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

High-grade atrioventricular block requiring pacemaker implantation after cardiac transplantation: An unusual complication

Self-limited bradyarrhythmias are commonly seen in postorthotopic heart transplantation patients. The most common cause of such bradyarrhythmias is sinus node dysfunction. Atrioventricular (AV) nodal blocks requiring pacemaker implantation remain distinctly uncommon. After ruling out reversible causes including dyselectrolytemia and drug toxicity, prolonged ischemia time of donor heart and transplant rejection should be considered as possible causes. The present case describes an uncommon occurrence of persistent high-grade AV block in postheart transplantation period ultimately requiring permanent pacemaker implantation

V-Sense episode in a biventricular pacemaker device: what is the likely mechanism?

Rajiv Mahajan, Manoj K. Rohit and Kewal K. Talwa

Long-term outcome of intracoronary microstent implantation: Lesion matched comparison with Palmaz-Schatz stent

We performed a lesion matched comparison of AVE Microstent and Palmaz‐Schatz stent implants with 6 month follow‐up angiography to compare the occurrence of restenosis. Thirty‐three pairs of lesions were matched for lesion location, ACC/AHA lesion type, reference diameter, lesion length, and angiographic descriptors. Age, sex, clinical profile, and indication for stenting were comparable. Quantitative coronary analysis before and after the procedure was comparable in the two groups but minimum lumen diameter (MLD) at follow‐up was less with Microstent—2.01 ± 1.01 mm than Palmaz‐Schatz stent—2.43 ± 0.96 mm (P = 0.05). Binary restenosis was present in 33% and 21% and was diffuse in 55% and 29% of the two groups, respectively. Typical angina at follow‐up was more frequent with Microstent (36%) than Palmaz‐Schatz stent (15%; P = 0.038). When implanted in lesions of similar complexity, Microstent yields similar post procedure angiographic results but smaller MLD at follow‐up and more frequent angina than Palmaz‐Schatz stent

Decreased myocardial expression of dystrophin and titin mRNA and protein in dilated cardiomyopathy: possibly an adverse effect of TNF-alpha

BACKGROUND AND AIMS: While the molecular basis of dilated cardiomyopathy (DCM) remains uncertain, concrete evidence is emerging that sarcomeric and cytoskeleton gene expression of myocardium isolated from failing versus non-failing patients differ dramatically. The central aim to this work was to find out the possible role of dystrophin and titin along with the TNF-α in the pathogenesis of cardiomyopathy. PATIENTS AND METHODS: mRNA levels and protein expression of a cytoskeletal protein, dystrophin and a sarcomeric protein, titin in endomyocardial biopsies of DCM patients were examined using RT-PCR and immunohistochemistry, respectively. Further, we examined the effect of TNF-α on myocardial expression of titin and dystrophin in vitro in rat cardiac myoblast cell line (H9c2). RESULTS: We observed significantly decreased mRNA and protein levels of dystrophin and titin in endomyocardial biopsy of DCM patients as compare to control group. The decreased levels of these proteins correlated with the severity of the disease. Plasma levels of both TNF-α and its soluble receptors TNFR1 and TNFR2 were found to be significantly higher in patients as compared to control group. Treatment of H9c2 cells with TNF-α resulted in a dose- and time-dependent decrease in mRNA levels of dystrophin and titin. Pretreatment of these cells with MG132, an inhibitor of nuclear factor kappa B (NF-κB) pathway, abolished TNF-α-induced reduction in mRNA levels of dystrophin and titin. CONCLUSION: Our results suggest that reduced expression of dystrophin and titin is associated with the pathophysiology of DCM, and TNF-α may modulate the expression of these proteins via NF-κB pathway.Shamim Ahmad, Taranjit Singh Rai, Madhu Khullar, Ajay Bahl, Uma Nahar Saikia, M. Thungapathra, Rohit Manoj Kumar, Rajiv Mahajan and Kewal K. Talwa