Current evidence-based therapy does not restore plasma apelin level in phenotypically diverse chronic heart failure patients

Background: Apelin, endogenous peptide acting through its receptor (APJ), is the most potent inotropic agent known to man. Plasma apelin and cardiac APJ mRNA levels rise in early stages of chronic heart failure (CHF) but fall later in decompensated CHF. The effect of current evidence-based management of CHF on plasma apelin level is not known. We estimated change in plasma apelin level in CHF patients of diverse phenotypes treated with standard pharmacotherapy and compared it with the corresponding change in left ventricular ejection fraction (LVEF), plasma brain natriuretic peptide (BNP) level and quality of life (QoL).Methods: With ethical approval and written informed consent, venous blood samples were collected from 39 CHF [dilated cardiomyopathy (DCM) (n=21), restrictive cardiomyopathy (RCM) (n=9) and chronic constrictive pericarditis (CCP) (n=9)] patients and 10 age-matched healthy controls, at baseline and after 12 weeks. Plasma apelin and BNP were estimated by competitive ELISA (RayBiotech Inc.) and an auto-analyzer (Triage, Allere Inc.), respectively. QoL was assessed using Kansas City Cardiomyopathy Questionnaire (KCCQ). Nonparametric tests were applied and p-value <0.05 was considered significant.Results: Low LVEF, KCCQ score and high BNP levels were observed in all CHF patients compared to controls. Plasma apelin level was depressed in RCM and CCP patients compared to controls but not in DCM patients. These parameters did not change in any group after 3 months of standard pharmacotherapy.Conclusions: Current evidence-based management of CHF does not restore the depressed apelin-APJ axis. New drugs are required for specifically modulating this promising therapeutic target in CHF

Protection against acute adriamycin-induced cardiotoxicity by garlic: Role of endogenous antioxidants and inhibition of TNF-α expression

BACKGROUND: Oxidative stress is the major etiopathological factor in adriamycin-induced cardiotoxicity. Relatively low amounts of endogenous antioxidant makes the heart vulnerable to oxidative stress-induced damage. Chronic oral administration of garlic has been reported to enhance the endogenous antioxidants of heart. We hypothesized that garlic-induced enhanced cardiac antioxidants may offer protection against acute adriamycin-induced cardiotoxicity. RESULTS: Rats were either administered freshly prepared garlic homogenate (250 and 500 mg/kg daily, orally, for 30 days) or probucol (cumulative dose, 120 mg/kg body weight divided in 12, i.p. over a period of 30 days) or double distilled water (vehicle), followed by a single dose of adriamycin (30 mg/kg i.p.). In the adriamycin group, increased oxidative stress was evidenced by a significant increase in myocardial TBARS (thiobarbituric acid reactive substances) and decrease in myocardial SOD (superoxide dismutase), catalase and GPx (glutathione peroxidase) activity. Histopathological studies showed focal as well as subendocardial myocytolysis with infiltration of macrophages, lymphocytes and edema. Immunocytochemistry showed marked expression of TNF-α (tumor necrosis factor-alpha) in the myocardium. Increase in myocardial TBARS and decrease in endogenous antioxidants by adriamycin was prevented significantly in the garlic treated rat hearts, which was comparable to the probucol-treated group. Histopathological evidence of protection was also evident in both garlic-treated and probucol-treated groups. Probucol, 250 mg/kg and 500 mg/kg of garlic reduced adriamycin induced TNF-α expression in the myocardium and was associated with reduced myocyte injury. CONCLUSIONS: It is concluded that chronic garlic administration prevents acute adriamycin-induced cardiotoxicity and decreases myocardial TNF-α expression

Effect of garlic on cardiovascular disorders: a review

Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficary of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic

Oxidative stress in cardiovascular diseases

Oxidative stress caused by various oxygen containing free radicals and reactive species (collectively called "Reactive Oxygen Species" or ROS) has long been attributed to cardiovascular diseases. In human body, major oxidizing species are super oxide, hydrogen peroxide, hydroxyl radical, peroxy nitrite etc. ROS are produced from distinct cellular sources, enzymatic and non-enzymatic; have specific physicochemical properties and often have specific cellular targets. Although early studies in nineteen sixties and seventies highlighted the deleterious effects of these species, later it was established that they also act as physiological modulators of cellular functions and diseases occur only when ROS production is deregulated. One of the major sources of cellular ROS is Nicotinamide adenine dinucleotide phosphate oxidases (Noxes) that are expressed in almost all cell types. Superoxide and hydrogen peroxide generated from them under various conditions act as signal transducers. Due to their immense importance in cellular physiology, various Nox inhibitors are now being developed as therapeutics. Another free radical of importance in cardiovascular system is nitric oxide (a reactive nitrogen species) generated from nitric oxide synthase(s). It plays a critical role in cardiac function and its dysregulated generation along with superoxide leads to the formation of peroxynitrite a highly deleterious agent. Despite overwhelming evidences of association between increased level of ROS and cardiovascular diseases, antioxidant therapies using vitamins and omega 3 fatty acids have largely been unsuccessful till date. Also, there are major discrepancies between studies with laboratory animals and human trials. It thus appears that the biology of ROS is far complex than anticipated before. A comprehensive understanding of the redox biology of diseases is thus needed for developing targeted therapeutics