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Reply to: “Cardiomyocyte apoptosis contributes to the development of catecholamine cardiomyopathy”
Clinica Chimica Acta 308 Ž2001. 185–186 www.elsevier.comrlocaterclinchim
Reply to Letter to the Editor Reply to: ACardiomyocyte apoptosis contributes to the development of catecholamine cardiomyopathyB
We thank Dr Beranek for his interesting comments on our study. To answer the questions raised in his comments, we provide some additional information. Recent studies have provided evidence that cardiac myocytes can undergo apoptosis in response to various pathological stimuli w1x under acute and chronic conditions in human and animal myocardium w2x: increased cytosolic free calcium levels, hypoxia, muscle stretch w3x. It has become possible to study the occurrence of cardiomyocyte apoptosis in myocardial tissue samples. Apoptosis can be recognized and differentiated from necrosis histologically w4x. However, the morphological differentiation between apoptosis and non-apoptotic cell death in acute myocardial ischemia remains controversial. Reports on the extent of apoptosis have varied depending on the method used for identifying apoptotic cells, and methodological factors may have contributed to an overestimation of its importance. In some tissues, apoptotic cells can be identified in routine histological stainings or using nuclear stains, but usually special techniques based on detection of biochemical or molecular markers of apoptosis are required to identify apoptotic cells in tissue samples or in cell culture w5x. Thus, to our opinion, in absence of confirmation of cardiomyocyte apoptosis based on established electron microscopic criteria for apoptosis and on the presence of nuclear DNA fragmentation, a commonly accepted key marker of the apoptosis process w1x, we consider that Dr Beranek cannot affirm apoptosis just looking at on such histological examinations illustrations obtained by using only light microscopic evaluation. Moreover, we do confirm Fig. 2B absolutely represents normal aspect of myocardial tissue and not myocardial defect created
by cardiomyocyte apoptosis and elimination of apoptotic antibodies. On the other hand, we entirely agree with Dr Beranek that a number of studies have documented that catecholamines have toxic effects on myocardial cells both in vivo and in vitro. Excessive adrenergic stimulation including cardiac norepinephrine release can produce myocyte necrosis in model systems w6x, and evidence suggests a direct toxic effect of norepinephrine on cardiac myocytes w7x. In addition, catecholamines have been reported to induce apoptosis in neonatal cardiocytes w8x. However, in catecholamine-induced cardiopathy accompanied pheochromocytoma w9x and in experimental catecholamine-induced necrosis, histologic pattern shows extensive myocardial degeneration and acute coagulative myocytolisis with inflammatory cell infiltration between myocardial fibers. The myocardial damage in the model we used is based on a relative, transient hypoxia during tachycardia with a subsequent injury of the cardiomyocytes. Comparison of the results of our study with a similar one w10x, suggests that animals treated with isoprenaline showed a histopathological response in terms of acute myofibrillar degeneration with mononuclear cell infiltration within 24 h after injection. A reparative fibrosis as a consequence of the acute myocardial cell damage has been also observed later after injection in this similar study. Finally, we are readily prepared to send sections of myocardial tissue examined to Dr Beranek.
References w1x Sharov VG, Sabbah HN, Shimoyama H, et al. Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure. Am J Pathol 1996;148:141–9.
0009-8981r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S 0 0 0 9 - 8 9 8 1 Ž 0 1 . 0 0 4 1 8 - 1
186
Reply to Letter to the Editor
w2x Freude B, Masters TN, Kostin S, Robicsek F, Schaper J. Cardiomyocyte apoptosis in acute and chronic conditions. Basic Res Cardiol 1998;93:85–9. w3x Schwartz K, Mercadier JJ. Molecular and cellular biology of heart failure. Curr Opin Cardiol 1996;11:227–36. w4x Bing OHL. Hypothesis: apoptosis may be a mechanism for the transition to heart failure with chronic pressure overload. J Mol Cell Cardiol 1994;26:943–8. w5x Saraste A. Morphologic criteria and detection of apoptosis. Herz 1999;24:189–95. w6x Baig MK, Mahon N, McKenna WJ, et al. The pathophysiology of advanced heart failure. Heart Lung1999;28:87–101. w7x Mann DL, Kent RL, Parsons B, et al. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation 1992;85:790–804. w8x Matsui T, Hajjar RJ, Kang JX, et al. Norepinephrine directly induces apoptosis in neonatal rat myocytes. J Am Coll Cardiol 1997;29:230A. w9x Cho T, Tanimura A, Saito Y. Catecholamine-induced cardiopathy accompanied with pheochromocytoma. Acta Pathol Jpn 1987;37:123–32. w10x Bertsch T, Bleuel H, Deschl U, Rebel W. A new sensitive
cardiac troponin T rapid test ŽTROPT w . for the detection of experimental acute myocardial damage in rats. Exp Toxicol Pathol 1999;51:565–9.
J.P. Bertinchant ) Laboratory of CardioÕascular Physiology, UniÕersity of Montpellier-Nımes, ˆ AÕenue Kennedy, 30900 Nımes ˆ Cedex, France E-mail: [email protected] C. Marty-Double Department of Pathology, UniÕersity Hospital, 5 rue Hoche, 30029 Nımes ˆ Cedex, France
)
Corresponding author.
Reply to Letter to the Editor Reply to: ACardiomyocyte apoptosis contributes to the development of catecholamine cardiomyopathyB
We thank Dr Beranek for his interesting comments on our study. To answer the questions raised in his comments, we provide some additional information. Recent studies have provided evidence that cardiac myocytes can undergo apoptosis in response to various pathological stimuli w1x under acute and chronic conditions in human and animal myocardium w2x: increased cytosolic free calcium levels, hypoxia, muscle stretch w3x. It has become possible to study the occurrence of cardiomyocyte apoptosis in myocardial tissue samples. Apoptosis can be recognized and differentiated from necrosis histologically w4x. However, the morphological differentiation between apoptosis and non-apoptotic cell death in acute myocardial ischemia remains controversial. Reports on the extent of apoptosis have varied depending on the method used for identifying apoptotic cells, and methodological factors may have contributed to an overestimation of its importance. In some tissues, apoptotic cells can be identified in routine histological stainings or using nuclear stains, but usually special techniques based on detection of biochemical or molecular markers of apoptosis are required to identify apoptotic cells in tissue samples or in cell culture w5x. Thus, to our opinion, in absence of confirmation of cardiomyocyte apoptosis based on established electron microscopic criteria for apoptosis and on the presence of nuclear DNA fragmentation, a commonly accepted key marker of the apoptosis process w1x, we consider that Dr Beranek cannot affirm apoptosis just looking at on such histological examinations illustrations obtained by using only light microscopic evaluation. Moreover, we do confirm Fig. 2B absolutely represents normal aspect of myocardial tissue and not myocardial defect created
by cardiomyocyte apoptosis and elimination of apoptotic antibodies. On the other hand, we entirely agree with Dr Beranek that a number of studies have documented that catecholamines have toxic effects on myocardial cells both in vivo and in vitro. Excessive adrenergic stimulation including cardiac norepinephrine release can produce myocyte necrosis in model systems w6x, and evidence suggests a direct toxic effect of norepinephrine on cardiac myocytes w7x. In addition, catecholamines have been reported to induce apoptosis in neonatal cardiocytes w8x. However, in catecholamine-induced cardiopathy accompanied pheochromocytoma w9x and in experimental catecholamine-induced necrosis, histologic pattern shows extensive myocardial degeneration and acute coagulative myocytolisis with inflammatory cell infiltration between myocardial fibers. The myocardial damage in the model we used is based on a relative, transient hypoxia during tachycardia with a subsequent injury of the cardiomyocytes. Comparison of the results of our study with a similar one w10x, suggests that animals treated with isoprenaline showed a histopathological response in terms of acute myofibrillar degeneration with mononuclear cell infiltration within 24 h after injection. A reparative fibrosis as a consequence of the acute myocardial cell damage has been also observed later after injection in this similar study. Finally, we are readily prepared to send sections of myocardial tissue examined to Dr Beranek.
References w1x Sharov VG, Sabbah HN, Shimoyama H, et al. Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure. Am J Pathol 1996;148:141–9.
0009-8981r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S 0 0 0 9 - 8 9 8 1 Ž 0 1 . 0 0 4 1 8 - 1
186
Reply to Letter to the Editor
w2x Freude B, Masters TN, Kostin S, Robicsek F, Schaper J. Cardiomyocyte apoptosis in acute and chronic conditions. Basic Res Cardiol 1998;93:85–9. w3x Schwartz K, Mercadier JJ. Molecular and cellular biology of heart failure. Curr Opin Cardiol 1996;11:227–36. w4x Bing OHL. Hypothesis: apoptosis may be a mechanism for the transition to heart failure with chronic pressure overload. J Mol Cell Cardiol 1994;26:943–8. w5x Saraste A. Morphologic criteria and detection of apoptosis. Herz 1999;24:189–95. w6x Baig MK, Mahon N, McKenna WJ, et al. The pathophysiology of advanced heart failure. Heart Lung1999;28:87–101. w7x Mann DL, Kent RL, Parsons B, et al. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation 1992;85:790–804. w8x Matsui T, Hajjar RJ, Kang JX, et al. Norepinephrine directly induces apoptosis in neonatal rat myocytes. J Am Coll Cardiol 1997;29:230A. w9x Cho T, Tanimura A, Saito Y. Catecholamine-induced cardiopathy accompanied with pheochromocytoma. Acta Pathol Jpn 1987;37:123–32. w10x Bertsch T, Bleuel H, Deschl U, Rebel W. A new sensitive
cardiac troponin T rapid test ŽTROPT w . for the detection of experimental acute myocardial damage in rats. Exp Toxicol Pathol 1999;51:565–9.
J.P. Bertinchant ) Laboratory of CardioÕascular Physiology, UniÕersity of Montpellier-Nımes, ˆ AÕenue Kennedy, 30900 Nımes ˆ Cedex, France E-mail: [email protected] C. Marty-Double Department of Pathology, UniÕersity Hospital, 5 rue Hoche, 30029 Nımes ˆ Cedex, France
)
Corresponding author.