Kenji Kada

Cell-to-cell interaction prevents cell death in cultured neonatal rat ventricular myocytes

OBJECTIVES Loss of cardiac cells and the anatomical or functional remodeling of intercellular coupling occur under several pathological conditions. We have assessed the significance of intercellular coupling for cell death. METHODS AND RESULTS Ventricular cells obtained from 1 day old Wistar rats were cultured. Apoptosis was detected by nick-end labeling. Cells were plated at low and high cell density (3x10(4)/ml and 12x10(4)/ml, respectively). Cultured myocytes died spontaneously by apoptosis in a time dependent manner. The increase of the apoptotic cell population in a culture with high cell density on day 4 (1+/-1.2%, n=4) was significantly lower than that in a culture with low cell density (20+/-5.5%, n=4). The progression of apoptosis in the culture of low cell density was prevented in part after application of the medium extract from the culture of high cell density; the apoptotic cell population on day 6 decreased from 57+/-8.0% (n=4) to 36+/-3.8% (n=4). Treatment of the cultured myocytes at high cell density with antisense oligonucleotide for connexin43 (Cx43) for 24 h on day 2 resulted in a significant decrease in Cx43 expression as judged by Western blot, dye transfer and immunocytochemistry using mouse monoclonal antibody for Cx43. In association with the down-regulation of Cx43, the progress of apoptosis was accelerated; the apoptotic cell population on day 5 in the antisense-treated cultures (27+/-5.7%, n=4) was significantly higher than the sense-treated cultures (5+/-1.1%, n=4). The effect of Cx43 antisense treatment to promote apoptosis was not reversed by application of high cell-density culture medium. CONCLUSIONS These findings suggest that cell-cell communication through gap junction formation and some humoral factors play important roles in the survival of cultured myocytes.

Unruptured Left Coronary Sinus of Valsalva Aneurysm Causing Mitral Valve Obstruction

A 77-year-old man was admitted for congestive heart failure. He had started to have palpitations after eating supper 2 days before the admission and had experienced dyspnea on exertion since then. He visited his family physician, who referred him to the cardiology clinic of our hospital. The patient was under the family physicians care for diabetes mellitus, hypertension, and paroxysmal atrial fibrillation. He had never been diagnosed as having any organic heart disease. He was an ex-smoker and drank alcohol on social occasions. The patient was on β-blockers and Coumadin. His cardiovascular physical examination was significant for a 3/6 systolic murmur and a rapid, irregular heart beat. His ECG showed atrial fibrillation with a ventricular rate of 150 bpm. His portable chest x-ray (Figure 1A) showed bilateral pleural effusion and pulmonary edema. An emergency transthoracic echocardiogram showed normal left and right ventricular function. A large mass in the left atrium was seen that was causing functional mitral stenosis. The patient was admitted to the hospital, given digoxin, and started on intravenous diuresis. His ECG on normal sinus rhythm (Figure 1B), which was …

Acute improvement of left ventricular relaxation as a predictor of volume reduction after cardiac resynchronization therapy: a pilot study assessing the value of left ventricular hemodynamic parameter.

Cardiac resynchronization therapy (CRT) improves cardiac function, but CRT recipients with advanced heart failure (HF) do not always respond well. Because the best parameters for the prediction of CRT response are not established, we investigated whether improvement of invasive left ventricular (LV) hemodynamic diastolic parameters could identify CRT responders.