- Email: [email protected]
TRPC6, a potential novel target for enhancing cardiac repair of bone marrow mesenchymal stem cells
Letters to the Editor
497
TRPC6, a potential novel target for enhancing cardiac repair of bone marrow mesenchymal stem cells Jing Zhao a,1, Pengzhou Hang b,1, Yue Li a,⁎ a Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, (Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University), Harbin, 150001, Heilongjiang Province, China b Institute of Clinical Pharmacy, the Second Affiliated Hospital, Harbin Medical University, (Key Laboratory of Drug Research, Harbin Medical University, Heilongjiang Higher Education Institutions), Harbin, 150086, Heilongjiang Province, China
a r t i c l e
i n f o
Article history: Received 30 November 2011 Accepted 25 December 2011 Available online 16 January 2012 Keywords: Bone marrow mesenchymal stem cells Myocardial infarction Transient receptor potential canonical 6 Brain derived neurotrophic factor
It has been well documented that bone marrow mesenchymal stem cells (BMSCs) therapy has been widely applied in ischemic diseases such as myocardial and hepatic ischemia, through promotion of angiogenesis and suppression of apoptosis [1,2]. Meanwhile, BMSCs transplantation has been demonstrated to be an effective therapy for cerebrovascular diseases, which could promote endogenous neurogenesis and behavioral recovery [3]. Previous studies have proved that the secretion of neurotrophins, such as nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), and their downstream signal pathways is important for understanding BMSCs transplantation in cerebral diseases [4–6]. In addition, BDNF modified BMSCs have also been employed to treat cerebral ischemic injury. They found that this therapy could effectively reduce the infarct size and improve the function of injured tissues [7,8]. Interestingly, a number of recent clinical studies have indicated that serum concentrations of BDNF and NGF were also deregulated in patients suffering from myocardial infarction [9–13]. Therefore, neurotrophins were indicated to play an important role in myocardial ischemia, which is probably contributable to BMSCs therapy. Transient receptor potential canonical (subtype) 6 (TRPC6), a Ca2 +permeable nonselective cation channel, belongs to the mammalian transient receptor potential (TRP) family of ion channels [14,15]. Among them, TRPC subfamily consists of TRPC1, TRPC2, TRPC3/6/7 and TRPC4/5 [16]. TRPC6 channel has been shown to be expressed in various tissues and implicated in many different diseases, such as cardiac hypertrophy and cerebral ischemia [16,17]. Kuwahara et al. found that TRPC6 was a positive regulator of calcineurin-NFAT signaling pathway and also was a key component of a calcium-dependent regulatory loop which drives pathological cardiac remodeling. On the other hand, Du et al. uncovered that TRPC6 proteolysis could lead to ischemic neuronal cell death, and the repression of its degradation could preserve neuronal survival and prevent ischemic brain damage. Based on the above findings, we proposed the hypothesis that neurotrophins may repair the ischemic myocardium via modulation of TRPC6 channel which might be one potential novel therapeutic target for myocardial infarction. Moreover, the plasma neurotrophins level may become a novel biomarker for the diagnosis of myocardial infarction. Our hypothesis is strongly supported by several following facts. First of all, the expression of TRPC6 protein was observed to be ⁎ Corresponding author at: The First Affiliated Hospital, Harbin Medical University, Youzheng Street 23#, Nangang District, Harbin 150001, Heilongjiang Province, China. Tel.: +86 451 85555673; fax: +86 451 53675733. E-mail address: [email protected] (Y. Li). 1 The first two authors made equal contributions.
altered in ischemic diseases. It has been found that TRPC6 channel played a critical role in cerebral ischemia whereas other subtypes were unaltered [17]. Moreover, our previous bioinformatical results implied that TRPC6 may also be involved in MI [18]. Thus, experiments were conducted and confirmed that the level of TRPC6 indeed changed in ischemic myocardium [18]. Secondly, many studies have proved that BMSCs implantation is beneficial to brain and heart infarct, which could reduce the infarcted areas and induce reborn of neuron and cardiomyocyte, at least partly via secretion of neurotrophins [4–6]. Importantly, recent studies revealed that the protective effect of BMSCs is likely associated with several functional ion channels such as IKCa, IKir, ICl and TRPM [19,20]. Meanwhile, it is confirmed that BDNF-TrkB could activate PLC which could regulate the activity of DAG and contribute to the activation of TRPC6 channel [21,22]. Taken together, it is believed that the potential mechanisms in this process may be relevant to BDNFTrkB/NGF-TrkA signaling pathway, which regulated TRPC6 channel in the membrane and further induces the activation of downstream survival molecules like extracellular regulated protein kinases (ERK) and calcium/calmodulin-dependent protein kinase (CAMK) [23]. In summary, the hypothesis is that employment of BMSCs in ischemic cardiomyopathy triggers the angiogenesis of injured heart through secretion of neurotrophins and regulation of TRPC6 channel. TRPC6 may serve as a potential target for the therapy of ischemic heart. We believe that stem cell therapy is correlated to amelioration of ischemic cardiomyocytes through secretion of neurotrophins. The pivotal role of TRPC6 in repairing injured tissues suggests its crucial involvement in the regeneration of MI. Of course, it needs further studies to prove it. If the hypothesis is true, agents regulating neurotrophins may also be effective for myocardial infarction patients in clinics. Once validated, TRPC6 may serve as a novel target in prevention and cure of MI. This work was supported by the National Natural Science Fund of China (No. 30971251, 81070160) and the Program for New Century Excellent Talents in University from the Department of Education of Heilongjiang Province (No. 1152-NCET-011). The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010; 144:1–2).
References [1] Li Y, Hiroi Y, Ngoy S, et al. Notch1 in bone marrow-derived cells mediates cardiac repair after myocardial infarction. Circulation 2011;123(8):866–76. [2] Kanazawa H, Fujimoto Y, Teratani T, et al. Bone marrow-derived mesenchymal stem cells ameliorate hepatic ischemia reperfusion injury in a rat model. PLoS One 2011;6(4):e19195. [3] Bao X, Wei J, Feng M, et al. Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats. Brain Res 2011;1367:103–13. [4] Wilkins A, Kemp K, Ginty M, Hares K, Mallam E, Scolding N. Human bone marrowderived mesenchymal stem cells secrete brain-derived neurotrophic factor which promotes neuronal survival in vitro. Stem Cell Res 2009;3:63–70. [5] Ding J, Cheng Y, Gao S, Chen J. Effects of nerve growth factor and Noggin-modified bone marrow stromal cells on stroke in rats. J Neurosci Res 2011;89(2):222–30. [6] Pisati F, Bossolasco P, Meregalli M, et al. Induction of neurotrophin expression via human adult mesenchymal stem cells: implication for cell therapy in neurodegenerative diseases. Cell Transplant 2007;16(1):41–55. [7] Nomura T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. I.V. infusion of brainderived neurotrophic factor gene-modified human mesenchymal stem cells protects
498
[8]
[9]
[10] [11]
[12]
[13]
[14]
Letters to the Editor against injury in a cerebral ischemia model in adult rat. Neuroscience 2005;136(1):161–9. Horita Y, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. Intravenous administration of glial cell line-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in the adult rat. J Neurosci Res 2006;84(7):1495–504. Swardfager W, Herrmann N, Marzolini S, et al. Brain derived neurotrophic factor, cardiopulmonary fitness and cognition in patients with coronary artery disease. Brain Behav Immun 2011;25(6):1264–71. Ejiri J, Inoue N, Kobayashi S, et al. Possible role of brain-derived neurotrophic factor in the pathogenesis of coronary artery disease. Circulation 2005;112(14):2114–20. Lorgis L, Amoureux S, de Maistre E, et al. Serum brain-derived neurotrophic factor and platelet activation evaluated by soluble P-selectin and soluble CD-40-ligand in patients with acute myocardial infarction. Fundam Clin Pharmacol 2010;24(4):525–30. Manni L, Nikolova V, Vyagova D, Chaldakov GN, Aloe L. Reduced plasma levels of NGF and BDNF in patients with acute coronary syndromes. Int J Cardiol 2005;102(1):169–71. Chaldakov GN, Fiore M, Stankulov IS, et al. Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease? Prog Brain Res 2004;146:279–89. Nilius B, Owsianik G. The transient receptor potential family of ion channels. Genome Biol 2011;12(3):218.
[15] Wu X, Eder P, Chang B, Molkentin JD. TRPC channels are necessary mediators of pathologic cardiac hypertrophy. Proc Natl Acad Sci U S A 2010;107(15):7000–5. [16] Kuwahara K, Wang Y, McAnally J, et al. TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling. J Clin Invest 2006;116(12):3114–26. [17] Du W, Huang J, Yao H, Zhou K, Duan B, Wang Y. Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats. J Clin Invest 2010;120(10):3480–92. [18] Zhou R, Hang P, Zhu W, Su Z, Liang H, Du Z. Whole genome network analysis of ion channels and connexins in myocardial infarction. Cell Physiol Biochem 2011;27(3– 4):299–304. [19] Cheng H, Feng JM, Figueiredo ML, et al. Transient receptor potential melastatin type 7 channel is critical for the survival of bone marrow derived mesenchymal stem cells. Stem Cells Dev 2010;19(9):1393–403. [20] Tao R, Lau CP, Tse HF, Li GR. Functional ion channels in mouse bone marrow mesenchymal stem cells. Am J Physiol Cell Physiol 2007;293(5):C1561–7. [21] Sossin WS, Barker PA. Something old, something new: BDNF-induced neuron survival requires TRPC channel function. Nat Neurosci 2007;10(5):537–8. [22] Numakawa T, Suzuki S, Kumamaru E, Adachi N, Richards M, Kunugi H. BDNF function and intracellular signaling in neurons. Histol Histopathol 2010;25(2):237–58. [23] Kermani P, Hempstead B. Brain-derived neurotrophic factor: a newly described mediator of angiogenesis. Trends Cardiovasc Med 2007;17(4):140–3.
0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.12.090
Correlations between myocardium selective videodensitometric perfusion parameters and corrected TIMI frame count in patients with normal epicardial coronary arteries Ferenc Tamás Nagy a, Viktor Sasi a, Tamás Ungi b, Zsolt Zimmermann a, Imre Ungi a, Anita Kalapos a, Tamás Forster a, Attila Nemes a,⁎ a b
Division of Invasive Cardiology, Department of Cardiology, Medical Faculty, Albert-Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary School of Computing, Queen's University, Kingston, Ontario, Canada
a r t i c l e
i n f o
Article history: Received 29 November 2011 Accepted 25 December 2011 Available online 17 January 2012 Keywords: Coronary Correlation Epicardial Myocardial blush TIMI frame count Videodensitometry
TIMI frame count (TFC), was introduced in the early 1990s, as a method to assess the efficacy of thrombolysis and risk stratification in acute myocardial infarction (AMI) [1]. TFC proved to be a simple, reproducible, quantitative and objective method to evaluate epicardial flow not only in acute coronary syndrome settings, but in stable conditions with microvascular dysfunction, as well [2]. Recently, 2 different angiographic methods myocardial blush grade (MBG), and TIMI myocardial perfusion grading (TMP) have been described for direct assessment of myocardial perfusion in AMI [3]. However, these methods are limited inherently by their subjective nature and
⁎ Corresponding author at: 2nd Department of Medicine and Cardiology Centre, Medical Faculty, University of Szeged, H-6720 Szeged, Korányi fasor 6. P.O. Box 427, Hungary. Tel.: + 36 62 545220; fax: +36 62 544568. E-mail address: [email protected] (A. Nemes).
categorical values, and are not defined in stable patients. Alongside others novel computer-assisted videodensiometric methods have been introduced, which supply additional, objective and quantitative information on myocardial perfusion in AMI [4–6]. The objective of the present study was to evaluate regional myocardial perfusion assessed by our novel computerized videodensitometric method, and its relation to corrected TFC in non-AMI patients without epicardial coronary stenoses. The current study comprised 43 patients with chest pain who had undergone elective coronary angiography with a negative result (b40% intraluminal epicardial coronary artery diameter stenosis) at Table 1 Clinical, demographic and echocardiographic data of the patients. Patients n Age (years) Males (%) Diabetes (%) Hypertension (%) Hypercholesterolemia (%) Smoking (%) Coronary angiography LAD — Gmax/Tmax LAD — cTFC CX — Gmax/Tmax CX — TFC RC — Gmax/Tmax RC — TFC
43 60.2 ± 9.8 29 (67) 5 (12) 34 (79) 32 (74) 15 (35) 2.85 ± 1.56 25.6 ± 12.1 2.63 ± 1.36 25.8 ± 9.7 2.39 ± 0.95 26.0 ± 9.9
Abbreviations. cTFC: corrected TIMI frame count, LAD: left anterior descending coronary artery, CX: left circumflex coronary artery, RC: right coronary artery.
497
TRPC6, a potential novel target for enhancing cardiac repair of bone marrow mesenchymal stem cells Jing Zhao a,1, Pengzhou Hang b,1, Yue Li a,⁎ a Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, (Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University), Harbin, 150001, Heilongjiang Province, China b Institute of Clinical Pharmacy, the Second Affiliated Hospital, Harbin Medical University, (Key Laboratory of Drug Research, Harbin Medical University, Heilongjiang Higher Education Institutions), Harbin, 150086, Heilongjiang Province, China
a r t i c l e
i n f o
Article history: Received 30 November 2011 Accepted 25 December 2011 Available online 16 January 2012 Keywords: Bone marrow mesenchymal stem cells Myocardial infarction Transient receptor potential canonical 6 Brain derived neurotrophic factor
It has been well documented that bone marrow mesenchymal stem cells (BMSCs) therapy has been widely applied in ischemic diseases such as myocardial and hepatic ischemia, through promotion of angiogenesis and suppression of apoptosis [1,2]. Meanwhile, BMSCs transplantation has been demonstrated to be an effective therapy for cerebrovascular diseases, which could promote endogenous neurogenesis and behavioral recovery [3]. Previous studies have proved that the secretion of neurotrophins, such as nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), and their downstream signal pathways is important for understanding BMSCs transplantation in cerebral diseases [4–6]. In addition, BDNF modified BMSCs have also been employed to treat cerebral ischemic injury. They found that this therapy could effectively reduce the infarct size and improve the function of injured tissues [7,8]. Interestingly, a number of recent clinical studies have indicated that serum concentrations of BDNF and NGF were also deregulated in patients suffering from myocardial infarction [9–13]. Therefore, neurotrophins were indicated to play an important role in myocardial ischemia, which is probably contributable to BMSCs therapy. Transient receptor potential canonical (subtype) 6 (TRPC6), a Ca2 +permeable nonselective cation channel, belongs to the mammalian transient receptor potential (TRP) family of ion channels [14,15]. Among them, TRPC subfamily consists of TRPC1, TRPC2, TRPC3/6/7 and TRPC4/5 [16]. TRPC6 channel has been shown to be expressed in various tissues and implicated in many different diseases, such as cardiac hypertrophy and cerebral ischemia [16,17]. Kuwahara et al. found that TRPC6 was a positive regulator of calcineurin-NFAT signaling pathway and also was a key component of a calcium-dependent regulatory loop which drives pathological cardiac remodeling. On the other hand, Du et al. uncovered that TRPC6 proteolysis could lead to ischemic neuronal cell death, and the repression of its degradation could preserve neuronal survival and prevent ischemic brain damage. Based on the above findings, we proposed the hypothesis that neurotrophins may repair the ischemic myocardium via modulation of TRPC6 channel which might be one potential novel therapeutic target for myocardial infarction. Moreover, the plasma neurotrophins level may become a novel biomarker for the diagnosis of myocardial infarction. Our hypothesis is strongly supported by several following facts. First of all, the expression of TRPC6 protein was observed to be ⁎ Corresponding author at: The First Affiliated Hospital, Harbin Medical University, Youzheng Street 23#, Nangang District, Harbin 150001, Heilongjiang Province, China. Tel.: +86 451 85555673; fax: +86 451 53675733. E-mail address: [email protected] (Y. Li). 1 The first two authors made equal contributions.
altered in ischemic diseases. It has been found that TRPC6 channel played a critical role in cerebral ischemia whereas other subtypes were unaltered [17]. Moreover, our previous bioinformatical results implied that TRPC6 may also be involved in MI [18]. Thus, experiments were conducted and confirmed that the level of TRPC6 indeed changed in ischemic myocardium [18]. Secondly, many studies have proved that BMSCs implantation is beneficial to brain and heart infarct, which could reduce the infarcted areas and induce reborn of neuron and cardiomyocyte, at least partly via secretion of neurotrophins [4–6]. Importantly, recent studies revealed that the protective effect of BMSCs is likely associated with several functional ion channels such as IKCa, IKir, ICl and TRPM [19,20]. Meanwhile, it is confirmed that BDNF-TrkB could activate PLC which could regulate the activity of DAG and contribute to the activation of TRPC6 channel [21,22]. Taken together, it is believed that the potential mechanisms in this process may be relevant to BDNFTrkB/NGF-TrkA signaling pathway, which regulated TRPC6 channel in the membrane and further induces the activation of downstream survival molecules like extracellular regulated protein kinases (ERK) and calcium/calmodulin-dependent protein kinase (CAMK) [23]. In summary, the hypothesis is that employment of BMSCs in ischemic cardiomyopathy triggers the angiogenesis of injured heart through secretion of neurotrophins and regulation of TRPC6 channel. TRPC6 may serve as a potential target for the therapy of ischemic heart. We believe that stem cell therapy is correlated to amelioration of ischemic cardiomyocytes through secretion of neurotrophins. The pivotal role of TRPC6 in repairing injured tissues suggests its crucial involvement in the regeneration of MI. Of course, it needs further studies to prove it. If the hypothesis is true, agents regulating neurotrophins may also be effective for myocardial infarction patients in clinics. Once validated, TRPC6 may serve as a novel target in prevention and cure of MI. This work was supported by the National Natural Science Fund of China (No. 30971251, 81070160) and the Program for New Century Excellent Talents in University from the Department of Education of Heilongjiang Province (No. 1152-NCET-011). The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010; 144:1–2).
References [1] Li Y, Hiroi Y, Ngoy S, et al. Notch1 in bone marrow-derived cells mediates cardiac repair after myocardial infarction. Circulation 2011;123(8):866–76. [2] Kanazawa H, Fujimoto Y, Teratani T, et al. Bone marrow-derived mesenchymal stem cells ameliorate hepatic ischemia reperfusion injury in a rat model. PLoS One 2011;6(4):e19195. [3] Bao X, Wei J, Feng M, et al. Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats. Brain Res 2011;1367:103–13. [4] Wilkins A, Kemp K, Ginty M, Hares K, Mallam E, Scolding N. Human bone marrowderived mesenchymal stem cells secrete brain-derived neurotrophic factor which promotes neuronal survival in vitro. Stem Cell Res 2009;3:63–70. [5] Ding J, Cheng Y, Gao S, Chen J. Effects of nerve growth factor and Noggin-modified bone marrow stromal cells on stroke in rats. J Neurosci Res 2011;89(2):222–30. [6] Pisati F, Bossolasco P, Meregalli M, et al. Induction of neurotrophin expression via human adult mesenchymal stem cells: implication for cell therapy in neurodegenerative diseases. Cell Transplant 2007;16(1):41–55. [7] Nomura T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. I.V. infusion of brainderived neurotrophic factor gene-modified human mesenchymal stem cells protects
498
[8]
[9]
[10] [11]
[12]
[13]
[14]
Letters to the Editor against injury in a cerebral ischemia model in adult rat. Neuroscience 2005;136(1):161–9. Horita Y, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. Intravenous administration of glial cell line-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in the adult rat. J Neurosci Res 2006;84(7):1495–504. Swardfager W, Herrmann N, Marzolini S, et al. Brain derived neurotrophic factor, cardiopulmonary fitness and cognition in patients with coronary artery disease. Brain Behav Immun 2011;25(6):1264–71. Ejiri J, Inoue N, Kobayashi S, et al. Possible role of brain-derived neurotrophic factor in the pathogenesis of coronary artery disease. Circulation 2005;112(14):2114–20. Lorgis L, Amoureux S, de Maistre E, et al. Serum brain-derived neurotrophic factor and platelet activation evaluated by soluble P-selectin and soluble CD-40-ligand in patients with acute myocardial infarction. Fundam Clin Pharmacol 2010;24(4):525–30. Manni L, Nikolova V, Vyagova D, Chaldakov GN, Aloe L. Reduced plasma levels of NGF and BDNF in patients with acute coronary syndromes. Int J Cardiol 2005;102(1):169–71. Chaldakov GN, Fiore M, Stankulov IS, et al. Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease? Prog Brain Res 2004;146:279–89. Nilius B, Owsianik G. The transient receptor potential family of ion channels. Genome Biol 2011;12(3):218.
[15] Wu X, Eder P, Chang B, Molkentin JD. TRPC channels are necessary mediators of pathologic cardiac hypertrophy. Proc Natl Acad Sci U S A 2010;107(15):7000–5. [16] Kuwahara K, Wang Y, McAnally J, et al. TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling. J Clin Invest 2006;116(12):3114–26. [17] Du W, Huang J, Yao H, Zhou K, Duan B, Wang Y. Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats. J Clin Invest 2010;120(10):3480–92. [18] Zhou R, Hang P, Zhu W, Su Z, Liang H, Du Z. Whole genome network analysis of ion channels and connexins in myocardial infarction. Cell Physiol Biochem 2011;27(3– 4):299–304. [19] Cheng H, Feng JM, Figueiredo ML, et al. Transient receptor potential melastatin type 7 channel is critical for the survival of bone marrow derived mesenchymal stem cells. Stem Cells Dev 2010;19(9):1393–403. [20] Tao R, Lau CP, Tse HF, Li GR. Functional ion channels in mouse bone marrow mesenchymal stem cells. Am J Physiol Cell Physiol 2007;293(5):C1561–7. [21] Sossin WS, Barker PA. Something old, something new: BDNF-induced neuron survival requires TRPC channel function. Nat Neurosci 2007;10(5):537–8. [22] Numakawa T, Suzuki S, Kumamaru E, Adachi N, Richards M, Kunugi H. BDNF function and intracellular signaling in neurons. Histol Histopathol 2010;25(2):237–58. [23] Kermani P, Hempstead B. Brain-derived neurotrophic factor: a newly described mediator of angiogenesis. Trends Cardiovasc Med 2007;17(4):140–3.
0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.12.090
Correlations between myocardium selective videodensitometric perfusion parameters and corrected TIMI frame count in patients with normal epicardial coronary arteries Ferenc Tamás Nagy a, Viktor Sasi a, Tamás Ungi b, Zsolt Zimmermann a, Imre Ungi a, Anita Kalapos a, Tamás Forster a, Attila Nemes a,⁎ a b
Division of Invasive Cardiology, Department of Cardiology, Medical Faculty, Albert-Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary School of Computing, Queen's University, Kingston, Ontario, Canada
a r t i c l e
i n f o
Article history: Received 29 November 2011 Accepted 25 December 2011 Available online 17 January 2012 Keywords: Coronary Correlation Epicardial Myocardial blush TIMI frame count Videodensitometry
TIMI frame count (TFC), was introduced in the early 1990s, as a method to assess the efficacy of thrombolysis and risk stratification in acute myocardial infarction (AMI) [1]. TFC proved to be a simple, reproducible, quantitative and objective method to evaluate epicardial flow not only in acute coronary syndrome settings, but in stable conditions with microvascular dysfunction, as well [2]. Recently, 2 different angiographic methods myocardial blush grade (MBG), and TIMI myocardial perfusion grading (TMP) have been described for direct assessment of myocardial perfusion in AMI [3]. However, these methods are limited inherently by their subjective nature and
⁎ Corresponding author at: 2nd Department of Medicine and Cardiology Centre, Medical Faculty, University of Szeged, H-6720 Szeged, Korányi fasor 6. P.O. Box 427, Hungary. Tel.: + 36 62 545220; fax: +36 62 544568. E-mail address: [email protected] (A. Nemes).
categorical values, and are not defined in stable patients. Alongside others novel computer-assisted videodensiometric methods have been introduced, which supply additional, objective and quantitative information on myocardial perfusion in AMI [4–6]. The objective of the present study was to evaluate regional myocardial perfusion assessed by our novel computerized videodensitometric method, and its relation to corrected TFC in non-AMI patients without epicardial coronary stenoses. The current study comprised 43 patients with chest pain who had undergone elective coronary angiography with a negative result (b40% intraluminal epicardial coronary artery diameter stenosis) at Table 1 Clinical, demographic and echocardiographic data of the patients. Patients n Age (years) Males (%) Diabetes (%) Hypertension (%) Hypercholesterolemia (%) Smoking (%) Coronary angiography LAD — Gmax/Tmax LAD — cTFC CX — Gmax/Tmax CX — TFC RC — Gmax/Tmax RC — TFC
43 60.2 ± 9.8 29 (67) 5 (12) 34 (79) 32 (74) 15 (35) 2.85 ± 1.56 25.6 ± 12.1 2.63 ± 1.36 25.8 ± 9.7 2.39 ± 0.95 26.0 ± 9.9
Abbreviations. cTFC: corrected TIMI frame count, LAD: left anterior descending coronary artery, CX: left circumflex coronary artery, RC: right coronary artery.