Search

Long-term monotherapy with the aldosterone receptor blocker eplerenone in dogs with HF was previously shown to improve LV systolic and diastolic function. This study examined the effects of long-term monotherapy with the aldosterone receptor blocker eplerenone on mRNA and protein expression of the cytoskeletal proteins titin, tubulin, fibronectin and vimentin, the matrix metalloproteinases (MMPs)-1, -2 and -9, and the tissue inhibitors of MMPs (TIMPs)-1 and -2 in left ventricular (LV) myocardium of dogs with heart failure (HF). HF was produced in 12 dogs by intracoronary microembolizations. Dogs were randomized to 3 months oral therapy with eplerenone (10 mg/kg twice daily, n = 6) or to no therapy at all (HF-control, n = 6). LV tissue from six normal dogs was used for comparison. mRNA expression was measured using reverse-transcriptase polymerase chain reaction (RT-PCR) and protein expression using Western blots. Compared to NL dogs, control dogs showed upregulation of mRNA and protein expression for tubulin, fibronectin, MMP-1, -2 and -9, and down-regulation of mRNA and protein expression for total titin. Normalization of mRNA and protein expression for all these genes was seen after treatment with eplerenone. N2BA/N2B-titin mRNA expression ratio increased significantly in dogs with HF treated with eplerenone. No differences in expression for vimentin, TIMP-1 and -2 were observed among groups. In dogs with HF, long-term eplerenone therapy normalizes mRNA and protein expression of key cytoskeletal proteins and MMPs. Reversal of these molecular maladaptations may partly explain the improvement in LV diastolic function seen after long-term therapy with eplerenone.

Major advances have been made over the past two decades in the pharmacologic treatment of chronic heart failure (HF). Angiotensin-converting enzyme inhibitors, beta-blockers, and aldosterone antagonists have had a substantial impact on reducing mortality and morbidity in patients with HF and low left ventricular ejection fraction. These treatments delayed the progression toward advanced intractable HF but did not arrest progressive worsening of the disease. Patients on optimal medical therapy continued to deteriorate, albeit at a much slower pace, ultimately requiring further intervention. This gave rise to a host of device-based therapies that emerged in recent years to address this unmet need. Device therapies such as cardiac resynchronization, the CorCap cardiac support device (Acorn Cardiovascular, Inc., St. Paul, MN), and the OPTIMIZER System (Impulse Dynamics USA, Inc., Orangeburg, NY) are a few examples. This review addresses the progress made to date in the development and implementation of cardiac contractility modulation (CCM) as a device-based therapy for the treatment of patients with advanced HF. Treatment of patients with HF using CCM electrical signals is at present an investigational form of therapy.

Population-based variations in frequency and distribution of dystrophin gene deletions have been recognized in Duchenne/Becker (DMD/BMD) muscular dystrophy patients. In the present study, DNA samples from 121 unrelated DMD/BMD patients from North India were analyzed for deletional studies with multiplex PCR and Southern hybridization. A total of 88 (73%) patients showed intragenic deletions in the dystrophin gene. The observed proportion of gene deletions is relatively high, particularly compared with that of Asian counterparts. However, the distribution of breakpoints across the gene does not show significant variations.