Papers - Katsumata, Yoshinori

Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury

Shinmura Ken, Tamaki Kayoko, Ito Kentaro, Yan Xiaoxiang, Yamamoto Tsunehisa, Katsumata Yoshinori, Matsuhashi Tomohiro, Sano Motoaki, Fukuda Keiichi, Suematsu Makoto, Ishii Isao

American Journal of Physiology - Heart and Circulatory Physiology 308 ( 8 ) H894 - H903 2015

ISSN  0363-6135

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<p>Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion injury (IRI). We previously found that treatment with N&lt;sup&gt;G&lt;/sup&gt;-nitro-L-arginine methyl ester completely abrogates CR-induced cardioprotection and increases nuclear sirtuin 1 (Sirt1) expression. However, it remains unclear whether endothelial nitric oxide (NO) synthase (eNOS) plays a role in CR-induced cardioprotection and Sirt1 activation. We subjected eNOS-deficient (eNOS&lt;sup&gt;−/−&lt;/sup&gt;) mice to either 3-mo ad libitum (AL) feeding or CR (−40%). Isolated perfused hearts were subjected to 25-min global ischemia followed by 60-min reperfusion. The degree of myocardial IRI in AL-fed eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice was more severe than that in AL-fed wild-type mice. Furthermore, CR did not exert cardioprotection in eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice. eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice exhibited elevated blood pressure and left ventricular hypertrophy compared with wild-type mice, although they underwent CR. Although nuclear Sir1 content was increased, the increases in cardiac Sirt1 activity with CR was absent in eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice. In eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice treated with hydralazine, blood pressure and left ventricular weight became comparable with CR-treated wild-type mice. However, CR-induced cardioprotection was not observed. Resveratrol enhanced cardiac Sirt1 activity but failed to mimic CR-induced cardioprotection in eNOS&lt;sup&gt;−/−&lt;/sup&gt;mice. Finally, combination therapy with resveratrol and hydralazine attenuated myocardial IRI and reduced infarct size in eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice, and their effects were comparable with those observed in CR-treated wild-type mice. These results demonstrate the essential roles of eNOS in the development of CR-induced cardioprotection and Sirt1 activation during CR. The combination of a relatively low dose of resveratrol with an adequate vasodilator therapy might be useful for managing patients with endothelial dysfunction associated with impaired NO bioavailability.</p>

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Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury

Shinmura Ken, Tamaki Kayoko, Ito Kentaro, Yan Xiaoxiang, Yamamoto Tsunehisa, Katsumata Yoshinori, Matsuhashi Tomohiro, Sano Motoaki, Fukuda Keiichi, Suematsu Makoto, Ishii Isao

American Journal of Physiology - Heart and Circulatory Physiology 308 ( 8 ) H894 - H903 2015

ISSN  0363-6135

　View Summary

<p>Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion injury (IRI). We previously found that treatment with N&lt;sup&gt;G&lt;/sup&gt;-nitro-L-arginine methyl ester completely abrogates CR-induced cardioprotection and increases nuclear sirtuin 1 (Sirt1) expression. However, it remains unclear whether endothelial nitric oxide (NO) synthase (eNOS) plays a role in CR-induced cardioprotection and Sirt1 activation. We subjected eNOS-deficient (eNOS&lt;sup&gt;−/−&lt;/sup&gt;) mice to either 3-mo ad libitum (AL) feeding or CR (−40%). Isolated perfused hearts were subjected to 25-min global ischemia followed by 60-min reperfusion. The degree of myocardial IRI in AL-fed eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice was more severe than that in AL-fed wild-type mice. Furthermore, CR did not exert cardioprotection in eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice. eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice exhibited elevated blood pressure and left ventricular hypertrophy compared with wild-type mice, although they underwent CR. Although nuclear Sir1 content was increased, the increases in cardiac Sirt1 activity with CR was absent in eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice. In eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice treated with hydralazine, blood pressure and left ventricular weight became comparable with CR-treated wild-type mice. However, CR-induced cardioprotection was not observed. Resveratrol enhanced cardiac Sirt1 activity but failed to mimic CR-induced cardioprotection in eNOS&lt;sup&gt;−/−&lt;/sup&gt;mice. Finally, combination therapy with resveratrol and hydralazine attenuated myocardial IRI and reduced infarct size in eNOS&lt;sup&gt;−/−&lt;/sup&gt; mice, and their effects were comparable with those observed in CR-treated wild-type mice. These results demonstrate the essential roles of eNOS in the development of CR-induced cardioprotection and Sirt1 activation during CR. The combination of a relatively low dose of resveratrol with an adequate vasodilator therapy might be useful for managing patients with endothelial dysfunction associated with impaired NO bioavailability.</p>

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Operator-blinded contact force monitoring during pulmonary vein isolation using conventional and steerable sheaths

Kimura Takehiro, Takatsuki Seiji, Oishi Ako, Negishi Masachika, Kashimura Shin, Katsumata Yoshinori, Nishiyama Takahiko, Nishiyama Nobuhiro, Tanimoto Yoko, Aizawa Yoshiyasu, Fukuda Keiichi

International Journal of Cardiology 177 ( 3 ) 970 - 976 2014.12

ISSN  0167-5273

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<p>Background We performed contact force (CF) monitoring during pulmonary vein (PV) isolation to evaluate CF according to sheath type, catheter position, and inadequate ablation.</p><p>Methods Thirty consecutive patients (paroxysmal atrial fibrillation, 23; CHADS₂ score, 0.5 ± 0.7; age, 56 ± 10 years) who underwent PV isolation using a CF-sensing catheter were included. Data for operator-blinded CF, impedance, and duration of the "first touch" (first round of ablation in each PV) was collected. We compared the CF, maximum CF, force-time integral, average impedance, and impedance drop (Δ impedance) between different sheaths (Swartz™ vs. Agilis™) in 12 different catheter positions, and in inadequate first touches requiring additional ablation.</p><p>Results A total of 1283 ablation points (Swartz™, 620 points; Agilis™, 663 points) were evaluated. The average CF was significantly higher in the Agilis™ group (17.8 ± 13.0 g) than the Swartz™ group (15.0 ± 12.4 g; P &lt; 0.001), especially in the anterior, inferior-anterior, and inferior-posterior sections of the right PV, and the top of the roof, and calina of the left PV. The Δ impedance showed a mildly significant negative relationship with the average CF (r = - 0.206; P &lt; 0.001) and with the force-time integral (r = - 0.279; P &lt; 0.001). Compared to first touches, the average CF and Δ impedance were significantly smaller in inadequate first touches in the Swartz™ group, but not in the Agilis™ group.</p><p>Conclusions CF for PV isolation was significantly different depending on the position of the catheter and the type of sheath.</p>

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Operator-blinded contact force monitoring during pulmonary vein isolation using conventional and steerable sheaths

Kimura Takehiro, Takatsuki Seiji, Oishi Ako, Negishi Masachika, Kashimura Shin, Katsumata Yoshinori, Nishiyama Takahiko, Nishiyama Nobuhiro, Tanimoto Yoko, Aizawa Yoshiyasu, Fukuda Keiichi

International Journal of Cardiology 177 ( 3 ) 970 - 976 2014.12

ISSN  0167-5273

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<p>Background We performed contact force (CF) monitoring during pulmonary vein (PV) isolation to evaluate CF according to sheath type, catheter position, and inadequate ablation.</p><p>Methods Thirty consecutive patients (paroxysmal atrial fibrillation, 23; CHADS₂ score, 0.5 ± 0.7; age, 56 ± 10 years) who underwent PV isolation using a CF-sensing catheter were included. Data for operator-blinded CF, impedance, and duration of the "first touch" (first round of ablation in each PV) was collected. We compared the CF, maximum CF, force-time integral, average impedance, and impedance drop (Δ impedance) between different sheaths (Swartz™ vs. Agilis™) in 12 different catheter positions, and in inadequate first touches requiring additional ablation.</p><p>Results A total of 1283 ablation points (Swartz™, 620 points; Agilis™, 663 points) were evaluated. The average CF was significantly higher in the Agilis™ group (17.8 ± 13.0 g) than the Swartz™ group (15.0 ± 12.4 g; P &lt; 0.001), especially in the anterior, inferior-anterior, and inferior-posterior sections of the right PV, and the top of the roof, and calina of the left PV. The Δ impedance showed a mildly significant negative relationship with the average CF (r = - 0.206; P &lt; 0.001) and with the force-time integral (r = - 0.279; P &lt; 0.001). Compared to first touches, the average CF and Δ impedance were significantly smaller in inadequate first touches in the Swartz™ group, but not in the Agilis™ group.</p><p>Conclusions CF for PV isolation was significantly different depending on the position of the catheter and the type of sheath.</p>

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Pericardial endoscopy-guided left atrial appendage ligation

Kimura Takehiro, Takatsuki Seiji, Miyoshi Shunichiro, Katsumata Yoshinori, Nishiyama Takahiko, Nishiyama Nobuhiro, Tanimoto Yoko, Aizawa Yoshiyasu, Jinzaki Masahiro, Fukuda Keiichi

Circulation: Cardiovascular Interventions 7 ( 6 ) 844 - 850 2014.12

ISSN  1941-7640

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<p>Background-Approaches for closing the left atrial appendage (LAA) have been developed for stroke prevention. However, the prevailing maneuvers require an open-chest surgery, intravascular access, or transseptal puncture. We evaluated the feasibility and safety of pericardial endoscopy-guided LAA ligation in a canine model. Methods and Results-We used a total of 8 canines and computed tomography was performed before the procedures. After a double percutaneous pericardiocentesis, a transurethral rigid endoscope was inserted into the pericardial space. The ENDOLOOP ligature was advanced to the ostium of the LAA by counter pulling the tip of the LAA with forceps. After confirming the positioning guided by transesophageal echocardiography, the ligature was securely tightened. Acute success was evaluated by transesophageal echocardiography and chronic success was evaluated by blood testing, computed tomography, and transesophageal echocardiography. The LAA ligation was safely achieved in all canines without major complications. One month after the ligation, the ligated LAA was replaced by fibrotic tissue, and both the transesophageal echocardiography and computed tomographic images revealed no residual shunt. There was only a localized adhesion of the pericardium, where the original LAA was located, without the need for antibiotic or steroid administration. The postprocedural internal surface of the ligated LAA was smooth by virtue of intimal growth. Blood tests showed a slight elevation of the inflammatory markers, but this normalized spontaneously. Conclusions-Pericardial endoscopy-guided LAA ligation could provide an alternative, minimally invasive, and feasible solution for LAA closure that does not require vascular access or a transseptal puncture.</p>

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Pericardial endoscopy-guided left atrial appendage ligation

Kimura Takehiro, Takatsuki Seiji, Miyoshi Shunichiro, Katsumata Yoshinori, Nishiyama Takahiko, Nishiyama Nobuhiro, Tanimoto Yoko, Aizawa Yoshiyasu, Jinzaki Masahiro, Fukuda Keiichi

Circulation: Cardiovascular Interventions 7 ( 6 ) 844 - 850 2014.12

ISSN  1941-7640

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<p>Background-Approaches for closing the left atrial appendage (LAA) have been developed for stroke prevention. However, the prevailing maneuvers require an open-chest surgery, intravascular access, or transseptal puncture. We evaluated the feasibility and safety of pericardial endoscopy-guided LAA ligation in a canine model. Methods and Results-We used a total of 8 canines and computed tomography was performed before the procedures. After a double percutaneous pericardiocentesis, a transurethral rigid endoscope was inserted into the pericardial space. The ENDOLOOP ligature was advanced to the ostium of the LAA by counter pulling the tip of the LAA with forceps. After confirming the positioning guided by transesophageal echocardiography, the ligature was securely tightened. Acute success was evaluated by transesophageal echocardiography and chronic success was evaluated by blood testing, computed tomography, and transesophageal echocardiography. The LAA ligation was safely achieved in all canines without major complications. One month after the ligation, the ligated LAA was replaced by fibrotic tissue, and both the transesophageal echocardiography and computed tomographic images revealed no residual shunt. There was only a localized adhesion of the pericardium, where the original LAA was located, without the need for antibiotic or steroid administration. The postprocedural internal surface of the ligated LAA was smooth by virtue of intimal growth. Blood tests showed a slight elevation of the inflammatory markers, but this normalized spontaneously. Conclusions-Pericardial endoscopy-guided LAA ligation could provide an alternative, minimally invasive, and feasible solution for LAA closure that does not require vascular access or a transseptal puncture.</p>

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Effect of Nocturnal Intermittent Hypoxia on Left Atrial Appendage Flow Velocity in Atrial Fibrillation

Kimura Takehiro, Kohno Takashi, Nakajima Kazuaki, Kashimura Shin, Katsumata Yoshinori, Nishiyama Takahiko, Nishiyama Nobuhiro, Tanimoto Yoko, Aizawa Yoshiyasu, Fukuda Keiichi, Takatsuki Seiji

Canadian Journal of Cardiology  2014.10

ISSN  0828-282X

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<p>Background: The mechanism underlying the associations of sleep-disordered breathing (SDB) with stroke and atrial fibrillation (AF) is not well established. We explored the relationship between nocturnal intermittent hypoxia, a marker of SDB, and left atrial (LA)/LA appendage (LAA) function among AF patients. Methods: We evaluated 134 consecutive AF candidates for catheter ablation (age, 59.6 ± 9.4 years; body mass index [BMI], 24.8 ± 3.2; Congestive Heart Failure, Hypertension, Age (≥75 years), Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age (65-74 years), Sex (Female) (CHA&lt;inf&gt;2&lt;/inf&gt;DS&lt;inf&gt;2&lt;/inf&gt;-VASc) score, 1.2 ± 1.1, paroxysmal AF, n= 83) using nocturnal pulse oximetry, a noninvasive screening method for nocturnal intermittent hypoxia. Based on 3% oxygen desaturation index (3% ODI), patients were divided into nocturnal intermittent hypoxia (3% ODI &gt; 15; n= 32) and control groups (3% ODI ≤ 15; n= 102). Results: The nocturnal intermittent hypoxia group demonstrated significantly higher weight, BMI, Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack (CHADS&lt;inf&gt;2&lt;/inf&gt;) and CHA&lt;inf&gt;2&lt;/inf&gt;DS&lt;inf&gt;2&lt;/inf&gt;-VASc scores, serum hemoglobin A1c and plasma brain natriuretic peptide levels, LA size, and prevalence of hypertension, vascular disease, and sick sinus syndrome. Echocardiographically, nocturnal intermittent hypoxia was associated with a higher grade of spontaneous echo contrast and low LAA flow velocity. Multiple regression analysis adjusted for type of AF, CHA&lt;inf&gt;2&lt;/inf&gt;DS&lt;inf&gt;2&lt;/inf&gt;-VASc score, BMI, plasma brain natriuretic peptide level, LA size, and rhythm on echocardiography revealed that 3% ODI was a factor independently associated with LAA flow velocity (β=-0.184; 95% confidence interval,-0.818 to-0.006). Conclusions: Nocturnal intermittent hypoxia was an independent determinant for low LAA flow velocity in patients with AF, suggesting that the connection between SDB and LAA function might underlie the association of AF with stroke.</p>

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Effect of Nocturnal Intermittent Hypoxia on Left Atrial Appendage Flow Velocity in Atrial Fibrillation

Kimura Takehiro, Kohno Takashi, Nakajima Kazuaki, Kashimura Shin, Katsumata Yoshinori, Nishiyama Takahiko, Nishiyama Nobuhiro, Tanimoto Yoko, Aizawa Yoshiyasu, Fukuda Keiichi, Takatsuki Seiji

Canadian Journal of Cardiology  2014.10

ISSN  0828-282X

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<p>Background: The mechanism underlying the associations of sleep-disordered breathing (SDB) with stroke and atrial fibrillation (AF) is not well established. We explored the relationship between nocturnal intermittent hypoxia, a marker of SDB, and left atrial (LA)/LA appendage (LAA) function among AF patients. Methods: We evaluated 134 consecutive AF candidates for catheter ablation (age, 59.6 ± 9.4 years; body mass index [BMI], 24.8 ± 3.2; Congestive Heart Failure, Hypertension, Age (≥75 years), Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age (65-74 years), Sex (Female) (CHA&lt;inf&gt;2&lt;/inf&gt;DS&lt;inf&gt;2&lt;/inf&gt;-VASc) score, 1.2 ± 1.1, paroxysmal AF, n= 83) using nocturnal pulse oximetry, a noninvasive screening method for nocturnal intermittent hypoxia. Based on 3% oxygen desaturation index (3% ODI), patients were divided into nocturnal intermittent hypoxia (3% ODI &gt; 15; n= 32) and control groups (3% ODI ≤ 15; n= 102). Results: The nocturnal intermittent hypoxia group demonstrated significantly higher weight, BMI, Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack (CHADS&lt;inf&gt;2&lt;/inf&gt;) and CHA&lt;inf&gt;2&lt;/inf&gt;DS&lt;inf&gt;2&lt;/inf&gt;-VASc scores, serum hemoglobin A1c and plasma brain natriuretic peptide levels, LA size, and prevalence of hypertension, vascular disease, and sick sinus syndrome. Echocardiographically, nocturnal intermittent hypoxia was associated with a higher grade of spontaneous echo contrast and low LAA flow velocity. Multiple regression analysis adjusted for type of AF, CHA&lt;inf&gt;2&lt;/inf&gt;DS&lt;inf&gt;2&lt;/inf&gt;-VASc score, BMI, plasma brain natriuretic peptide level, LA size, and rhythm on echocardiography revealed that 3% ODI was a factor independently associated with LAA flow velocity (β=-0.184; 95% confidence interval,-0.818 to-0.006). Conclusions: Nocturnal intermittent hypoxia was an independent determinant for low LAA flow velocity in patients with AF, suggesting that the connection between SDB and LAA function might underlie the association of AF with stroke.</p>

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Evaluation of differences in automated QT/QTc measurements between Fukuda Denshi and Nihon Koden systems

Sano Motoaki, Aizawa Yoshiyasu, Katsumata Yoshinori, Nishiyama Nobuhiro, Takatsuki Seiji, Kamitsuji Shigeo, Kamatani Naoyuki, Fukuda Keiichi

PLoS One 9 ( 9 )  2014.09

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<p>Background: Automatic measurement becomes a preference, and indeed a necessity, when analyzing 1000 s of ECGs in the setting of either drug-inducing QT prolongation screening or genome-wide association studies of QT interval. The problem is that individual manufacturers apply different computerized algorithms to measure QT interval. We conducted a comparative study to assess the outcomes with different automated measurements of QT interval between ECG machine manufacturers and validated the related heart rate correction methods.</p><p>Methods and Results: Herein, we directly compared these different commercial systems using 10,529 Fukuda Denshi ECGs and 72,754 Nihon Kohden ECGs taken in healthy Japanese volunteers. Log-transformed data revealed an equal optimal heart rate correction formula of QT interval for Fukuda Denshi and Nihon Kohden, in the form of QTc = QT/RR-^0.347. However, with the raw data, the optimal heart rate correction formula of QT interval was in the form of QTc = QT+0.1566(1- RR) for Fukuda Denshi and QTc = QT+0.1526(1-RR) for Nihon Kohden. After optimization of heart rate correction of QT interval by the linear regression model using either log-transformed data or raw data, QTc interval was ,10 ms longer in Nihon Kohden ECGs than in those recorded on Fukuda Denshi machines. Indeed, regression analysis revealed that differences in the ECG machine used had up to a two-fold larger impact on QT variation than gender difference. Such an impact is likely to be of considerable importance when ECGs for a given individual are recorded on different machines in the setting of multi-institutional joint research.</p><p>Conclusions: We recommend that ECG machines of the same manufacturer should be used to measure QT and RR intervals in the setting of multi-institutional joint research. It is desirable to unify the computer algorithm for automatic QT and RR measurements from an ECG.</p>

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Evaluation of differences in automated QT/QTc measurements between Fukuda Denshi and Nihon Koden systems

Sano Motoaki, Aizawa Yoshiyasu, Katsumata Yoshinori, Nishiyama Nobuhiro, Takatsuki Seiji, Kamitsuji Shigeo, Kamatani Naoyuki, Fukuda Keiichi

PLoS ONE 9 ( 9 )  2014.09

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<p>Background: Automatic measurement becomes a preference, and indeed a necessity, when analyzing 1000 s of ECGs in the setting of either drug-inducing QT prolongation screening or genome-wide association studies of QT interval. The problem is that individual manufacturers apply different computerized algorithms to measure QT interval. We conducted a comparative study to assess the outcomes with different automated measurements of QT interval between ECG machine manufacturers and validated the related heart rate correction methods.</p><p>Methods and Results: Herein, we directly compared these different commercial systems using 10,529 Fukuda Denshi ECGs and 72,754 Nihon Kohden ECGs taken in healthy Japanese volunteers. Log-transformed data revealed an equal optimal heart rate correction formula of QT interval for Fukuda Denshi and Nihon Kohden, in the form of QTc = QT/RR-^0.347. However, with the raw data, the optimal heart rate correction formula of QT interval was in the form of QTc = QT+0.1566(1- RR) for Fukuda Denshi and QTc = QT+0.1526(1-RR) for Nihon Kohden. After optimization of heart rate correction of QT interval by the linear regression model using either log-transformed data or raw data, QTc interval was ,10 ms longer in Nihon Kohden ECGs than in those recorded on Fukuda Denshi machines. Indeed, regression analysis revealed that differences in the ECG machine used had up to a two-fold larger impact on QT variation than gender difference. Such an impact is likely to be of considerable importance when ECGs for a given individual are recorded on different machines in the setting of multi-institutional joint research.</p><p>Conclusions: We recommend that ECG machines of the same manufacturer should be used to measure QT and RR intervals in the setting of multi-institutional joint research. It is desirable to unify the computer algorithm for automatic QT and RR measurements from an ECG.</p>

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Thoracic impedance as a therapeutic marker of acute decompensated heart failure

Aizawa Yoshiyasu, Takatsuki Seiji, Kashimura Shin, Katsumata Yoshinori, Nishiyama Takahiko, Kimura Takehiro, Nishiyama Nobuhiro, Tanimoto Yoko, Tanimoto Kojiro, Fukuda Yukiko, Sato Toshiaki, Ogawa Satoshi, Fukuda Keiichi

International Journal of Cardiology 174 ( 3 ) 840 - 842 2014.07

ISSN  0167-5273

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Thoracic impedance as a therapeutic marker of acute decompensated heart failure

Aizawa Yoshiyasu, Takatsuki Seiji, Kashimura Shin, Katsumata Yoshinori, Nishiyama Takahiko, Kimura Takehiro, Nishiyama Nobuhiro, Tanimoto Yoko, Tanimoto Kojiro, Fukuda Yukiko, Sato Toshiaki, Ogawa Satoshi, Fukuda Keiichi

International Journal of Cardiology 174 ( 3 ) 840 - 842 2014.07

ISSN  0167-5273

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Clinical characteristics of atrial fibrillation detected by implanted devices and its association with ICD therapy

Aizawa Yoshiyasu, Takatsuki Seiji, Negishi Masachika, Kashimura Shin, Katsumata Yoshinori, Nishiyama Takahiko, Kimura Takehiro, Nishiyama Nobuhiro, Tanimoto Yoko, Tanimoto Kojiro, Kohsaka Shun, Sano Motoaki, Fukuda Keiichi

International Journal of Cardiology 172 ( 3 )  2014.04

ISSN  0167-5273

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Clinical characteristics of atrial fibrillation detected by implanted devices and its association with ICD therapy

Aizawa Yoshiyasu, Takatsuki Seiji, Negishi Masachika, Kashimura Shin, Katsumata Yoshinori, Nishiyama Takahiko, Kimura Takehiro, Nishiyama Nobuhiro, Tanimoto Yoko, Tanimoto Kojiro, Kohsaka Shun, Sano Motoaki, Fukuda Keiichi

International Journal of Cardiology 172 ( 3 )  2014.04

ISSN  0167-5273

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Lung natural killer cells play a major counter-regulatory role in pulmonary vascular hyperpermeability after myocardial infarction

Yan Xiaoxiang, Hegab Ahmed E., Endo Jin, Anzai Atsushi, Matsuhashi Tomohiro, Katsumata Yoshinori, Ito Kentaro, Yamamoto Tsunehisa, Betsuyaku Tomoko, Shinmura Ken, Shen Weifeng, Vivier Eric, Fukuda Keiichi, Sano Motoaki

Circulation Research 114 ( 4 ) 637 - 649 2014.02

ISSN  0009-7330

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<p>RATIONALE:: Natural killer (NK) cells are lymphocytes of the innate immune system that play specialized and niche-specific roles in distinct organs. OBJECTIVE:: We investigated the possible function of NK cells in the pathogenesis of congestive heart failure after myocardial infarction. METHODS AND RESULTS:: Depletion of NK cells from mice had little effect on cytokine expression (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β), neutrophil and macrophage infiltration into infarcted myocardium, or left ventricular remodeling after myocardial infarction. However, these mice exhibited severe respiratory distress associated with protein-rich, high-permeability alveolar edema accompanied by neutrophil infiltration. In addition, there were 20-fold more NK cells in the mouse lungs than in heart, and these cells were accumulated around the vasculature. CD107a-positive and interferon-γ-positive cell populations were unchanged, whereas IL-10-positive populations increased. Adoptive transfer of NK cells from wild-type mice, but not from IL-10 knockout mice, into the NK cell-depleted mice rescued the respiratory phenotype. IL-1β-mediated dextran leakage from a lung endothelial cell monolayer was also blocked by coculture with NK cells from wild-type mice but not from IL-10 knockout mice. CONCLUSIONS:: This study is the first to identify a critical role for lung NK cells in protecting lung from the development of cardiogenic pulmonary edema after myocardial infarction.</p>

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Lung natural killer cells play a major counter-regulatory role in pulmonary vascular hyperpermeability after myocardial infarction

Yan Xiaoxiang, Hegab Ahmed E., Endo Jin, Anzai Atsushi, Matsuhashi Tomohiro, Katsumata Yoshinori, Ito Kentaro, Yamamoto Tsunehisa, Betsuyaku Tomoko, Shinmura Ken, Shen Weifeng, Vivier Eric, Fukuda Keiichi, Sano Motoaki

Circulation Research 114 ( 4 ) 637 - 649 2014.02

ISSN  0009-7330

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<p>RATIONALE:: Natural killer (NK) cells are lymphocytes of the innate immune system that play specialized and niche-specific roles in distinct organs. OBJECTIVE:: We investigated the possible function of NK cells in the pathogenesis of congestive heart failure after myocardial infarction. METHODS AND RESULTS:: Depletion of NK cells from mice had little effect on cytokine expression (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β), neutrophil and macrophage infiltration into infarcted myocardium, or left ventricular remodeling after myocardial infarction. However, these mice exhibited severe respiratory distress associated with protein-rich, high-permeability alveolar edema accompanied by neutrophil infiltration. In addition, there were 20-fold more NK cells in the mouse lungs than in heart, and these cells were accumulated around the vasculature. CD107a-positive and interferon-γ-positive cell populations were unchanged, whereas IL-10-positive populations increased. Adoptive transfer of NK cells from wild-type mice, but not from IL-10 knockout mice, into the NK cell-depleted mice rescued the respiratory phenotype. IL-1β-mediated dextran leakage from a lung endothelial cell monolayer was also blocked by coculture with NK cells from wild-type mice but not from IL-10 knockout mice. CONCLUSIONS:: This study is the first to identify a critical role for lung NK cells in protecting lung from the development of cardiogenic pulmonary edema after myocardial infarction. © 2014 American Heart Association, Inc.</p>

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Endogenous prostaglandin D₂ and its metabolites protect the heart against ischemia-reperfusion injury by activating Nrf2

Katsumata Yoshinori, Shinmura Ken, Sugiura Yuki, Tohyama Shugo, Matsuhashi Tomohiro, Ito Hideyuki, Yan Xiaoxiang, Ito Kentaro, Yuasa Shinsuke, Ieda Masaki, Urade Yoshihiro, Suematsu Makoto, Fukuda Keiichi, Sano Motoaki

Hypertension 63 ( 1 ) 80 - 87 2014.01

ISSN  0194-911X

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<p>We recently demonstrated that glucocorticoids markedly upregulate the expression of cyclooxygenase-2 in cardiomyocytes and protect hearts from ischemia-reperfusion (I/R) injury by activating lipocalin-type prostaglandin D (PGD) synthase (L-PGDS)-derived PGD2 biosynthesis. We examined a downstream mechanism of cardioprotection elicited by PGD2 biosynthesis. Acute PGD2 treatment did not protect hearts against I/R injury. We then speculated that PGD2 and its metabolite 15-deoxy-Δ12,14-PGJ2 activate gene expression networks to mediate the glucocorticoid-mediated cardioprotection. Using an unbiased approach, we identified that glucocorticoids induce a number of well-known erythroid-derived 2-like 2 (Nrf2) target genes in the heart in an L-PGDS-dependent manner and that the cardioprotective effect of glucocorticoids against I/R injury was not seen in Nrf2-knockout hearts. We showed relatively low expression of PGD2 receptors (ie, DP1 and DP2) in the heart but abundant expression of PGF2α receptor (FP), which binds PGF2α and PGD2 with equal affinity. Glucocorticoids also failed to induce the expression of L-PGDS-dependent Nrf2 target genes in FP-knockout hearts. PGD2 acted through its metabolite 15-deoxy-Δ12,14-PGJ2 in the heart as evidenced by the glucocorticoid-mediated activation of peroxisome proliferator-activated receptor-γ. In turn, glucocorticoids failed to induce the expression of L-PGDS-dependent Nrf2 target genes in hearts pretreated with peroxisome proliferator-activated receptor-γ antagonist GW9662, and glucocorticoid-mediated cardioprotection against I/R injury was compromised in FP-knockout mice and GW9662-treated mice. In conclusion, PGD2 protects heart against I/R injury by activating Nrf2 predominantly via FP receptor. In addition, we propose activation of peroxisome proliferator-activated receptor-γ by the dehydrated metabolite of PGD2 (15-deoxy-Δ12,14- PGJ2) as another mechanism by which glucocorticoids induce cardioprotection. © 2013 American Heart Association, Inc.</p>

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Endogenous prostaglandin D₂ and its metabolites protect the heart against ischemia-reperfusion injury by activating Nrf2

Katsumata Yoshinori, Shinmura Ken, Sugiura Yuki, Tohyama Shugo, Matsuhashi Tomohiro, Ito Hideyuki, Yan Xiaoxiang, Ito Kentaro, Yuasa Shinsuke, Ieda Masaki, Urade Yoshihiro, Suematsu Makoto, Fukuda Keiichi, Sano Motoaki

Hypertension 63 ( 1 ) 80 - 87 2014.01

ISSN  0194-911X

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<p>We recently demonstrated that glucocorticoids markedly upregulate the expression of cyclooxygenase-2 in cardiomyocytes and protect hearts from ischemia-reperfusion (I/R) injury by activating lipocalin-type prostaglandin D (PGD) synthase (L-PGDS)-derived PGD2 biosynthesis. We examined a downstream mechanism of cardioprotection elicited by PGD2 biosynthesis. Acute PGD2 treatment did not protect hearts against I/R injury. We then speculated that PGD2 and its metabolite 15-deoxy-Δ12,14-PGJ2 activate gene expression networks to mediate the glucocorticoid-mediated cardioprotection. Using an unbiased approach, we identified that glucocorticoids induce a number of well-known erythroid-derived 2-like 2 (Nrf2) target genes in the heart in an L-PGDS-dependent manner and that the cardioprotective effect of glucocorticoids against I/R injury was not seen in Nrf2-knockout hearts. We showed relatively low expression of PGD2 receptors (ie, DP1 and DP2) in the heart but abundant expression of PGF2α receptor (FP), which binds PGF2α and PGD2 with equal affinity. Glucocorticoids also failed to induce the expression of L-PGDS-dependent Nrf2 target genes in FP-knockout hearts. PGD2 acted through its metabolite 15-deoxy-Δ12,14-PGJ2 in the heart as evidenced by the glucocorticoid-mediated activation of peroxisome proliferator-activated receptor-γ. In turn, glucocorticoids failed to induce the expression of L-PGDS-dependent Nrf2 target genes in hearts pretreated with peroxisome proliferator-activated receptor-γ antagonist GW9662, and glucocorticoid-mediated cardioprotection against I/R injury was compromised in FP-knockout mice and GW9662-treated mice. In conclusion, PGD2 protects heart against I/R injury by activating Nrf2 predominantly via FP receptor. In addition, we propose activation of peroxisome proliferator-activated receptor-γ by the dehydrated metabolite of PGD2 (15-deoxy-Δ12,14- PGJ2) as another mechanism by which glucocorticoids induce cardioprotection.</p>

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Serum Inflammation Markers Predicting Successful Initial Catheter Ablation for Atrial Fibrillation

Kimura Takehiro, Takatsuki Seiji, Inagawa Kohei, Katsumata Yoshinori, Nishiyama Takahiko, Nishiyama Nobuhiro, Fukumoto Kotaro, Aizawa Yoshiyasu, Tanimoto Yoko, Tanimoto Kojiro, Fukuda Keiichi

Heart Lung and Circulation 23 ( 7 ) 636 - 643 2014

ISSN  1443-9506

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<p>Background: We investigated various serum inflammatory markers to predict ablation responders who have no atrial fibrillation (AF) relapse after the initial ablation. Methods: Forty-four consecutive AF patients (age: 59 ± 8 years, paroxysmal: 31, CHADS₂: 1.1 ± 1.1) who underwent an initial pulmonary vein isolation were investigated. Various serum inflammatory markers, such as adiponectin, ANP, BNP, 1CTP, F1+2, hs-CRP, IL-6, intact P1NP, MDA-LDL, MMP-2, TGF-β, TIMP-2, and TNF-α, were evaluated prior to ablation. AF relapse was defined as AF documented in telemonitoring electrocardiograms twice a day during 9.7 ± 2.4 months of follow-up with three months of a blanking-period. Results: A total of 29 patients (paroxysmal: 21) maintained sinus rhythm after the initial catheter ablation. These ablation responders had significantly lower MMP-2 (Sinus vs. Relapsed: 748 ± 132.7 vs. 841.2 ± 152.4 ng/mL, P=0.042) and TNF-α (1.1 ± 0.4 vs. 1.8 ± 1.7 pg/mL, P=0.046) levels prior to ablation. A BNP-adjusted Cox multivariate regression analysis revealed that the independent predictive factor for AF recurrence was high MMP-2 levels (&gt;766 ng/mL) accompanied by high TNF-α levels (&gt;1.2 pg/mL). Conclusions: The levels of MMP-2 and TNF-α might be useful for predicting initial AF catheter ablation responders. © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).</p>

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Thrombus Formation in the Left Atrial Appendage During Catheter Ablation for Atrial Fibrillation Under Sufficient Heparinization

Kimura Takehiro, Takatsuki Seiji, Tanimoto Kojiro, Katsumata Yoshinori, Nishiyama Takahiko, Inagawa Kohei, Nishiyama Nobuhiro, Tanimoto Yoko, Aizawa Yoshiyasu, Fukuda Keiichi

Canadian Journal of Cardiology 30 ( 4 )  2014

ISSN  0828-282X

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