The significance of chymase in the progression of abdominal aortic aneurysms in dogs.

In this study, we investigated the effect of a specific chymase inhibitor, NK3201, in the progression of abdominal aortic aneurysm in a dog experimental model. Abdominal aortic aneurysms were induced in dogs by injecting elastase into the abdominal aorta. NK3201 (1 mg/kg per day, p.o.) or a placebo was started 3 days before elastase injection and continued for 8 weeks after the injection. On abdominal ultrasound, the aortic diameter was seen to gradually expand in the placebo-treated group, but not in the NK3201-treated group. Eight weeks after elastase injection, the ratio of the medial area to the total area in the placebo-treated group was significantly smaller than that in the normal group, but it was significantly larger than that in the NK3201-treated group. In addition to chymase activity, angiotensin II-forming and matrix metalloproteinase-9 activities were significantly higher in the placebo-treated group than in the normal group; in the NK3201-treated group, all of these activities were significantly decreased. On immunohistochemical analyses, there was a significantly greater number of chymase-positive cells in the placebo-treated group than in the normal group, but the number was significantly smaller in the NK3201-treated group than in the placebo-treated group. Thus, chymase inhibition may become a useful strategy for preventing abdominal aortic aneurysms.

Young adult patients with short dissection length and thrombosed false lumen without ulcer-like projections are liable to have false-negative results of D-dimer testing for acute aortic dissection based on a study of 113 cases.

BACKGROUND: Previous reports indicate that D-dimer testing (DT) for acute aortic dissection (AAD) has a sensitivity of 100%, but each study comprised less than 30 patients. The aim of this study was to evaluate the positive rate and factors related to the results of DT for AAD in a larger population. METHODS AND RESULTS: DT (cutoff; upper normal limit) was performed for 113 consecutive AAD patients within 24 h of symptom onset. In total, 104 (92%) patients exhibited positive DT. The positive rate of DT showed a low tendency in patients aged less than 70 years and for a time interval from symptom onset to admission within 120 min, and there were significant differences between those with and without a thrombosed false lumen (TFL) (86.4% (n=59) vs 98.1% (n=54), p=0.033), complete TFL (excluding patients with ulcer-like projection (ULP) from those with a TFL) (81.1% (n=37) vs 97.4% (n=76), p=0.005) and length score (1 (n=28); 78.6%, 2 (n=40); 95.0%, 3 (n=45); 97.8%, p=0.005). Multivariate analysis demonstrated age (odds ratio =1.164, p=0.013), complete TFL (0.048, 0.030) and length score (6.271, 0.033) as independent factors. CONCLUSIONS: Physicians should be aware that younger patients with short dissection length and a TFL without ULP are liable to have false-negative DT results.

Serum heart-type fatty acid-binding protein concentration positively correlates with the length of aortic dissection.

BACKGROUND: Patients with aortic dissection (AD) often demonstrate positive heart-type fatty acid-binding protein (H-FABP), but its significance is unclear. METHODS AND RESULTS: In 63 of 64 consecutive AD patients, the serum H-FABP concentration was measured and the H-FABP positive rate calculated (cutoff value: 6.2 ng/ml) for each of following factors: (1) with or without dissection of the ascending aorta; and (2) a thrombosed false lumen; (3) length score; (4) presence of shock; (5) malperfusion of limbs; (6) ST elevation and/or depression on electrocardiogram; and (7) renal dysfunction. In total 36 AD patients had a positive H-FABP test. Statistically significant differences in the H-FABP positive rate were observed between those with and without ascending AD (76.7% vs 39.4%, p = 0.003), and in the length score (p < 0.001). Multivariate logistic regression test demonstrated that the most significant factor was the length score (odds ratio: 2.239 (95% confidence interval: 1.119-4.481), p = 0.023). Moreover, a significant correlation was observed between length score and absolute H-FABP value (r = 0.420, p = 0.001). CONCLUSIONS: In patients with AD, an increased serum H-FABP concentration is caused by the protein being released not only from the cardiac muscle but also from skeletal muscle, or possibly the aortic wall. Physicians using H-FABP for detection of myocardial injury need to be aware that patients with a long or ascending AD will show an elevation of H-FABP.

Simple and useful tests for discriminating between acute aortic dissection of the ascending aorta and acute myocardial infarction in the emergency setting.

BACKGROUND: It is important to rapidly distinguish patients with acute aortic dissection of the ascending aorta (AADa) from those with acute myocardial infarction (AMI), because minimizing the time to initiation of reperfusion therapy leads to maximum benefits for AMI and erroneous reperfusion therapy for AADa can produce harmful outcomes. The aim of this study was to find a simple test to distinguish such patients. METHODS AND RESULTS: Data were collected from 29 consecutive patients with AADa and 49 consecutive patients with AMI who were admitted within 4 h of the onset of symptoms. The D-dimer concentration and the ratio of the maximum upper mediastinal diameter to the maximum thoracic diameter on plain chest radiograph (M-ratio) in the emergency room were studied retrospectively. Setting the cutoff values of the D-dimer concentration and the M-ratio to 0.8 or 0.9 microg/ml and 0.309, respectively, gave a sensitivity of 93.1% and 93.1% for AADa, respectively, and a sensitivity of 91.8% and 85.7% for AMI, respectively. CONCLUSIONS: The D-dimer value and the M-ratio, with appropriate cutoff values, have potential as tests that can be routinely used to exclude AADa patients from patients diagnosed with AMI prior to reperfusion therapy.

Stent-supported angioplasty of a residual coronary artery dissection following replacement of the ascending aorta for acute type A aortic dissection.

The patient was a 54-year-old male who suddenly noted severe back pain while eating. A diagnosis of acute type A aortic dissection was made on contrast enhanced CT. As a result, emergency surgical repair was performed on the same day. Through median sternotomy, graft replacement of the ascending aorta, including removal of the site of the intimal tear, was carried out under deep hypothermia and retrograde cerebral perfusion. Although the postoperative course was satisfactory, the patient complained of severe chest pain with ECG change on the 23rd postoperative day. Emergency coronary angiography revealed the presence of wide coronary artery dissection from an entry of the left anterior descending aorta (LAD) to a reentry of the left circumflex artery (LCX). Multiple stents were implanted in the LAD and LCX. After stenting, chest symptoms were relieved, and ECG change disappeared. He was discharged from our hospital on the 42nd postoperative day.

A specific chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[[3,4-dioxo-1-phenyl-7-(2-pyridyloxy)]-2-heptyl]acetamide (NK3201), suppresses development of abdominal aortic aneurysm in hamsters.

In this study, we investigated the effect of a specific chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[[3,4-dioxo-1-phenyl-7-(2-pyridyloxy)]-2-heptyl]acetamide (NK3201), in the development of abdominal aortic aneurysm in a hamster experimental model. The abdominal aortic aneurysm was induced by application of elastase onto the abdominal aorta in hamster. Each hamster was administered NK3201 (30 mg/kg/day p.o.) or placebo beginning 4 days before application of elastase and continuing through the experiments. Sham-operated hamsters received saline application onto the abdominal aorta. Two weeks after application of elastase, the aortic diameter in the placebo-treated group was significantly increased to 1.6-fold compared with the value for the sham-operated group, whereas that in the NK3201-treated group was significantly reduced. The chymase activities in the sham-operated and the placebo-treated groups were 0.35 +/- 0.01 and 3.44 +/- 0.62 mU/mg protein, respectively, and this difference was significant. NK3201 significantly reduced the chymase activity in the placebo-treated group. Here, we demonstrated for the first time that a chymase inhibitor prevented the development of abdominal aortic aneurysm in a hamster experimental model.

Stent-graft placement for mycotic aneurysm of the thoracic aorta: report of a case.

A 66-year-old man was found to have a mycotic aneurysm of the thoracic aorta. It was first suspected to be a pseudoaneurysm of the descending thoracic aorta on computed tomography scan, and the blood cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA). It was subsequently diagnosed as a mycotic aneurysm, but because the patient continued to do so poorly with septicemia, conventional surgery (ie, aortic exclusion and extraanatomic bypass, or surgical placement of in situ graft) was not performed. A stent-graft device composed of several units of self-expandable Z stents covered with ultra-thin woven Dacron was inserted through 21F sheath via the left external iliac artery and aortography showed successful deployment without blood endoleaks. The procedure was completed without incident and the patient has continued to do well. Endovascular stent-grafts may offer significant advantages for patients at high surgical risk.

Surgical treatment of traumatic thoracic aorta rupture: a 7-year experience.

OBJECTIVES: Traumatic aortic rupture is highly lethal and an ongoing therapeutic challenge. We review our 7-year experience with traumatic aortic disruption. METHODS: We treated 12 cases of traumatic rupture of the thoracic aorta (TRTA) from December 1994 to June 2001 at our institution. Of these, 9 were male, and the average age 26 years. Injuries were caused by traffic accidents in 9 cases and falls in 3. Contrast-enhanced helical computed tomography was used to diagnose10 cases and digital subtraction angiography to diagnose 2 at other hospitals. Six of 12 (50%) disruptions were located in the aortic isthms. All surgery was conducted under cardiopulmonary bypass. A percutaneous cardiopulmonary support system (heparin-bonded artificial lung and centrifugal pump) was used in 6 cases since 1998. RESULTS: Among the 12 patients, 6 had early surgical repair within 2 days after the accident, and all survived free of neurological problems. Six other had repair delayed more than 2 days and all were doing well. CONCLUSION: Immediate repair of aortic lesions should be the rule because the majority of deaths from TRTA occur within 24 hours. We believe, however, that immediate surgery may not be necessary for some patients with severe, multiple associated lesions who survive initial traumatic aortic disruption of the aorta.

Possible roles of angiotensin II-forming enzymes, angiotensin converting enzyme and chymase-like enzyme, in the human aneurysmal aorta.

Aortic aneurysm is a chronic degenerative condition associated with atherosclerosis. Recent studies have revealed that angiotensin (Ang) II plays important roles in atherosclerosis. In this study, to investigate the relationship between aortic aneurysm and Ang II, we measured the activities of the angiotensin (Ang) II-forming enzymes, angiotensin converting enzyme (ACE) and chymase-like enzyme, in human aneurysmal and control aortae. Aneurysmal aortic specimens were obtained from 16 aneurysm patients and control aortic specimens were obtained from 16 patients who underwent coronary artery bypass surgery (8 patients in each group were administered ACE inhibitors). The ACE and chymase-like enzyme activities were determined using extracts from vascular tissues. Both the ACE and chymase-like enzyme activities in the aneurysmal aortae were significantly higher than those in the control aortae (p < 0.01). In the patients treated with ACE inhibitors, the ACE activity in the aneurysmal aortae tended to be low, but the chymase-like enzyme activity tended to be high. In the aneurysmal aortae, the chymase-like enzyme activity in the adventitia was significantly higher than that in the intimal or medial layers (p < 0.01), while differences in ACE activity were not observed. Our results suggest that increases in local Ang II formation induced by chymase-like enzymes may play important roles in the pathogenesis of aneurysmal formation.

Increased local angiotensin II formation in aneurysmal aorta.

We investigated the levels and locations of angiotensin II-forming enzymes, angiotensin converting enzyme (ACE) and chymase, in aneurysmal and normal aortas. Aneurysmal aortic specimens (n = 14) were obtained at the time of operative aneurysm repair from 14 patients ranging in age from 57 to 84 y. Normal aortic specimens (n = 16) were obtained from 16 patients (48 to 72 y) who underwent coronary artery bypass surgery. The ACE and chymase activities were determined using each specimen. Sections of each specimen were immunostained with antibodies for ACE and chymase. The ACE activities in the aneurysmal and normal aortas were 0.82 +/- 0.10 and 0.14 +/- 0.05 mU/mg protein, respectively, and this difference was significant. The chymase activities in the aneurysmal and normal aortas were 17.9 +/- 2.40 and 1.02 +/- 0.18 mU/mg protein, respectively, and this difference was also significant. In the aneurysmal aorta, ACE-positive cells were detected with macrophages in the intima and media and chymase-positive cells were detected with mast cells in the media and adventitia, whereas positive ACE and chymase cells in the normal aorta were located only in the endothelium and adventitia, respectively. Angiotensin II-forming enzymes, chymase and ACE, were significantly increased in the aneurysmal aorta, and increased angiotensin II may be associated with the development of aneurysmal formations.

CD35 expression on peripheral blood granulocytes of patients with atopic dermatitis.

We examined CD35 expression on granulocytes from 45 patients with atopic dermatitis (AD) (male, 21, female, 24) and 25 age and sex-matched controls (male, 15; female, 10). There was no significant difference in the peripheral blood neutrophil count between AD patients and controls, whereas the eosinophil count in AD patients was significantly higher than that of controls. The percentages of CD35 positive eosinophils and neutrophils were determined by using two-color flow cytometric analysis. As regards eosinophils, we found CD35 expression from AD patients to be lower than that of controls (P < 0.05), but there was no correlation between the CD35 expression and disease severity. In contrast, the CD35 expression on neutrophils from AD patients was much lower than that of controls (P < 0.005). Furthermore, CD35 expression on neutrophils of severe AD group was significantly higher than that of the mild AD group (P < 0.05). This suggests that the CD35 expression of neutrophils but not eosinophils reflects disease severity in AD patients and the CD35 expression on neutrophils in AD patients may associate with susceptibility to bacterial infection.