Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation

Abstract Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.

Interleukin-6 contributes to myocardial damage in pregnant rats with reduced uterine perfusion pressure

Preeclampsia is one of the most frequent and difficult illnesses in pregnancy, which jeopardizes both mother and fetus. There are several diagnostic criteria for preeclampsia. However, the preeclampsia-associated myocardial damage has not been described. In this study, we employed reduced uterine perfusion pressure (RUPP) to generate a rat model of preeclampsia for the evaluation of myocardial damage in late-gestation rats. The expressions of cardiac injury markers were analyzed by immunohistochemistry and ELISA. The arterial pressure and myocardial tissue velocities were also measured. The role of interleukin (IL)-6 in RUPP-associated myocardial damage was further explored. The results showed that RUPP rats had significant myocardial damage, as demonstrated by the high expressions of myoglobin, creatine kinase isoenzyme, cardiac troponin I, and brain natriuretic peptide. In addition, RUPP increased the mean arterial pressure and the early transmitral flow velocity to mitral annulus early diastolic velocity ratio (E/Ea). Furthermore, IL-6 deteriorated these abnormalities, whereas inhibition of IL-6 significantly relieved them. In conclusion, our study demonstrated that RUPP rats displayed myocardial damage in an IL-6-dependent manner.

Pseudoinfarto agudo do miocárdio devido à síndrome da disfunção ventricular apical transitória (síndrome de Takotsubo) / Pseudo-acute myocardial infarction due to transient apical ventricular dysfunction syndrome (Takotsubo syndrome)

A síndrome de Takotsubo caracteriza-se por disfunção ventricular esquerda transitória, predominantemente medioapical, desencadeada caracteristicamente por estresse físico ou emocional. Relata-se aqui o caso de uma paciente de 61 anos de idade, admitida com tontura, sudorese profusa e mal-estar súbito, após intenso estresse emocional. Exame físico e eletrocardiograma inicial foram normais, porém havia elevação de troponina I e CKMB massa. Suspeitou-se de infarto agudo do miocárdio sem supradesnivelamento do segmento ST, indicando cineangiocoronariografia de urgência. Foram evidenciados ventrículo esquerdo com hipocinesia difusa grave, balonamento sistólico medioapical e coronárias sem lesões significativas. A paciente foi encaminhada aos cuidados intensivos, evoluindo satisfatoriamente com terapia de suporte. Conforme visto, a cardiomiopatia de Takotsubo pode simular infarto agudo do miocárdio, sendo a cineangiocoronariografia importante para distinção na fase aguda. Neste caso, a paciente evoluiu com resolução espontânea da disfunção ventricular, sem sequelas.

Takotsubo syndrome is characterized by predominantly medial-apical transient left ventricular dysfunction, which is typically triggered by physical or emotional stress. The present article reports the case of a 61-year-old female patient presenting with dizziness, excessive sweating, and sudden state of ill feeling following an episode involving intense emotional stress. The physical examination and electrocardiogram were normal upon admission, but the troponin I and creatine kinase-MB concentrations were increased. Acute myocardial infarction without ST segment elevation was suspected, and coronary angiography was immediately performed, which showed severe diffuse left ventricular hypokinesia, medial-apical systolic ballooning, and a lack of significant coronary injury. The patient was referred to the intensive care unit and was successfully treated with supportive therapy. As this case shows, Takotsubo syndrome might simulate the clinical manifestations of acute myocardial infarction, and coronary angiography is necessary to distinguish between both myocardial infarction and myocardial infarction in the acute stage. The present patient progressed with spontaneous resolution of the ventricular dysfunction without any sequelae.

Changes of CK-MB and HSP 60 in electrical-injuried rats / 法医学杂志

OBJECTIVE@#To investigate the changes of creatine kinase-MB (CK-MB) and heat shock protein 60 (HSP 60) in rats without electric marks after electric injury, to identify the relationship of the CK-MB, HSP 60 and the time of electric injuries, and to evaluate the damage to cells after electric injury.@*METHODS@#The animal model of electric injury without electric marks was established by alternating current (voltage 110 V). Automatic biochemistry analyzer was used to detect the serum CK-MB and immunohistochemical staining technology was used to analyze the tissues of myocardium and left lobe of liver.@*RESULTS@#The amount of serum CK-MB was increased when the rats were injuried, and reached the peak at 30min. Then the amount of CK-MB began to decrease and showed a slight downward trend in 3-5 h after electric injury, and leveled off at 6 h. Immunohistochemistry staining also showed the changes of HSP 60 of rats' myocardial cells and hepatic cells regularly after electric injury.@*CONCLUSION@#The regular changes of serum CK-MB and tissular HSP 60 in rats can be used to diagnosis electric injury and assess the injury of internal organs after the electric injury without electric marks.

Effect of Inula racemosa root extract on cardiac function and oxidative stress against isoproterenol-induced myocardial infarction.

The cardioprotective potential of Inula racemosa root hydroalcoholic extract against isoproterenol-induced myocardial infarction was investigated in rats. The rats treated with isoproterenol (85 mg/kg, s.c.) exhibited myocardial infarction, as evidenced by significant (P<0.05) decrease in mean arterial pressure, heart rate, contractility, relaxation along with increased left ventricular end diastolic pressure, as well as decreased endogenous myocardial enzymatic and non-enzymatic antioxidants. Isoproterenol also significantly (P<0.05) induced lipid peroxidation and increased leakage of myocyte injury marker enzymes. Pretreatment with I. racemosa extract (50, 100 or 200 mg/kg per day, p.o.) for 21 consecutive days, followed by isoproterenol injections on days 19th and 20th significantly (P<0.05) improved cardiac function by increasing the heart rate, mean arterial pressure, contractility and relaxation along with decreasing left ventricular end diastolic pressure. Pretreatment with I. racemosa also significantly (P<0.05) restored the reduced form of glutathione and endogenous antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase from the heart, which were depleted after isoproterenol administration. In addition to restoration of antioxidants, I. racemosa significantly (P<0.05) inhibited lipid peroxidation and prevented the leakage of myocytes specific marker enzymes creatine phosphokinase-MB and lactate dehydrogenase from the heart. Thus, it is concluded that I. racemosa protects heart from isoproterenol-induced myocardial injury by reducing oxidative stress and modulating hemodynamic and ventricular functions of the heart. Present study findings demonstrate the cardioprotective effect of I. racemosa and support the pharmacological relevance of its use and cardioprotection mechanism in ischemic heart disease as well as substantiate its traditional claim

The application of biochemical indexes detecting in sudden cardiac death in forensic autopsy / 法医学杂志

Sudden cardiac death(SCD) from early myocardial ischemia is often lack of typically morphological findings and clinical manifestation, thus cases of SCD may be suspected as criminal cases. It is necessary to clarify the cause of death, which is significance for medico-legal investigation. This article reviewed the latest advancement in the studies on the application of inorganic ions, CK-MB, cTn, ANP and BNP for certification of death from SCD in order to provide a practical way for diagnosis of SCD in forensic pathology.