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Department Introduction

Department Introduction

Ischemia Heart Disease Group

(1) Ischemic Heart Disease Group

Ischemic Heart Disease Group

The Ischemic Heart Disease (IHD) Group performs approximately ~700 cardiac catheterization and ~300 percutaneous coronary interventions in a year. Since launching Tohoku University Hospital Emergency Center in October 2006, the number of patients with acute covonary syndrome have been increasing. We actively work on the clinical researches to clarify the pathology of IHD and advanced treatment (e.g., external shockwave treatment) for patients.

Serial changes in the number of cardiac catheterization and PCIsFigure: Serial changes in the number of cardiac catheterization and PCIs

1. The Pathology of Vasospastic Angina

Figure 1A coronary spasm temporarily reduces the blood flow by the sudden narrowing of the coronary artery and induces myocardial ischemia (supply/primary ischemia). Coronary spasm is particularly important in the pathogenesis of IHD in Japanese. Coronary Spasm Association (CSA) was launched in August 2006 conducts the research from basic to clinical perspectives. Under the direction of Tohoku University (Professor Hiroaki Shimokawa) and Kumamoto University (Professor Hisao Ogawa), 68 facilities are participating nationwide in this research group. The CSA is funded by the Japan Heart Foundation and its secretarial office is located in our department. (Figure 1). In the basic researches, it has been revealed that Rho-kinase activation plays an important role as a molecular mechanism of coronary vasospasm and it has been expected to apply the Rho-kinase inhibitor for the clinical setting.

2. Evidence-Based Medicine (EBM) for Percutaneous Coronary Intervention

Figure 2Percutaneous coronary intervention including coronary artery stents is rapidly developed over 30 years in the treatment of IHD. Today, we can use two different types of stents. One is bare metal stent (BMS) and the other is drug eluting stent (DES). We scientifically evaluate advantages and disadvantages of these two types of stents to make a right choice and to perform procedural assessment (Figure 2) by using intravascular ultrasound (IVUS) and/or quantitative coronary angiography (QCA). It is also important to evaluate myocardial ischemia and perform ischemia-oriented coronary interventions. Moreover, we conduct researches on evaluation for myocardial ischemia and myocardial viability using magnetic resonance imaging(MRI).

3. Pathology of Out-of-hospital Cardiac Arrest

In Japan there are 30,000 to 50,000 deaths of out-of-hospital cardiac arrest per a year, which is 3 to 4 times of the number of traffic accident victims. The survival rate of these patients has been increased because of the recent spread of by-stander cardiopulmonary resuscitation and automated external defibrillators (AED). It is a very important issue to elucidate the pathology of out-of-hospital cardiac arrest. In our department, when we can not find organic abnormalities, we perform functional evaluations by provoking coronary spasm (acetylcholine provocation test) and inducing ventricular fibrillation (electrophysiological study).

Fig.3: Out-of-hospital Cardiac Arrest and Fuctional Assessment

Fig.3: Elucidation of Pathology of Out-of-hospital Cardiac Arrest

4. Low-energy External Shockwave Treatment for Severe Ischemic Heart Disease

We are conducting clinical trials of a new angiogenesis therapy using external shockwaves. The low-energy shockwaves radiates externally on ischemic myocardium to promote angiogenesis as a non-invasive treatment. With the approval of the University Review Board, clinical trials were begun in November 2005 for cases of severe angina (Figure 4) and in February 2007 for cases of acute myocardial infarction (Figure 5).
>>Click here to go to the “Shockwave Treatment” site.

Fig. 4: Improvement of Myocardial Blood Flow using External Shockwave Treatment

Fig. 4: Improvement of Myocardial Blood Flow using External Shockwave Treatment

Fig. 5:Fig. 5

Publications (since 2005)
2012
  1. Nochioka K, Tanaka S, Miura M, Zhulanqiqige DE, Fukumoto Y, Shiba N, Shimokawa H. Ezetimibe improves endothelial function and inhibits Rho-kinase activity associated with inhibition of cholesterol absorption in humans. Circ J. (in press)
  2. Serizawa F, Ito K, Kawamura K, Tsuchida K, Hamada Y, Zukeran T, Shimizu T, Akamatsu D, Hashimoto M, Goto H, Watanabe T, Sato A, Shimokawa H, Satomi S. Extracorporeal shock wave therapy ameliorates walking ability of patients with peripheral artery disease and intermittent claudication. Circ J. (in press)PubMed
  3. Tsuburaya R, Yasuda S, Shiroto T, Ito Y, Gao JY, Aizawa K, Kikuchi Y, Ito K, Takahashi J, Ishibashi-Ueda H, Shimokawa H. Long-term treatment with nifedipine suppresses coronary hyperconstricting responses and inflammatory changes induced by paclitaxel-eluting stent in pigs in vivo: possible involvement of Rho-kinase pathway. Eur Heart J. 33 : 791-799, 2012.PubMed
  4. Satoh K, Fukumoto Y, Nakano M, Kagaya Y, Shimokawa H. Emergence of the erythropoietin/erythropoietin receptor system as a novel cardiovascular therapeutic target. J Cardiovasc Pharmacol. 58 : 570-574, 2012.PubMed
  5. Kromhout D, Yasuda S, Geleijnse JM, Shimokawa H. Fish oil and omega-3 fatty acids in cardiovascular disease: do they really work? Eur Heart J. 33 : 436-443, 2012.PubMed
  6. Hao K, Yasuda S, Takii T, Ito Y, Takahashi J, Ito K, Nakayama M, Shiba N, Fukumoto Y, Shimokawa H. Urbanization, life-style changes and incidence and in-hospital mortality from acute myocardial infarction in Japan -Report from the MIYAGI-AMI Registry- Circ J. 76 : 1136-1144, 2012.PubMed
2011
  1. Ito K, Fukumoto Y, Shimokawa H. Extracorporeal shock wave therapy for ischemic cardiovascular disorders. Am J Cardiovasc Drugs. 11 : 295-302, 2011.PubMed
  2. Kikuchi Y, Yasuda S, Aizawa K, Tsuburaya R, Ito Y, Takeda M, Nakayama M, Ito K, Takahashi J, Shimokawa H. Enhanced Rho-kinase activity in circulating neutrophils of patients with vasospastic angina: a possible biomarker for diagnosis and disease activity assessment. J Am Coll Cardiol. 58 : 1231-1237, 2011.PubMed
  3. Satoh K, Fukumoto Y, Shimokawa H. Rho-kinase: Important new therapeutic target in cardiovascular diseases. Am J Physiol. 301 : 287-296, 2011.PubMed
  4. Satoh K, Berk BC, Shimokawa H. Vascular-derived reactive oxygen species for homeostasis and diseases. Nitric Oxide. 25 : 211-215, 2011. (Review)PubMed
  5. Tsuburaya R, Yasuda S, Ito Y, Shiroto T, Gao JY, Ito K, Shimokawa H. Eicosapentaenoic acid reduces ischemic ventricular fibrillation via altering monophasic action potential in pigs. J Mol Cell Cardiol. 51 : 329-336, 2011. PubMed
  6. Nakayama M, Osaki S, Shimokawa H. Validation of the mortality risk stratification models for cardiovascular disease. Am J Cardiol. 108 : 391-396, 2011. PubMed
  7. Gao JY, Yasuda S, Tsuburaya R, Ito Y, Shiroto T, Hao K, Aizawa K, Kikuchi Y, Ito K, Shimokawa H. Long-term treatment with eicosapentaenoic acid ameliorates myocardial ischemia-reperfusion injury in pigs in vivo -Involvement of Rho-kinase pathway inhibition- Circ J. 75 : 1843-1851, 2011.PubMed
  8. Takagi Y, Yasuda S, Tsunoda R, Ogata Y, Seki A, Sumiyoshi T, Matsui M, Goto T, Tanabe Y, Sueda S, Sato T, Ogawa S, Kubo N, Momomura S, Ogawa H, Shimokawa H. Clinical characteristics and long-term prognosis of vasospastic angina patients who survived out-of-hospital cardiac arrest. -Multicenter registry study of the Japanese Coronary Spasm Association- Circulation Arrhythmia & Electrophysiology. 4 : 295-302, 2011.PubMed
2010
  1. Shimokawa H, Ito K. Extracorporeal cardiac shock wave therapy for ischemic heart disease. In: Achim M. Loske (ed.), New Trends in Shock Wave Applications to Medicine and Biotechnology, Research Signpost, India, 211-224, 2010.
  2. Ito K, Kagaya Y, Shimokawa H. Thyroid hormone and chronically unloaded hearts. Vasc Pharmacol. 52 : 138-141, 2010.PubMed
  3. Ito Y, Ito K, Shiroto T, Tsuburaya R, Yi GJ, Takeda M, Fukumoto Y, Yasuda S, Shimokawa H. Cardiac shock wave therapy ameliorates left ventricular remodeling after myocardial ischemia-reperfusion injury in pigs in vivo. Coron Artery Dis. 21 : 304-311, 2010.PubMed
  4. Kikuchi Y, Ito K, Ito Y, Shiroto T, Tsuburaya R, Aizawa K, Hao K, Fukumoto Y, Takahashi J, Takeda M, Nakayama M, Yasuda S, Kuriyama S, Tsuji I, Shimokawa H. Double-blind and placebo-controlled study of the effectiveness and safety of extracorporeal cardiac shock wave therapy for severe angina pectoris. Circ J. 74 : 589-591, 2010.PubMed
  5. Takagi Y, Sugi M, Hanawa K, Shimokawa H. Successful recanalization of chronic total occlusion using retrograde approach in a patient with acute coronary syndrome due to aortosaphenous vein graft occlusion. JC Cases. 1 : e112-115, 2010.
  6. Takii T, Yasuda S, Takahashi J, Ito K, Shiba N, Shirato K, Shimokawa H; MIYAGI-AMI Study Investigators. Trends in acute myocardial infarction incidence and mortality over 30 years in Japan: report from the MIYAGI-AMI Registry Study. Circ J. 74 : 93-100, 2010.PubMed
  7. Yasuda S, Shimokawa H. Potential usefulness of fish oil in the primary prevention of acute coronary syndrome. Eur Heart J. 31 : 15-16, 2010.PubMed
2009
  1. Ito K, Fukumoto Y, Shimokawa H. Extracorporeal shock wave therapy as a new and non-invasive angiogenic strategy. Tohoku J Exp Med. 219 : 1-9, 2009.PubMed
  2. Shiroto T, Yasuda S, Tsuburaya R, Ito Y, Takahashi J, Ito K, Ishibashi-Ueda H, Shimokawa H. Role of Rho-kinase in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stents in pigs in vivo. J Am Coll Cardiol. 54 : 2321-2329, 2009.PubMed
  3. Takagi Y, Yasuda S, Takahashi J, Takeda M, Nakayama M, Ito K, Hirose M, Wakayama Y, Fukuda K, Shimokawa H. Importance of dual induction tests for coronary vasospasm and ventricular fibrillation in patients surviving out-of-hospital cardiac arrest. Circ J. 73 : 767-769, 2009.PubMed
  4. Yasuda S, Shimokawa H. Acute myocardial infarction: the enduring challenge for cardiac protection and survival. Circ J. 73 : 2000-2008, 2009.PubMed
2008
  1. Fukumoto Y, Yasuda S, Ito A, Shimokawa H. Prognostic effects of benidipine in patients with vasospastic angina:comparison with diltiazem and amlodipine. J Cardiovasc Pharmacol. 51 : 253-257, 2008.PubMed
  2. Kokusho Y, Komaru T, Takeda S, Takahashi K, Koshida R, Shirato K, Shimokawa H. Hydrogen peroxide derived from beating heart mediates coronary microvascular dilation during tachycardia. Arterioscler Thromb Vasc Biol. 27 : 1057-1063, 2008.PubMed
  3. Oi K, Fukumoto Y, Ito K, Uwatoku T, Abe K, Hizume T, Shimokawa H. Extracorporeal shock wave therapy ameliorates hindlimb ischemia in rabbits. Tohoku J Exp Med. 214 : 151-158, 2008.PubMed
  4. Shimokawa H, Ito K, Fukumoto Y, Yasuda S. Extracorporeal cardiac shock wave therapy for ischemic heart disease. Shock Waves 17 : 449-455, 2008.
  5. Shimokawa H, Yasuda S. Myocardial ischemia: Current concepts and future perspectives. J Cardiol. 52 : 67-78, 2008.PubMed
  6. Tada T, Nawata J, Wang H, Onoue N, Zhulanqiqige D, Ito K, Sugimura K, Fukumoto Y, Shimokawa H. Enhanced pulsatile pressure accelerates vascular smooth muscle migration: implications for atherogenesis of hypertension.Cardiovasc Res. 17 : 449-455, 2008.PubMed
  7. Yasuda S, Ikuta K, Uwatoku T, Oi K, Abe K, Hyodo F, Yoshimitsu K, Sugimura K, Utsumi H, Katayama Y, Shimokawa H. In vivo magnetic resonance imaging of atherosclerotic lesions with a newly developed Evans blue-DTPA-gadolinium contrast medium in apolipoprotein-E-deficient mice. J Vasc Res. 45 : 123-128, 2008.PubMed
2007
  1. Asaumi Y, Kagaya Y, Takeda M, Yamaguchi N, Tada H, Ito K, Ohta J, Shiroto T, Shirato K, Minegishi N, Shimokawa H. Protective role of endogenous erythropoietin system in nonhematopoietic cells against pressure overload-induced left ventricular dysfunction in mice. Circulation. 115 : 2022-2032, 2007.PubMed
  2. Minatoya Y, Ito K, Kagaya Y, Asaumi Y, Takeda M, Nakayama M, Takahashi J, Iguchi A, Shirato K, Shimokawa H. Depressed contractile reserve and impaired calcium handling of cardiac myocytes from chronically unloaded hearts are ameliorated with the administration of physiological treatment dose of T3 in rats. Acta Physiol (Oxf). 189 : 221-231, 2007.PubMed
  3. Uwatoku T, Ito K, Abe K, Oi K, Hizume T, Sunagawa K, Shimokawa H. Extracorporeal cardiac shock wave therapy improves left ventricular remodeling after acute myocardial infarction in pigs. Coron Artery Dis. 18 : 397-404, 2007.PubMed
2006
  1. Satoh K, Kagaya Y, Nakano M, Ito Y, Ohta J, Tada H, Karibe A, Minegishi N, Suzuki N, Yamamoto M, Ono M, Watanabe J, Shirato K, Ishii N, Sugamura K, Shimokawa H. Important role of endogenous erythropoietin system in recruitment of endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice. Circulation. 113 : 1442-1450, 2006.PubMed
  2. Tada H, Kagaya Y, Takeda M, Ohta J, Asaumi Y, Satoh K, Ito K, Karibe A, Shirato K, Minegishi N, Shimokawa H. Endogenous erythropoietin system in non-hematopoietic lineage cells plays a protective role in myocardial ischemia/reperfusion. Cardiovasc Res. 71 : 466-477, 2006.PubMed
2005
  1. Namiuchi S, Kagaya Y, Ohta J, Shiba N, Sugi M, Oikawa M, Kunii H, Yamao H, Komatsu N, Yui M, Tada H, Sakuma M, Watanabe J, Ichihara T, Shirato K. High serum erythropoietin level is associated with smaller infarct size in patients with acute myocardial infarction who undergo successful primary percutaneous coronary intervention. J Am Coll Cardiol. 45 : 1406-1412, 2005.PubMed

(Text by Jun Takahashi)

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