- Email: [email protected]
Baroreceptor dysfunction, diabetes mellitus, and takotsubo syndrome: An intricate triangle needing exploration
International Journal of Cardiology 184 (2015) 517–518
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Baroreceptor dysfunction, diabetes mellitus, and takotsubo syndrome: An intricate triangle needing exploration John E. Madias ⁎ Icahn School of Medicine at Mount Sinai, New York, NY, United States Division of Cardiology, Elmhurst Hospital Center, Elmhurst, NY, United States
a r t i c l e
i n f o
Article history: Received 15 January 2015 Accepted 26 February 2015 Available online 27 February 2015 Keywords: Takotsubo syndrome Autonomic sympathetic nervous system Baroreceptor dydfunction Diabetes mellitus Adrenal catecholamine hyposectretion in diabetes mellitus Diabetic autonomic neuropathy
To the Editor: In the intriguing contribution by Ali et al. [1], published ahead of print, in the December 30, 2014 issue of the Journal, the authors propose that an impaired baroreceptor function (IBF) leads to an excessive sympathetic activity which could cause Takotsubo syndrome (TTS), via an unopposed inotropic and chronotropic stimulation which in turn results in the development of excess wall tension within certain regions in the left ventricle. In this conceptualization, TTS emerges via a regional shutdown of contractile activity (a form of protective myocardial stunning), engendered by the cardiomyocytes, which have perceived the above described excess wall tension, as a demand:supply mismatch, as the authors have proposed previously [2,3]. The authors point out that postmenopausal women, known for their predilection to TTS, are susceptible to an increased sympathetic tone, and IBF [4]. Additional support for the above is provided by the authors' previous work with their rat model of the TTS phenotype elicited with isoprenaline, which due to resultant low blood pressure, does not activate the autonomic sympathetic storm-harnessing role of the baroreflex, while epinephrine and phenylephrine, due to resultant higher blood pressure, activate the baroreflex, thus obviating an unbridled autonomic sympathetic ⁎ Division of Cardiology, Elmhurst Hospital Center, 79-01 Broadway, Elmhurst, NY 11373, United States. E-mail address: [email protected].
http://dx.doi.org/10.1016/j.ijcard.2015.02.108 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
stimulation of the cardiomyocytes [5]. One could further speculate that strokes and intracerebral bleeding, causing damage of the nucleus tractus solitarius in the medullary area of the brainstem (which is part of the baroreflex arc), deprive the body of the “breaking effect” of the baroreflex, which, if intact, would have opposed an autonomic sympathetic seethe. The above framework is contradicted by the following: IBF is common in patients with diabetes mellitus (DM) [6], in whom it is a component of the autonomic and peripheral neuropathy, which they often develop [7]. Thus one would expect patients with DM to be prone to TTS; however it has just been reported that the prevalence of DM is lower than expected in patients with DM [8], and that the disease may have a “protective” effect for the emergence of TTS. Accordingly the DM-related autonomic neuropathy [7,8] (often associated with IBF [6]) ameliorates the capacity of the autonomic sympathetic nervous system to injure the myocardium [9]. Even if one assumes that TTS is pathogenetically linked to high levels of blood borne catecholamines [10], and not to a locally exerted catecholamine release from the cardiac autonomic nerve terminals [9], DM is characterized by a “catecholamine hyposecretion state”, by both the nerve endings and the adrenals, as the vast animal and human literature on the topic attest [8,11–21]. I wish to congratulate the authors for their contribution [1], and I will appreciate their thoughts on the above. Conflicts of interest None. References [1] A. Ali, B. Redfors, E. Omerovic, How baroreceptor dysfunction could predispose to the takotsubo syndrome, Int. J. Cardiol. 182C (Dec 30 2014) 105–106. [2] B. Redfors, Y. Shao, A. Ali, E. Omerovic, Are ischemic stunning, conditioning, and takotsubo different sides to the same coin? Int. J. Cardiol. 172 (2014) 490–491. [3] B. Redfors, Y. Shao, A. Ali, E. Omerovic, Are the different patterns of stress-induced (takotsubo) cardiomyopathy explained by regional mechanical overload and demand: supply mismatch in selected ventricular regions? Med. Hypotheses 81 (2013) 954–960. [4] S. Lavi, O. Nevo, I. Thaler, et al., Effect of aging on the cardiovascular regulatory systems in healthy women, Am. J. Physiol. Regul. Integr. Comp. Physiol. 292 (2007) R788–R793. [5] B. Redfors, A. Ali, Y. Shao, J. Lundgren, L.M. Gan, E. Omerovic, Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner, Int. J. Cardiol. 174 (2014) 330–336. [6] O.O. Rowaiye, E.A. Jankowska, B. Ponikowska, Baroreceptor sensitivity and diabetes mellitus, Cardiol. J. 20 (2013) 453–463.
518
J.E. Madias / International Journal of Cardiology 184 (2015) 517–518
[7] D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds.), Harrison's Principles of Internal Medicine, 18th ed.MacGraw Hill Medical, New York, 2012, p. 2042 (2968, 2969, 2984). [8] J.E. Madias, Low prevalence of diabetes mellitus in patients with takotsubo syndrome: a plausible “protective” effect with pathophysiologic connotations, Eur. Heart J. Acute Cardiovasc. Care (2015 Feb 11) http://dx.doi.org/2048872615570761. [Epub ahead of print]. [9] M.A. Samuels, The brain–heart connection, Circulation 116 (2007) 77–84. [10] I.S. Wittstein, D.R. Thiemann, J.A. Lima, et al., Neurohumoral features of myocardial stunning due to sudden emotional stress, N. Engl. J. Med. 352 (2005) 539–548. [11] R.D. Hoeldtke, G. Boden, C.R. Shuman, O.E. Owen, Reduced epinephrine secretion and hypoglycemia unawareness in diabetic autonomic neuropathy, Ann. Intern. Med. 96 (1982) 459–462. [12] R.D. Hoeldtke, K.M. Cilmi, Norepinephrine secretion and production in diabetic autonomic neuropathy, J. Clin. Endocrinol. Metab. 59 (1984) 246–252. [13] R.D. Hoeldtke, G. Boden, Epinephrine secretion, hypoglycemia unawareness, and diabetic autonomic neuropathy, Ann. Intern. Med. 120 (1994) 512–517. [14] M.J. Fowler, Hypoglycemia, Clin. Diabetes 26 (2008) 170–173. [15] K.E. Inouye, O. Chan, J.T.Y. Yue, S.G. Matthews, M. Vranic, Effects of diabetes and recurrent hypoglycemia on the regulation of the sympathoadrenal system and
[16]
[17]
[18]
[19]
[20] [21]
hypothalamo-pituitary-adrenal axis, Am. J. Physiol.-Endocrinol. Metab. 288 (2005) E422–E429. R.A. Wilke, D.A. Riley, P.I. Lelkes, C.J. Hillard, Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats, Diabetes 42 (1993) 862–868. R.A. Wilke, C.J. Hillard, Decreased adrenal medullary catecholamine release in spontaneously diabetic BB-Wistar rats. Role of hypoglycemia, Diabetes 43 (1994) 724–729. O. Chan, S. Chan, K. Inouye, K. Shum, S.G. Matthews, M. Vranic, Diabetes impairs hypothalamo-pituitary-adrenal (HPA) responses to hypoglycemia, and insulin treatment normalizes HPA but not epinephrine responses, Diabetes 51 (2002) 1681–1689. R.R. Vollmer, J.J. Balcita, A.F. Sved, D.J. Edwards, Adrenal epinephrine and norepinephrine release to hypoglycemia measured by microdialysis in conscious rats, Am. J. Physiol. Regul. Integr. Comp. Physiol. 273 (1997) R1758–R1763. C. Burgdorf, D. Richardt, T. Kurz, et al., Norepinephrine release is reduced in cardiac tissue of type 2 diabetic patients, Diabetologia 46 (2003) 520–523. C. Burgdorf, G. Richardt, F. Schütte, A. Dendorfer, T. Kurz, Impairment of presynaptic alpha2-adrenoceptor-regulated norepinephrine overflow in failing hearts from Zucker diabetic fatty rats, J. Cardiovasc. Pharmacol. 47 (2006) 256–262.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Baroreceptor dysfunction, diabetes mellitus, and takotsubo syndrome: An intricate triangle needing exploration John E. Madias ⁎ Icahn School of Medicine at Mount Sinai, New York, NY, United States Division of Cardiology, Elmhurst Hospital Center, Elmhurst, NY, United States
a r t i c l e
i n f o
Article history: Received 15 January 2015 Accepted 26 February 2015 Available online 27 February 2015 Keywords: Takotsubo syndrome Autonomic sympathetic nervous system Baroreceptor dydfunction Diabetes mellitus Adrenal catecholamine hyposectretion in diabetes mellitus Diabetic autonomic neuropathy
To the Editor: In the intriguing contribution by Ali et al. [1], published ahead of print, in the December 30, 2014 issue of the Journal, the authors propose that an impaired baroreceptor function (IBF) leads to an excessive sympathetic activity which could cause Takotsubo syndrome (TTS), via an unopposed inotropic and chronotropic stimulation which in turn results in the development of excess wall tension within certain regions in the left ventricle. In this conceptualization, TTS emerges via a regional shutdown of contractile activity (a form of protective myocardial stunning), engendered by the cardiomyocytes, which have perceived the above described excess wall tension, as a demand:supply mismatch, as the authors have proposed previously [2,3]. The authors point out that postmenopausal women, known for their predilection to TTS, are susceptible to an increased sympathetic tone, and IBF [4]. Additional support for the above is provided by the authors' previous work with their rat model of the TTS phenotype elicited with isoprenaline, which due to resultant low blood pressure, does not activate the autonomic sympathetic storm-harnessing role of the baroreflex, while epinephrine and phenylephrine, due to resultant higher blood pressure, activate the baroreflex, thus obviating an unbridled autonomic sympathetic ⁎ Division of Cardiology, Elmhurst Hospital Center, 79-01 Broadway, Elmhurst, NY 11373, United States. E-mail address: [email protected].
http://dx.doi.org/10.1016/j.ijcard.2015.02.108 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
stimulation of the cardiomyocytes [5]. One could further speculate that strokes and intracerebral bleeding, causing damage of the nucleus tractus solitarius in the medullary area of the brainstem (which is part of the baroreflex arc), deprive the body of the “breaking effect” of the baroreflex, which, if intact, would have opposed an autonomic sympathetic seethe. The above framework is contradicted by the following: IBF is common in patients with diabetes mellitus (DM) [6], in whom it is a component of the autonomic and peripheral neuropathy, which they often develop [7]. Thus one would expect patients with DM to be prone to TTS; however it has just been reported that the prevalence of DM is lower than expected in patients with DM [8], and that the disease may have a “protective” effect for the emergence of TTS. Accordingly the DM-related autonomic neuropathy [7,8] (often associated with IBF [6]) ameliorates the capacity of the autonomic sympathetic nervous system to injure the myocardium [9]. Even if one assumes that TTS is pathogenetically linked to high levels of blood borne catecholamines [10], and not to a locally exerted catecholamine release from the cardiac autonomic nerve terminals [9], DM is characterized by a “catecholamine hyposecretion state”, by both the nerve endings and the adrenals, as the vast animal and human literature on the topic attest [8,11–21]. I wish to congratulate the authors for their contribution [1], and I will appreciate their thoughts on the above. Conflicts of interest None. References [1] A. Ali, B. Redfors, E. Omerovic, How baroreceptor dysfunction could predispose to the takotsubo syndrome, Int. J. Cardiol. 182C (Dec 30 2014) 105–106. [2] B. Redfors, Y. Shao, A. Ali, E. Omerovic, Are ischemic stunning, conditioning, and takotsubo different sides to the same coin? Int. J. Cardiol. 172 (2014) 490–491. [3] B. Redfors, Y. Shao, A. Ali, E. Omerovic, Are the different patterns of stress-induced (takotsubo) cardiomyopathy explained by regional mechanical overload and demand: supply mismatch in selected ventricular regions? Med. Hypotheses 81 (2013) 954–960. [4] S. Lavi, O. Nevo, I. Thaler, et al., Effect of aging on the cardiovascular regulatory systems in healthy women, Am. J. Physiol. Regul. Integr. Comp. Physiol. 292 (2007) R788–R793. [5] B. Redfors, A. Ali, Y. Shao, J. Lundgren, L.M. Gan, E. Omerovic, Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner, Int. J. Cardiol. 174 (2014) 330–336. [6] O.O. Rowaiye, E.A. Jankowska, B. Ponikowska, Baroreceptor sensitivity and diabetes mellitus, Cardiol. J. 20 (2013) 453–463.
518
J.E. Madias / International Journal of Cardiology 184 (2015) 517–518
[7] D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds.), Harrison's Principles of Internal Medicine, 18th ed.MacGraw Hill Medical, New York, 2012, p. 2042 (2968, 2969, 2984). [8] J.E. Madias, Low prevalence of diabetes mellitus in patients with takotsubo syndrome: a plausible “protective” effect with pathophysiologic connotations, Eur. Heart J. Acute Cardiovasc. Care (2015 Feb 11) http://dx.doi.org/2048872615570761. [Epub ahead of print]. [9] M.A. Samuels, The brain–heart connection, Circulation 116 (2007) 77–84. [10] I.S. Wittstein, D.R. Thiemann, J.A. Lima, et al., Neurohumoral features of myocardial stunning due to sudden emotional stress, N. Engl. J. Med. 352 (2005) 539–548. [11] R.D. Hoeldtke, G. Boden, C.R. Shuman, O.E. Owen, Reduced epinephrine secretion and hypoglycemia unawareness in diabetic autonomic neuropathy, Ann. Intern. Med. 96 (1982) 459–462. [12] R.D. Hoeldtke, K.M. Cilmi, Norepinephrine secretion and production in diabetic autonomic neuropathy, J. Clin. Endocrinol. Metab. 59 (1984) 246–252. [13] R.D. Hoeldtke, G. Boden, Epinephrine secretion, hypoglycemia unawareness, and diabetic autonomic neuropathy, Ann. Intern. Med. 120 (1994) 512–517. [14] M.J. Fowler, Hypoglycemia, Clin. Diabetes 26 (2008) 170–173. [15] K.E. Inouye, O. Chan, J.T.Y. Yue, S.G. Matthews, M. Vranic, Effects of diabetes and recurrent hypoglycemia on the regulation of the sympathoadrenal system and
[16]
[17]
[18]
[19]
[20] [21]
hypothalamo-pituitary-adrenal axis, Am. J. Physiol.-Endocrinol. Metab. 288 (2005) E422–E429. R.A. Wilke, D.A. Riley, P.I. Lelkes, C.J. Hillard, Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats, Diabetes 42 (1993) 862–868. R.A. Wilke, C.J. Hillard, Decreased adrenal medullary catecholamine release in spontaneously diabetic BB-Wistar rats. Role of hypoglycemia, Diabetes 43 (1994) 724–729. O. Chan, S. Chan, K. Inouye, K. Shum, S.G. Matthews, M. Vranic, Diabetes impairs hypothalamo-pituitary-adrenal (HPA) responses to hypoglycemia, and insulin treatment normalizes HPA but not epinephrine responses, Diabetes 51 (2002) 1681–1689. R.R. Vollmer, J.J. Balcita, A.F. Sved, D.J. Edwards, Adrenal epinephrine and norepinephrine release to hypoglycemia measured by microdialysis in conscious rats, Am. J. Physiol. Regul. Integr. Comp. Physiol. 273 (1997) R1758–R1763. C. Burgdorf, D. Richardt, T. Kurz, et al., Norepinephrine release is reduced in cardiac tissue of type 2 diabetic patients, Diabetologia 46 (2003) 520–523. C. Burgdorf, G. Richardt, F. Schütte, A. Dendorfer, T. Kurz, Impairment of presynaptic alpha2-adrenoceptor-regulated norepinephrine overflow in failing hearts from Zucker diabetic fatty rats, J. Cardiovasc. Pharmacol. 47 (2006) 256–262.