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Effect of Thermal Therapy on Oxidative Stress in Patients with Chronic Heart Failure
S50 Journal of Cardiac Failure Vol. 13 No. 6 Suppl. 2007 Method and Result: Total 247 patients who were admitted in our institution because of VT/VF. Mean follow-up period was 57 6 42 months. We examined the following parameters on the all-cause mortality: ejection fraction (LVEF), underlying heart diseases (ischemic or nonischemic), presence or absence of ICD. Multivariate analysis revealed that LVEF !40% is the most predictive factor for all-cause mortality. Among the patients with LVEF !40%, univariate analysis revealed that the most benefit of ICD was obtained in patients with ischemic heart disease with LVEF !40% (Fig). Conclusion: These data demonstrated that ischemic VT/VF patients with severe LV dysfunction should be implanted ICDs.
116 Physiologically Active BNP and C-reactive Protein Contributes the Regulation of Plasma Adiponectin in Patients with Chronic Heart Failure TOSHINARI TANAKA, TAKAYOSHI TSUTAMOTO, KEIZOU NISHIYAMA, HIROSHI SAKAI, MASANORI FUJII, MINORU HORIE Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan Purpose: Recent studies reported that negative correlation was observed between plasma adiponectin and CRP in patients with diabetes mellitus and atherosclerosis. However, relation between CRP and adiponectin in patients with CHF remains unknown. Method: We measured the plasma adiponectin and high sensitive CRP, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL), BNP, N terminal pro BNP (NTpBNP) and hemodynamic parameters in 156 CHF patients. Result: There were no correlation between plasma adiponectin and hemodynamic parameters, such as left ventricular ejection fraction and cardiac index. A negative correlation was observed between plasma adiponectin and body mass index (p ! 0.0001, r 5 0.497), male gender (p ! 0.0001, r 5 0.311), CRP (p 5 0.0012, r 5 0.257). A positive correlation was observed between plasma adiponectin and age (p 5 0.0142, r 5 0.196), HDL (p ! 0.0001, r 5 0.354), log BNP (p ! 0.0001, r 5 0.407), NTpBNP (p ! 0.0001, r 5 0.347). Stepwise multivariate analysis showed that male (p 5 0.0061), high HDL (p 5 0.0093), high BNP (p ! 0.0001) and low CRP (p 5 0.0015) were significant independent factors for regulation of plasma adiponectin in CHF patients. Conclusion: These findings suggest that inflammation and BNP contributes the regulation of plasma adiponectin in patients with CHF.
117 Effect of Thermal Therapy on Oxidative Stress in Patients with Chronic Heart Failure SHOJI FUJITA, TAKASHI KIHARA, MASAAKI MIYATA, TAKUROU SHINNSATO, TAKUROU KUBOZONO, SOU KUWAHATA, SYUUITI HAMASAKI, TYUUWA TEI Graduate School of Medicine, Kagoshima University, Kagoshima, Japan Background: In patients with chronic heart failure (CHF), excessive oxidative stress has been linked to peripheral hypoperfusion as a consequence of low cardiac output and peripheral endothelial dysfunction. We have applied thermal therapy using the 60 C dry sauna to patients with CHF and have found that thermal therapy improves cardiac function, endothelial function, neurohormonal factors, sympathetic nerve system, ventricular arrhythmias, and clinical symptoms in CHF patients. The purpose of this study is to clarify the effect of thermal therapy on oxidative stress in patients with CHF. Methods: Thermal therapy was performed in 20 patients with CHF for 4 weeks. Serum levels of hydroperoxide as a marker of oxidative stress were measured with FRAS systems at three points; before and just after the first thermal therapy, and after 4-week thermal therapy. Results: Serum levels of hydroperoxide significantly increased in patients with CHF compared with healthy control subjects. Serum levels of hydroperoxide did not changed just after the first thermal therapy. Serum levels of hydroperoxide and BNP significantly decreased after 4-week thermal therapy (Hydroperoxide: 437 6 27 to 384 6 26 U, p ! 0.05; BNP: 545 6 87 to 368 6 76 pg/ml, p ! 0.01). Conclusion: Thermal therapy decreased oxidative stress and improved cardiac function in patients with CHF.
118 Effects of Cardiac Resynchronization (CRT) in Patients with Right Bundle Branch Block (RBBB) and Left Ventricular (LV) Dysfunction TOSHIHIRO HONDA, SHINJI TAYAMA, JYUNJIRO KOYAMA, RYOKO OHE Division of Cardiology, Cardiovascular Center, Saiseikai Kumamoto Hospital, Kumamoto, Japan Background: The effect of CRT in patients LV dysfunction and intraventricular dyssynchrony is widely recognized. However, in patients with RBBB, the effect is poorly discussed. Patients and Methods: Four patients with RBBB and LV dysfunction are included in this study (age 66 6 9, male 4). Underlying diseases are old myocardial infarction in 3, and dilated cardiomyopathy in 1, and QP interval is longer than 0.20 in 4. We implanted CRTs in the 4 patients, and compared symptoms, cardiothoracic ratio (CTR), brain natriuretic peptide (BNP) level, and echocardiography parameters between before and after the implantation. Results: In all patients, symptoms improved, but the improvement was a little (from NYHA III to NYHA IIm in 3, and from III to III in 1). CTR changed from 60 6 3% to 55 6 2% (P 5 0.067), and BNP level decreased from 892 6 496 pg/ml to 674 6 307 pg/ml (P 5 0.144). Tissue velocity images showed that the motion of the lateral wall was delayed from that of the septum in 3 patients in spite of CRBBB. End-diastolic dimension of LV changed from 67 6 5 mm to 67 6 6 mm (P 5 0.785). Ejection fraction improved from 21 6 4 % to 27 6 8 % (P 5 0.067). In 1 patient, severe mitral regurgitation disappeared by CRT. Conclusion: The possibility that CRT is useful in patients with RBBB and LV dysfunction was suggested.
119 Oxidative Stress Induces GLUT4 Translocation by Dual AMPK Kinase Activation in Cardiac Myocytes TAKAHIRO HORIE1, KOH ONO1, KAZUYA NAGAO1, HITOO NISHI1, MINAKO KINOSHITA1, TORU KITA1, KOJI HASEGAWA2 1 Department of Cardiovascular Medicine, Kyoto University, Kyoto, Japan, 2Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan Cardiac-selective GLUT4 deficiency develop profound and irreversible dysfunction after ischemia. Therefore, translocation of GLUT4 represents an important phenomenon for protecting against ischemic injury. To investigate the precise mechanisms of GLUT4 translocation in cardiomyocytes, we established a method for quantifying the relative proportion of sarcolemmal GLUT4 to total GLUT4 by monitoring c-MycGLUT4-GFP reporter gene. Stimulation with H2O2 resulted in a concentrationdependent increase in GLUT4 translocation, which peaked at 15 min. The dominant-negative (DN) form of PI3K or the PI3K inhibitor inhibited H2O2-induced GLUT4 translocation as well as the phosphorylation of Akt. The DN form of AMP-activated protein kinase (AMPK)a2 also inhibited H2O2-induced GLUT4 translocation as well as the phosphorylation of Akt. We further examined the effect of two AMPK kinases (AMPKKs), calmodulin-dependent protein kinase kinase (CaMKK)b and LKB1, on the translocation of GLUT4. The DN form of CaMKKb or LKB1 partialy inhibited translocation. These two AMPKKs had an additive effect. Thus, these results demonstrate that oxidative stress causes the translocation of myocardial GLUT4 to the sarcolemma through the dual activation of CaMKKb and LKB1, which leads to activation of the AMPK-PI3K/Akt pathway.
120 Renin may Have an Important Role in Cardio-Renal Interaction in Patients with Heart Failure TOSHINARI TANAKA, TAKAYOSHI TSUTAMOTO, KEIZOU NISHIYAMA, HIROSHI SAKAI, MASANORI FUJII, MINORU HORIE Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan Purpose: Renin receptors have been recently identified in the human heart and cardiac renin mainly derived from the kidney may contribute to the development of ventricular dysfunction, suggesting the cardio-renal interaction. Method: To evaluate whether plasma active renin concentration (ARC) is a useful prognostic predictor, we measured the ARC, angiotensin II, aldosterone, BNP, and hemodynamic parameters in 214 patients with left ventricular dysfunction [left ventricular ejection fraction (LVEF) !45%] who underwent cardiac catheterization.
116 Physiologically Active BNP and C-reactive Protein Contributes the Regulation of Plasma Adiponectin in Patients with Chronic Heart Failure TOSHINARI TANAKA, TAKAYOSHI TSUTAMOTO, KEIZOU NISHIYAMA, HIROSHI SAKAI, MASANORI FUJII, MINORU HORIE Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan Purpose: Recent studies reported that negative correlation was observed between plasma adiponectin and CRP in patients with diabetes mellitus and atherosclerosis. However, relation between CRP and adiponectin in patients with CHF remains unknown. Method: We measured the plasma adiponectin and high sensitive CRP, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL), BNP, N terminal pro BNP (NTpBNP) and hemodynamic parameters in 156 CHF patients. Result: There were no correlation between plasma adiponectin and hemodynamic parameters, such as left ventricular ejection fraction and cardiac index. A negative correlation was observed between plasma adiponectin and body mass index (p ! 0.0001, r 5 0.497), male gender (p ! 0.0001, r 5 0.311), CRP (p 5 0.0012, r 5 0.257). A positive correlation was observed between plasma adiponectin and age (p 5 0.0142, r 5 0.196), HDL (p ! 0.0001, r 5 0.354), log BNP (p ! 0.0001, r 5 0.407), NTpBNP (p ! 0.0001, r 5 0.347). Stepwise multivariate analysis showed that male (p 5 0.0061), high HDL (p 5 0.0093), high BNP (p ! 0.0001) and low CRP (p 5 0.0015) were significant independent factors for regulation of plasma adiponectin in CHF patients. Conclusion: These findings suggest that inflammation and BNP contributes the regulation of plasma adiponectin in patients with CHF.
117 Effect of Thermal Therapy on Oxidative Stress in Patients with Chronic Heart Failure SHOJI FUJITA, TAKASHI KIHARA, MASAAKI MIYATA, TAKUROU SHINNSATO, TAKUROU KUBOZONO, SOU KUWAHATA, SYUUITI HAMASAKI, TYUUWA TEI Graduate School of Medicine, Kagoshima University, Kagoshima, Japan Background: In patients with chronic heart failure (CHF), excessive oxidative stress has been linked to peripheral hypoperfusion as a consequence of low cardiac output and peripheral endothelial dysfunction. We have applied thermal therapy using the 60 C dry sauna to patients with CHF and have found that thermal therapy improves cardiac function, endothelial function, neurohormonal factors, sympathetic nerve system, ventricular arrhythmias, and clinical symptoms in CHF patients. The purpose of this study is to clarify the effect of thermal therapy on oxidative stress in patients with CHF. Methods: Thermal therapy was performed in 20 patients with CHF for 4 weeks. Serum levels of hydroperoxide as a marker of oxidative stress were measured with FRAS systems at three points; before and just after the first thermal therapy, and after 4-week thermal therapy. Results: Serum levels of hydroperoxide significantly increased in patients with CHF compared with healthy control subjects. Serum levels of hydroperoxide did not changed just after the first thermal therapy. Serum levels of hydroperoxide and BNP significantly decreased after 4-week thermal therapy (Hydroperoxide: 437 6 27 to 384 6 26 U, p ! 0.05; BNP: 545 6 87 to 368 6 76 pg/ml, p ! 0.01). Conclusion: Thermal therapy decreased oxidative stress and improved cardiac function in patients with CHF.
118 Effects of Cardiac Resynchronization (CRT) in Patients with Right Bundle Branch Block (RBBB) and Left Ventricular (LV) Dysfunction TOSHIHIRO HONDA, SHINJI TAYAMA, JYUNJIRO KOYAMA, RYOKO OHE Division of Cardiology, Cardiovascular Center, Saiseikai Kumamoto Hospital, Kumamoto, Japan Background: The effect of CRT in patients LV dysfunction and intraventricular dyssynchrony is widely recognized. However, in patients with RBBB, the effect is poorly discussed. Patients and Methods: Four patients with RBBB and LV dysfunction are included in this study (age 66 6 9, male 4). Underlying diseases are old myocardial infarction in 3, and dilated cardiomyopathy in 1, and QP interval is longer than 0.20 in 4. We implanted CRTs in the 4 patients, and compared symptoms, cardiothoracic ratio (CTR), brain natriuretic peptide (BNP) level, and echocardiography parameters between before and after the implantation. Results: In all patients, symptoms improved, but the improvement was a little (from NYHA III to NYHA IIm in 3, and from III to III in 1). CTR changed from 60 6 3% to 55 6 2% (P 5 0.067), and BNP level decreased from 892 6 496 pg/ml to 674 6 307 pg/ml (P 5 0.144). Tissue velocity images showed that the motion of the lateral wall was delayed from that of the septum in 3 patients in spite of CRBBB. End-diastolic dimension of LV changed from 67 6 5 mm to 67 6 6 mm (P 5 0.785). Ejection fraction improved from 21 6 4 % to 27 6 8 % (P 5 0.067). In 1 patient, severe mitral regurgitation disappeared by CRT. Conclusion: The possibility that CRT is useful in patients with RBBB and LV dysfunction was suggested.
119 Oxidative Stress Induces GLUT4 Translocation by Dual AMPK Kinase Activation in Cardiac Myocytes TAKAHIRO HORIE1, KOH ONO1, KAZUYA NAGAO1, HITOO NISHI1, MINAKO KINOSHITA1, TORU KITA1, KOJI HASEGAWA2 1 Department of Cardiovascular Medicine, Kyoto University, Kyoto, Japan, 2Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan Cardiac-selective GLUT4 deficiency develop profound and irreversible dysfunction after ischemia. Therefore, translocation of GLUT4 represents an important phenomenon for protecting against ischemic injury. To investigate the precise mechanisms of GLUT4 translocation in cardiomyocytes, we established a method for quantifying the relative proportion of sarcolemmal GLUT4 to total GLUT4 by monitoring c-MycGLUT4-GFP reporter gene. Stimulation with H2O2 resulted in a concentrationdependent increase in GLUT4 translocation, which peaked at 15 min. The dominant-negative (DN) form of PI3K or the PI3K inhibitor inhibited H2O2-induced GLUT4 translocation as well as the phosphorylation of Akt. The DN form of AMP-activated protein kinase (AMPK)a2 also inhibited H2O2-induced GLUT4 translocation as well as the phosphorylation of Akt. We further examined the effect of two AMPK kinases (AMPKKs), calmodulin-dependent protein kinase kinase (CaMKK)b and LKB1, on the translocation of GLUT4. The DN form of CaMKKb or LKB1 partialy inhibited translocation. These two AMPKKs had an additive effect. Thus, these results demonstrate that oxidative stress causes the translocation of myocardial GLUT4 to the sarcolemma through the dual activation of CaMKKb and LKB1, which leads to activation of the AMPK-PI3K/Akt pathway.
120 Renin may Have an Important Role in Cardio-Renal Interaction in Patients with Heart Failure TOSHINARI TANAKA, TAKAYOSHI TSUTAMOTO, KEIZOU NISHIYAMA, HIROSHI SAKAI, MASANORI FUJII, MINORU HORIE Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan Purpose: Renin receptors have been recently identified in the human heart and cardiac renin mainly derived from the kidney may contribute to the development of ventricular dysfunction, suggesting the cardio-renal interaction. Method: To evaluate whether plasma active renin concentration (ARC) is a useful prognostic predictor, we measured the ARC, angiotensin II, aldosterone, BNP, and hemodynamic parameters in 214 patients with left ventricular dysfunction [left ventricular ejection fraction (LVEF) !45%] who underwent cardiac catheterization.