Rhynchophylline Regulates Calcium Homeostasis by Antagonizing Ryanodine Receptor 2 Phosphorylation to Improve Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to heart failure and death, for which there is no effective treatment. Rhynchophylline (Rhy) is the main effective component of the Chinese herbal medicine Uncaria rhynchophylla, which mainly acts on the cardiovascular and nervous systems. However, its role in protecting against DCM remains unexplored. The present study sought to reveal the mechanism of Rhy in improving type 2 diabetes mellitus (T2DM) myocardial lesions from the perspective of regulating calcium homeostasis in cardiomyocytes. We prepared a mouse model of T2DM using a high-fat diet combined with low doses of streptozotocin. The T2DM mice were given 40 mg/kg of Rhy for 8 weeks. The results showed that Rhy can attenuate cardiac pathological changes, slow down the heart rate, decrease serum cardiac enzyme levels, reduce cardiomyocyte apoptosis, enhance cardiomyocyte contractility, and raise the calcium transient amplitude in T2DM mice. Further, Rhy downregulated the phosphorylation level of ryanodine receptor 2, upregulated the phosphorylation level of phospholamban, protected mitochondrial structure and function, and increased adenosine triphosphate levels in the cardiac tissue of T2DM mice. Our results demonstrated that Rhy may protect against myocardial damage in T2DM mice and promote cardiomyocyte contraction, and its mechanism of action seems to be related to the regulation of intracellular calcium homeostasis.

In vivo Lesion Index (LSI) validation in percutaneous radiofrequency catheter ablation.

INTRODUCTION: Lesion Index (LSI) has been developed to predict lesion efficacy during radiofrequency (RF) catheter ablation. However, its value in predicting lesions size has still to be established. The aim of our study was to assess the lesions size reproducibility for prespecified values of LSI reached during RF delivery in an in vivo beating heart. METHODS: Ablation lesions were created with different values of LSI in seven domestic pigs by means of a contact force-sensing catheter (TactiCathTM , Abbott). Lesions were identified during RF delivery by means of a three-dimensional mapping system (EnSiteTM Precision, Abbott) and measured after heart explantation. Histology was carried out after gross examination on the first three lesions to confirm the accuracy of the macroscopic evaluation. RESULTS: A total of 64 myocardial lesions were created. Thirty-nine lesions were excluded from the analysis for the following reasons: histological confirmation of macroscopic lesion measurement (n = 3), transmurality (n = 24), unfavorable anatomic position (n = 10), not macroscopically identifiable (n = 2). In a final set of 25 nontransmural lesions, injury width and depth were, respectively, 4.6 ± 0.6 and 2.6 ± 0.8 mm for LSI = 4, 7.3 ± 0.8 and 4.7 ± 0.6 mm for LSI = 5, and 8.6 ± 1.2 and 7.2 ± 1.1 mm for LSI = 6. A strong linear correlation was observed between LSI and lesion width (r = .87, p < .00001) and depth (r = .89, p < .00001). Multiple linear regression analysis identified LSI as the only ablation parameter that significantly predicted lesion width (p < .001) and depth (p < .001). CONCLUSION: In our in vivo study, LSI proved highly predictive of lesion size and depth.

Recent advances in cardiac positron emission tomography for quantitative perfusion analyses and molecular imaging.

Positron emission tomography (PET) has been used to noninvasively evaluate myocardial perfusion and metabolism. For clinical assessments of myocardial perfusion, the quantitative capability of PET permits precise assessments of ischemia and microcirculatory dysfunction, playing an important role in patient management and outcome analyses. 18F-fluorodeoxyglucose (FDG) PET has recently been used to identify active cardiovascular lesions such as cardiac sarcoidosis, endocarditis, and aortitis. This may hold promise for the early and accurate diagnosis of such fatal diseases, as well as for patient management. This review covers new and clinical roles of cardiac PET in treatment strategies and patient outcomes.

The Use of Mesenchymal Stem Cells and their Derived Extracellular Vesicles in Cardiovascular Disease Treatment.

BACKGROUND: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. METHODS: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. RESULTS: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. CONCLUSION: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

The effects of L-carnitine on abnormal myocardial enzymes of HFMD / 实用医学杂志

Objective To observe the clinical effects of L-carnitine in myocardial enzyme abnormality caused by enterovirus in children with hand foot and mouth disease (HFMD). Methods 660 HFMD children patients with myocardial enzyme abnormality from May 2013 to June 2016 were enrolled and randomly divided into three groups. Group A(n=220)was treated with 1′6-FDP,group B with L-carnitine and group C with L-carnitine combined with 1′6-FDP. All groups were given routine anti-virus and symptomatic treatment. The clinical efficacy was compared across the three groups in terms of myocardial enzyme spectrum,heart rate,ECG,severe conver-sion rate before and after treatment. Results (1)Before treatment,there was no significant difference between the three groups in gender,age,course of disease,heart rate,myocardial enzyme spectrum and other indicators. (2)After treatment,the cure rate of HFMD in group B and group C were significantly higher than that in group A (both P<0.05);the rate of severe cases and the ECG normal rate in group B and group C were significantly lower than those in group A(both P<0.05),the time for heart rate resuming to normal in group B and in group C was all significantly shorter than that in group A(both P<0.05). There were no significant differences between group B and group C in clinical cure rate,severe conversion rate,recovery rate of ECG and heart rate recovery(all P>0.05).(3)In comparison with group A,after treatment,the levels of myocardial enzyme in group A and group B were decreased significantly(P < 0.05)and the recovery rates of myocardial enzyme in group A and the group B were significantly higher (P < 0.05),but no significant difference were observed between group A and group B (P>0.05). Conclusions For HFMD children with myocardial enzyme abnormality caused by enterovirus ,L-car-nitine together with myocardial nutritional therapy can significantly improve the myocardial enzyme indexes and electrocardiogram abnormality. It reduces the rate of severe cases and improve the prognosis.

The effects of L-carnitine on abnormal myocardial enzymes of HFMD / 实用医学杂志

Objective To observe the clinical effects of L-carnitine in myocardial enzyme abnormality caused by enterovirus in children with hand foot and mouth disease (HFMD). Methods 660 HFMD children patients with myocardial enzyme abnormality from May 2013 to June 2016 were enrolled and randomly divided into three groups. Group A(n=220)was treated with 1′6-FDP,group B with L-carnitine and group C with L-carnitine combined with 1′6-FDP. All groups were given routine anti-virus and symptomatic treatment. The clinical efficacy was compared across the three groups in terms of myocardial enzyme spectrum,heart rate,ECG,severe conver-sion rate before and after treatment. Results (1)Before treatment,there was no significant difference between the three groups in gender,age,course of disease,heart rate,myocardial enzyme spectrum and other indicators. (2)After treatment,the cure rate of HFMD in group B and group C were significantly higher than that in group A (both P<0.05);the rate of severe cases and the ECG normal rate in group B and group C were significantly lower than those in group A(both P<0.05),the time for heart rate resuming to normal in group B and in group C was all significantly shorter than that in group A(both P<0.05). There were no significant differences between group B and group C in clinical cure rate,severe conversion rate,recovery rate of ECG and heart rate recovery(all P>0.05).(3)In comparison with group A,after treatment,the levels of myocardial enzyme in group A and group B were decreased significantly(P < 0.05)and the recovery rates of myocardial enzyme in group A and the group B were significantly higher (P < 0.05),but no significant difference were observed between group A and group B (P>0.05). Conclusions For HFMD children with myocardial enzyme abnormality caused by enterovirus ,L-car-nitine together with myocardial nutritional therapy can significantly improve the myocardial enzyme indexes and electrocardiogram abnormality. It reduces the rate of severe cases and improve the prognosis.

Troponina C na detecção imuno-histoquímica de alterações regressivas precoces no miocárdio de bovinos e ovinos intoxicados por monofluoroacetato de sódio / Troponin C in immunohistochemical detection of early regressive myocardial lesions in cattle and sheep poisoned with sodium monofluoroacetate

Ao que tudo indica, o monofluoroacetato de sódio (MF) é o princípio tóxico das numerosas plantas que causam "morte súbita" no Brasil. Eventualmente, observam-se, nos animais intoxicados por MF, grupos de cardiomiócitos com aumento da eosinofilia citoplasmática. Essas alterações cardíacas, no entanto, na maioria dos casos, ainda são incipientes, de difícil interpretação, não há reação inflamatória e devem ser diferenciadas de artefato. O presente trabalho teve como objetivo detectar a presença de alterações regressivas precoces no miocárdio de bovinos e ovinos intoxicados experimentalmente por MF, através da imuno-histoquímica com troponina C (cTnC). Fragmentos de coração de seis bovinos (três que receberam, por via oral, doses únicas de 0,5mg/kg e, os demais, 1,0mg/kg de MF) e cinco ovinos (um recebeu, por via oral, dose única de 0,5mg/kg, outros dois receberam doses de 1,0mg/kg; um ovino recebeu, por via oral, doses subletais repetidas diariamente de 0,1mg/kg/dia, por quatro dias, e outro, 0,2mg/kg/dia por seis dias) foram submetidos à técnica de imuno-histoquímica com anticorpo anti-cTnC. Nos cardiomiócitos dos bovinos e ovinos verificou-se redução dos níveis de expressão da cTnC no citoplasma de grupos de fibras musculares. Diminuição significativa na imunorreatividade ocorreu, sobretudo, em cardiomiócitos que apresentavam, no exame histopatológico, aumento da eosinofilia citoplasmática. A diminuição ou ausência da expressão da cTnC nos animais intoxicados por MF permitiu estabelecer a diferença entre necrose coagulativa de cardiomiócitos e artefato ocasionado pelo fixador. Isso indica que este método pode ser utilizado com segurança para identificação de lesões regressivas precoces, ou não, no miocárdio, independentemente da causa. Adicionalmente, é possível afirmar que, dependendo do tempo de evolução, a toxicose por MF, bem como por plantas causadoras de "morte súbita" em bovinos e ovinos, podem cursar com lesões necrotizantes no miocárdio.

Sodium monofluoroacetate (MF) is the toxic principle of several plants that cause "sudden death" of cattle in Brazil. Groups of cardiomyocites with high cytoplasmic eosinophilia are sometimes observed in animals poisoned by MF. However, this cardiac alteration is difficult to interpret, as there is no inflammatory reaction and it must be differentiated from artifacts. The present study had the objective to detect the presence of early regressive lesions in the myocardium of sheep and cattle experimentally poisoned by MF through immunohistochemistry with troponin C (cTnC). Fragments of the heart muscle from six cattle (three received, orally, single doses of 0.5mg/kg and the others, single doses of 1.0mg/kg) and five sheep (one received, orally, single dose of 0.5mg/kg, the other two received single doses of 1.0mg/kg, one received sublethal daily doses of 0.1mg/kg for four days, and another received daily sublethal doses of 0.2mg/kg for six days) were submitted to immunohistochemistry with antibody anti-cTnC. In the cardiomyocites of cattle and sheep, it was possible to observe reduction of the expression levels for cTnC in the cytoplasm of groups of cardiac muscle fibers. Significant reduction of immunoreactivity ocurred overall in cardiomyocites that presented high cytoplasmic eosinophilia. The decrease or absence of expression for cTnC in animals poisoned by MF allowed to estabilish the difference between coagulative necrosis of cardiomyocites and artifacts caused by fixation. This indicates that this method can be used safely to identify any lesions, early regressive or not, in the myocardium independently of the cause. It is also possible to affirm that poisoning by MF as well as the one caused by "sudden death" causing plants can progress with necrotizing myocardial lesions.