Takanori Kusuyama

Effects of eplerenone on transcriptional factors and mRNA expression related to cardiac remodelling after myocardial infarction

Objective: To examine the effects of eplerenone, a selective aldosterone blocker, on cardiac function after myocardial infarction (MI) and myocardial remodelling related transcriptional factors and mRNA expression in non-infarcted myocardium. Methods: MI was induced by ligation of the coronary artery in Wistar rats. Rats were randomly assigned to a vehicle treated group or an eplerenone treated group (100 mg/kg/day). Results: At four weeks after MI, left ventricular (LV) end diastolic pressure, LV weight, and LV end diastolic dimension were increased in MI rats. Eplerenone significantly reduced the increase in LV end diastolic pressure, LV weight, and LV end diastolic dimension. In the MI rats the decreased ejection fraction indicated systolic dysfunction and the increased E wave to A wave ratio and E deceleration rate indicated diastolic dysfunction. Eplerenone significantly attenuated this systolic and diastolic dysfunction. Myocardial interstitial fibrosis, transcriptional activities of activator protein 1 and nuclear factor κB, and mRNA expression of monocyte chemoattractant protein 1, plasminogen activator inhibitor 1, atrial natriuretic peptide, brain natriuretic peptide, and collagen types I and III were significantly increased at four weeks after MI. Eplerenone significantly attenuated interstitial fibrosis and suppressed transcriptional activity and mRNA expression of these genes. Conclusions: When administered after MI, eplerenone prevents cardiac remodelling accompanied by systolic and diastolic dysfunction and inhibits abnormal myocardial transcriptional activities and gene expression.

Involvement of c-Jun NH2 terminal kinase and p38MAPK in rapamycin-mediated inhibition of neointimal formation in rat carotid arteries.

Objective: Rapamycin-coated stents in coronary artery lesions have recently been shown to be effective in inhibiting neointimal formation. However, little is known about the effects of rapamycin on mitogen-activated protein kinase (MAPK), which is an important signal for neointimal formation. Therefore, we examined the effects of rapamycin on MAPK and transcriptional factors in cultured human coronary artery smooth muscle cells (CASMC) and in balloon-injured rat carotid arteries. Methods and Results: Activation of ERK, JNK, p38MAPK, AP-1, and NF-kB in coronary artery smooth muscle cells was increased by 2% fetal bovine serum. Ten nmol/L of rapamycin prevented the activation of JNK, p38MAPK, AP-1, and NF-kB (65%, 65%, 67%, and 26% respectively, P < 0.01). In an in vivo study, remarkable neointimal formation was observed 14 days after injury. Coating Pluronic gel with 20 and 50 μg rapamycin around the injured artery significantly decreased the intimal area/medial area ratio, compared with vehicle (0.75 vs. 1.2, P < 0.01). Rapamycin prevented the increase in activation of JNK, p38MAPK, AP-1, and NF-kB in injured artery (42%, 70%, 75%, and 60% respectively, P < 0.05). Conclusions: Neointimal formation after balloon injury is inhibited by rapamycin, which is partially mediated by inhibition of JNK and p38MAPK, followed by AP-1 and NF-kB.

Microbubble destruction with ultrasound augments neovascularisation by bone marrow cell transplantation in rat hind limb ischaemia

Objective: To examine the effects of microbubble destruction with ultrasound (MB) combined with bone marrow derived mononuclear cell transplantation (BMT) into ischaemic tissues in rat hind limb ischaemia. Methods and results: Unilateral hind limb ischaemia was surgically induced in Lewis rats. At postoperative day 7, rats were randomly divided into three groups: a vehicle treated group, an ultrasound treated group, and an MB treated group. MB treatment increased vascular endothelial growth factor mRNA as assessed by real time polymerase chain reaction (3.0-fold, p < 0.05). At four weeks, the MB group had increases in laser Doppler blood flow index (LDBFI; 1.2-fold, p < 0.05), angiographically detectable collateral vessels (angiographic score: 1.4-fold, p < 0.01), and capillary to muscle fibre ratio (1.4-fold, p < 0.01) in ischaemic limbs compared with the vehicle treated group. No differences were seen between the vehicle and ultrasound treated groups. Secondly, rats were allocated to vehicle treatment, BMT (5 × 106 cells/rat), or a combination of MB and BMT (MB+BMT) at seven days after hind limb ischaemia. BMT treatment significantly increased LDBFI, angiographic score, and capillary to muscle fibre ratio compared with vehicle treatment. Interestingly, MB+BMT treatment produced significantly greater LDBFI (1.2-fold, p < 0.01), angiographic score (1.5-fold, p < 0.01), and capillary to muscle fibre ratio (1.5-fold, p < 0.05) than BMT treatment alone. Conclusions: MB may be a useful technique to enhance BMT induced neovascularisation.

Intravascular ultrasound complements the diagnostic capability of carbon dioxide digital subtraction angiography for patients with allergies to iodinated contrast medium.

Carbon dioxide digital subtraction angiography (CO2 DSA) is a useful and safe alternative for patients with renal dysfunction or allergies to iodinated contrast medium. However, CO2 DSA image quality is worse than that of angiography with iodinated contrast medium, primarily because of movement during imaging and stent struts. In angioplasty of arteries of the lower extremities, CO2 DSA cannot be used to sufficiently evaluate target lesions and determine the most efficient intervention. However, in the current case report, we describe a patient with severe allergies to iodinated contrast medium (Stevens–Johnson syndrome), because of which we were unable to use any iodinated contrast medium when conducting angioplasty. Therefore, we used intravascular ultrasound (IVUS), which facilitated the complete observation of the target lesion after stent implantation without requiring iodinated contrast medium. In this case, IVUS was used to complement the diagnostic capabilities of CO2 DSA.

Cough syncope induced by gastroesophageal reflux disease

A 52-year-old Japanese man was admitted to our hospital for evaluation of syncope and convulsions. An electrocardiogram on admission revealed normal sinus rhythm. However, after repeated bouts of coughing, the heart rate showed bradycardia associated with convulsion. He was diagnosed with cough syncope secondary to laryngopharyngitis, which was caused by gastroesophageal reflux disease (GERD). Once the patient was administrated lansoprazole (Takeda Pharmaceutical Co., Osaka, Japan) for GERD, the syncope disappeared. The causes of syncope are diverse and may manifest in disorders of different organ systems in the body. Therefore, clinicians should perform a careful whole body examination to obtain the correct diagnosis.

Effects of Azilsartan Compared to Other Angiotensin Receptor Blockers on Left Ventricular Hypertrophy and the Sympathetic Nervous System in Hemodialysis Patients

Hypertension is a major risk factor for cardiovascular and cerebrovascular events, and most patients with hypertension are administered antihypertensive drugs. However, not all patients achieve normal blood pressure levels. The new angiotensin receptor blocker azilsartan (Takeda Pharmaceutical Company Limited, Osaka, Japan) has been reported to have a strong hypotensive effect. Our study investigated the efficacy of azilsartan compared with other angiotensin receptor blockers. This study included 17 hypertensive patients on HD, who had been administered angiotensin receptor blockers, except for azilsartan, for more than 6 months before enrolling, and after enrollment, they were switched to azilsartan. Blood tests, Holter electrocardiogram, ambulatory blood pressure monitoring, and echocardiography were performed at baseline and at the 6‐month follow‐up. The blood pressure from baseline to 6 months had significantly decreased (24‐h systolic blood pressure from 150.9 ± 16.2 mm Hg to 131.3 ± 21.7 mm Hg, P = 0.008), awakening time systolic blood pressure from 152.1 ± 16.9 mm Hg to 131.7 ± 23.2 mm Hg, P = 0.01, sleep‐time systolic blood pressure from 148.1 ± 19.7 mm Hg to 130.0 ± 20.1 mm Hg, P = 0.005). There was a significant reduction in serum noradrenaline levels as well as left ventricular mass index after switching to azilsartan (from 550.1 ± 282.9 pg/mL, to 351.7 ± 152.3 pg/mL, P = 0.002; from 117.0 ± 26.4 g/m2 to 111.3 ± 23.9 g/m2, P = 0.01, respectively). Azilsartan had a significantly stronger hypotensive effect than other angiotensin receptor blockers. Thus, the switch to azilsartan might improve prognosis of hemodialysis patients. We suggest that the strong anti‐hypertensive effect of azilsartan originated from a combination of primary angiotensin receptor blocker class‐effect and a stronger suppression of sympathetic nervous system.

Ruptured Aneurysm of the Sinus of Valsalva Demonstrated by 3-Dimensional Echocardiography

![Figure][1] [![Graphic][3] ][3][![Graphic][4] ][4][![Graphic][5] ][5][![Graphic][6] ][6] A 67-year-old Japanese woman was admitted to our hospital because of orthopnea. Transthoracic echocardiography (Vivid7, GE Healthcare, Milwaukee, Wisconsin) demonstrated a ruptured

Patient with a massive idiopathic thrombosis in the inferior vena cava.

A 50 year-old man with no significant medical history was admitted for dyspnea and left femoral swelling. Contrast-enhanced computed tomography revealed pulmonary thromboembolism (PTE) and a thrombus in the inferior vena cava (IVC). The thrombus extended from the proximal IVC to the left popliteal vein. Therefore, we decided that an IVC filter insertion was difficult to indicate. Urgent IVC and peripheral vein thrombectomy was performed under cardiopulmonary bypass. On postoperative day 1, venous ultrasonography showed residual deep vein thrombosis in the left external iliac-femoral vein and the popliteal vein. The IVC filter insertion was performed to prevent the recurrence of PTE.

History of Coronary Angiography

Diagnostic cardiac catheterization is recommended whenever it is clinically important to define the presence of cardiac disease that cannot be evaluated adequately by noninvasive techniques. Because the risk of a major complication from cardiac catheterization is less than 1% with mortality of less than 0.08%, many doctors can perform the catheterization safely now. We discuss the history of coronary angiography.