Coronary artery bypass grafting is associated with a significant worsening of QT dynamicity and heart rate variability

BACKGROUND: Imbalance in autonomic nervous system and impaired myocardial repolarization has been shown to increase the risk for arrhythmias in patients with coronary artery disease. This study evaluated the effects of coronary artery bypass grafting (CABG) on heart rate variability and QT interval dynamicity in subjects with coronary artery disease undergoing elective CABG surgery. METHODS: The study group consisted of 68 consecutive patients (mean age +/-SD: 61 +/- 9 years) with coronary artery disease who underwent elective CABG. Twenty-four-hour Holter monitoring was performed 2-5 days before cardiac surgery and was repeated 10 days after CABG. ELATEC holter software was used to calculate heart rate variability and QT dynamicity parameters. All subjects had a complete history, laboratory examination and transthoracic echocardiography. RESULTS: All patients had beta-blocking agent medication pre- and postoperatively. Standard deviation of all NN intervals for a selected time period, square root of the mean of the sum of the squares of differences between adjacent RR intervals, the proportion of differences in successive NN intervals greater than 50 ms, normalized low-frequency power, and normalized high-frequency power were significantly decreased after CABG surgery, whereas low-frequency/high-frequency ratio was significantly increased after CABG. QT/RR slopes over 24 h were significantly increased after CABG surgery for QT end and QT apex (QTapex/RR: 0.16 +/- 0.13 vs. 0.28 +/- 0.19, p < 0.001; QTend/RR: 0.18 +/- 0.13 vs. 0.36 +/- 0.23, p < 0.001). CONCLUSION: This prospective study showed for the first time that CABG was associated with a significant worsening of heart rate variability and QT dynamicity parameters in the postoperative period.     

Advances in malignant pleural mesothelioma therapy: targeting EphA2 a novel approach

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with a poor prognosis. MPM grows from the mesothelial cells lining the surface of the lung and chest wall called Pleura. Exposure to asbestos is mainly linked to the development of MPM. Approximately 80% of the tumors are pleural in origin, and up to 3000 people are diagnosed with MPM in the United States annually. The incidence of MPM is expected to rise in the coming decades particularly in the developing countries. Although there is an increase in the awareness of danger associated with the use of asbestos, its use is still prevalent in Australia and Asia because of its durability and low cost. This further warns and adds to the mortality and morbidity of patients with MPM globally. The traditional treatment strategies have shown only modest improvement towards the disease. MPM is difficult to treat because of the fact that the time between the exposure to asbestos and the appearance of symptoms is extremely delayed, and also due to tumor involvement with the pleural surface and the adjoining tissues such as the chest wall, pericardium and sub-diaphragmatic organs. Despite advances in the diagnostic and treatment approaches the median survival rate for MPM is between 9 to 17 months. The standard care with double agent has shown modest improvement however, multimodality approach using novel targets may have potential to achieve the improvement in the survival rate. In this review we give an update on the conventional treatment modalities and discuss about various molecular targets including receptor EphA2, a novel target gene which may be considered as a biomarker for the diagnosis and treatment of MPM.     

Minor thalassemia as a protective factor against cerebrovascular accidents

Hypertension, hypercholesterolemia, and coronary artery disease are among the risk factors of cerebrovascular accidents. After age, hypertension is the most powerful stroke risk factor. Abnormalities of serum lipids are regarded as risk factors for cerebrovascular accidents. A significant reduction in stroke risk among persons treated with cholesterol-reducing medicines known as statins are reported. Stroke risk nearly doubles in those with antecedent coronary artery disease. Moreover, polycythemia and high hematocrit levels are considered to be potential stroke risk factors. Minor thalassemia is associated with decreased prevalence of arterial hypertension and myocardial infarction (the second effect observed only in males.) Total cholesterol and LDL levels are lower in minor thalassemics, as is the blood viscosity. Therefore, it could be hypothesized that minor thalassemia could afford some protection against cerebrovascular accidents.     

Role of endothelin-1 in tamoxifen resistance: Mechanism for a new possible treatment strategy in breast cancer

Breast cancer is the prevalent cancer worldwide. Excessive exposure to endogenous estrogen across a woman's lifespan contributes to and may be a causal factor in breast cancer. Tamoxifen is a mixed estrogen agonist and antagonist, which is used in treatment and prevention of breast cancer as an estrogen antagonist. Many patients experience resistance to tamoxifen for which many mechanisms have been suggested. Endothelin-1 acts as a mitogen for human breast fibroblasts and it affects tumor cell proliferation, invasion, angiogenesis, neovascularization, mitogenesis, and apoptosis inhibition. Previous studies have shown that estradiol is effective in inhibiting endothelin synthesis in breast tissue and cardiovascular system. Tamoxifen as an estrogen receptor (ER) agonist in cardiovascular system has a cardioprotective effect and decreases endothelin level as a vasoconstrictor in cardiovascular system. But in breast tissue tamoxifen acts as an ER antagonist. According to the role of endothelin in breast cancer and inhibitory effect of estrogen on endothelin, we hypothesized that tamoxifen causes increasing in endothelin level or endothelin receptors probably by inhibitory effect on ER in breast tissue, leading to tamoxifen resistance. Therefore a combination of tamoxifen with endothelin antagonist seems to be a reasonable therapeutic strategy.