Na+/H+ Exchanger and Reperfusion-Induced Ventricular Arrhythmias in Isolated Perfused Heart: Possible Role of Amiloride

1993 ◽  
pp. 151-157
Author(s):  
Seibu Mochizuki ◽  
Shingo Seki ◽  
Masa-aki Ejima ◽  
Tatsuyuki Onodera ◽  
Masayuki Taniguchi ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Isolated Perfused Heart ◽  
Perfused Heart

Na+/H+ exchanger and reperfusion-induced ventricular arrhythmias in isolated perfused heart: possible role of amiloride

1993 ◽  
Vol 119 (1-2) ◽  
pp. 151-157 ◽  
Author(s):  
Seibu Mochizuki ◽  
Shingo Seki ◽  
Masa-aki Ejima ◽  
Tatsuyuki Onodera ◽  
Masayuki Taniguchi ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Isolated Perfused Heart ◽  
Perfused Heart

Mechanisms of Erythropoietin-Mediated Cardioprotection during Ischemia-Reperfusion Injury: Role of Protein Kinase C Signaling.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2907-2907
Author(s):  
Murat O. Arcasoy ◽  
Paul Hanlon ◽  
Ping Fu ◽  
Charles Steenbergen ◽  
Elizabeth Murphy
Keyword(s):  
Protein Kinase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Cardioprotective Effect ◽  
Isolated Perfused Heart ◽  
Perfused Heart ◽  
Biologic Effects

Abstract The biologic effects of erythropoietin (EPO) are mediated by its cellular receptor EPOR, a member of the cytokine receptor superfamily. EPOR expression in non-hematopoietic cells is associated with novel biologic effects for EPO in diverse organ systems. We recently demonstrated functional EPOR expression in adult rat cardiac myocytes and found that recombinant EPO exerts a rapid cardioprotective effect during ischemia-reperfusion injury of the isolated, perfused heart. Here we investigated the mechanisms of the cardioprotective effect of EPO using Langendorff-perfused rat hearts while left-ventricular-developed pressure (LVDP) was measured continuously to assess contractile function. Hearts were treated directly with EPO in the presence or absence of inhibitors of specific signal transduction pathways prior to normothermic global ischemia followed by reperfusion. Post-ischemic recovery of contractile function was determined by measuring LVDP at the end of reperfusion and expressed as a percentage of the baseline pre-treatment measurement. We investigated EPO-mediated activation of signal transduction pathways in the isolated, perfused heart and observed phosphorylation of p44/p42 MAP kinases ERK 1/2 (Thr202/Tyr204) and protein kinase B/Akt (Ser473), a downstream target of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Furthermore, EPO treatment of the isolated, perfused heart was associated with translocation of protein kinase C (PKC) ε and δ isoforms to the membrane fraction. We investigated the role of specific signaling pathways in EPO-mediated cardioprotection by employing inhibitors targeting PI3K, PKC and MAP kinase kinase (MEK1). PI3K inhibitors LY294002 and wortmannin attenuated EPO-induced phosphorylation of Akt but had no effect on EPO-mediated cardioprotection. MEK1 inhibitor U0126 had no effect on EPO-mediated cardioprotection. The PKC catalytic inhibitor chelerythrine (chel) significantly inhibited EPO-mediated improvement in post-ischemic recovery of LVDP (figure 1). Hearts pre-treated with EPO exhibited significantly improved post-ischemic recovery of LVDP compared to control hearts (mean±SE: 72±3 in EPO-treated versus 35±3% in control hearts, P<0.05 by ANOVA and Bonferroni post-hoc test, n=10 experiments each group) and the protective effect of EPO was significantly inhibited in chel-treated hearts (52±4% in EPO+chel versus 72±3% in EPO-treated hearts, P<0.05, n=10). As a control, treatment of the hearts with chelerythrine alone had no significant effect on LVDP (49±4%) compared to control hearts. These data demonstrate that EPO-mediated activation of the PKC signaling pathway is required for the cardioprotective effect of EPO during ischemia-reperfusion injury. Figure Figure

Abstract 276: The Role of Diacylglycerol Acetyltransferase 1 and 2 in Cardiac Metabolism and Function

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Nathan D Roe ◽  
Michal K Handzlik ◽  
Tao Li ◽  
Rong Tian
Keyword(s):  
Fatty Acids ◽  
Cardiac Function ◽  
Specific Inhibitor ◽  
Lipid Lowering ◽  
Rate Pressure Product ◽  
Mouse Heart ◽  
Lipid Lowering Therapy ◽  
Isolated Perfused Heart ◽  
Perfused Heart

Cardiac triglyceride (TG) plays an important role in myocardial metabolism. TG synthesis is catalyzed by diacylglycerol:acetyltransferase (DGAT). Enhancing cardiac TG synthesis and turnover, by means of overexpression DGAT1, has protected hearts against stresses while blocking the TG turnover causes cardiomyopathy. In the meantime DGAT inhibitors are being developed for lipid lowering therapy, raising concerns whether DGAT inhibition affects cardiac function. Here we determined the role of the two cardiac DGAT isoforms in TG synthesis and turnover in the heart and their contribution to cardiac fatty acid metabolism. Using an inducible cardiac specific DGAT1 deletion mouse (iKO) together with DGAT2-specific inhibitor, we were able to achieve graded inhibition of TG synthesis and turnover as determined by 13 C-NMR spectroscopy of isolated perfused mouse heart. The iKO heart has normal TG level (CON 5.7±1.2 vs. 6.9±0.7 μg/mg wwt) and perfusing hearts with glucose (5.5mM), fatty acids (0.4mM) and lactate (1.2mM) for 1hr did not change the TG content in control (CON, pre-perfusion 3.9 ± 0.6 vs. post-perfusion 4.5 ± 0.7 μg/mg wwt), iKO (3.8±0.6 vs. 4.2±0.5 μg/mg wwt) or iKO+DGAT2 inhibitor (3.8±0.6 vs. 5.0±0.8 μg/mg wwt). Relative to CON, the rate of 13 C labeled fatty acids incorporation into the TG pool decreased by 32% in iKO (AUC 5.170 of 7.547, p<0.05) which was accompanied by an increase the oxidation of exogenous fatty acids (relative FAO: 48.5±5.3 for CON vs. 67.0±4.1% for iKO, p<0.05). Cardiac function, assessed by echocardiography (FS: CON 47.5±1.3 vs. iKO 45.8±3.0%, p>0.05) or by rate pressure product of the isolated perfused heart (CON 39149±1047 vs. iKO 40836±3424 bpm*mmHg, p>0.05) is normal in iKO hearts and remained unchanged after treatment with the DGAT2 inhibitor (37083±8507 bpm*mmHg). Coinhibition of DGAT1 and 2 abrogated 13 C labeled fatty acids incorporation into the TG pool by 58% (AUC 5.042 of 11.82, p<0.05) and suppressed expression of PPARα target genes relative to non-treated control hearts (p<0.05). Taken together, our data show that both DGAT1 and 2 contribute TG synthesis in the heart. Inhibition of both isoforms abrogated TG synthesis and reduced PPARα activity in the heart but did not affect cardiac function in isolated perfused heart.

RESEARCH THE VALUE OF THE COMBINATION OF T WAVE ALTERNANS AND NT-PROBNT IN PREDICTING SUDDEN CARDIAC DEATH

2012 ◽  
pp. 74-83
Author(s):  
Anh Tien Hoang ◽  
Nhat Quang Nguyen
Keyword(s):  
Myocardial Infarction ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Healthy Person ◽  
Treadmill Test ◽  
T Wave ◽  
T Wave Alternans

Background: Decades of research now link TWA with inducible and spontaneous clinical ventricular arrhythmias. This bench-to-bedside foundation makes TWA, NT-ProBNP a very plausible index of susceptibility to ventricular arrythmia, and motivates the need to define optimal combination of TWA and NT-ProBNP in predicting ventricular arrythmia in myocardial infarction patients. We research this study with 2 targets: 1. To evaluate the role of TWA in predicting sudden cardiac death in myocardial infarction patients. 2. To evaluate the role of NT-ProBNP in predicting sudden cardiac death in myocardial infarction patients 3. Evaluate the role of the combined NT-ProBNP and TWA in predicting sudden cardiac death in myocardial infarction patients. Methods: Prospective study with follow up the mortality in 2 years: 71 chronic myocardial infarction patients admitted to hospital from 5/2009 to 5/20011 and 50 healthy person was done treadmill test to caculate TWA; ECG, echocardiography, NT-ProBNP. Results: Cut-off point of NT-ProBNP in predicting sudden cardiac death is 3168 pg/ml; AUC = 0,86 (95% CI: 0,72 - 0,91); Cut-off point of TWA in predicting sudden cardiac death is 107 µV; AUC = 0,81 (95% CI: 0,69 - 0,87); NT-ProBNP can predict sudden cardiac death with OR= 7,26 (p<0,01); TWA can predict sudden cardiac death with OR= 8,45 (p<0,01). The combined NT-ProBNP and TWA in predicting ventricular arrythmia in heart failure patients: OR= 17,91 (p<0,001). Conclusions: The combined NT-ProBNP and TWA have the best predict value of sudden cardiac death in myocardial infarction patients, compare to NT-ProBNP or TWA alone

Myocardial Noncompaction

2018 ◽  
Vol 69 (8) ◽  
pp. 2209-2212
Author(s):  
Alexandru Radu Mihailovici ◽  
Vlad Padureanu ◽  
Carmen Valeria Albu ◽  
Venera Cristina Dinescu ◽  
Mihai Cristian Pirlog ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Specific Treatment ◽  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Genetic Transmission ◽  
Asymptomatic Patients ◽  
Increased Risk ◽  
Patients With Heart Failure

Left ventricular noncompaction is a primary cardiomyopathy with genetic transmission in the vast majority of autosomal dominant cases. It is characterized by the presence of excessive myocardial trabecularities that generally affect the left ventricle. In diagnosing this condition, echocardiography is the gold standard, although this method involves an increased risk of overdiagnosis and underdiagnosis. There are also uncertain cases where echocardiography is inconclusive, a multimodal approach is needed, correlating echocardiographic results with those obtained by magnetic resonance imaging. The clinical picture may range from asymptomatic patients to patients with heart failure, supraventricular or ventricular arrhythmias, thromboembolic events and even sudden cardiac death. There is no specific treatment of left ventricular noncompaction, but the treatment is aimed at preventing and treating the complications of the disease. We will present the case of a young patient with left ventricular noncompactioncardiomyopathy and highlight the essential role of transthoracic echocardiography in diagnosing this rare heart disease.

scholarly journals The role of calcium homeostasis remodeling in inherited cardiac arrhythmia syndromes

2021 ◽  
Author(s):  
Shanna Hamilton ◽  
Roland Veress ◽  
Andriy Belevych ◽  
Dmitry Terentyev
Keyword(s):  
Cardiac Arrhythmia ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Polymorphic Ventricular Tachycardia ◽  
Genetic Mutations ◽  
Strong Basis ◽  
Functional Changes ◽  
Intracellular Ca ◽  
Qt Syndrome

AbstractSudden cardiac death due to malignant ventricular arrhythmias remains the major cause of mortality in the postindustrial world. Defective intracellular Ca2+ homeostasis has been well established as a key contributing factor to the enhanced propensity for arrhythmia in acquired cardiac disease, such as heart failure or diabetic cardiomyopathy. More recent advances provide a strong basis to the emerging view that hereditary cardiac arrhythmia syndromes are accompanied by maladaptive remodeling of Ca2+ homeostasis which substantially increases arrhythmic risk. This brief review will focus on functional changes in elements of Ca2+ handling machinery in cardiomyocytes that occur secondary to genetic mutations associated with catecholaminergic polymorphic ventricular tachycardia, and long QT syndrome.

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