Excessive EP4 Signaling in Smooth Muscle Cells Induces Abdominal Aortic Aneurysm by Amplifying Inflammation.

OBJECTIVE: Excessive prostaglandin E2 production is a hallmark of abdominal aortic aneurysm (AAA). Enhanced expression of prostaglandin E2 receptor EP4 (prostaglandin E receptor 4) in vascular smooth muscle cells (VSMCs) has been demonstrated in human AAAs. Although moderate expression of EP4 contributes to vascular homeostasis, the roles of excessive EP4 in vascular pathology remain uncertain. We aimed to investigate whether EP4 overexpression in VSMCs exacerbates AAAs. Approach and Results: We constructed mice with EP4 overexpressed selectively in VSMCs under an SM22α promoter (EP4-Tg). Most EP4-Tg mice died within 2 weeks of Ang II (angiotensin II) infusion due to AAA, while nontransgenic mice given Ang II displayed no overt phenotype. EP4-Tg developed much larger AAAs than nontransgenic mice after periaortic CaCl2 application. In contrast, EP4fl/+;SM22-Cre;ApoE-/- and EP4fl/+;SM22-Cre mice, which are EP4 heterozygous knockout in VSMCs, rarely exhibited AAA after Ang II or CaCl2 treatment, respectively. In Ang II-infused EP4-Tg aorta, Ly6Chi inflammatory monocyte/macrophage infiltration and MMP-9 (matrix metalloprotease-9) activation were enhanced. An unbiased analysis revealed that EP4 stimulation positively regulated the genes binding cytokine receptors in VSMCs, in which IL (interleukin)-6 was the most strongly upregulated. In VSMCs of EP4-Tg and human AAAs, EP4 stimulation caused marked IL-6 production via TAK1 (transforming growth factor-ß-activated kinase 1), NF-κB (nuclear factor-kappa B), JNK (c-Jun N-terminal kinase), and p38. Inhibition of IL-6 prevented Ang II-induced AAA formation in EP4-Tg. In addition, EP4 stimulation decreased elastin/collagen cross-linking protein LOX (lysyl oxidase) in both human and mouse VSMCs. CONCLUSIONS: Dysregulated EP4 overexpression in VSMCs promotes inflammatory monocyte/macrophage infiltration and attenuates elastin/collagen fiber formation, leading to AAA exacerbation.

An appropriately sized soft polyester external stent prevents enlargement and neointimal hyperplasia of a saphenous vein graft in a canine model.

Although the efficacy of external stents for vein grafts in coronary artery bypass grafting has been recognized, the ideal diameter and material of the stent remain controversial. We created a new external stent made of soft polyester mesh and performed an animal experiment using canines. Bilateral saphenous vein grafts were interposed in the bilateral common carotid artery of 10 beagles. The grafts in the left carotid artery were designated as the control group, and those in the right rolled by a soft polyester mesh external stent were designated as mesh group. Two of the 10 animals were sacrificed due to severe wound infection. The other eight were observed by echography for 6 months, and then grafts were extracted and thickness of the neointima of the grafts was measured. The control group showed 146% ± 26% postoperative enlargement of the internal diameter of the vein grafts after 6 months, whereas the mesh group showed only 115% ± 15% after the same duration (P = 0.0003). The median thickness of the neointima in the mesh group (170 µm [range: 150-190]) was significantly thinner than that in the control group (260 µm [range: 220-310], P < 0.0001). Some degree of correlation between the thickness of neointima and proportion of enlargement was noted (r = 0.518, P = 0.0024). A soft polyester mesh external stent for vein grafts successfully suppressed the enlargement of the vein grafts and thickness of the neointima after 6 months.

Proteomic analysis of aortic smooth muscle cell secretions reveals an association of myosin heavy chain 11 with abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a life-threatening disease, and no disease-specific circulating biomarkers for AAA screening are currently available. We have identified a smooth muscle cell (SMC)-specific biomarker for AAA. We cultured aneurysmal tunica media that were collected from eight patients undergoing elective open-repair surgeries. Secreted proteins in culture medium were subjected to liquid chromatography/tandem mass spectrometry. Myosin heavy chain 11 (myosin-11) was identified as a SMC-specific protein in the tunica media-derived secretions of all patients. We then examined myosin-11 protein concentrations by ELISA in plasma samples from patients with AAA ( n = 35) and age-matched healthy control subjects ( n = 34). Circulating myosin-11 levels were significantly higher in patients with AAA than control subjects. The area under the receiver-operating characteristic curve (AUC) of myosin-11 was 0.77, with a specificity of 65% at a sensitivity of 91%. Multivariate logistic regression analysis showed a significant association between the myosin-11 level and presence of AAA. When the myosin-11 level was combined with hypertension, it improved the prediction of AAA (AUC 0.88) more than hypertension per se. We then investigated the correlation between aortic diameter and circulating myosin-11 levels using AAA serum samples from patients undergoing endovascular aneurysm repair ( n = 20). Circulating myosin-11 levels were significantly correlated with maximum aortic diameter. Furthermore, changes in myosin-11 concentrations from the baseline 12 mo after endovascular aneurysm repair were associated with those in aortic diameter. These data suggest that circulating levels of myosin-11, which is a SMC-specific myosin isoform, may be useful as a biomarker for AAA. NEW & NOTEWORTHY Extensive studies have revealed that inflammation- or proteolysis-related proteins are proposed as biomarkers for abdominal aortic aneurysm (AAA). Changes in these protein concentrations are not specific for smooth muscle, which is a major part of AAA pathologies. Hence, no disease-specific circulating markers for AAA are currently available. We found, using secretome-based proteomic analysis on human AAA tunica media, that myosin heavy chain 11 was associated with AAA. Circulating myosin heavy chain 11 may be a new tissue-specific AAA marker.

The AB Portable Driver Generates Higher Drive-Line Pressures Possibly Leading to Accelerated Hemolysis.

The AB5000 Circulatory Support System is paracorporeal pulsatile ventricular assist device. The AB Portable Driver is a portable console for this system. We experienced two cases with accelerated hemolysis while receiving support by the AB Portable Driver. The purpose of this study was to clarify the mechanical differences associated with the hemolysis between the AB5000 console and the AB Portable Driver. The mock circulatory system modeled by an AB5000 ventricle and a blood sampling bag of vinyl chloride was run with an AB5000 console or AB Portable Driver. The peak drive-line pressure, the mean arterial cannula pressure and the pumping rate of the VAD were recorded. The AB5000 console generated a peak drive-line pressure of 280-300 mm Hg in LVAD mode and 210-220 mm Hg in RVAD mode, approximately 100 mm Hg lower than officially documented. In contrast, the AB Portable Driver generated pressures of 310-330 mm Hg in LVAD mode and 230-250 mm Hg in RVAD mode, 65-95 mm Hg higher than officially documented. The AB Portable Driver console generates higher drive-line pressures than the AB5000 console, possibly explaining the accelerated hemolysis.

Evaluation and Influence of Brachiocephalic Branch Re-entry in Patients With Type A Acute Aortic Dissection.

BACKGROUND: Stanford type A acute aortic dissection (A-AAD) extends to the brachiocephalic branches in some patients. After ascending aortic replacement, a remaining re-entry tear in the distal brachiocephalic branches may act as an entry and result in a patent false lumen in the aortic arch. However, the effect of brachiocephalic branch re-entry concomitant with A-AAD remains unknown.Methods and Results:Eighty-five patients with A-AAD who underwent ascending aortic replacement in which both preoperative and postoperative multiple-detector computed tomography (MDCT) scans could be evaluated were retrospectively studied. The presence of a patent false lumen in at least one of the brachiocephalic branches on preoperative MDCT was defined as brachiocephalic branch re-entry, and 41 patients (48%) had this. Postoperatively, 47 of 85 (55%) patients had a patent false lumen in the aortic arch. False lumen remained patent after operation in 34 out of the 41 (83%) patients with brachiocephalic branch re-entry, as compared to that in 13 of the 44 (30%) patients without such re-entry (P<0.001). Brachiocephalic branch re-entry was a significant risk factor for a late increase in the aortic arch diameter greater than 10 mm (P=0.047). CONCLUSIONS: Brachiocephalic branch re-entry in patients with A-AAD is related to a patent false lumen in the aortic arch early after ascending aortic replacement and is a risk factor for late aortic arch enlargement.

Mechanical support of the pressure overloaded right ventricle: an acute feasibility study comparing low and high flow support.

The objectives of this study were to assess the feasibility of low flow right ventricular support and to describe the hemodynamic effects of low versus high flow support in an animal model of acute right ventricular pressure overload. A Synergy Pocket Micro-pump (HeartWare International, Framingham, MA) was implanted in seven sheep. Blood was withdrawn from the right atrium to the pulmonary artery. Hemodynamics and pressure-volume loops were recorded in baseline conditions, after banding the pulmonary artery, and after ligating the right coronary artery in these banded sheep. End-organ perfusion (reflected by total cardiac output and arterial blood pressure) improved in all conditions. Intrinsic right ventricular contractility was not significantly impacted by support. Diastolic unloading of the pressure overloaded right ventricle (reflected by decreases in central venous pressure, end-diastolic pressure and volume, and ventricular capacitance) was successful, but with a concomitant and flow-dependent increase of the systolic afterload. This unloading diminished with right ventricular ischemia. Right ventricular mechanical support improves arterial blood pressure and cardiac output. It provides diastolic unloading of the right ventricle, but with a concomitant and right ventricular assist device flow-dependent increase of systolic afterload. These effects are most distinct in the pressure overloaded right ventricle without profound ischemic damage. We advocate the low flow strategy, which is potentially beneficial for the afterload sensitive right ventricle and has the advantage of avoiding excessive increases in pulmonary artery pressure when pulmonary hypertension exists. This might protect against the development of pulmonary edema and hemorrhage.

Lipoprotein Apheresis Alleviates Treatment-Resistant Peripheral Artery Disease Despite the Normal Range of Atherogenic Lipoproteins: The LETS-PAD Study.

AIM: Peripheral artery disease (PAD) severely impairs patient prognosis and quality of life (QOL). Although lipoprotein apheresis (LA) has been applied to patients with PAD and elevated serum atherogenic lipoproteins, we hypothesized that LA can be effective for treating PAD even in patients with controlled serum lipoproteins through pleiotropic anti-atherosclerotic effects beyond lipoprotein removal. This study aimed to evaluate the efficacy of LA in patients with treatment-resistant PAD and controlled serum lipoproteins focusing on QOL. METHODS: In a single-arm prospective study, 30 patients with refractory PAD who had controlled serum lipoproteins underwent sequential LA sessions using dextran sulfate adsorption columns, aiming to complete 10 sessions. The ankle-brachial pressure index (ABI) and vascular QOL (VascuQOL) score were evaluated as the primary outcomes. Secondary outcomes included reactive hyperemia index (RHI) and biological antioxidant potential (BAP) as an endothelial function test and serum antioxidative-capacity evaluation, respectively. RESULTS: ABI significantly increased after LA sessions (pre-treatment 0.60±0.09 vs. post-treatment 0.65±0.13, p=0.023). Total VascuQOL score (3.7±1.1 vs 4.6±1.1, p＜0.001) and RHI (1.70±0.74 vs 2.34±1.76, p=0.023) significantly improved after the LA sessions. BAP tended to increase after the LA sessions, and the change reached statistical significance 3 months after treatment. CONCLUSION: ABI and QOL improved after a series of LA sessions in conventional treatment-resistant PAD patients with controlled serum lipoprotein levels. Increased antioxidative capacity and ameliorated endothelial function were observed after the LA treatment.

Mechanism of autograft insufficiency after the Ross operation in children.

BACKGROUND: It is unclear how autografts grow and dilate after the Ross operation in children. We analysed autograft growth and dilatation in children who underwent the Ross operation and examined the relationship of these factors to autograft failure. METHODS: From our institutional database, we retrospectively identified 33 children who underwent the Ross operation without aortic root reinforcement (mean age 9.9 years) and had normal body measurements and echocardiographic data throughout follow-up. RESULTS: Autograft insufficiency developed in 10 patients 5.1 years after the Ross operation. The average Z score at the development of autograft insufficiency was -0.1 (range from -2.0 to 6.1). The proportions of patients who remained free of autograft insufficiency at 5 and 10 years were 87.2% and 55.7%, respectively. A consistent trend in the time course of Z score was not found in any age group studied. CONCLUSIONS: Autograft growth and dilation after the Ross operation varied widely among patients, and the incidence of autograft insufficiency was independent of annulus size.

A case of ventricular triple rupture after an acute myocardial infarction.

Cardiac rupture, such as ventricular free-wall rupture, ventricular septal perforation, and papillary muscle rupture, is a life-threatening complication of acute myocardial infarction. Herein, we report a very rare case of combining these three types of ventricular rupture. A 71-year-old woman underwent mitral valve replacement and left ventricular free-wall rupture repair after an acute myocardial infarction. She was transferred to our hospital under mechanical support by venoarterial extracorporeal membrane oxygenation and intra-aortic balloon pump due to circulatory collapse. Transthoracic echocardiography revealed a left-to-right shunt caused by ventricular septal perforation. The patient underwent endoventricular patch plasty for septal defect closure. Unfortunately, a prolonged postoperative course led to the development of multi-organ failure followed by fatal outcome on day 32 postoperatively. To our best knowledge, this is the first reported case of ventricular triple rupture associated with acute myocardial infarction.

Rapid anticalcification treatment for glutaraldehyde-fixed autologous tissue in cardiovascular surgery.

BACKGROUND: Glutaraldehyde (GA)-fixed autologous tissues, including the pericardium, are widely used as patches and valve substitutes in cardiovascular surgery. However, GA treatment causes tissue calcification. No rapid anticalcification method has been established for use during surgery. Here, we aimed to establish a rapid anticalcification method using ethanol, as has already been demonstrated for bioprosthetic valves. METHODS: Thoracic aorta tissues were first fixed with GA for 3 min and then treated with ethanol for 0 (group 2), 10 (group 3), 20 (group 4), and 30 (group 5) min; untreated tissues (group 1) served as the control. The treated tissues were subdermally implanted into 3-week-old male Wistar rats and kept in place for 28 days. The calcification in each explant was semiquantitatively evaluated by annotating and measuring the area using virtual slides, and the data obtained were statistically analyzed. RESULTS: Semiquantitative analysis revealed that calcification of the implants from the untreated group (group 1; P = 0.0014) and groups 4 (P = 0.0014) and 5 (P = 0.0031) was significantly lower than that of implants from group 2. Moreover, implants from group 3 showed a tendency toward decreased calcification, although it was not significant (P = 0.0503). CONCLUSIONS: A rapid ethanol treatment prevents calcification of GA-fixed tissues in a rat model of subdermal implantation. This method may facilitate effective and rapid anticalcification of autologous tissues for use during cardiovascular surgery.

Prognostic significance of the preoperative C-reactive protein-to-albumin ratio in patients with colorectal cancer.

BACKGROUND: The aim of the present study was to determine the utility of the C-reactive protein-to-albumin ratio (CAR) for predicting the overall survival (OS) in locally advanced colorectal cancer (CRC) patients. PATIENTS AND METHODS: This retrospective multicenter study was performed using data from a prospectively maintained database of pathological Stage II or III patients undergoing CRC surgery at the Yokohama City University, Department of Surgery, and its affiliated institutions between April 2000 and March 2016. The risk factors for the OS were identified. RESULTS: A CAR of 0.03 was considered to be the optimal cutoff point for classification based on the 1-, 3-, and 5-year survival rates and receiver operating characteristic curve. The OS rates at 3 and 5 years after surgery were 92.4% and 85.7% in the CAR-low group, respectively, and 86.7% and 81.1% in the CAR-high group. A multivariate analysis showed that the CAR was a significant independent risk factor for the OS. When comparing the patients' demographic and clinical characteristics between the CAR ≤0.03 and >0.03 groups, the incidence of patients who received adjuvant chemotherapy and the incidence of postoperative complications were significantly different between the two groups. CONCLUSION: The present study showed that the preoperative CAR was a risk factor for the OS in patients who underwent surgery for CRC. To improve the patients' survival, CAR might be a useful tool for devising treatment strategies.

[Chemotherapy with linezolid for chronic synthetic graft infection].

Infection of thoracic synthetic grafts is a serious problem, potentially leading to septicemia. Total removal of infected grafts might be too invasive for patients in poor general condition or who have long synthetic grafts. Effective and safe chemotherapy regimens are needed to control infection. A 75-year-old man with infected synthetic grafts of the ascending aorta, aortic arch, descending aorta, and thoracoabdominal aorta caused by methicillin-resistant Staphylococcus aureus was admitted to our hospital because of septicemia. He had previously received vancomycin for about 1 year at an outpatient clinic. The blood culture after admission was positive for vancomycin-intermediate Staphylococcus aureus. Linezolid was effective against septicemia, but caused side effects, such as blurred vision, severe diarrhea, and thrombocytopenia. Intermittent oral treatment with linezolid (1,200 mg/day) was then given for 7 days every 2 weeks. This treatment decreased the incidence of the side effects and had a beneficial effect on the infection.

Tracheo-innominate artery fistula with continuous bleeding successfully treated through the suprasternal approach: a case report.

BACKGROUND: Tracheo-innominate artery fistula (TIF) is a rare but fatal complication occurring after tracheotomy. Brachiocephalic trunk transection, one of the surgical treatments for TIF, is mostly associated with a full or partial median sternotomy. We describe a case of TIF with continuous bleeding, which was successfully treated with brachiocephalic trunk transection through a collar incision without the need for median sternotomy. CASE PRESENTATION: Case 1. An 18-year-old man was referred to our hospital with bleeding from a tracheal stoma, which had ceased prior to admission. TIF was suspected after examination. Innominate artery transection was performed through a collar incision. TIF was not revealed when we cut the innominate artery anterior wall open; therefore, we opted for preventive surgical intervention. The post-operative course was uneventful, and the patient was asymptomatic at the 3-year follow-up. Case 2. A 14-year-old male patient was admitted to our hospital with bleeding from a tracheal stoma, and TIF was suspected after examination. There was persistent bleeding when the cuff of the tracheotomy tube was deflated. Brachiocephalic trunk transection was performed through a collar incision using balloon occlusion. The post-operative course was uneventful, and rebleeding has not occurred 2 years later. CONCLUSIONS: Brachiocephalic trunk transection without any median sternotomy may offer the benefits of post-operative infection prevention. In patients with suspected continuous bleeding, using a balloon catheter may be a safe and effective method of treatment.

Low-density-lipoprotein apheresis-mediated endothelial activation therapy to severe-peripheral artery disease study: Rationale and study design.

A novel approach is required for standard therapy-resistant peripheral arterial disease (PAD). This is a single-center, single-arm, interventional study (LDL Apheresis-Mediated Endothelial Activation Therapy to Severe-Peripheral Artery Disease study), which aims to evaluate the efficacy and safety of lipoprotein apheresis (LA) with a dextran sulfate cellulose column in PAD with controlled serum cholesterol levels. The study participants have standard therapy-resistant PAD with controlled serum cholesterol levels. A total of 35 patients undergo 10 sessions of LA therapy. The ankle-brachial index and vascular quality of life questionnaire are assessed before and after the treatment period as primary outcomes. Registration of patients began in November 2015 and is planned to be concluded in October 2020.

[Mitral valve papillary fibroelastoma; report of a case].

A 65-year-old woman was admitted to our hospital with a diagnosis of cerebral infarction. She had incomplete paralysis of the right upper extremity. The echocardiogram showed a soft, mobile mass on the atrial side of the mitral posterior leaflet. Surgical treatment was performed 3 weeks after the episode of cerebral infarction. The mass originated from the P1 portion of the posterior leaflet. It was soft and fragile and was carefully resected along with the endocardium of the leaflet, from which it arose. The leaflet was reconstructed with direct 6-0 proline sutures. There was no mitral insufficiency. The histological diagnosis was a papillary fibroelastoma of the mitral valve. The postoperative course was uneventful, with no neurologic complications.

Aortic erosion occurring in over 5 years after Amplatzer septal Occluder implantation for secundum atrial septal defect: a case report.

BACKGROUND: Aortic erosion is a serious complication that usually occurs shortly after Amplazter Septal Occluder (ASO) implantation for atrial septal defect (ASD). CASE PRESENTATION: A seven-year-old girl was diagnosed with secundum ASD without symptoms. Transesophageal echocardiography (TEE) showed a defect of 20 mm in diameter in the fossa ovalis without aortic rim. An ASO device of 24 mm in diameter was selected and electively implanted. The "A-shape" of the device was confirmed by intraoperative TEE, a landmark finding indicating the proper implantation of ASO in patients without aortic rim. After an uneventful postoperative course of 5 years and 10 months, she was transferred to our unit due to cardiogenic shock. Her echocardiogram in emergency room showed pericardial effusion with collapsed right ventricle. Given her history of ASO and the observation of the sequentially increasing pericardial effusion, we diagnosed her with acute cardiac tamponade due to aortic erosion. Emergency pericardiotomy was then performed to improve the hemodynamic condition. Fresh clots were found, so we immediately prepared the cardiopulmonary bypass circuit and explored the damage to the aorta, in which the clots had accumulated. Bleeding suddenly started when the clots were removed. We then inserted the cannulae for perfusion and venous drainage. The clots were removed, and tears were found in both the lateral side of the ascending aorta and the right atrial wall. Intraoperative TEE showed that an edge of the ASO device was directly touching the aortic wall and the Doppler color-flow imaging showed blood flow through this lesion. The erosive lacerations of both the ascending aorta and right atrium were detected from the inside after achieving cardioplegic cardiac arrest. The ascending aorta was obliquely incised, and the laceration was closed from inside the aortic root. The postoperative course was uneventful. She has been doing well for 5 years since the surgery. CONCLUSIONS: We experienced and successfully treated a rare case of acute cardiac tamponade caused by aortic erosion 5 years and 10 months after ASO implantation.

Differences of patients' characteristics in acute type A aortic dissection - surgical data from Belgian and Japanese centers.

BACKGROUND: It is well known that there are major differences between the Japanese and Western population regarding the incidence of ischemic heart disease and stroke. The purpose of this study was to evaluate differences of patients' characteristics between Belgian and Japanese cohort with acute type A aortic dissection. METHODS: In 487 patients (297 male patients, mean age 61.9 ± 12.2 yrs) who underwent surgery for acute type A aortic dissection, baseline preoperative and intraoperative data were collected. Belgian patients (n = 237) were compared to Japanese patients (n = 250). Clinical data included patient demographics, history, status at presentation, imaging study results and intraoperative findings. RESULTS: The Japanese cohort had significantly more women (48.8% vs. 28.7%, p < 0.0001), lower BMI (24.2 vs. 26.4, p < 0.0001) and lower prevalence of hypertension (49.2% vs. 65.8%, p = 0.0002). More DeBakey type I dissections and less type III dissections with retrograde extension were reported in Belgium than in Japan (77.2% vs. 48.4%, p < 0.0001, 3.4% vs. 38.7%, p < 0.0001, respectively). More entries were found in the ascending aorta (78.5% vs. 58.5%, p < 0.0001) and aortic arch (24.9% vs. 13.7%, p = 0.0018) in Belgian patients than in Japanese patients, who had more entries in the descending aorta or undetected entries. CONCLUSIONS: In acute type A aortic dissection, Belgian patients reveal striking differences from Japanese patients regarding gender distribution, entry tear location and type of dissection. Japanese women are more likely to develop acute type A aortic dissection than Belgian women. (234 words).

Stanford type B aortic dissection is more frequently associated with coronary artery atherosclerosis than type A.

BACKGROUND: The relationship between aortic dissection and coronary artery disease is not clear. The purpose of this study was to clarify the difference in the rate of coronary artery atherosclerosis between Stanford type A and type B aortic dissection by reviewing our institutional database. METHODS: One hundred and forty-five patients (78 males, 67 females; mean age: 60 ± 12 years) admitted to our hospital with acute aortic dissection who underwent coronary angiography during hospitalization from 2000 through 2002 were enrolled in this study. The background characteristics, coronary risk factors, and coronary angiography findings (number of significant stenoses, stenoses according to Bogaty standards, extent index) of patients were compared between type A (Group A; n = 71) and type B dissection (Group B; N = 74). RESULTS: Significantly more patients had prior histories of complications from ischemic heart disease in Group B than in Group A (P = 0.04), with no significant differences in comparison to other risk factors observed except for hypertension. Significantly (p = 0.005) more stenoses were observed in Group B (1.54 ± 0.04) than in Group A (0.38 ± 0.1). A significantly higher (P < 0.05) index score indicating the severity of coronary atherosclerosis was observed in Group B (1.49 ± 0.09) than in Group A (0.72 ± 0.07). CONCLUSIONS: Stanford type B acute aortic dissection was significantly more frequently associated with coronary artery atherosclerosis than type A.

Early reperfusion strategy improves the outcomes of surgery for type A acute aortic dissection with malperfusion.

OBJECTIVE: The control of malperfusion is the key to improving the outcomes of surgery for type A acute aortic dissection. We revised our treatment strategy to reperfuse each ischemic organ before central repair. METHODS: Our current early reperfusion strategy consists of percutaneous coronary artery intervention for coronary malperfusion, direct surgical fenestration for carotid artery occlusion, active perfusion of the superior mesenteric artery for visceral malperfusion, and external shunting from the brachial artery to the femoral artery for lower limb ischemia. Central repair is performed without delay after reperfusion therapy, but if irreversible organ damage is recognized, further aggressive treatment is discontinued. RESULTS: Among 438 patients who underwent initial treatment for type A acute aortic dissection, malperfusion in one or more organs was diagnosed in 108 patients (24%). We applied an early reperfusion strategy in 33 patients, (coronary, 14 patients; carotid, 4; visceral, 7; lower extremity, 8). Central repair was then performed in 28 patients. One patient (3.6%) died of pneumonia; 27 patients overcame the ischemic organ damage and survived. Among the 108 patients with malperfusion, 10 patients (9.3%) were treated medically without early reperfusion and central repair. During the same period, mortality from central repair procedures in patients with malperfusion who had not received early reperfusion therapy was 12 of 65 (18%), and the mortality of patients without malperfusion was 9 of 262 (3.4%). Malperfusion was a serious risk factor for hospital death, but the mortality rate of the patients with an early reperfusion strategy was significantly (P < .01) lower than the patients without early reperfusion. CONCLUSIONS: Our strategy might improve the outcomes of surgery for type A acute aortic dissection with malperfusion. This strategy enables us to avoid unproductive central repair procedures in irreversibly damaged patients.

A selective antagonist of prostaglandin E receptor subtype 4 attenuates abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a progressive disease that has an increasing prevalence with aging, but no effective pharmacological therapy to attenuate AAA progression is currently available. We reported that the prostaglandin E receptor EP4 plays roles in AAA progression. Here, we show the effect of CJ-42794, a selective EP4 antagonist, on AAA using two mouse models (angiotensin II- and CaCl2 -induced AAAs) and human aortic smooth muscle cells isolated from AAA tissue. Oral administration of CJ-42794 (0.2 mg/kg per day) for 4 weeks significantly decreased AAA formation in ApoE-/- mice infused with angiotensin II (1 µg/kg per min), in which elastic fiber degradation and activations of matrix metalloproteinase (MMP)-2 and MMP-9 were attenuated. Interleukin-6 (IL-6) proteins were highly expressed in the medial layer of angiotensin II-induced mouse AAA tissues, whereas this expression was significantly decreased in mice treated with CJ-42794. AAA formation induced by periaortic CaCl2 application in wild-type mice was also reduced by oral administration of CJ-42794 for 4 weeks. After oral administration of CJ-42794 beginning 2 weeks after periaortic CaCl2 application and continuing for an additional 4 weeks, the aortic diameter and elastic fiber degradation grade were significantly smaller in CJ-42794-treated mice than in untreated mice. Additionally, in smooth muscle cells isolated from human AAA tissues, stimulation of CJ-42794 inhibited PGE2 -induced IL-6 secretion in a dose-dependent manner and decreased PGE2 -induced MMP-2 activity. These data suggest that inhibition of EP4 has the potential to be a pharmacological strategy for attenuation of AAA progression.