Dedifferentiation and Proliferation of Mammalian Cardiomyocytes

It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1) cardiomyocyte purification from rat hearts, and 2) genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs), while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP) continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+).Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness, including the expression of c-kit and the capacity for multipotency

Ruptured Aneurysm of the Sinus of Valsalva into the Right Atrium without Ventricular Septal Defect: A Case Report and Literature Review

Aneurysm of the sinus of Valsalva (ASV), frequently associated with ventricular septal defect (VSD), is a rare cardiac disease that may be acquired or congenital. Rupture of an ASV, rare in the noncoronary cusp, usually produces serious hemodynamic change and carries poor prognosis if not treated surgically. We present the case of a 55-year-old female who came to us complaining of exertional dyspnea. Transthoracic echocardiography and aortography showed a noncoronary cusp ASV with rupture into the right atrium but without VSD. Because of high left to right shunt flow, she underwent successful surgical intervention with aneurysm repair approached from both the aorta and right atrium with a knitted Dacron patch. This was a rare case of noncoronary cusp involvement in ASV that ruptured into the right atrium without VSD

Ruptured Sinus of Valsalva and Complete Atrioventricular Block Complicating Fulminant Course of Infective Endocarditis: A Case Report and Literature Review

Patients with infective endocarditis usually developed persistent fever and heart failure, especially when the valve structures are invaded and destroyed. Persistent bacteremia often leads to severe sepsis or overwhelming septic shock. Septic emboli from the vegetation will possibly result in systemic thromboembolism with multiple organ infarction. Patients with infective endocarditis have been reported to present with either ruptured sinus of Valsalva or complete atrioventricular block. However, both of these serious complications occurring in a single patient is rare. In this case report, we present a 54-year-old man with a previous history of alcoholic cirrhosis and chronic renal failure who suffered from a fulminant course of infective endocarditis. Simultaneously, ruptured sinus of Valsalva and complete atrioventricular block further complicated the preexisting septic shock and multiple organ failure

Successful Retrieval of Dislodged Paclitaxel-eluting Stent with a Nitinol Loop Snare: A Case Report

Coronary stent dislodgment or embolization before deployment is a rare but challenging complication in interventional cardiology. Intracoronary embolization of the dislodged stent is associated with a high risk of coronary occlusion, due to thrombus formation and subsequent myocardial infarction. Furthermore, systemic embolization may cause severe cerebrovascular events. Nonsurgical retrieval strategies for this complication have been suggested, but bailout cardiac surgery may be indicated if percutaneous retrieval attempts fail. To our knowledge, this is the first case report of intracoronary drug-eluting stent dislodgment, and successful retrieval was accomplished by a loop snare technique. With the increasing trend of using drug-eluting stents in percutaneous coronary intervention, the likelihood of stent dislodgment or embolization may increase. It should be kept in mind, especially by coronary interventionists, how to manage this complication

Tolerability of Ramipril 10 mg Daily in High-risk Cardiovascular Patients in Taiwan: Experience from Kaohsiung Medical University Chung-Ho Memorial Hospital

The Heart Outcomes Prevention Evaluation (HOPE) study demonstrated that the angiotensin-converting enzyme inhibitor, ramipril, significantly reduces mortality, myocardial infarction and stroke in high-risk cardiovascular patients, beyond the benefits from blood pressure lowering. The tolerability of ramipril 10 mg/day has been an important concern when applying these results. Following the same criteria as the HOPE study, we investigated the adverse effects profile and tolerability of 10 mg ramipril in high-risk patients at our institution. In total, 92 patients with high cardiovascular risk were eligible for this study. Initially, ramipril was prescribed 2.5 mg orally once daily, and then titrated up to 5.0, 7.5, and 10.0 mg/day at 1-month intervals. The target maintenance dose was 10 mg/day. All adverse events were recorded during at least 3 months of follow-up. After 4-6 months of the titration protocol, only 18 patients (25.3%) reached and remained on ramipril 10 mg/day; 11 (15.5%), 22 (30.9%), and 20 patients (28.2%) remained on 2.5, 5.0, and 7.5 mg/day, respectively. Twenty-one patients (22.6%) had at least one adverse event. Twelve patients (13.0%) stopped treatment because of adverse effects. A total of 23 episodes of adverse events were reported, including cough (15.1%), dizziness (6.0%), and hypotension (2.4%). Ramipril was relatively well tolerated in our study population. However, only one-quarter of our patients reached the target maintenance dose of 10 mg/day. Dry cough, dizziness, and hypotension were the major side effects. About 15% of our patients discontinued ramipril treatment, which is comparable with previous reports