Implications of protease activation in cardiac dysfunction and development of genetic cardiomyopathy in hamsters

2012 ◽  
Vol 90 (8) ◽  
pp. 995-1004 ◽  
Author(s):  
Alison L. Müller ◽  
Darren Freed ◽  
Larry Hryshko ◽  
Naranjan S. Dhalla
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Ischemic Cardiomyopathy ◽  
Important Determinant ◽  
Proteolytic Enzymes ◽  
Cardiomyopathic Hamsters ◽  
Protease Activation ◽  
Proteolytic Activities ◽  
Different Strains ◽  
Genetically Determined

It has become evident that protein degradation by proteolytic enzymes, known as proteases, is partly responsible for cardiovascular dysfunction in various types of heart disease. Both extracellular and intracellular alterations in proteolytic activities are invariably seen in heart failure associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, hypertensive cardiomyopathy, diabetic cardiomyopathy, and ischemic cardiomyopathy. Genetic cardiomyopathy displayed in different strains of hamsters provides a useful model for studying heart failure due to either cardiac hypertrophy or cardiac dilation. Alterations in the function of several myocardial organelles such as sarcolemma, sarcoplasmic reticulum, myofibrils, mitochondria, as well as extracellular matrix have been shown to be due to subcellular remodeling as a consequence of changes in gene expression and protein content in failing hearts from cardiomyopathic hamsters. In view of the increased activities of various proteases, including calpains and matrix metalloproteinases in the hearts of genetically determined hamsters, it is proposed that the activation of different proteases may also represent an important determinant of subcellular remodeling and cardiac dysfunction associated with genetic cardiomyopathy.

Abstract P323: Waon Therapy, a Form of Thermal Therapy, Reduces Oxidative Stress Systemically and Inhibits the Progression of Cardiac Dysfunction in TO-2 Cardiomyopathic Hamsters with Heart Failure

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Yoshiyuki Ikeda ◽  
Masaaki Miyata ◽  
Yuichi Akasaki ◽  
Takahiro Miyauchi ◽  
Yuko Furusho ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Therapy Group ◽  
Left Ventricular ◽  
Thermal Therapy ◽  
Control Group ◽  
Vascular Endothelial ◽  
Cardiac Apoptosis ◽  
Cardiomyopathic Hamsters

Background: Oxidative stress is one of the most crucial factors that develop chronic heart failure (CHF), leading to cardiac apoptosis and fibrosis and vascular endothelial dysfunction. We have reported that Waon therapy, which is a form of thermal therapy using a far infrared-ray dry sauna at 60 degrees centigrade, improves cardiac and vascular endothelial functions and prognosis in patients with CHF. The aim of this study is to investigate whether Waon therapy reduces oxidative stress and prevents from developing cardiac dysfunction in CHF. Methods: Thirty-week old male TO-2 cardiomyopathic hamsters with CHF were divided into Waon therapy or control group. Waon therapy group underwent Waon therapy daily for 4 weeks. Control hamsters did not take any treatment. We examined the amounts of reactive oxygen species of serum, hearts and aortas using ELISA and immunohistochemistry. We measured left ventricular % fractional shortening (LV%FS), and performed TUNEL and Azan staining of hearts to assess cardiac function, apoptosis and fibrosis, respectively. Anti-oxidants and apoptotic and angiogenetic factors were assessed by Western blot. All examinations were performed after 4 weeks of treatment. Results: Four-week Waon therapy significantly decreased oxidative stress of serum, hearts and aortas compared to those of controls. Waon therapy significantly increased LV%FS and decreased cardiac apoptosis and fibrosis (LV%FS, Waon therapy: 23.3±4.3 vs. control: 16.5±4.2%, P<0.01, TUNEL positive nuclei, 22.0±2.6 vs. 49.3±7.2%, P<0.01, % fibrosis, 20.6±5.3 vs. 47.6±4.8%, P<0.01). Waon therapy significantly increased the expressions of manganese superoxide dismutase, heat shock protein 27 (HSP27) and HSP32 of hearts and aortas, which negatively modulate oxidative stress, compared to those of controls. Waon therapy significantly increased endothelial nitric oxide synthase and decreased plasminogen activator inhibitor-1 of aortas. In addition, Waon therapy significantly decreased Bax, cleaved caspase 3 and cytochrome c and increased Bcl-2 and hypoxia-inducible factor-1α of the failing hearts. Conclusions: Waon therapy reduces oxidative stress systemically and inhibits the progression of cardiac dysfuntion in TO-2 cardiomyopathic hamsters.

Quantitative Relation Between Myocardial Viability and Improvement in Heart Failure Symptoms After Revascularization in Patients With Ischemic Cardiomyopathy

Circulation ◽  
1995 ◽  
Vol 92 (12) ◽  
pp. 3436-3444 ◽  
Author(s):  
Marcelo F. Di Carli ◽  
Farbod Asgarzadie ◽  
Heinrich R. Schelbert ◽  
Richard C. Brunken ◽  
Hillel Laks ◽  
...  
Keyword(s):  
Heart Failure ◽  
Myocardial Viability ◽  
Ischemic Cardiomyopathy ◽  
Quantitative Relation

scholarly journals Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mouzarllem B. Reis ◽  
Fernanda L. Rodrigues ◽  
Natalia Lautherbach ◽  
Alexandre Kanashiro ◽  
Carlos A. Sorgi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Acetylcholine Release ◽  
Interleukin 1 ◽  
Clinical Manifestations ◽  
Prostaglandin E ◽  
High Dose ◽  
Scorpion Envenomation ◽  
Risk Of Death ◽  
Include Heart Failure

Abstract Scorpion envenomation is a leading cause of morbidity and mortality among accidents caused by venomous animals. Major clinical manifestations that precede death after scorpion envenomation include heart failure and pulmonary edema. Here, we demonstrate that cardiac dysfunction and fatal outcomes caused by lethal scorpion envenomation in mice are mediated by a neuro-immune interaction linking IL-1 receptor signaling, prostaglandin E2, and acetylcholine release. IL-1R deficiency, the treatment with a high dose of dexamethasone or blockage of parasympathetic signaling using atropine or vagotomy, abolished heart failure and mortality of envenomed mice. Therefore, we propose the use of dexamethasone administration very early after envenomation, even before antiserum, to inhibit the production of inflammatory mediators and acetylcholine release, and to reduce the risk of death.

scholarly journals Homogeneous 2D and 3D alignment of cardiomyocyte in dilated cardiomyopathy revealed by intravital heart imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kiyoshi Masuyama ◽  
Tomoaki Higo ◽  
Jong-Kook Lee ◽  
Ryohei Matsuura ◽  
Ian Jones ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Three Dimensional ◽  
Single Layer ◽  
Specific Pattern ◽  
Two Dimensional ◽  
Heart Imaging ◽  
Novel Method ◽  
2D And 3D

AbstractIn contrast to hypertrophic cardiomyopathy, there has been reported no specific pattern of cardiomyocyte array in dilated cardiomyopathy (DCM), partially because lack of alignment assessment in a three-dimensional (3D) manner. Here we have established a novel method to evaluate cardiomyocyte alignment in 3D using intravital heart imaging and demonstrated homogeneous alignment in DCM mice. Whilst cardiomyocytes of control mice changed their alignment by every layer in 3D and position twistedly even in a single layer, termed myocyte twist, cardiomyocytes of DCM mice aligned homogeneously both in two-dimensional (2D) and in 3D and lost myocyte twist. Manipulation of cultured cardiomyocyte toward homogeneously aligned increased their contractility, suggesting that homogeneous alignment in DCM mice is due to a sort of alignment remodelling as a way to compensate cardiac dysfunction. Our findings provide the first intravital evidence of cardiomyocyte alignment and will bring new insights into understanding the mechanism of heart failure.

scholarly journals Implications of multiple late gadolinium enhancement lesions on the frequency of left ventricular reverse remodeling and prognosis in patients with non‐ischemic cardiomyopathy

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Shingo Ota ◽  
Makoto Orii ◽  
Tsuyoshi Nishiguchi ◽  
Mao Yokoyama ◽  
Ryoko Matsushita ◽  
...  
Keyword(s):  
Heart Failure ◽  
Late Gadolinium Enhancement ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Reverse Remodeling ◽  
Cardiac Events ◽  
Gadolinium Enhancement ◽  
Systolic Volume ◽  
Linear Pattern ◽  
Multiple Lesions

Abstract Background Non-ischemic cardiomyopathy (NICM) is a heterogeneous disease, and its prognosis varies. Although late gadolinium enhancement (LGE)-cardiovascular magnetic resonance (CMR) demonstrates a linear pattern in the mid-wall of the septum or multiple LGE lesions in patients with NICM, the therapeutic response and prognosis of multiple LGE lesions have not been elucidated. This study aimed to investigate the frequency of left ventricular (LV) reverse remodeling (LVRR) and prognosis in patients with NICM who have multiple LGE lesions. Methods This single-center retrospective study included 101 consecutive patients with NICM who were divided into 3 groups according to LGE-CMR results: patients without LGE (no LGE group = 48 patients), patients with a typical mid-wall LGE pattern (n = 29 patients), and patients with multiple LGE lesions (n = 24 patients). LVRR was defined as an increase in LV ejection fraction (LVEF) ≥ 10 % and a final value of LVEF > 35 %, which was accompanied by a decrease in LV end-systolic volume ≥ 15 % at 12-month follow-up using echocardiography. The frequency of composite cardiac events, defined as sudden cardiac death (SCD), aborted SCD (non-fatal ventricular fibrillation, sustained ventricular tachycardia, or adequate implantable cardioverter-defibrillator therapies), and heart failure death or hospitalization for worsening heart failure, were summarized and compared between the groups. Results Among the 3 groups, the frequency of LVRR was significantly lower in the multiple lesions group than in the no LGE and mid-wall groups (no LGE vs. mid-wall vs. multiple lesions: 49 % vs. 52 % vs. 19 %, p = 0.03). There were 24 composite cardiac events among the patients: 2 in patients without LGE (hospitalization for worsening heart failure; 2), 7 in patients of the mid-wall group (SCD; 1, aborted SCD; 1 and hospitalization for worsening heart failure; 5), and 15 in patients of the multiple lesions group (SCD; 1, aborted SCD; 8 and hospitalization for worsening heart failure; 6). The multiple LGE lesions was an independent predictor of composite cardiac events (hazard ratio: 11.40 [95 % confidence intervals: 1.49−92.01], p = 0.020). Conclusions Patients with multiple LGE lesions have a higher risk of cardiac events and poorer LVRR. The LGE pattern may be useful for an improved risk stratification in patients with NICM.

scholarly journals Clinical significance of Q waves in ischemic cardiomyopathy

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
E Rodenas Alesina ◽  
P Jordan ◽  
L Herrador ◽  
C Espinet-Coll ◽  
N Pizzi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Primary Endpoint ◽  
Ischemic Cardiomyopathy ◽  
Cox Regression ◽  
Cox Model ◽  
Cardiovascular Death ◽  
P Value ◽  
Heart Failure Hospitalization ◽  
Total Cohort

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): CIBER-CV AIMS The scintigraphic translation of Q waves in patients with ischemic cardiomyopathy and LVEF &lt; 40% has not yet been assessed. The aim of this study was to explore the relationship between Q waves and necrotic tissue and to analyze their impact in prognosis. METHODS AND RESULTS A retrospective study enrolling 487 consecutive patients (67,0 [57,4 – 75,4] years), with ischemic cardiomyopathy, LVEF &lt;40% and narrow QRS who underwent stress-rest SPECT was conducted. Patients with Q waves (320 patients [65,7%]) had less comorbidity and ischemia, but more necrosis. Q waves correlated poorly with lack of viability (AUC = 0,63) and were independently associated with the subendocardial extent of the necrosis. After a follow-up of 5,07 years, the primary outcome (cardiovascular death, heart failure hospitalization or myocardial infarction) occurred in 192 (39,4%) patients, without differences between groups in multivariate analysis. After accounting for non-cardiovascular death as a competitive risk, the interaction between &gt;10% of ischemia and revascularization remained in Cox model both in the total cohort (aHR= 0,46 [0,24 – 0,86]), and in patients with Q waves (aHR = 0,27 [0,11–0,69]). CONCLUSION Patients with ischemic cardiomyopathy with Q waves have larger subendocardial scarring and more transmural necrosis, although correlation between Q waves and transmural scarring is poor. Revascularization if &gt;10% ischemia is present is associated with a better prognosis. Ischemia burden should be assessed and accordingly treated in these patients, and no differences in management should be made in the presence of Q waves. Table 1. Cox proportional hazards model Total cohort (N = 471) Patients with Q waves (N = 315) aHR p-value 95% CI aHR p-value 95% CI Age (per year) 1,02 0,007 1,01 - 1,04 n.s. Diabetes mellitus 1,35 0,047 1,00 - 1,81 1,54 0,016 1,09 - 2,20 eGFR &lt; 60 ml/min 1,59 0,005 1,15 - 2,21 1,96 &lt;0,001 1,36 - 2,82 Previous HF hospitalization 1,71 0,002 1,23 - 2,38 1,76 0,007 1,17 - 2,64 Previous PCI 1,32 0,069 0,98 - 1,78 n.s. Previous CABG n.s. 1,77 0,009 1,15 - 2,72 Angina or dyspnea 1,68 0,001 1,24 - 2,28 1,71 0,004 1,19 - 2,46 Indexed TDV (per quartile) 1,16 0,047 1,02 - 1,33 n.s. Revascularization*ischemia &gt; 10% 0,46 0,015 0,24 - 0,86 0,27 0,006 0,11 - 0,69 Cox regression for the primary endpoint (cardiovascular death, heart failure hospitalization or myocardial infarction), accounting for non-cardiovascular death as a competitive risk. Abstract Figure. Survival for the primary endpoint

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