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Influence of heme on cultured cells from heart
S160 Journal of Cardiac Failure Vol. 14 No. 7S September 2008 051 An autopsy for a patient with hypertrophic cardiomyopathy suddenly died by ventricular fibrillation MASATO OHNISHI, TAKEHIRO MATSUMOTO, ATSUYUKI WADA Cardiovascular and Heart Failure Center, Kusatsu General Hospital, Kusatsu, Japan A 41-year-old man collapsing on the table of a restaurant was found by a waiter and the emergency service was called. Electrocardiogram showed ventricular fibrillation(VF) and electrical defibrillation was performed by an emergency medical technician. Nevertheless, VF persisted and the patient was brought to our hospital by ambulance continuing cardiopulmonary resuscitation. In the emergency room, endotracheal intubation and artificial respiration were carried out and cardioversion was attempted after the intravenous administration of each of epinephrine, lidocaine, magnesium sulfate, and sodium bicarbonate, and the patient’s cardiac rhythm altered to ventricular rhythm of 40beats/min. The patient was moved to the catheter laboratory for emergency cardiac catheterization examination and mechanical circulatory support system. Coronary angiography showed no significant stenosis and percutaneous cardiopulmonary support with intraaortic balloon pumping were operated and the hypothrmia therapy was started after admitting to the intensive cardiac care unit. Echocardiography revealed that the left ventricular (LV) wall motion was diffusely akinetic or severe hypokinetic and thickness was around 20 mm. Although sinus rhythm was restored on the 2nd hospital day, the patient’s general state gradually deteriorated, and he died on the 4th hospital day. Autopsy proved that LV and septal walls were markedly thickening and was consistent with hypertrophic cardiomyopathy (HCM). We will report additional pathological investigation of a HCM patient with sudden death caused by VF.
052 Management of obesity hypoventilation syndrome with heart failure YUKI HASHIMURA, YOSHIFUMI TAKATA, YASUHIRO USUI, KIHIRO ASANO, KOTA KATO, HIROKAZU SARUHARA, KAZUKI SIINA, AKIRA YAMASHINA The Second Department of Internal Medicine (Cardiology), Tokyo Medical University, Tokyo, Japan Obesity hypoventilation syndrome (OHS), which is defined as a combination of obesity, obstructive sleep apnea (OSA) and chronic hypoventilation, ultimately results in pulmonary hypertension (PH) and heart failure (HF). However, OHS is under-recognized, and under-treated, especially at the time of onset of HF. We present 3 cases diagnosed as OHS with HF on emergency admission in our hospital. Case 1: 54-year old man, right side HF with PH. Case 2: 60-year old man, bilateral HF. Case 3: 64-years old man, right side HF with PH and CO2 narcosis. All cases had severe obesity, excessive hypersomnolence, exertional dyspnea, edema, awake arterial hypercapnia and left ventricular hypertrophy. The polysomnography of all patients performed during hospitalization revealed severe OSA. While giving guidance for weight reduction, noninvasive positive pressure ventilation (NPPV) therapy was employed in each patient. Case 1 was treated with continuous positive airway pressure without medical treatment, whereas cases 2 and 3 required ventilatory support because of hypercapnea and OSA events, so we treated them with bilevel positive airway pressure. NPPV therapy during sleep provided a significant improvement in theclinical status of all patients after discharge. In conclusion, we must consider the possibility of OHS in cases of HF accompanied by obesity and hypercapnia and be willing to perform NPPV therapy for OHS patients.
053 The role of MDA5 in enterovirus persistence in heart tissues of DCM patients AKIRA UKIMURA, AKIO IIMORI, YASUSHI KITAURA Third Department if Internal Medicine, Osaka Medical College, Takatsuki, Japan Background: Enteroviruses (EV) have been implicated in the pathogenesis of DCM and myocarditis. The cytoplasmic helicase proteins, such as Melanoma differentiation-associated gene-5 (MDA-5) and Retinotic-Acid-Inducible Protein-I (RIG-I) recognize different type of dsRNAs. RIG-I is essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza and Japanese encephalitis virus, whereas MDA-5 is critical for picornaviruses including EV. Association between EV infection and MDA-5 SNPs. Purpose and Methods: To analyze the role of MDA5, we performed quantitative PCR of MDA-5 and RIG-I mRNA, and RT-PCR of EV in heart tissues of 29 DCM patients. We analyzed SNP of MDA5 (re1990760 A-G A946 T). Results: EV was positive in 9 patients, and negative in 20 patients. MDA-5 mRNA expression in heart tissues of EV-positive patients
had a tendency to be higher than EV-negative patients. The ratio of MDA-5/RIG-I of EV-positive patients was significantly higher than EV-negative patients. Genotyping showed 2 GA and 7 AA in EV-positive patients, and 7 GA, 12 AA and 1 GG in EVnegative patients. Conclusion: MDA-5 mRNA overexpression or MDA-5/RIG-I ratio should be a marker of active replication of EV infection in DCM patients. Association between EV infection and SNP of MDA-5 was unclear in this small study.
054 The Assessment of Diastolic Dyssynchrony by Tc99 m-sestamibi-gated-SPECT using a Novel Program ‘‘cardioGRAF’’ in Heart Failure with Preseerved Ejection Fraction MASAHIRO ISHIKAWA1, NAOTO TAKAHASHI1, JYUNNKO ABE1, KENICHI AMITANI1, TOMOYOSHI YAMAGUCHI1, NAOMI KAWAGUCHI1, TAKAHIRO UCHIDA1, AKIRA YAMAMOTO2, KAZUO MUNAKATA1 1 Nippon Medical School Musashikosugi Hospital, Kawasaki, Japan, 2Nippon Medical School Tamanagayama Hospital, Tama, Japan Background: Left ventricular dyssynchrony (LVD) has not been fully understood in the early staged heart failure (HF). We assessed the relationship between diastolic LVD and LV functions in HF with preserved ejection fraction (HFPEF) by Tc99 msestamibi-gated-SPECT (GMPS) using a novel program cardioGRAF. Methods: The subjects comprised 40 HFPEF patients and were examined by 16-frame GMPS. The cardioGRAF provides global (g-)/regional (r-) LV functions (EF, 1/3FF, 1/3FR, and PFR) and temporal paramerters (time from end systole to PFR: TPF1, time from 0 to PFR: TPF2). Diastolic LVD was evaluated by the difference between earliest and latest r-TPF2 in 17 segments of LV, named maximal difference (MD-TPF2). HFPEF patients were classified into 4 groups according to g-TPF1 and MD-TPF2: globally normal & segmentally synchronous (NS), globally normal & segmentally dyssynchronous (ND), globally abnormal & segmentally dyssynchronous (AD) and globally abnormal & segmentally synchronous (AS). Three diastolic functions of those groups were compared. Results: 1/3FF of NS & ND were significantly greater than those of AD & AS. 1/3FR of NS was only significantly greater than those of AS. However, PFR of AS was significantly greater than those of NS, ND, and AD. Conclusions: We confirmed 4 different subsets of diastole in HFPEF. A new classification would make minute differences of diastolic dysfunctions among 4 groups.
055 Influence of heme on cultured cells from heart KAZUHISA HAO, HARUO HANAWA, KEITA OTAKI, LIMIN DING, MAKOTO KODAMA, YOSHIHUSA AIZAWA Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
(Background) Heart possess a lot of heme proteins such as myoglobin. Therefore, once heart injury such as myocarditis or myocardial infarction is induced, heme proteins may be destabilized, heme is freed from its linkage with its respective protein moiety and free heme or free iron is predicted to be scattered. Augmentation in cellular content of heme can damage cells through prooxidant mechanism and free heme is though to be involved in regulation of various genes. On the other hand, we have recently shown that newly discovered iron metabolic genes are induced in myocarditis hearts. (Purpose) In this study, we investigated how cultured cells from hearts were influenced by free heme. (Method) Reactive oxygen species (ROS) in H9c2 cardiomyoblasts in medium containing 20 mM hemin were analyzed by flow cytometry with CM-H2DCFDA. Moreover, changes of gene expression assosiated with immunologic reaction or iron metabolism in cells cultured from the early phase of experimental autoimmune myocarditis (EAM) hearts were analyzed by quantitative RT-PCR. (Result) Hemin markedly induced ROS in H9c2 cells after 60 minutes and gene expression levels of IL-1, MCP-1, IL-6, lipocarin-2 and HO-1 influenced by hemin increased over 10-fold in cultured cells from EAM hearts. (Conclusion) Free heme, which is suspected to be generated in injured hearts, may play an important role in progressing and remodeling of heart diseases.
052 Management of obesity hypoventilation syndrome with heart failure YUKI HASHIMURA, YOSHIFUMI TAKATA, YASUHIRO USUI, KIHIRO ASANO, KOTA KATO, HIROKAZU SARUHARA, KAZUKI SIINA, AKIRA YAMASHINA The Second Department of Internal Medicine (Cardiology), Tokyo Medical University, Tokyo, Japan Obesity hypoventilation syndrome (OHS), which is defined as a combination of obesity, obstructive sleep apnea (OSA) and chronic hypoventilation, ultimately results in pulmonary hypertension (PH) and heart failure (HF). However, OHS is under-recognized, and under-treated, especially at the time of onset of HF. We present 3 cases diagnosed as OHS with HF on emergency admission in our hospital. Case 1: 54-year old man, right side HF with PH. Case 2: 60-year old man, bilateral HF. Case 3: 64-years old man, right side HF with PH and CO2 narcosis. All cases had severe obesity, excessive hypersomnolence, exertional dyspnea, edema, awake arterial hypercapnia and left ventricular hypertrophy. The polysomnography of all patients performed during hospitalization revealed severe OSA. While giving guidance for weight reduction, noninvasive positive pressure ventilation (NPPV) therapy was employed in each patient. Case 1 was treated with continuous positive airway pressure without medical treatment, whereas cases 2 and 3 required ventilatory support because of hypercapnea and OSA events, so we treated them with bilevel positive airway pressure. NPPV therapy during sleep provided a significant improvement in theclinical status of all patients after discharge. In conclusion, we must consider the possibility of OHS in cases of HF accompanied by obesity and hypercapnia and be willing to perform NPPV therapy for OHS patients.
053 The role of MDA5 in enterovirus persistence in heart tissues of DCM patients AKIRA UKIMURA, AKIO IIMORI, YASUSHI KITAURA Third Department if Internal Medicine, Osaka Medical College, Takatsuki, Japan Background: Enteroviruses (EV) have been implicated in the pathogenesis of DCM and myocarditis. The cytoplasmic helicase proteins, such as Melanoma differentiation-associated gene-5 (MDA-5) and Retinotic-Acid-Inducible Protein-I (RIG-I) recognize different type of dsRNAs. RIG-I is essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza and Japanese encephalitis virus, whereas MDA-5 is critical for picornaviruses including EV. Association between EV infection and MDA-5 SNPs. Purpose and Methods: To analyze the role of MDA5, we performed quantitative PCR of MDA-5 and RIG-I mRNA, and RT-PCR of EV in heart tissues of 29 DCM patients. We analyzed SNP of MDA5 (re1990760 A-G A946 T). Results: EV was positive in 9 patients, and negative in 20 patients. MDA-5 mRNA expression in heart tissues of EV-positive patients
had a tendency to be higher than EV-negative patients. The ratio of MDA-5/RIG-I of EV-positive patients was significantly higher than EV-negative patients. Genotyping showed 2 GA and 7 AA in EV-positive patients, and 7 GA, 12 AA and 1 GG in EVnegative patients. Conclusion: MDA-5 mRNA overexpression or MDA-5/RIG-I ratio should be a marker of active replication of EV infection in DCM patients. Association between EV infection and SNP of MDA-5 was unclear in this small study.
054 The Assessment of Diastolic Dyssynchrony by Tc99 m-sestamibi-gated-SPECT using a Novel Program ‘‘cardioGRAF’’ in Heart Failure with Preseerved Ejection Fraction MASAHIRO ISHIKAWA1, NAOTO TAKAHASHI1, JYUNNKO ABE1, KENICHI AMITANI1, TOMOYOSHI YAMAGUCHI1, NAOMI KAWAGUCHI1, TAKAHIRO UCHIDA1, AKIRA YAMAMOTO2, KAZUO MUNAKATA1 1 Nippon Medical School Musashikosugi Hospital, Kawasaki, Japan, 2Nippon Medical School Tamanagayama Hospital, Tama, Japan Background: Left ventricular dyssynchrony (LVD) has not been fully understood in the early staged heart failure (HF). We assessed the relationship between diastolic LVD and LV functions in HF with preserved ejection fraction (HFPEF) by Tc99 msestamibi-gated-SPECT (GMPS) using a novel program cardioGRAF. Methods: The subjects comprised 40 HFPEF patients and were examined by 16-frame GMPS. The cardioGRAF provides global (g-)/regional (r-) LV functions (EF, 1/3FF, 1/3FR, and PFR) and temporal paramerters (time from end systole to PFR: TPF1, time from 0 to PFR: TPF2). Diastolic LVD was evaluated by the difference between earliest and latest r-TPF2 in 17 segments of LV, named maximal difference (MD-TPF2). HFPEF patients were classified into 4 groups according to g-TPF1 and MD-TPF2: globally normal & segmentally synchronous (NS), globally normal & segmentally dyssynchronous (ND), globally abnormal & segmentally dyssynchronous (AD) and globally abnormal & segmentally synchronous (AS). Three diastolic functions of those groups were compared. Results: 1/3FF of NS & ND were significantly greater than those of AD & AS. 1/3FR of NS was only significantly greater than those of AS. However, PFR of AS was significantly greater than those of NS, ND, and AD. Conclusions: We confirmed 4 different subsets of diastole in HFPEF. A new classification would make minute differences of diastolic dysfunctions among 4 groups.
055 Influence of heme on cultured cells from heart KAZUHISA HAO, HARUO HANAWA, KEITA OTAKI, LIMIN DING, MAKOTO KODAMA, YOSHIHUSA AIZAWA Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
(Background) Heart possess a lot of heme proteins such as myoglobin. Therefore, once heart injury such as myocarditis or myocardial infarction is induced, heme proteins may be destabilized, heme is freed from its linkage with its respective protein moiety and free heme or free iron is predicted to be scattered. Augmentation in cellular content of heme can damage cells through prooxidant mechanism and free heme is though to be involved in regulation of various genes. On the other hand, we have recently shown that newly discovered iron metabolic genes are induced in myocarditis hearts. (Purpose) In this study, we investigated how cultured cells from hearts were influenced by free heme. (Method) Reactive oxygen species (ROS) in H9c2 cardiomyoblasts in medium containing 20 mM hemin were analyzed by flow cytometry with CM-H2DCFDA. Moreover, changes of gene expression assosiated with immunologic reaction or iron metabolism in cells cultured from the early phase of experimental autoimmune myocarditis (EAM) hearts were analyzed by quantitative RT-PCR. (Result) Hemin markedly induced ROS in H9c2 cells after 60 minutes and gene expression levels of IL-1, MCP-1, IL-6, lipocarin-2 and HO-1 influenced by hemin increased over 10-fold in cultured cells from EAM hearts. (Conclusion) Free heme, which is suspected to be generated in injured hearts, may play an important role in progressing and remodeling of heart diseases.