2,5-Dimethyl-celecoxib induces early termination of inflammatory responses by transient macrophage accumulation and inhibits the progression of cardiac remodeling in a mouse model of cryoinjury-induced myocardial infarction.

In our previous study, we reported that 2, 5-dimethyl-celecoxib (DM-C), a derivative of celecoxib, prevents cardiac remodeling in different mouse models of heart failure, including myocardial infarction (MI). The inflammatory response after MI affects the progression of cardiac remodeling, wherein the immune cells, mainly macrophages, play crucial roles. Therefore, we evaluated the effect of DM-C on macrophages in a cryoinjury-induced myocardial infarction (CMI) mouse model. We observed that DM-C attenuated the deterioration of left ventricular ejection fraction and cardiac fibrosis 14 d after CMI. Gene expression of pro-inflammatory cytokines at the infarct site was reduced by DM-C treatment. Analysis of macrophage surface antigens revealed that DM-C induced transient accumulation of macrophages at the infarct site without affecting their polarization. In vitro experiments using peritoneal monocytes/macrophages revealed that DM-C did not directly increase the phagocytic ability of the macrophages but increased their number, thereby upregulating the clearance capacity. Moreover, DM-C rapidly excluded the cells expressing necrotic cell marker from the infarct site. These results suggested that DM-C enhanced the clearance capacity of macrophages by transiently increasing their number at the infarct site, and terminated the escape from the inflammatory phase earlier, thereby suppressing excessive cardiac remodeling and ameliorating cardiac dysfunction.

Impact of sarcopenia on long-term survival after cardiac surgery for end-stage renal disease patients.

BACKGROUND: The long-term mortality of end-stage renal disease (ESRD) patients is still unsatisfactory. Therefore, long-term risk assessments in ESRD patients undergoing cardiac surgery are needed. Recently, sarcopenia is major concern in cardiac surgery because of its association with poor long-term survival. However, the impact of sarcopenia on the long-term survival of ESRD patients undergoing cardiac surgery is not well understood. METHODS: Eighty-two ESRD patients who underwent elective cardiac surgery were enrolled. Sarcopenia was identified based on noncontrast abdominal computed tomography. The impact of preoperative and intraoperative factors on long-term survival was investigated. RESULTS: Forty-three patients (52%) were diagnosed with sarcopenia. The in-hospital mortality rate was 4.9%. The 5-year overall survival rate was 48%. The multivariate analyses revealed that STS score ≥ 4 (odds ratio, 6.0; confidence interval, 2.5-14.7; p < 0.01) and presence of sarcopenia (odds ratio, 2.4; confidence interval, 1.3-4.5; p = 0.03) were independent risk factors for overall survival. The 5-year survival rates of low-risk (Society of Thoracic Surgeons score of < 4) patients without sarcopenia, low-risk with sarcopenia, more than intermediate-risk (Society of Thoracic Surgeons score of ≥ 4) without sarcopenia, and more than intermediate-risk with sarcopenia groups were 80%, 51%, 50%, and 26%, respectively. CONCLUSIONS: Among the ESRD patients, the low risk without sarcopenia group showed an excellent long-term survival, in contrast to more than intermediate-risk patients with sarcopenia, who can expect poor long-term survival. Preoperative assessment of sarcopenia in addition to the surgical risk score can be useful in developing a therapeutic strategy.

2,5-Dimethylcelecoxib attenuates cardiac fibrosis caused by cryoinjury-induced myocardial infarction by suppressing the fibroblast-to-myofibroblast transformation via inhibition of the TGF-ß signaling pathway.

We previously reported that 2,5-dimethylcelecoxib (DM-C), a derivative of celecoxib, lacks cyclooxygenase-2 inhibitory effects and suppresses cardiac remodeling by activating glycogen synthase kinase-3 (GSK-3). However, it remains unclear whether DM-C attenuates fibroblast-to-myofibroblast transformation (FMT), which plays a key role in cardiac fibrosis. Therefore, we evaluated the effect of DM-C on FMT using a cryoinjury-induced myocardial infarction (CMI) mouse model. We found that DM-C attenuated the deterioration of left ventricular ejection fraction after CMI by decreasing cardiac fibrosis. Analysis of the expression level of α-smooth muscle actin (α-SMA), a marker for myofibroblasts, indicated that DM-C decreased FMT at the cardiac injury site. To investigate the mechanism by which DM-C attenuated FMT, fibroblasts obtained from the heart were stimulated with TGF-ß to induce FMT, and the effect of DM-C was analyzed. DM-C suppressed the expression of α-SMA and the phosphorylation levels of Smad 2/3 and GSK-3, indicating that DM-C suppressed α-SMA expression by inhibiting the transforming growth factor (TGF)-ß signaling pathway via activation of GSK-3. DM-C decreased the expression of collagen, connective tissue growth factor (CTGF) and Snail, which are also known to accelerate cardiac fibrosis. These results suggested that DM-C attenuated cardiac fibrosis by suppressing FMT at the injured site after CMI by inhibiting the TGF-ß signaling pathway via activation of GSK-3. Thus, DM-C has potential against cardiac disease as a novel anti-fibrotic agent.

Significant delayed aortic dilatation after tetralogy of Fallot repair: a case report.

BACKGROUND: Aortic dilatation may occur in some patients even after complete repair of tetralogy of Fallot (TOF). The progression rate of the aortic diameter is so slow, and the incidence of aortic dissection is so low that it is suspected that frequent imaging of the aorta may not be necessary. CASE PRESENTATION: We describe an asymptomatic 41-year-old man with hypertension in whom aortic dilatation was accidentally discovered 39 years after TOF repair. He underwent ambulatory follow-up without any difficulty for 21 years after the repair. Contrast-enhanced computed tomography revealed significant aortic dilatation (maximum diameter of 88 mm at the sinus of Valsalva), and echocardiography revealed severe aortic regurgitation, which seemed to progress during the last 18 years without any evaluation or follow-up. The Bentall procedure was successfully performed using a valved graft, under deep hypothermic circulatory arrest with antegrade cerebral perfusion, and his postoperative course was uneventful. Histopathological examination of ascending aorta specimens revealed severe cystic medial degeneration. CONCLUSIONS: Keeping in mind that a patient with rapid progression of the aortic dilatation after TOF repair exist, periodic follow-up for evaluation of the aorta is essential in patients with TOF.

A case of giant right coronary artery aneurysm due to IgG4-related disease.

A man diagnosed with immunoglobulin G4 (IgG4)-related disease at the age of 65 years underwent abdominal aortic replacement due to an abdominal aortic aneurysm. In the same hospitalization period, a small coronary artery aneurysm was noticed. He was treated with corticosteroids and his serum IgG levels returned to normal. After experiencing sudden chest pain at age 74 years, coronary angiography showed that the size of the aneurysm had increased dramatically. He underwent coronary artery bypass graft and coronary artery resection without using cardiopulmonary bypass. Thus, we conclude that observation of aneurysms in patients with IgG4-related disease is important, even under corticosteroid therapy.

[A Case of Successful Surgery for Adult Partial Atrioventricular Septal Defect].

We report a case of a 55-year-old male who had been diagnosed with mitral regurgitation and atrial septal defect 5 years earlier. He was referred to our institution because of worsening of mitral regurgitation accompanied by exertional dyspnea. As an echocardiography showed atrioventricular valve regurgitation and ostium primum atrial septal defect, but without ventricular septal defect, he was diagnosed as having partial atrioventricular septal defect (pAVSD). An operation was performed through median sternotomy. The anterior atrioventricular leaflet had a cleft and thickening with calcification. Suturing the cleft could not control the regurgitation. Incomplete coaptation was seen at the edge of the anastomosis site of the cleft, where the severe calcification had been identified. A rough zone including a part of the chordae tendineae was sutured in order to compensate for the gap. The atrioventricular septal defect was closed with an autologous pericardial patch. He was discharged uneventfully on the 24th postoperative day and has been followed up without complications for 1.5 years.