Details of a Researcher - Katsumata, Yoshinori

Papers - Katsumata, Yoshinori

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Visualization of in vivo metabolic flows reveals accelerated utilization of glucose and lactate in penumbra of ischemic heart

Sugiura Yuki, Katsumata Yoshinori, Sano Motoaki, Honda Kurara, Kajimura Mayumi, Fukuda Keiichi, Suematsu Makoto

Scientific Reports 6 2016.09

ISSN 2045-2322

Acute ischemia produces dynamic changes in labile metabolites. To capture snapshots of such acute metabolic changes, we utilized focused microwave treatment to fix metabolic flow in vivo in hearts of mice 10 min after ligation of the left anterior descending artery. The left ventricle was subdivided into short-Axis serial slices and the metabolites were analyzed by capillary electrophoresis mass spectrometry and matrix-Assisted laser desorption/ionization imaging mass spectrometry. These techniques allowed us to determine the fate of exogenously administered 13 C 6-glucose and 13 C 3-lactate. The penumbra regions, which are adjacent to the ischemic core, exhibited the greatest adenine nucleotide energy charge and an adenosine overflow extending from the ischemic core, which can cause ischemic hyperemia. Imaging analysis of metabolic pathway flows revealed that the penumbra executes accelerated glucose oxidation, with remaining lactate utilization for tricarboxylic acid cycle for energy compensation, suggesting unexpected metabolic interplays of the penumbra with the ischemic core and normoxic regions.

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A Novel SCN5A Mutation Found in a Familial Case of Long QT Syndrome Complicated by Severe Left Ventricular Dysfunction

Kimura Mai, Kohno Takashi, Aizawa Yoshiyasu, Inohara Taku, Shiraishi Yasuyuki, Katsumata Yoshinori, Egashira Toru, Fukushima Hiroyuki, Kosaki Kenjiro, Fukuda Keiichi

Canadian Journal of Cardiology 2016.08

ISSN 0828-282X

A 16-year-old boy with long QT syndrome type 3 (LQT3) was admitted for decompensated heart failure resulting from dilated cardiomyopathy (DCM). His brother was also diagnosed with LQT3 and DCM. A comprehensive genetic analysis identified a novel . SCN5A missense mutation-p.Q371E-in these 2 affected living family members. It might be important to suspect the coexistence of DCM and LQT3 (which is rare according to previous articles) in cases with this novel . SCN5A missense mutation.

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Assessment of atrial fibrillation ablation outcomes with clinic ECG, monthly 24-h Holter ECG, and twice-daily telemonitoring ECG

Kimura Takehiro, Aizawa Yoshiyasu, Kurata Naomi, Nakajima Kazuaki, Kashimura Shin, Kunitomi Akira, Nishiyama Takahiko, Katsumata Yoshinori, Nishiyama Nobuhiro, Fukumoto Kotaro, Tanimoto Yoko, Fukuda Keiichi, Takatsuki Seiji

Heart and Vessels 1 - 9 2016.07

ISSN 0910-8327

Differences in the methodologies for evaluating atrial fibrillation (AF) ablation outcomes should be evaluated. In the present study, we compared the AF ablation outcomes among periodic clinic electrocardiography (ECG), 24-h Holter ECG, and telemonitoring ECG to evaluate the differences among these methods. In addition, we evaluated the AF-free survival rate for each method with different durations of the blanking period. A total of 30 AF patients were followed up for 6 months after initial catheter ablation, with clinic ECG on every clinic visit, monthly 24-h Holter ECG, and telemonitoring ECG twice daily and upon symptoms. AF relapse was defined as AF or atrial tachycardia detected with any of the methods. Two patients dropped out of the study, and 28 patients were followed up for 8.8 ± 2.7 months. Patients underwent 3.6 ± 0.8 clinic ECG, 5.1 ± 0.8 Holter ECG, and 273 ± 68 telemonitoring ECG examinations. During the first, second, third, fourth, fifth, and sixth months of follow-up, Holter ECG detected relapses in 11.1, 8.3, 11.5, 15.4, 4.2, and 4.8 % of patients and telemonitoring ECG detected relapses in 32.1, 25.0, 25.0, 17.9, 28.6, and 17.9 % of patients, respectively. When no duration was set for the blanking period, the AF-free survival rate was significantly lower with telemonitoring ECG (46.4 %) than with Holter ECG (78.6 %, P = 0.013) or clinic ECG (85.7 %, P = 0.002). In addition, when the duration of the blanking period was set to 3 months, the AF-free survival rate was significantly lower with telemonitoring ECG than with clinic ECG (92.9 vs. 71.4 %, P = 0.041). The AF ablation outcomes with twice-daily telemonitoring ECG might differ from those with clinic ECG when the duration of the blanking period is 0–3 months. A follow-up based solely on clinic ECG might underestimate AF recurrence.

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Comparison of circadian, weekly, and seasonal variations of electrical storms and single events of ventricular fibrillation in patients with Brugada syndrome

Aizawa Yoshiyasu, Takatsuki Seiji, Kaneko Yoshiaki, Noda Takashi, Katsumata Yoshinori, Nishiyama Takahiko, Kimura Takehiro, Nishiyama Nobuhiro, Fukumoto Kotaro, Niwano Shinichi, Kurita Takashi, Mitsuhashi Takeshi, Kamakura Shiro, Shimizu Akihiko, Horie Minoru, Aizawa Yoshifusa, Fukuda Keiichi

IJC Heart and Vasculature 11 104 - 110 2016.06

ISSN 2352-9067

In patients with Brugada syndrome (BS), VF occurred predominantly during the nocturnal period. Some patients also developed ESs. In addition to the circadian rhythm, patients showed weekly and seasonal patterns. The patients with ESs had peak episodes of VF on Saturday and in the winter and spring, while episodes of VF in patients with single VF events occurred most often on Monday with smaller seasonal variation. Except for age, there was no difference in the clinical or ECG characteristics between the patients with ESs and those with single VF episodes.

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Cardiac sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion

Yamamoto Tsunehisa, Tamaki Kayoko, Shirakawa Kohsuke, Ito Kentaro, Yan Xiaoxiang, Katsumata Yoshinori, Anzai Atsushi, Matsuhashi Tomohiro, Endo Jin, Inaba Takaaki, Tsubota Kazuo, Sano Motoaki, Fukuda Keiichi, Shinmura Ken

American Journal of Physiology - Heart and Circulatory Physiology 310 ( 8 ) H1003 - H1014 2016.04

ISSN 0363-6135

Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia- reperfusion injury. Am J Physiol Heart Circ Physiol 308: H894– H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (CM-Sirt1^-/-) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (-40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM-Sirt1^-/- mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM-Sirt1^-/- mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventional C3 knockout (C3^-/-) mice treated with CR was similar to that in the ad libitum-fed C3^-/- mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting that cardiac Sirt1 regulates the local complement system during CR.

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Electrical superior vena cava isolation using photodynamic therapy in a canine model

Kimura Takehiro, Takatsuki Seiji, Miyoshi Shunichiro, Takahashi Mei, Ogawa Emiyu, Nakajima Kazuaki, Kashimura Shin, Katsumata Yoshinori, Nishiyama Takahiko, Nishiyama Nobuhiro, Tanimoto Yoko, Aizawa Yoshiyasu, Arai Tsunenori, Fukuda Keiichi

Europace 18 ( 2 ) 294 - 300 2016.02

ISSN 1099-5129

Aims With the new era of multi-tip radiofrequency or balloon ablation catheters replacing the point-to-point ablation strategy, we aimed to determine the feasibility of a ring-laser catheter ablation technology to electrically isolate the superior vena cava (SVC) by exploring the advantages of the limitless catheter tip size possibly with the photodynamic therapy (PDT)-mediated ablation. Methods and results We developed a first-generation prototype of a circular-laser-mapping catheter by fitting a 7 cm plastic optical fibre onto a circular variable-loop Lasso™ mapping catheter. Following SVC venography, both the laser catheter and another ring catheter for monitoring the SVC potentials were placed at the SVC. After the systemic infusion of a photosensitizer (talaporfin sodium), we initiated the irradiation with an output of 1 W in three canines and 0.3 W in four. The creation of electrical isolation as well as occurrence of phrenic nerve injury, sinus node injury, and SVC stenosis were evaluated before, immediately after, and 1 month after the procedure. A PDT-mediated SVC isolation was successfully performed in all seven canines. The isolation was completed with a laser irradiation of 70.4 ± 71.4 J/cm under 30.9 ± 5.0 μg/mL of a photosensitizer without any sinus node injury, phrenic nerve palsy, or SVC stenosis in both the acute and chronic evaluations. The minimum isolation time of 270 s was not correlated with the laser input power or the photosensitizer concentration. Conclusion The electrical SVC isolation was successfully and instantly achieved using the PDT laser-ring catheter without any complications.

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Diagnostic accuracy of commercially available automated external defibrillators

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

Journal of the American Heart Association 4 ( 12 ) 2015.12

ISSN 2047-9980

Background-Although automated external defibrillators (AEDs) have contributed to a better survival of out-of-hospital cardiac arrests, there have been reports of their malfunctioning. We investigated the diagnostic accuracy of commercially available AEDs using surface ECGs of ventricular fibrillation (VF), ventricular tachycardia (VT), and supraventricular tachycardia (SVT). Methods and Results-ECGs(VF 31, VT 48, SVT 97) were stored during electrophysiological studies and transmitted to 4 AEDs, the LifePak CR Plus (CR Plus), HeartStart FR3 (FR3), and CardioLife AED-2150 (CL2150) and -9231 (CL9231), through the pad electrode cables. For VF, the CL2150 and CL9231 advised shocks in all cases, and the CR Plus and FR3 advised shocks in all but one VF case. For VTs faster than 180 bpm, the ratios for advising shocks were 79%, 36%, 89%, and 96% for the CR Plus, FR3, CL2150, and CL9231, respectively. The FR3 and CR Plus did not advise shocks for narrow QRS SVTs, whereas the CL9231 tended to treat high-rate tachycardias faster than 180 bpm even with narrow QRS complexes. The characteristics of the shock advice for the FR3 differed from that for the CL9231 (kappa coefficient [κ]=0.479, P < 0.001), and the CR Plus and CL2150 had characteristics somewhere between the 2 former AEDs (κ=0.818, P < 0.001). Conclusions-Commercially available AEDs diagnosed VF almost always correctly. For VT and SVT diagnoses, a discrepancy was evident among the 4 investigated AEDs. The differences in the arrhythmia diagnosis algorithms for differentiating SVT from VT were thought to account for these differences.

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Predictive factors of lead failure in patients implanted with cardiac devices

Aizawa Yoshiyasu, Negishi Masachika, Kashimura Shin, Nakajima Kazuaki, Kunitomi Akira, Katsumata Yoshinori, Nishiyama Takahiko, Kimura Takehiro, Nishiyama Nobuhiro, Fukumoto Kotaro, Tanimoto Yoko, Kohsaka Shun, Takatsuki Seiji, Fukuda Keiichi

International Journal of Cardiology 199 277 - 281 2015.09

ISSN 0167-5273

Introduction Lead failures (LFs) are one of the most common complications in patients implanted with cardiovascular implantable electronic devices. LFs often cause serious secondary complications such as inappropriate ICD shocks or asystole. This study aimed to identify the clinical factors associated with the occurrence of LFs. Methods A total of 735 consecutive device implantations (mean age 67 ± 15 years, males 64%) performed at a single university hospital setting from 1997 to 2014 were included. The implanted devices consisted of 421 pacemakers, 250 implantable cardioverter defibrillators (ICD), 9 cardiac resynchronization therapy pacemakers (CRT-P), and 55 CRT defibrillators (CRT-D). The primary endpoint was the development of an LF. Results During a mean duration of 5.8 ± 4.3 years, 38 LFs developed in 31 patients (mean age 56 ± 14 years). LFs included 32 ICD (7 Sprint Fidelis, 2 Riata), and 6 pacing leads. Nine patients received inappropriate ICD shocks and 1 had syncope due to an LF. All patients underwent lead reinsertions with device replacements. Eight patients required opposite site implantations due to venous occlusions. The predictive factors of LFs were the age, male sex, taller body length, ICD vs. pacemaker, lesser lead number, extra-thoracic puncture of the axillary vein vs. a cut-down of the cephalic vein, use of recalled leads and patients with idiopathic ventricular fibrillation (IVF) and Brugada syndrome (BrS). Conclusion LFs occurred mainly with ICD leads. A lesser age, the puncture method, lead model, and diagnosis of IVF/BrS were associated with the development of LFs.

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Predictive factors of lead failure in patients implanted with cardiac devices

International Journal of Cardiology 199 277 - 281 2015.09

ISSN 0167-5273

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Optimal conditions for cardiac catheter ablation using photodynamic therapy

Kimura Takehiro, Takatsuki Seiji, Miyoshi Shunichiro, Takahashi Mei, Ogawa Emiyu, Katsumata Yoshinori, Nishiyama Takahiko, Nishiyama Nobuhiro, Tanimoto Yoko, Aizawa Yoshiyasu, Arai Tsunenori, Fukuda Keiichi

Europace 17 ( 8 ) 1309 - 1315 2015.06

ISSN 1099-5129

Aims Photodynamic therapy (PDT) is based on non-thermal injury mediated by singlet oxygen species and is used clinically in cancer therapy. In our continuing efforts to apply this technology to cardiac catheter ablation, we clarified the optimal condition for creating PDT-mediated lesions using a laser catheter. Methods and results In a total of 35 canines, we applied a laser directly to the epicardium of the beating heart during open-chest surgery at 15 min after administration of a photosensitizer, talaporfin sodium. We evaluated the lesion size (depth and width) using hematoxylin-eosin staining under varying conditions as follows: laser output (5, 10, 20 W/cm2), irradiation time (0-60 s), photosensitizer concentration (0, 2.5, 5 mg/kg), blood oxygen concentration (103.5 ± 2.1 vs. 548.0 ± 18.4 torr), and contact force applied during irradiations (low: <20 g, high: >20 g). A laser irradiation at 20 W/cm2 for 60 s under 5 mg/kg (29 μg/mL) of photosensitizer induced a lesion 8.7 ± 0.8 mm deep and 5.2 ± 0.2 mm wide. The lesion size was thus positively correlated to the laser power, irradiation time, and photosensitizer concentration, and was independent of the applied contact force and oxygen concentration. In addition, the concentration of the photosensitizer strongly correlated with the changes in the pulse oximetry data and fluorescence of the backscattering laser, suggesting that a clinically appropriate condition could be estimated in real time. Conclusion Photodynamic therapy-mediated cardiac lesions might be controllable by regulating the photosensitizer concentration, laser output, and irradiation time.

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Optimal conditions for cardiac catheter ablation using photodynamic therapy

Europace 17 ( 8 ) 1309 - 1315 2015.06

ISSN 1099-5129

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A cost-utility analysis for catheter ablation of atrial fibrillation in combination with warfarin and dabigatran based on the CHADS₂ score in Japan

Kimura Takehiro, Igarashi Ataru, Ikeda Shunya, Nakajima Kazuaki, Kashimura Shin, Kunitomi Akira, Katsumata Yoshinori, Nishiyama Takahiko, Nishiyama Nobuhiro, Fukumoto Kotaro, Tanimoto Yoko, Aizawa Yoshiyasu, Fukuda Keiichi, Takatsuki Seiji

Journal of Cardiology 2015.06

ISSN 0914-5087

Background: We aimed to clarify the cost-effectiveness of an expensive combination therapy for atrial fibrillation (AF) using both catheter ablation and dabigatran compared with warfarin at each CHADS₂ score for patients in Japan. Methods: A Markov model was constructed to analyze costs and quality-adjusted life years associated with AF therapeutic options with a time horizon of 10 years. The target population was 60-year-old patients with paroxysmal AF. The indication for anticoagulation was determined according to the Japanese guideline. Anticoagulation-related data were derived from the RE-LY study and the AF recurrence rate was set at 2.7% per month during the first 12 months and at 0.40% per month afterwards. Stroke risk was determined according to AF recurrence, anticoagulation, and CHADS₂ score. The risks for stroke recurrence and stroke death were also considered. Costs were calculated from the healthcare payer's perspective, and only direct medical costs were included. Results: Warfarin was the most preferred option for patients with a CHADS₂ score of 0 from a health economics aspect. Ablation under warfarin was preferred for a CHADS₂ score of 1-3, while ablation under dabigatran was preferred for a CHADS₂ score ≥4. The quality of life score for AF had the largest impact on the incremental cost-effectiveness ratios in the analysis between the anticoagulation arm and the anticoagulation+ablation arm for a CHADS₂ score of 2. Within the range of the Japanese willingness-to-pay threshold (¥5,000,000), the ablation+warfarin arm became the best option with its probability of 81.7% for a CHADS₂ score of 2; the dabigatran+ablation arm was the most preferred option with its probability of 56.1% for a CHADS₂ score of 4. Conclusions: Ablation under dabigatran therapy is an expensive therapeutic option, but it might benefit patients with a low quality of life and a high CHADS₂ score.

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Activation of pyruvate dehydrogenase by dichloroacetate has the potential to induce epigenetic remodeling in the heart

Matsuhashi Tomohiro, Hishiki Takako, Zhou Heping, Ono Tomohiko, Kaneda Ruri, Iso Tatsuya, Yamaguchi Aiko, Endo Jin, Katsumata Yoshinori, Atsushi Anzai, Yamamoto Tsunehisa, Shirakawa Kohsuke, Yan Xiaoxiang, Shinmura Ken, Suematsu Makoto, Fukuda Keiichi, Sano Motoaki

Journal of Molecular and Cellular Cardiology 82 116 - 124 2015.05

ISSN 0022-2828

Dichloroacetate (DCA) promotes pyruvate entry into the Krebs cycle by inhibiting pyruvate dehydrogenase (PDH) kinase and thereby maintaining PDH in the active dephosphorylated state. DCA has recently gained attention as a potential metabolic-targeting therapy for heart failure but the molecular basis of the therapeutic effect of DCA in the heart remains a mystery. Once-daily oral administration of DCA alleviates pressure overload-induced left ventricular remodeling. We examined changes in the metabolic fate of pyruvate carbon (derived from glucose) entering the Krebs cycle by metabolic interventions of DCA. 13C<inf>6</inf>-glucose pathway tracing analysis revealed that instead of being completely oxidized in the mitochondria for ATP production, DCA-mediated PDH dephosphorylation results in an increased acetyl-CoA pool both in control and pressure-overloaded hearts. DCA induces hyperacetylation of histone H3K9 and H4 in a dose-dependent manner in parallel to the dephosphorylation of PDH in cultured cardiomyocytes. DCA administration increases histone H3K9 acetylation in in vivo mouse heart. Interestingly, DCA-dependent histone acetylation was associated with an up-regulation of 2.3% of genes (545 out of 23,474 examined). Gene ontology analysis revealed that these genes are highly enriched in transcription-related categories. This evidence suggests that sustained activation of PDH by DCA results in an overproduction of acetyl-CoA, which exceeds oxidation in the Krebs cycle and results in histone acetylation. We propose that DCA-mediated PDH activation has the potential to induce epigenetic remodeling in the heart, which, at least in part, forms the molecular basis for the therapeutic effect of DCA in the heart.

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Activation of pyruvate dehydrogenase by dichloroacetate has the potential to induce epigenetic remodeling in the heart

Journal of Molecular and Cellular Cardiology 82 116 - 124 2015.05

ISSN 0022-2828

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Visualization of the left atrial appendage by phased-array intracardiac echocardiography from the pulmonary artery in patients with atrial fibrillation

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

Europace 17 ( 4 ) 546 - 551 2015.04

ISSN 1099-5129

Aims The left atrial appendage (LAA) represents the major source of cardiac thrombus formation in patients with atrial fibrillation (AF). Phased-array intracardiac echocardiography (ICE) has become available and frequently used during catheter ablation of AF. We attempted to study the feasibility of using ICE for the visualization and evaluation of the LAA from the pulmonary artery (PA) in patients with AF. Methods and Results Eighty patients with AF undergoing catheter ablation (70 males, 57.5 ± 9.1 years) were included. Transoesophageal echocardiography was performed on the prior day before the catheter ablation, and ICE was performed just before the transseptal puncture during the catheter ablation. The ICE catheter was advanced up into the PA from the femoral vein, where the LAA was clearly and entirely visualized by manipulating the ICE catheter. We compared the degree of spontaneous echo contrast, and the correlation was obtained between the ICE and TEE (κ = 0.534, P < 0.001). Furthermore, the LAA flow velocity (LAA emptying and filling velocities) measured by ICE had a good correlation to that measured by TEE (R = 0.872, P < 0.01 and R = 0.753, P < 0.01, respectively). No patients developed any complications. Conclusion The utilization of ICE in the PA is feasible for the observation and evaluation of the LAA.

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Visualization of the left atrial appendage by phased-array intracardiac echocardiography from the pulmonary artery in patients with atrial fibrillation

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

Europace 17 ( 4 ) 546 - 551 2015.04

ISSN 1099-5129

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Adventitial CXCL1/G-CSF expression in response to acute aortic dissection triggers local neutrophil recruitment and activation leading to aortic rupture

Anzai Atsushi, Shimoda Masayuki, Endo Jin, Kohno Takashi, Katsumata Yoshinori, Matsuhashi Tomohiro, Yamamoto Tsunehisa, Ito Kentaro, Yan Xiaoxiang, Shirakawa Kosuke, Shimizu-Hirota Ryoko, Yamada Yoshitake, Ueha Satoshi, Shinmura Ken, Okada Yasunori, Fukuda Keiichi, Sano Motoaki

Circulation Research 116 ( 4 ) 612 - 623 2015.02

ISSN 0009-7330

Rationale: In-hospital outcomes are generally acceptable in patients with type B dissection; however, some patients present with undesirable complications, such as aortic expansion and rupture. Excessive inflammation is an independent predictor of adverse clinical outcomes. Objective: We have investigated the underlying mechanisms of catastrophic complications after acute aortic dissection (AAD) in mice. Methods and Results: When angiotensin II was administered in lysyl oxidase inhibitor-preconditioned mice, AAD emerged within 24 hours. The dissection was initiated at the proximal site of the descending thoracic aorta and propagated distally into an abdominal site. Dissection of the aorta caused dilatation, and ≈70% of the mice died of aortic rupture. AAD triggered CXCL1 and granulocyte-colony stimulating factor expression in the tunica adventitia of the dissected aorta, leading to elevation of circulating CXCL1/granulocyte-colony stimulating factor levels. Bone marrow CXCL12 was reduced. These chemokine changes facilitated neutrophil egress from bone marrow and infiltration into the aortic adventitia. Interference of CXCL1 function using an anti-CXCR2 antibody reduced neutrophil accumulation and limited aortic rupture post AAD. The tunica adventitia of the expanded dissected aorta demonstrated high levels of interleukin-6 (IL-6) expression. Neutrophils were the major sources of IL-6, and CXCR2 neutralization significantly reduced local and systemic levels of IL-6. Furthermore, disruption of IL-6 effectively suppressed dilatation and rupture of the dissected aorta without any influence on the incidence of AAD and neutrophil mobilization. Conclusions: Adventitial CXCL1/granulocyte-colony stimulating factor expression in response to AAD triggers local neutrophil recruitment and activation. This leads to adventitial inflammation via IL-6 and results in aortic expansion and rupture.

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Adventitial CXCL1/G-CSF expression in response to acute aortic dissection triggers local neutrophil recruitment and activation leading to aortic rupture

Circulation Research 116 ( 4 ) 612 - 623 2015.02

ISSN 0009-7330

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Risk factors for early replacement of cardiovascular implantable electronic devices

Aizawa Yoshiyasu, Kunitomi Akira, Nakajima Kazuaki, Kashimura Shin, Katsumata Yoshinori, Nishiyama Takahiko, Kimura Takehiro, Nishiyama Nobuhiro, Tanimoto Yoko, Kohsaka Shun, Takatsuki Seiji, Fukuda Keiichi

International Journal of Cardiology 178 99 - 101 2015.01

ISSN 0167-5273

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Risk factors for early replacement of cardiovascular implantable electronic devices

International Journal of Cardiology 178 99 - 101 2015.01

ISSN 0167-5273

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