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Mechanism of Iron Deficiency via Inappropriate Hepcidin Expression in Pulmonary Artery Hypertension with Liver Congestion
The 17th Annual Scientific Meeting Exercise-induced MR can be a cause of FPE in patients with deteriorating left ventricular function and can be a useful indicator of the adequacy of HF treatment.
JHFS
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became evident. This arrhythmogenesis was inhibited by combination treatment with sildenafil and beraprost (SIL+BERA). RT-PCR showed mRNA upregulation of type I collagen and downregulation of connexin43 in RV at 5 weeks after MCT injection. Immunohistochemistry also revealed connexin43 degradation in the RV with PH. In contrast, connexin43 was well preserved, and no lethal arrhythmias were induced by burst pacing to RV in the absence of PH after SIL+BERA. Conclusions: RV electrical remodeling including impaired APDd causes arrhythmogenesis in PH, potentially associated with SCD due to PH.
O-039 Mechanism of Iron Deficiency via Inappropriate Hepcidin Expression in Pulmonary Artery Hypertension with Liver Congestion YUKAKO OHNO, HARUO HANAWA, SHUANG JIAO, YUKA HAYASHI, TOMOYASU SUZUKI, HIROAKI OBATA, TAKESHI KASHIMURA, TOHRU MINAMINO Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Science
O-037 Potential Role of Iron Metabolism and Inflammation in Right Ventricular Remodeling of Pulmonary Hypertension SHUANG JIAO, HARUO HANAWA, YUKAKO OHNO, YUKA HAYASHI, TOMOYASU SUZUKI, TAKESHI KASHIMURA, HIROAKI OBATA, TOHRU MINAMINO Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences Background: Right heart failure from pulmonary arterial hypertension PAH is a major cause of morbidity and mortality, but its mechanism is incompletely understood. We recently found that gene expression of iron related proteins increased in myocarditis and myocardial infarction and free heme as a danger signal might induce various pro-inflammatory proteins in injured hearts. Objective: We estimate whether immunological factor and iron metabolism involved in right ventricular remodeling in pulmonary arterial hypertension. Method: Gene expression of immunological factors and iron related proteins and histopathological finding in heart of monocrotaline MCT induced PAH rats was sequentially examined by real time PCR. Result: Right ventricular hypertrophy and dilatation appeared from 4 week after the injection of MCT. CD68+ macrophages, part of which laded with hemosiderin, and MHC class II+ antigen presenting cells were seen at right ventricles (RV) especially at the junction of the right and left ventricles (JRL). Gene expression of iron related proteins, leukocyte markers and proinflammatory proteins initially increased at RV and JRL then increased also at left ventricle (LV). Conclusion: Immunological factor and iron metabolism may be important for mechanisms of right ventricular remodeling in pulmonary arterial hypertension.
O-038 Right Ventricular Failure and Arrhythmogenesis; Analysis by Optical Mapping in Monocrotaline-Induced Rat Pulmonary Hypertension BONPEI TAKASE1, YOSHIHIRO TANAKA2, MASAYUKI ISHIHARA2 1 Department of Intensive Care Medicine, National Defense Medical College, 2 Devision of Biomedical Engineering, National Defense Medical College Research Institute
Background: Iron deficiency was reported to be common in idiopathic pulmonary arterial hypertension (PAH) and correlated negatively with exercise capacity, a surrogate of prognosis. We recently found that liver congestion by ligating inferior vena cava (IVC) of rat caused inappropriate expression of hepcidin master regulator of iron homeostasis and iron deficiency anemia. Purpose: Here, we examined iron metabolism in monocrotaline (MCT)-induced pulmonary hypertension to test hypothesis in relation to liver congestion and iron deficiency in PAH. Method: Rats received a subcutaneous injection of MCT 60 mg/kg and we examined the time course of the presence of anemia, serum iron and hepcidin, transferrin saturations and gene expression and pathological finding in the liver. Results: Liver congestion appeared 4 week after the injection of MCT and macrophages laden with hemosiderin appeared 5 week after the injection. Serum iron and transferrin saturarions decreased 4 or 5 week after the injection. However, liver congestion in this model was milder than that of model by ligating IVC and decreased serum iron and transferrin saturations recovered 6 week after the injection. Conclusion: Liver congestion in pulmonary artery hypertension may involve iron deficiency via inappropriate expression of hepcidin but severity of liver congestion may decide whether to continue iron deficiency.
O-040 Cardiac Function in Heart Failure Patients With Chronic Obstructive Pulmonary Diseases SATOSHI ABE, AKIOMI YOSHIHISA, HIROYUKI YAMAUCHI, TAKASHI OWADA, MAKIKO MIYATA, TAKAMASA SATO, SATOSHI SUZUKI, MASAYOSHI OIKAWA, ATSUSHI KOBAYASHI, YASUCHIKA TAKEISHI Cardiology and Hematology, Fukushima Medical University Background: Chronic obstructive pulmonary disease (COPD) often coexists with heart failure (HF), and is thought to have a critical association with mortality and morbidity in HF patients. However, the influence of COPD on cardiac function remains unclear. Methods and Results: Consecutive 589 patients with HF who performed spirometry were divided into 2 groups according to the presence of COPD: HF with COPD (FEV1/FVC !70%: COPD group, n5148) and without COPD (Non-COPD group, n5441). We compared echocardiographic findings and circulating levels of BNP, CRP, uric acid (UA) and estimated GFR between COPD and NonCOPD groups. In echocardiographic paremeters, LVEF, left atrial volume (LAV), tricuspid regurgitation pressure gradient (TR-PG), and right atrial diameter (RAD) were higher in COPD group than in Non-COPD group (LVEF: 49.8 vs. 44.7%, LAV: 136.0 vs. 94.5 ml, TR-PG: 62.4 vs. 30.4 mmHg, RAD: 59.3 vs. 52.5 mm, P!0.05, respectively). In laboratory data, UA was higher and GFR was lower in COPD group than in Non-COPD group (UA; 7.6 vs. 6.7 mg/dl, GFR; 48.4 vs. 53.4 ml/min/1.73cm2, P! 0.05, respectively). BNP and CRP did not differ between 2 groups. Conclusions: These results suggest that HF patients with COPD have larger dimensions of right and left arterium, higher right heart pressure, and lower renal function. These may result in poor prognosis in HF patients with COPD.
O-041 Right ventricular (RV) dysfunction caused by severe pulmonary hypertension (PH) is associated with high mortality due to RV failure. However, some patients could suffer from sudden cardiac death (SCD). We hypothesize that PH can cause RV arrhythmogenesis leading to SCD. To investigate arrhythmogenesis in PH, optical mapping analysis (OMP) with electrophysiological study (EPS) and pathological examination were performed in the monocrotaline (MCT)-induced rat PH model. Rats were injected with MCT (60 mg/kg), and OMP was performed in isolated Langendorffperfused hearts. OMP revealed abnormal RV conduction delay and abnormal pattern in PH. Impaired action potential duration dispersion (APDd), an index of myocardial repolarization instability, was observed only in RV with PH. EPS demonstrated that lethal arrhythmias were induced by burst pacing to RV when deteriorated APDd
Constrictive Pericarditis NOBUHIKO UEDA Cardilvascular Medicine, Saiseikai-Senri Hospital Case: 74 years, female Chief complaint: dyspnea of exertion History of present illness: She has attended a hospital for chronic atrial flutter and a chronic heart and had been hospitalized 2 times for this heart failure within the past one and a half years. She developed dyspnea and had been worsening on day in 2013. This condition did not improve being relaxed and so she attended our hospital. Pulmonary congestion and pleural effusion was confirmed, and so she was hospitalized for a diagnosis of heart failure exacerbation. Her both ventricular contraction is preserved, both atrium
JHFS
S141
became evident. This arrhythmogenesis was inhibited by combination treatment with sildenafil and beraprost (SIL+BERA). RT-PCR showed mRNA upregulation of type I collagen and downregulation of connexin43 in RV at 5 weeks after MCT injection. Immunohistochemistry also revealed connexin43 degradation in the RV with PH. In contrast, connexin43 was well preserved, and no lethal arrhythmias were induced by burst pacing to RV in the absence of PH after SIL+BERA. Conclusions: RV electrical remodeling including impaired APDd causes arrhythmogenesis in PH, potentially associated with SCD due to PH.
O-039 Mechanism of Iron Deficiency via Inappropriate Hepcidin Expression in Pulmonary Artery Hypertension with Liver Congestion YUKAKO OHNO, HARUO HANAWA, SHUANG JIAO, YUKA HAYASHI, TOMOYASU SUZUKI, HIROAKI OBATA, TAKESHI KASHIMURA, TOHRU MINAMINO Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Science
O-037 Potential Role of Iron Metabolism and Inflammation in Right Ventricular Remodeling of Pulmonary Hypertension SHUANG JIAO, HARUO HANAWA, YUKAKO OHNO, YUKA HAYASHI, TOMOYASU SUZUKI, TAKESHI KASHIMURA, HIROAKI OBATA, TOHRU MINAMINO Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences Background: Right heart failure from pulmonary arterial hypertension PAH is a major cause of morbidity and mortality, but its mechanism is incompletely understood. We recently found that gene expression of iron related proteins increased in myocarditis and myocardial infarction and free heme as a danger signal might induce various pro-inflammatory proteins in injured hearts. Objective: We estimate whether immunological factor and iron metabolism involved in right ventricular remodeling in pulmonary arterial hypertension. Method: Gene expression of immunological factors and iron related proteins and histopathological finding in heart of monocrotaline MCT induced PAH rats was sequentially examined by real time PCR. Result: Right ventricular hypertrophy and dilatation appeared from 4 week after the injection of MCT. CD68+ macrophages, part of which laded with hemosiderin, and MHC class II+ antigen presenting cells were seen at right ventricles (RV) especially at the junction of the right and left ventricles (JRL). Gene expression of iron related proteins, leukocyte markers and proinflammatory proteins initially increased at RV and JRL then increased also at left ventricle (LV). Conclusion: Immunological factor and iron metabolism may be important for mechanisms of right ventricular remodeling in pulmonary arterial hypertension.
O-038 Right Ventricular Failure and Arrhythmogenesis; Analysis by Optical Mapping in Monocrotaline-Induced Rat Pulmonary Hypertension BONPEI TAKASE1, YOSHIHIRO TANAKA2, MASAYUKI ISHIHARA2 1 Department of Intensive Care Medicine, National Defense Medical College, 2 Devision of Biomedical Engineering, National Defense Medical College Research Institute
Background: Iron deficiency was reported to be common in idiopathic pulmonary arterial hypertension (PAH) and correlated negatively with exercise capacity, a surrogate of prognosis. We recently found that liver congestion by ligating inferior vena cava (IVC) of rat caused inappropriate expression of hepcidin master regulator of iron homeostasis and iron deficiency anemia. Purpose: Here, we examined iron metabolism in monocrotaline (MCT)-induced pulmonary hypertension to test hypothesis in relation to liver congestion and iron deficiency in PAH. Method: Rats received a subcutaneous injection of MCT 60 mg/kg and we examined the time course of the presence of anemia, serum iron and hepcidin, transferrin saturations and gene expression and pathological finding in the liver. Results: Liver congestion appeared 4 week after the injection of MCT and macrophages laden with hemosiderin appeared 5 week after the injection. Serum iron and transferrin saturarions decreased 4 or 5 week after the injection. However, liver congestion in this model was milder than that of model by ligating IVC and decreased serum iron and transferrin saturations recovered 6 week after the injection. Conclusion: Liver congestion in pulmonary artery hypertension may involve iron deficiency via inappropriate expression of hepcidin but severity of liver congestion may decide whether to continue iron deficiency.
O-040 Cardiac Function in Heart Failure Patients With Chronic Obstructive Pulmonary Diseases SATOSHI ABE, AKIOMI YOSHIHISA, HIROYUKI YAMAUCHI, TAKASHI OWADA, MAKIKO MIYATA, TAKAMASA SATO, SATOSHI SUZUKI, MASAYOSHI OIKAWA, ATSUSHI KOBAYASHI, YASUCHIKA TAKEISHI Cardiology and Hematology, Fukushima Medical University Background: Chronic obstructive pulmonary disease (COPD) often coexists with heart failure (HF), and is thought to have a critical association with mortality and morbidity in HF patients. However, the influence of COPD on cardiac function remains unclear. Methods and Results: Consecutive 589 patients with HF who performed spirometry were divided into 2 groups according to the presence of COPD: HF with COPD (FEV1/FVC !70%: COPD group, n5148) and without COPD (Non-COPD group, n5441). We compared echocardiographic findings and circulating levels of BNP, CRP, uric acid (UA) and estimated GFR between COPD and NonCOPD groups. In echocardiographic paremeters, LVEF, left atrial volume (LAV), tricuspid regurgitation pressure gradient (TR-PG), and right atrial diameter (RAD) were higher in COPD group than in Non-COPD group (LVEF: 49.8 vs. 44.7%, LAV: 136.0 vs. 94.5 ml, TR-PG: 62.4 vs. 30.4 mmHg, RAD: 59.3 vs. 52.5 mm, P!0.05, respectively). In laboratory data, UA was higher and GFR was lower in COPD group than in Non-COPD group (UA; 7.6 vs. 6.7 mg/dl, GFR; 48.4 vs. 53.4 ml/min/1.73cm2, P! 0.05, respectively). BNP and CRP did not differ between 2 groups. Conclusions: These results suggest that HF patients with COPD have larger dimensions of right and left arterium, higher right heart pressure, and lower renal function. These may result in poor prognosis in HF patients with COPD.
O-041 Right ventricular (RV) dysfunction caused by severe pulmonary hypertension (PH) is associated with high mortality due to RV failure. However, some patients could suffer from sudden cardiac death (SCD). We hypothesize that PH can cause RV arrhythmogenesis leading to SCD. To investigate arrhythmogenesis in PH, optical mapping analysis (OMP) with electrophysiological study (EPS) and pathological examination were performed in the monocrotaline (MCT)-induced rat PH model. Rats were injected with MCT (60 mg/kg), and OMP was performed in isolated Langendorffperfused hearts. OMP revealed abnormal RV conduction delay and abnormal pattern in PH. Impaired action potential duration dispersion (APDd), an index of myocardial repolarization instability, was observed only in RV with PH. EPS demonstrated that lethal arrhythmias were induced by burst pacing to RV when deteriorated APDd
Constrictive Pericarditis NOBUHIKO UEDA Cardilvascular Medicine, Saiseikai-Senri Hospital Case: 74 years, female Chief complaint: dyspnea of exertion History of present illness: She has attended a hospital for chronic atrial flutter and a chronic heart and had been hospitalized 2 times for this heart failure within the past one and a half years. She developed dyspnea and had been worsening on day in 2013. This condition did not improve being relaxed and so she attended our hospital. Pulmonary congestion and pleural effusion was confirmed, and so she was hospitalized for a diagnosis of heart failure exacerbation. Her both ventricular contraction is preserved, both atrium