Doxorubicin cardiotoxicity and Camellia sinensis cardioprotection determined by speckle-tracking echocardiography

Abstract Doxorubicin (Dox) is a medication used in the treatment of cancerous tumors and hematologic malignancies with potentially serious side effects, including the risk of cardiotoxicity. Flavonoids are plant metabolites with antioxidant properties and can be extracted from Camellia sinensis (CS). The aim of this study is to evaluate the possible cardioprotective effect of CS against injuries induced by Dox in rats. A total of 32 animals were distributed into four groups: (1) control - intraperitoneal injection (I.P.) of 0.5 mL saline weekly and 1.0 mL water by gavage daily; (2) CS - 0.5 mL saline I.P. weekly and 200 mg/kg CS by gavage daily; (3) Dox - 5.0 mg/kg Dox I.P. weekly and 1.0 mL water by gavage daily; and (4) Dox+CS -5.0 mg/kg Dox I.P. weekly and 200 mg/kg CS by gavage daily. Clinical examinations, blood profiles, electrocardiograms, echocardiograms, and histological analyses of hearts were performed over 25 days. The animals in the Dox group showed changes in body weight and in erythrogram, leukogram, electrocardiography, and echocardiography readings. However, animals from the dox+CS group had significantly less change in body weight, improved cardiac function, and showed more preserved cardiac tissue. This study demonstrated that CS prevents dox-induced cardiotoxicity, despite enhancing the cytotoxic effect on blood cells

18ß-glycyrrhetinic acid attenuates global cerebral ischemia/reperfusion-induced cardiac damage in C57BL/J6 mice

Abstract The aim of the present study is to investigate the cardioprotective effects of 18ß-glycyrrhetinic acid (18ß -GA) against oxidative and histological damage caused by global cerebral ischemia/ reperfusion (I/R) in C57BL/J6 mice. All male mice (n:40) were randomly divided into four groups: (1) sham-operated (Sham), (2) I/R, (3) 18ß-GA, and (4) 18ß -GA+I/R. Ischemia was not applied to the sham and 18ß-GA groups. In the I/R group, the bilateral carotid arteries were clipped for 15 min to induce ischemia, and the mice were treated with the vehicle for 10 days. In the 18ß-GA group, the mice were given 18ß-GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the 18ß-GA+I/R group, the ischemic procedure performed to the I/R model was applied to the animals and afterwards they were intraperitoneally (i.p.) treated with 18ß-GA (100 mg/kg) for 10 days. It was found that global cerebral I/R increased TBARS levels and decreased antioxidant parameters. The 18ß-GA treatment decreased the level of TBARS and increased GSH, GPx, CAT, SOD activities. Also, the control group cardiac tissue samples were observed to have a normal histological appearance with the Hematoxylin-Eosin staining method. Histopathological damage was observed in the heart tissue samples belonging to the I/R group. The 18ß-GA treatment ameliorates oxidative and histological injury in the heart tissue after global ischemia reperfusion, and may be a beneficial alternative treatment

Pharmacovigilance study on drug-induced cardiac injury during treatment of COVID-19 / 中国中药杂志

Because coronavirus disease 2019(COVID-19) is highly contagious and serious, it has posed a major threat to public health worldwide. The curative effects of integrated traditional Chinese medicine and Western medicine in the treatment of COVID-19 have been widely recognized and confirmed. However, medical workers shall pay attention to drug-induced heart injury in clinical application. Based on the guideline from the Diagnosis and Treatment Plans for COVID-19(trial seventh edition), taking the recommended drugs as examples, by Western medicine, traditional Chinese medicine, Chinese herbal injection and integrated traditional Chinese and Western medicine, the study analyzed the basic characteristics of recommended drugs for cardiac injury by means of literature review and bioinformatics methods, and summarized cardiac adverse reactions, toxicity mechanisms, combined pharmacotherapy, special population and drug monitoring, focusing on the clinical manifestations, toxic components, targets and regulatory mechanisms of drug-induced cardiac injury. The findings suggested being vigilant to drug-induced cardiac injury during the treatment of COVID-19, playing the advantages of clinical pharmacists and clinical Chinese pharmacists, improving the knowledge reserve of pharmacovigilance, strengthening the prescription review, medication notification and medication monitoring, promoting rational drug use and paying attention to special populations and high-risk groups. The study aims to provide suggestions and reference for pharmacovigilance and pharmaceutical care for front-line doctors and pharmacists against COVID-19, in order to avoid the occurrence of drug-induced heart injury for patients with COVID-19.

Potential therapies for COVID-19 cardiovascular complications using artemisinin and its derivatives intervene based on its cardiovascular protection / 中国中药杂志

Corona virus disease 2019(COVID-19) has brought untold human sufferings and economic tragedy worldwide. It causes acute myocardial injury and chronic damage of cardiovascular system, which has attracted much attention from researchers. For the immediate strategy for COVID-19, "drug repurposing" is a new opportunity for developing drugs to fight COVID-19. Artemisinin and its derivatives have a wide range of pharmacological activities. Recent studies have shown that artemisinin has clear cardiovascular protective effects. This paper summarizes the research progress on the pathogenesis the pathogenesis of COVID-19 in cardiovascular damage by 2019 novel coronavirus(2019-nCoV) virus from myocardial cell injury directly by 2019-nCoV virus,viral ligands competitively bind to ACE2 and then reduce the protective effect of ACE2 on cardiovascular disease, "cytokine storm" related myocardial damage, arrhythmia and sudden cardiac death induced by the infection and stress, myocardial injury by hypoxemia, heart damage side effects from COVID-19 drugs and summarizing the cardiovascular protective effects of artemisinin and its derivatives have activities of anti-arrhythmia, anti-myocardial ischemia, anti-atherosclerosis and plaque stabilization. Then analyzed the possible multi-pathway intervention effects of artemisinin-based drugs on multiple complications of COVID-19 based on its specific immunomodulatory effects, protective effects of tissue and organ damage and broad-spectrum antiviral effect, to provide clues for the treatment of cardiovascular complications of COVID-19, and give a new basis for the therapy of COVID-19 through "drug repurposing".

Predictive value of neutrophil/lymphocyte ratio on myocardial injury in severe COVID-19 patients / 中华心血管病杂志

Objective: To explore the predictive value of neutrophil/lymphocyte ratio (NLR) on myocardial injury in severe COVID-19 patients. Methods: In this single-center retrospective cohort study, we collected and analyzed data form 133 severe COVID-19 patients admitted to Renmin Hospital of Wuhan University (Eastern District) from January 30 to February 18, 2020. Patients were divided into myocardial injury group (n=29) and non-myocardial injury group (n=104) according the presence or absence of myocardial injury. The general information of patients was collected by electronic medical record database system. All patients were followed up for 30 days, the organ injury and/or dysfunction were monitored, the in-hospital death was compared between the two groups, and the disease progression was reevaluated and classified at 14 days after initial hospitalization. Logistic regression analysis was performed to identify risk factors of myocardial injury in severe COVID-19 patients. The ROC of NLR was calculated, and the AUC was determined to estimate the optimal cut-off value of NLR for predicting myocardial injury in severe cases of COVID-19. Results: There was statistical significance in age, respiratory frequency, systolic blood pressure, symptoms of dyspnea, previous chronic obstructive pulmonary disease, coronary heart disease history, white blood cells, neutrophils, lymphocytes, platelets, C-reactive protein, platelet counting, aspartate transaminase, albumin, total bilirubin, direct bilirubin, urea, estimated glomerular filtration rate, total cholesterol, low-density lipoprotein cholesterol, D-dimer, CD3+, CD4+, partial pressure of oxygen, partial pressure of CO2, blood oxygen saturation, other organ injury, clinical outcome and prognosis between patients with myocardial injury and without myocardial injury (all P<0.05). Multivariate logistic regression analysis showed that NLR was a risk factor for myocardial injury (OR=1.066，95%CI 1.021-1.111，P=0.033). ROC curve showed that NLR predicting AUC of myocardial injury in severe COVID-19 patients was 0.774 (95%CI 0.694-0.842), the optimal cut-off value of NLR was 5.768, with a sensitivity of 82.8%, and specificity of 69.5%. Conclusion: NLR may be used to predict myocardial injury in severe COVID-19 patients.

A dedicated stitch to allow early safe mobilization avoiding drain-induced heart injury

Abstract Placement of a mediastinal drain is a routine procedure following heart surgery. Postoperative bed rest is often imposed due to the fear of potential risk of drain displacement and cardiac injury. We developed an encapsulating stitch as a feasible, effective and low-cost technique, which does not require advanced surgical skills for placement. This simple, novel approach compartmentalizes the drain allowing for safe early mobilization following cardiac surgery.

Research progress of radiation-induced heart injury——clinical / 中华放射肿瘤学杂志

At present,the heart has become an important organ at risk during radiotherapy for thoracic,mediastinal and breast carcinoma.Heart is relatively sensitive to radiation because of its anatomical location and structure.Long-term survival of patients have been affected by cardiac adverse effect postradiotherapy.In this paper,the progress of clinical manifestations,risk factors,screening methods,prevention and treatment of radiation-induced cardiac damage were reviewed as follows.

Mechanism of heart injury in brain death rabbits / 中华器官移植杂志

Objective To study the mechanism of brain death-induced heart damage by observing the change patterns of morphological damage to the heart and related inflammatory factors after brain death and provide the experimental basis for heart transplantation by brain-dead donor.Methods The 30 rabbits were equally divided into two groups by the random digital table method:sham-operation group and brain death group.The rabbit brain death model was established in the brain death group,and the sham-operation group was given slow intracranial pressure.The rest treatments in the two groups were the same.At 2nd,6th and 8th h after operation,blood pressure,heart rate and respiratory rate were recorded.The damage of heart tissues was observed by HE staining.The plasma concentrations of IL-1,IL-6 and IL-8 were tested by ELISA.The expression of some inflammatory factors in heart issues was detected by RT-PCR and immunohistochemistry.Results At 8 h after brain death,there was no signifiant difference in blood pressure and heart rate between two groups (P＞0.05).The damage of heart issues in the brain death group was more serious than in the shamoperation group.With the prolongation of brain death,the plasma concentrations of IL-6 and IL-8 increased significantly in the brain death group (P＜0.05),but the concentration of IL-1β showed no siginificant difference between the two groups at 2 h after brain death (P＜0.05).Besides,the expression of HSP27 and HSP70 mRNA as well as the protein expression of ICAM and NF-κB was significantly increased in the brain death group as compared with that in the sham-operation group (P＜0.05).Conclusion With the prolongation of brain death time,the inflammatory factors in the heart tissues and plasma interleukin were increased,suggesting the inflammatory reaction occurs in donor heart under the condition of brain death,which influences the quality of donor in the heart transplantation.

Protective effect of Addie in treatment of cardiac injury induced by radiotherapy and chemotherapy in patients with cervical cancer / 中国生化药物杂志

Objective To investigate the protective effect of Addie on cardiac injury induced by radiotherapy and chemotherapy in patients with cervical cancer.Methods 74 cases of cervical cancer were collected from the oncology department of Zhousha Hospital, those were treated with surgery and radiotherapy and chemotherapy according to postoperative staging and classification of cases.The patients were randomly divided into the experimental group and the control group, with 37 cases in each group.Control group received leukogenic and antiemetic treatment,the experimental group were given Addie injection 100 mL intravenous drip on the basis of the control group, one times per day,10 days as one courses, and two groups were all received 6 courses of treatment.Atthe end of treatment, the condition of heart function, left ventricular ejection fraction, left ventricular end diastolic diameter, 6 minutes walk test, myocardial enzymes, troponin T, C reactive protein /Barhel quality of life score index, EORTC-QLQ score and the incidence of adverse reactions were detected and compared with two groups.Results After treatment, the cardiac function of the experimental group was significantly better than that of the control group (P<0.05).After treatment,LVEDD of two groups decreased (P<0.05), LVEF, 6 minutes walk test distance increased (P<0.05),and LVEDD of experimental group was lower than control group (P<0.05), LVEF, 6 minutes walk test distance higher (P<0.05).After treatment, creatine kinase and creatine kinase levels were increased in two groups (P<0.05).Compared with the control group, the level of creatine kinase and creatine kinase in experimental group were higher(P <0.05).After treatment,the levels of troponin T and C reactive protein in two groups were decreased ( P <0.05 ) .Compared with the control group, the levels of troponin T and C reactive protein in experimental group were lower (P<0.05).After treatment,the scores of Barhel index and EORTC-QLQ score of two groups were significantly higher than before treatment, and the quality of life of the experimental group was significantly higher than that of control group ( P <0.05 ) .There was no significant difference in the incidence of adverse reactions between two groups.Conclusion Addie has an obvious protective effect on cardiac injury induced by radiotherapy and chemotherapy in patients with cervical cancer, and can improve the quality of life of patients.

Protective Mechanism of Tempol on Hypobaric Hypoxia-Induced Heart Damage in Mice / 中国药学杂志

OBJECTIVE: To study the effect mechanism of tempol against hypobaric hypoxia-induced heart damage in mice. METHODS: One hundred and ten BALB/c mice were randomly divided into normal control group, hypoxia model group, acetazolamide group and tempol group. After single intraperitoneal injection for 30 min, the mice were exposed to a simulated high altitude of 8 000 m for 12 h. After hypoxic exposure, blood was collected from the eye sockets and separated into serum to measure the activities of lactic dehydrogenase (LDH)and creatine kinase (CK). Then the mice were sacrificed and the content of H2O2 and malondialdehyde (MDA) as well as ATPase and antioxidant enzyme activity in heart were determined. HIF-1, VEGF, Nrf2, and HO-1 were detected by immunohistochemistry. RESULTS: Compared with normal control group, the activities of plasma CK and LDH in hypoxia model group significantly increased. In addition, the content of H2O2 and MDA in hypoxia model group significantly increased while ATPase and antioxidant enzymes activity markedly decreased compared with the normal control group. Moreover, the expression of HIF-1α, VEGF, Nrf2 and HO-1 increased. Prior administration of tempol effectively decreased the activities of plasma CK and LDH as well as the content of H2O2 and MDA in heart tissue. Tempol could increase ATPase and antioxidant enzyme activities and decreased the expression of HIF-1α and VEGF compared with hypoxia model, while it could further increase the expression of Nrf2 and HO-1. CONCLUSION: Tempol has protective effect on heart injury induced by hypobaric hypoxia in mice. Its mechanism may be attributed to the amelioration of energy metabolism, scavenging free radical, improvement of antioxidant enzyme activity the activation of the Nrf2/HO-1 pathway as well as alleviation of oxidative stress.

Adverse Cardiovascular Events after a Venomous Snakebite in Korea

PURPOSE: Although cardiac involvement is an infrequently recognized manifestation of venomous snakebites, little is known of the adverse cardiovascular events (ACVEs) arising as a result of snakebite in Korea. Accordingly, we studied the prevalence of ACVEs associated with venomous snakebites in Korea and compared the clinical features of patients with and without ACVEs. MATERIALS AND METHODS: A retrospective review was conducted on 65 consecutive venomous snakebite cases diagnosed and treated at the emergency department of Wonju Severance Christian Hospital between May 2011 and October 2014. ACVEs were defined as the occurrence of at least one of the following: 1) myocardial injury, 2) shock, 3) ventricular dysrhythmia, or 4) cardiac arrest. RESULTS: Nine (13.8%) of the 65 patients had ACVEs; myocardial injury (9 patients, 13.8%) included high sensitivity troponin I (hs-TnI) elevation (7 patients, 10.8%) or electrocardiogram (ECG) determined ischemic change (2 patients, 3.1%), and shock (2 patient, 3.1%). Neither ventricular dysrhythmia nor cardiac arrest was observed. The median of elevated hs-TnI levels observed in the present study were 0.063 ng/mL (maximum: 3.000 ng/mL) and there was no mortality in the ACVEs group. Underlying cardiac diseases were more common in the ACVEs group than in the non-ACVEs group (p=0.017). Regarding complications during hospitalization, 3 patients (5.4%) in the non-ACVEs group and 3 patients (33.3%) in the ACVEs group developed bleeding (p=0.031). CONCLUSION: Significant proportion of the patients with venomous snakebite is associated with occurrence of ACVEs. Patients with ACVEs had more underlying cardiac disease and bleeding complication.

Establishment of irradiation induced heart injury in C57 mice model and identification of serum marker / 安徽医科大学学报

Objective To establish and investigate C57 BL/6 mice model of radiation induced heart injury and ser-um marker. Methods Twenty eight female C57BL/6 mice were randomly divided into 3 groups:normal group (n=4 ) , 18 Gy radiation therapy group ( n=12 ) , 25 Gy radiation therapy group ( n=12 ) . The mice were weighed every week. Respectively, 0, 8 and 16 weeks after irradiation, the pathological changes of myocardial tissue were observed by hemetoxylin-eosin( HE) staining and made pathological score. Inferior vena cava blood was collected to take cardiac troponin I ( cTnI) test. Results Compared with the normal group,the weight of radiation group went down first then went up slowly. The myocardial tissue from mice had obvious histopathological changes. Acute in-flammation was the main change in the early days. At the late stage, progressive fibrosis was the main characteris-tic. With the increase of the dose, the inflammatory reaction and fibrosis degree had aggravated, pathological chan-ges had occurred earlier. cTnI showed a trend of higher performance over time, and had a correlation with patholo-gy. Conclusion We successfully established radiation induced myocaridal injury model. As a noninvasive serum marker, cTnI can be used as the evaluation standard of radiation induced myocardial injury animal model.

Protective effect of pioglitazone in rat models of radiation-induced heart injury / 中国组织工程研究

BACKGROUND:There are many positive effects by activation of peroxisome proliferator activated receptor-gamma (PPARγ) signal pathway in cardiovascular system. Angiotensin II is closely related with myocardial fibrosis, however, there are few articles demonstrating that the activation of PPARγsignal pathway can weaken the expression of angiotensin II to improve the radiation-induced heart injury. OBJECTIVE:To evaluate the effect of angiotensin II type 1 receptor in the rat model of radiation-induced heart injury after PPARγsignal pathway is activated. METHODS:Sixty rats were randomly and equal y divided into five groups:control, pioglitazone, model, radiation+low-dose pioglitazone, radiation+high-dose pioglitazone. In the model, radiation+low-dose pioglitazone, radiation+high-dose pioglitazone groups, rats received 6 MV high energy X-ray irradiation at the range of 1.5 cm × 1.5 cm and the irradiation dose of 300 cGy/min, for 6 hours. Furthermore, rats in the radiation+low-dose pioglitazone and radiation+high-dose pioglitazone groups were given 10 and 20 mg/kg pioglitazone by lavage, for 30 days;rats in the model group were given 2 mL distil ed water. In the pioglitazone group, rats were treated with 10 mg/kg pioglitazone by lavage. RESULTS AND CONCLUSION:After rats were treated with pioglitazone, the heart injury and the heart fibrosis in the irradiated rats were decreased. The expressions of angiotensin II type 1 receptor mRNA and protein in the heart tissue were down-regulated. Experimental findings indicate that, pioglitazone intervention downregulates the expression of angiotensin II type 1 receptor in the rat models of radiation-induced heart injury and activation of PPARγsignal pathway al eviates the radiation-induced heart injury.

Effect of resveratrol on levels of serum interleukin family of acute hemorrhagic shock patients and its protective effect for secondary heart and lung injury / 中国生化药物杂志

Objective To investigate the effect of resveratrol on levels of serum interleukin family of acute hemorrhagic shock patients and study its protective effect for secondary heart and lungs injury.Methods 42 cases of acute hemorrhagic shock were collected and divided into experimental group and control group according to different drugs treatment, each group had 21 cases.Control group were given continuous low flow oxygen, fluid infusion and other basic treatment, given blood transfusion if necessary.On the basis of control group, experimental group was given resveratrol 30 mg/kg, orally, one time per day for 4 consecutive weeks.The life index were detected during the treatment period.Then the levels of serum CK, LDH, IL-6, IL-10, IL-12, LVP, +dp/dtmax ,-dp /dtmax and arterial blood gas of all patients were detected after treatment.ResuIts Compared with control group, the levels of CK and LDH in experimental group decreased significantly (P<0.05);IL-6, IL-10, IL-12 levels decreased significantly (P<0.05).LVP,+dp /dtmax , -dp /dtmax level increased significantly ( P<0.05 ); PaCO2 and pH levels decreased significantly, the level of PaO2 increased significantly (P<0.05).ConcIusion Resveratrol can significantly reduce the serum IL-6, IL-10, IL-12l, reduce the CK, LDH level of hemorrhagic shock patients, and alleviate the injury of heart and lung.

Papillary Muscle Rupture of the Mitral Valve Caused by Traffic Accident / 日本心臓血管外科学会雑誌

A 59-year-old man was admitted to our hospital because of multiple traumas in a motorcycle accident. On admission, his vital signs were stable, however, 4 h later his respiratory condition suddenly worsened and be needed ventilatory support. Cardiogenic shock was suspected, however, the conventional echocardiograph findings were indistinct because of the presence of subcutaneous air. On the third day of hospitalization day, the Swan-Ganz catheter revealed high pulmonary arterial pressure. The subsequently performed trans-esophageal echocardiography showed severe mitral regurgitation. Therefore, semi-emergency mitral valve replacement was planned on the 5th hospital day. Operative findings showed that the anterolateral papillary muscle had torn off from the left ventricular wall and the associated strut chordae was also torn from the anterior leaflet. The post-operative course was uneventful, and the patient was discharged on the 40th postoperative day.

The effects of radiation-induced heart injury on cardiac troponin I and endothelin-1 and the preventive and therapeutic effect of fluvastatin / 解放军医学杂志

Objective To investigate the effect of radiation-induced heart injury on cardiac troponin I (cTnI)and endothelin-1(ET-1) and observe the preventive and therapeutic effect of fluvastatin. Methods Healthy female SD rats were randomly divided into three groups: control group(c), irradiation alone group(R) and fluvastatin therapeutic group (F). Rats of F group had been gastrogavaged with fluvastatin at dose of 20mg?kg -1?d -1 from 1week before irradiation to the end of the experiment. In C group and R group, rats were gastrogavaged with the same volume isotonic sodium chloride. The rats of R and F group were irradiated with accelerator linear at a dose of 20Gy thoracically. Rats were executed at 5,15,30d and 60d after irradiation, then cTnI in serum and ET-1 in blood plasma were detected. Results On 5d, the content of cTnI in R group increased significantly than that in C group(P