Sykora_EU Neurology 10/03/2010 09:54 Page 47
Modulation of Baroreceptor Reflex Sensitivity in Acute Stroke
regulation could be demonstrated. Both insulae seem to participate in day only enhanced the BRS. Fatal stroke incidences were markedly
baroreceptor information processing in a complex manner, with the left reduced by treatment with both doses (p<0.0001 versus control
insula being more dominant in baroreflex control, presumably through group).
Clonidine, moxonidine, folic acid and mecobalamin may
parasympathetic outflow modulation.
improve baroreflex sensitivity as well. Central mechanism of action
is supposed in the effects of clonidine and moxonidine, versus
How baroreflex dysfunction influences outcome in acute stroke has peripheral mechanism in mecobalamin.
New devices stimulating
not yet been clearly established. Patients with shifted autonomic baroreceptors are emerging in the treatment of chronic refractory
balance seemed to be at increased risk of cardiac complications hypertension. Mediated through the central sympathoinhibitory effect
and have significantly higher cardiovascular morbidity and by stimulating the carotid baroreceptors electrically, these devices
Suggested pathophysiological mechanisms include raised ameliorate baroreflex sensitivity and reduce hypertension. Ongoing
arrhythmogenic potential, increased platelet aggregability, coronary trials are finding significant and sustained reductions in blood
vasoconstriction and impaired ventricular remodelling, all of which are pressure, a good safety profile and tolerable side effects;
thought to be associated with increased sympathetic activity. Moreover, the evidence is still scarce.
autonomic impairment possibly plays an important role in secondary
brain injury after stroke. Decreased baroreflex sensitivity and impaired Whether baroreflex modulation may change the course of acute stroke
blood pressure regulation are consistent with increased sympathetic remains an important but unresolved question. The implications of
activation. A shift to sympathetic predominance has been previously autonomic dysfunction in acute stroke, including baroreflex
shown to be associated with pro-inflammatory cytokine production, impairment, are poorly understood – in particular how autonomic
hyperglycaemia and increased blood–brain barrier permeability.
In derangement effects outcome in stroke. However, previous studies
turn, these mechanisms have been proposed to be involved in brain uniformly confirm the association between autonomic impairment and
oedema formation and secondary brain injury.
Arterial baroreflex worse short- or long-term outcome after ischaemic or haemorrhagic
function has been shown to be an important determinant of acute stroke. Unfortunately, the proposed underlying mechanisms are still
cerebral ischaemia in rats with middle cerebral artery occlusion. speculative. More studies focusing on this topic are urgently required.
Baroreflex dysfunction significantly increased the levels of the pro- Nevertheless, it definitely seems that baroreflex should become a novel
inflammatory factors interleukin (IL)-1 and IL-6 and the infarct volume.
research and potentially also therapeutic target in acute stroke. n
Therefore, the question of therapeutic modulation of autonomic
baroreflex dysfunction with the aim of influencing outcome of stroke
Marek Sykora is a Neurologist in the Department of
seems to become relevant. Baroreflex can be positively influenced by
Neurology at Comenius University in Bratislava and the
pharmacological treatment, especially with beta-blockers.
Department of Neurology at the University of Heidelberg.
Interestingly, a recent study by Loawattana et al. including 111
His research focuses on autonomic dysfunction, cerebral
autoregulation and neurological intensive care. He holds
ischaemic stroke patients showed that beta-blocker use was
both a PhD and a certificate in neurology. Dr Sykora
independently associated with less severe stroke on presentation and studied medicine in Bratislava and Brussels and
that sympatholytic effects may have cerebroprotective properties.
graduated summa cum laude.
an animal model, beta-blockers given before experimental ischaemia
reduced infarct volume by 40%.
Analogously, beta-blockers reduced
Jennifer Diedler is a Clinical Fellow in the Department of
histologic brain oedema in a model of traumatic brain injury.
Neurology at the University of Heidelberg, where her
research focuses on multimodality monitoring, cerebral
effects of beta-blockade on outcome have also been reported in
autoregulation and neurological intensive care. Dr Diedler
traumatic brain injury patients.
undertook medical studies and training in Germany,
China, France and Switzerland and a doctoral thesis at
the Rockefeller University in New York.
In the study by Liu et al., ketanserin in doses of 3mg/kg per day
decreased blood pressure and enhanced BRS, whereas 0.3mg/kg per
1. Henderson LA, Richard CA, Macey PM, et al., J Appl Physiol, 13. Stead LG, Gilmore RM, Vedula KC, et al., Neurology, 26. Castillo J, Davalos A, Alvarez-Sabin J, et al., Neurology,
2004;96:693–703. 2006;66:1878–81. 2002;58:624–9.
2. Nouraei SA, Al-Rawi PG, Sigaudo-Roussel D, et al., J Vasc 14. Dawson SL, Manktelow BN, Robinson TG, et al., Stroke, 27. Song EC, Chu K, Jeong SW, et al., Stroke, 2003;34:2215–20.
Surg, 2005;41:631–7. 2000;31:463–8. 28. Xi G, Keep RF, Hoff JT, Lancet Neurol, 2006;5:53–63.
3. Schrezenmaier C, Singer W, Swift NM, et al., Arch Neurol, 15. Immink RV, van Montfrans GA, Stam J, et al., Stroke, 29. Liu AJ, Ling G, Wu J, et al., Life Sci, 2008;83: 388–93.
2007;64:381–6. 2005;36:2595–2600. 30. Elghozi JL, Julien C, Fundam Clin Pharmacol, 2007;21:337–47.
4. Phillips AM, Jardine DL, Parkin PJ, et al., Stroke, 16. Kuwata N, Kuroda K, Funayama M, et al., Neurosurg Rev, 31. Mortara A, La Rovere MT, Pinna GD, et al., J Am Coll Cardiol,
2000;31:1997–2001. 1995;18:237–45. 2000;36:1612–18.
5. Robinson TG, James M, Youde J, et al., Stroke, 17. Diedler J, Sykora M, Rupp A, et al., Stroke, 32. Laowattana S, Oppenheimer SM, Neurology,
1997;28:1671–6. 2009;40(3):815–19. 2007;68:509–14.
6. Nasr N, Pavy-Le Traon A, Larrue V, Stroke, 2005; 36:1891–5. 18. Vemmos KN, Tsivgoulis G, Spengos K, et al., J Hypertens, 33. Savitz SI, Erhardt JA, Anthony JV, et al., J Cereb Blood Flow
7. La Rovere MT, Bigger JT Jr, Marcus FI, et al., Lancet, 2003;21:2167–73. Metab, 2000;20:1197–1204.
1998;351:478–84. 19. Kazui S, Minematsu K, Yamamoto H, et al., Stroke, 34. Liu MY, J Formos Med Assoc, 1995;94:386–90.
8. Mortara A, La Rovere MT, Pinna GD, et al., Circulation, 1997;28:2370–75. 35. Inaba K, Teixeira PG, David JS, et al., J Am Coll Surg,
1997;96:3450–58. 20. Oppenheimer S, Stroke, 2003;34: 705–12. 2008;206:432–8.
9. Schmidt H, Muller-Werdan U, Hoffmann T, et al., Crit Care 21. Sykora M, Diedler J, Rupp A, et al., Stroke, 2009;40(3):737–42. 36. Cotton BA, Snodgrass KB, Fleming SB, et al., J Trauma,
Med, 2005;33:1994–2002. 22. La Rovere MT, Specchia G, Mortara A, Schwartz PJ, 2007;62:26–33, discussion 33–25.
10. Robinson TG, Dawson SL, Eames PJ, et al., Stroke, Circulation, 1988;78:816–24. 37. Liu AJ, Ma XJ, Shen FM, et al., Stroke, 2007;38:1916–23.
2003;34:705–12. 23. van der Poll T, Lowry SF, Infect Immun, 1997;65:2378–81. 38. Ma XJ, Shen FM, Liu AJ, et al., Acta Pharmacol Sin,
11. Sykora M, Diedler J, Rupp A, et al., Crit Care Med, 24. Watanabe M, Tomiyama-Miyaji C, Kainuma E, et al., 2007;28:1550–58.
2008;36:3074–9. Immunol Lett, 2008;115:43–9. 39. Turcani M, J Cardiovasc Pharmacol, 2008;52:524–35.
12. Willmot M, Leonardi-Bee J, Bath PM, Hypertension, 25. Raichle ME, Hartman BK, Eichling JO, Sharpe LG, Proc Natl 40. Uppuluri SC, Storozynsky E, Bisognano JD, Curr Hypertens
2004;43:18–24. Acad Sci U S A, 1975;72: 3726–30. Rep, 2009;11:69–75.
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