Ayako Takasaka

Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Attenuates Restenosis of the Artery After Injury

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a membrane protein that can support the binding, internalization, and proteolytic degradation of oxidized low-density lipoprotein. The LOX-1 expression increases in the neointima after balloon injury. To develop an efficient compound to inhibit LOX-1, we designed and synthesized a novel gene silencer pyrrole-imidazole (PI) polyamide targeting the rat LOX-1 gene promoter (PI polyamide to LOX-1) to the activator protein-1 binding site. We examined the effects of PI polyamide to LOX-1 on the LOX-1 promoter activity, the expression of LOX-1 mRNA and protein, and neointimal hyperplasia of the rat carotid artery after balloon injury. PI polyamide to LOX-1 significantly inhibited the rat LOX-1 promoter activity and decreased the expression of LOX-1 mRNA and protein. After balloon injury of the arteries, PI polyamide to LOX-1 was incubated for 10 minutes. Fluorescein isothiocyanate–labeled PI polyamide was distributed to almost all of the nuclei in the injured artery. PI polyamide to LOX-1 (100 &mgr;g) significantly inhibited the neointimal thickening by 58%. PI polyamide preserved the re-endothelialization in the injured artery. PI polyamide significantly inhibited the expression of LOX-1, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9 mRNAs in the injured artery. The synthetic PI polyamide to LOX-1 decreased the expression of LOX-1 and inhibited neointimal hyperplasia after arterial injury. This novel gene silencer PI polyamide to LOX-1 is, therefore, considered to be a feasible agent for the treatment of in-stent restenosis.

Surgery for Ruptured Abdominal Aortic Aneurysm with an Aortocaval and Iliac Vein Fistula

The purpose of this study was evaluate the operative procedure and outcome of abdominal aortic aneurysm (AAA) patients with aortocaval fistula (ACF) and iliac vein fistula. From 1982 through 2004, we experienced five AAA patients associated with spontaneous aortocaval and aortoiliac venous fistula who underwent repair of AAA. Three patients were in hypovolemic shock, including one patient with cardiopulmonary arrest on admission who required cardiopulmonary resuscitation before surgery. These three ACF patients with hypovolemic shock underwent emergency operation and two patients with stable hemodynamic state underwent urgent operation. One of two ACF patients with stable condition was associated with unstable angina. One AAA patient with ACF-complicated angina underwent AAA repair with coronary artery bypass grafting; the remaining four patients underwent 3 bifurcated graft and 1 tube graft implantation. All surgical treatment of the fistula included direct closure within the aorta under digital compression in four patients and inferior vena cava clamp in one. The mortality rate was 25%. One ACF patient with retroperitoneal hematoma died of bleeding. Survival for ACF depends on early diagnosis and prompt surgical repair. Aortocaval fistula complicated with a rupture of aneurysm into retroperitoneal space had a severe fatal prognosis compared with uncomplicated ACF.

Long-Term Results (Three-Year) of Emergency Coronary Artery Bypass Grafting for Patients With Unstable Angina Pectoris

Satisfactory results are achieved by elective coronary artery bypass grafting (CABG), but the results of emergency CABG are less than satisfactory and readmission for cardiac events is common. We examined long-term results of emergency CABG for unstable angina pectoris from the viewpoints of preoperative, intraoperative, and postoperative factors. Subjects were 154 patients who underwent emergency CABG for unstable angina pectoris. Operative mortality rate was 1.9%. Univariate analysis showed female gender, chronic renal failure, hemodialysis, nonuse of human atrial natriuretic peptide (hANP), nonuse of angiotensin II receptor blockers and aldosterone blockers, 3-month postoperative brain natriuretic peptide level > or =200 pg/ml, and 3-month postoperative aldosterone level > or =100 pg/ml as risk factors for late cardiac events. Multivariate analysis confirmed nonuse of hANP, nonuse of aldosterone blockers, 3-month brain natriuretic peptide level > or =200 pg/ml, and 3-month aldosterone level > or =100 pg/ml as risk factors. Intraoperative hANP infusion and postoperative treatment with aldosterone blockers and angiotensin II receptor blockers can control the renin-angiotensin-aldosterone system, inhibit left ventricular remodeling, decrease extent of infarction, and improve cardiac function, yielding a favorable long-term prognosis. The best results are obtained by combining good surgical technique and perioperative management with the long-term outcome in mind.

Efficacy of prophylactic treatment with selective serotonin reuptake inhibitors for depression after open-heart surgery

PurposeThe aim of the present study was to evaluate the efficacy of prophylactic treatment with selective serotonin reuptake inhibitors (SSRIs) in female patients at high risk of suffering depression after cardiac surgery.MethodsFemale patients (n = 58; group I) who were over 70 years of age or who had undergone emergency surgery were administered prophylactic treatment with paroxetine immediately after surgery. The hospital mortality and morbidity data of these patients were compared with those of 59 patients (group II) without prophylactic medication.ResultsThe Center for Epidemiological Studies Depression Scale (CES-D) score at 10 days after surgery was significantly lower in group I (15.2 ± 7.8) than in group II (21.8 ± 7.5, P = 0.0018). The incidence of depression (I: 12.1% vs II: 64.4%, P < 0.0001) and pneumonia (I: 0% vs II: 10.2%, P = 0.0127) were significantly lower in group I than in group II. In addition, the duration of postoperative hospital stay was significantly shorter for group I than for group II (I: 15.9 ± 56.5 vs II: 23.4 ± 20.5 days, P = 0.0102). The hospital mortality rates were similar.ConclusionThe quality of life of patients with depression after open-heart surgery is poor. The early administration of prophylactic medication is therefore necessary for those patients at risk for developing depression.

Total arch replacement and open stent graft implantation using a newly developed stent graft: Report of a case

We experienced a case in which a total arch replacement and an open stent implantation were performed for a distal aortic arch aneurysm using a newly developed stent graft (Ube CL-0201; Ube Medical, Tokyo, Japan). This novel stent graft is composed of a woven polyester graft and a nickel-titanium alloy stent, and has been under evaluation in clinical trials at four institutions in Japan, including our hospital, since 2008. The patient was weaned from the respirator on the day after surgery, and 9 months have passed since the surgery with no complications. A follow-up computed tomography scan showed that the stent part was sufficiently open, and no complications, such as an endoleak, have been observed.

Rapid aortic enlargement requiring surgery in patients with chronic type B aortic dissection.

We report the relationship between rapid aortic enlargement of chronic type B aortic dissection and sleep disorder due to anxiety after Tohoku disaster. Five patients underwent surgical procedures due to rapid aortic enlargement after the earthquake disaster. They reported that their morning blood pressure increased to approximately 190 mm Hg after the disaster. They were troubled with severe insomnia due to anxiety about the continuing aftershocks. In primary care for patients with mental stress after a big disaster, it is important to keep a careful monitoring of blood pressure besides assessment of anxiety and sleep.