (5): e484. doi:10.1097/MD.0000000000000484. ISSN 0025-7974. PMID 25654391. 
  3. ↑ 3.0 3.1 3.2 Schaller, B. (2004-06-01). "Trigeminocardiac reflex" (in en). Journal of Neurology 251 (6): 658–665. doi:10.1007/s00415-004-0458-4. ISSN 1432-1459. PMID 15311339. https://doi.org/10.1007/s00415-004-0458-4. 
  4. ↑ Arasho, Belachew; Sandu, Nora; Spiriev, Toma; Prabhakar, Hemanshu; Schaller, Bernhard (2009). "Management of the trigeminocardiac reflex: Facts and own experience" (in en). Neurology India 57 (4): 375. doi:10.4103/0028-3886.55577. ISSN 0028-3886. PMID 19770535. 
  5. ↑ Lemaitre, Frederic; Chowdhury, Tumul; Schaller, Bernhard (2015). "State of the art paper The trigeminocardiac reflex – a comparison with the diving reflex in humans". Archives of Medical Science 2 (2): 419–426. doi:10.5114/aoms.2015.50974. ISSN 1734-1922. PMID 25995761. 
  6. ↑ 6.0 6.1 6.2 Conti, Massimo; Traina, Giovanna; Tonlorenzi, Daniele (2026). "Mandibular extension as a trigger of the proprioceptive trigeminocardiac reflex". Turkish Journal of Medical Sciences 56 (1): 1–6. doi:10.55730/1300-0144.6131. ISSN 1303-6165. PMID 41816756. 
  7. ↑ 7.0 7.1 Kumada, Mamoru; Dampney, Roger A. L.; Reis, Donald J. (1977-01-07). "The trigeminal depressor response: A novel vasodepressor response originating from the trigeminal system". Brain Research 119 (2): 305–326. doi:10.1016/0006-8993(77)90313-4. ISSN 0006-8993. PMID 830389. https://dx.doi.org/10.1016/0006-8993%2877%2990313-4. 
  8. ↑ 8.0 8.1 Lang, Scott; Lanigan, Dennis T.; van der Wal, Mike (1991-09-01). "Trigeminocardiac reflexes: maxillary and mandibular variants of the oculocardiac reflex" (in en). Canadian Journal of Anaesthesia 38 (6): 757–760. doi:10.1007/BF03008454. ISSN 1496-8975. PMID 1914059. https://doi.org/10.1007/BF03008454. 
  9. ↑ Schaller, Bernhard; Cornelius, Jan F.; Prabhakar, Hemanshu; Koerbel, Andrei; Gnanalingham, Kanna; Sandu, Nora; Ottaviani, Giulia; Filis, Andreas et al. (July 2009). "The Trigemino-cardiac Reflex: An Update of the Current Knowledge" (in en). Journal of Neurosurgical Anesthesiology 21 (3): 187–195. doi:10.1097/ANA.0b013e3181a2bf22. ISSN 0898-4921. PMID 19542994. https://journals.lww.com/00008506-200907000-00001. 
  10. ↑ Lübbers, Heinz-Theo; Zweifel, Daniel; Grätz, Klaus Wilhelm; Kruse, Astrid (June 2010). "Classification of Potential Risk Factors for Trigeminocardiac Reflex in Craniomaxillofacial Surgery". Journal of Oral and Maxillofacial Surgery 68 (6): 1317–1321. doi:10.1016/j.joms.2009.12.039. ISSN 0278-2391. PMID 20347202. https://linkinghub.elsevier.com/retrieve/pii/S0278239110000789. 
  11. ↑ Chowdhury, Tumul; Schaller, Bernhard (2016-10-26). "The Role of Acute Trigemino-Cardiac Reflex in Unusual, Non-Surgical Cases: A Review" (in English). Frontiers in Neurology 7: 186. doi:10.3389/fneur.2016.00186. ISSN 1664-2295. PMID 27833585. 
  12. ↑ 12.0 12.1 12.2 Brunelli, Marcello; Coppi, Erika; Tonlorenzi, Daniele; Del Seppia, Cristina; Lapi, Dominga; Colantuoni, Antonio; Scuri, Rossana; Ghione, Sergio (December 2012). "Prolonged hypotensive and bradycardic effects of passive mandibular extension: evidence in normal volunteers". Archives Italiennes de Biologie 150 (4): 231–237. doi:10.4449/aib.v150i4.1420. ISSN 0003-9829. PMID 23479456. 
  13. ↑ Chowdhury, Tumul; Schaller, Bernhard (2017-01-30). "Chronic Trigemino-Cardiac Reflex: An Underestimated Truth" (in English). Frontiers in Neurology 8: 22. doi:10.3389/fneur.2017.00022. ISSN 1664-2295. PMID 28194134. 
  14. ↑ 14.0 14.1 Campbell, R.; Rodrigo, D.; Cheung, L. (1994). "Asystole and bradycardia during maxillofacial surgery". Anesthesia Progress 41 (1): 13–16. ISSN 0003-3006. PMID 8629742. 
  15. ↑ Yilmaz, Turgut; Erol, Fatih Serhat; Yakar, Huseyin; Köhle, Ülkü; Akbulut, Mehmet; Faik Ozveren, Mehmet (2006). "Delayed Trigeminocardiac Reflex Induced by an Intraorbital Foreign Body" (in en). Ophthalmologica 220 (1): 65–68. doi:10.1159/000089277. ISSN 0030-3755. PMID 16374051. https://karger.com/article/doi/10.1159/000089277. 
  16. ↑ Reed, W. Gary; Anderson, Ron J. (1986-01-01). "Effects of rapid blood pressure reduction on cerebral blood flow". American Heart Journal 111 (1): 226–228. doi:10.1016/0002-8703(86)90585-5. ISSN 0002-8703. PMID 3946155. https://dx.doi.org/10.1016/0002-8703%2886%2990585-5. 
  17. ↑ Lapi, Dominga; Scuri, Rossana; Colantuoni, Antonio (2016-10-20). "Trigeminal Cardiac Reflex and Cerebral Blood Flow Regulation". Frontiers in Neuroscience 10: 470. doi:10.3389/fnins.2016.00470. ISSN 1662-453X. PMID 27812317. 
  18. ↑ Schaller, B.; Filis, A.; Sandu, N.; Rasper, J.; Noethen, C.; Buchfelder, M.; for the Trigemino-Cardiac-Reflex-Examination-Group (T.C.R.E.G.) (2008-09-01). "Trigemino-cardiac reflex may be refractory to conventional management in adults" (in en). Acta Neurochirurgica 150 (9): 929–930. doi:10.1007/s00701-008-0010-x. ISSN 0942-0940. PMID 18726064. https://doi.org/10.1007/s00701-008-0010-x. 
  19. ↑ Singh, Gyaninder Pal; Chowdhury, Tumul; Bindu, Barkha; Schaller, Bernhard (2016-12-05). "Sudden Infant Death Syndrome – Role of Trigeminocardiac Reflex: A Review" (in English). Frontiers in Neurology 7: 221. doi:10.3389/fneur.2016.00221. ISSN 1664-2295. PMID 27994573. 
  20. ↑ Del Seppia, Cristina; Ghione, Sergio; Foresi, Paola; Lapi, Dominga; Fommei, Enza; Colantuoni, Antonio; Scuri, Rossana (2017-07-01). "Evidence in the human of a hypotensive and a bradycardic effect after mouth opening maintained for 10 min" (in en). European Journal of Applied Physiology 117 (7): 1485–1491. doi:10.1007/s00421-017-3643-8. ISSN 1439-6327. PMID 28509954. https://doi.org/10.1007/s00421-017-3643-8. 
  21. ↑ Cornelius, Jan F; Sadr-Eshkevari, Pooyan; Arasho, Belachew D; Sandu, Nora; Spiriev, Toma; Lemaitre, Frederic; Schaller, Bernhard (July 2010). "The trigemino-cardiac reflex in adults: own experience" (in en). Expert Review of Cardiovascular Therapy 8 (7): 895–898. doi:10.1586/erc.10.74. ISSN 1477-9072. PMID 20602549. http://www.tandfonline.com/doi/full/10.1586/erc.10.74. 
  22. ↑ Sugrue, Alan; DeSimone, Christopher V.; Gaba, Prakriti; El-Harasis, Majd A.; Deshmukh, Abhishek J.; Asviravtham, Samuel J. (August 2018). "Grinding to a halt: Stimulation of the trigeminal cardiac reflex from severe bruxism". HeartRhythm Case Reports 4 (8): 329–331. doi:10.1016/j.hrcr.2017.06.013. ISSN 2214-0271. PMID 30112280. 
  23. ↑ Chiluwal, Amrit; Narayan, Raj K.; Chaung, Wayne; Mehan, Neal; Wang, Ping; Bouton, Chad E.; Golanov, Eugene V.; Li, Chunyan (2017-07-28). "Neuroprotective Effects of Trigeminal Nerve Stimulation in Severe Traumatic Brain Injury" (in en). Scientific Reports 7 (1): 6792. doi:10.1038/s41598-017-07219-3. ISSN 2045-2322. PMID 28754973. Bibcode: 2017NatSR...7.6792C. 
  24. ↑ Schaller, Bernhard; Probst, Rudolf; Strebel, Stephan; Gratzl, Otmar (February 1999). "Trigeminocardiac reflex during surgery in the cerebellopontine angle". Journal of Neurosurgery 90 (2): 215–220. doi:10.3171/jns.1999.90.2.0215. ISSN 0022-3085. https://thejns.org/view/journals/j-neurosurg/90/2/article-p215.xml. 
  25. ↑ Sandu, Nora; Chowdhury, Tumul; Schaller, Bernhard J.; for the Trigemino-Cardiac Reflex Examination Group (TCREG) (2016-04-06). "How to apply case reports in clinical practice using surrogate models via example of the trigeminocardiac reflex" (in en). Journal of Medical Case Reports 10 (1): 84. doi:10.1186/s13256-016-0849-z. ISSN 1752-1947. PMID 27048202. 
  26. ↑ Lapi, D.; Colantuoni, A.; Del Seppia, C.; Ghione, S.; Tonlorenzi, D.; Brunelli, M.; Scuri, R. (2013). "Persistent effects after trigeminal nerve proprioceptive stimulation by mandibular extension on rat blood pressure, heart rate and pial microcirculation". Archives Italiennes de Biologie 151 (1): 11–23. doi:10.4449/aib.v151i1.1470. ISSN 0003-9829. PMID 23807620. 
  27. ↑ Del Seppia, C. (2016). "Further evidence of a prolonged hypotensive and a bradycardic effect after mandibular extension in normal volunteers". Archives Italiennes de Biologie 154 (4): 143–150. doi:10.12871/00039829201645. ISSN 0003-9829. http://www.architalbiol.org/. 



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