Philippe Piquet

Hyperhomocysteinemia-Induced Vascular Damage in the Minipig Captopril-Hydrochlorothiazide Combination Prevents Elastic Alterations

BACKGROUND Previous attempts in animals failed to reproduce the metabolic, pathological, and clinical situations encountered in homocystinuric patients. Minipigs on a methionine-rich caseinate-based diet, however, have a special long-lasting postprandial plasma accumulation of methionine, the metabolic precursor of homocysteine. We hypothesized that these minipigs develop hyperhomocysteinemia in the long term. Angiotensin-converting enzyme (ACE) inhibition prevents atherogenic alteration of viscoelastic functions of arterial pulsatility and compliance and reduces fragmentation of vascular elastic laminae in the minipigs. We consequently analyzed the therapeutic effects of the captopril-hydrochlorothiazide combination against the typical hyperhomocysteinemia-induced alterations of vascular elastic features. METHODS AND RESULTS Thirty-two Götingen minipigs were randomized as control diet-fed (C), captopril (25 mg/d)/hydrochlorothiazide (12.5 mg/d)-treated C (C+Cp), caseinate-based diet-fed (M), and M+Cp minipigs. After 4 months, M and M+Cp animals had hyperhomocysteinemia (9.64 +/- 4.10 mumol/L, n = 16) compared with C and C+Cp minipigs (5.67 +/- 1.14 mumol/L, n = 16) (P < .05). In the M group, one minipig died from thromboembolic syndrome, and one had pulmonary infarction. M minipigs presented with systolic-diastolic hypertension and extended reactive hyperemia, as well as a mega-artery syndrome in hyperpulsatile arteries due to expanded volumetric compliance, curtailed stiffness, strengthened vascular tension, and prevalence of the viscous wall component. In their arterial tree, hypertrophic endothelial cells covered a thickened subendothelial space. Major elastic lamina dislocations were observed, as well as hypertrophy and reorientation of smooth muscle cells, resulting in the settlement of spreading pathways for medial cells between muscular laminae. In C+Cp and M+Cp animals, serum and lung ACE activity were inhibited by 74% and 40%, respectively. Although the treatment with captopril-hydrochlorothiazide did not modify the hyperhomocysteinemia per se, the therapeutic effects of the drug combination are made evident by the absence of death and ischemic diseases in the M+Cp group. Specifically, the drug combination prevented diastolic hypertension and improved aortic blood flow by normalizing peripheral resistances, abolished the vascular hyperpulsatile characters, and restrained the fragmentation and the splitting of elastic fibers in capacitance arteries. In contrast, the drugs slightly prevented systolic and mean hypertension. In addition, the aortic stiffness and stress response remained altered and vascular smooth muscle cell hypertrophy was still observed in the M+Cp group. CONCLUSIONS In minipigs, the present methionine-rich caseinate-based diet induced hyperhomocysteinemia, which reproduces the metabolic and histopathological situation found in homocysteic patients. Our results show that hyperhomocysteinemia-induced vascular alterations favor the viscous component of the wall rheology to the detriment of the elastic component. Furthermore, they extend to hyperhomocysteinemia the therapeutic effects characteristically shared by ACE inhibitors in association with hydrochlorothiazide against the atherogenic activation of elastinolytic processes.

Incidence and Determinants of Spinal Cord Ischaemia in Stent-graft Repair of the Thoracic Aorta

OBJECTIVES Endovascular repair of descending thoracic aortic lesions is associated with a substantial risk of perioperative spinal cord ischaemia (SCI) which may lead to permanent paraplegia. We performed a retrospective analysis of our experience in the endovascular treatment of descending thoracic aortic lesions to define the incidence of SCI and to identify factors that contributed to its development. METHODS 67 consecutive patients underwent stent graft repair for descending thoracic aortic lesions including degenerative aneurysm (n=19), type B dissection (acute n=2, chronic n=15), traumatic rupture (acute n=14, chronic n=4), penetrating aortic ulcer (n=5), anastomotic false aneurysm (n=4), mycotic aneurysm (n=3) and embolic aortic lesion (n=1) between June 2000 and June 2005. All procedures were performed with the patient under general anaesthesia and strict blood pressure monitoring. No patient had intra-operative monitoring of spinal evoked potential or cerebrospinal fluid (CSF) drainage to prevent SCI. Neurological evaluation was realized after recovery from general anaesthesia. Fifteen factors, including nature of aortic disease, length of aortic coverage, number of stent-grafts, coverage of the distal third of the thoracic aorta and subclavian artery coverage, were investigated as possible predictors of postoperative SCI. RESULTS Five patients (7.5%) had postoperative neurological deficits (immediate n=2, delayed n=3) referable to SCI. Univariate analysis showed that length of aortic coverage (p<0.001) and number of stent-grafts deployed (p=0.02) were significant predictors of SCI. Multivariate logistic regression analysis showed that length of aortic coverage was the only independent significant predictor of SCI. ROC curve analysis revealed 205mm of aortic length coverage as the threshold for increased risk of postoperative SCI (p=0.001), with specificity and sensitivity of 95.2 and 80% respectively. CONCLUSION In our study, length of aortic coverage is the only independent predictive factor of SCI after endovascular treatment with 205mm as a threshold for increased risk. Hence, methods to prevent SCI, especially those aimed at restoration of an adequate spinal cord perfusion pressure, should be offered to patients requiring extensive coverage of the descending thoracic aorta.

Coxiella burnetii Infection of Aneurysms or Vascular Grafts: Report of Seven Cases and Review

The most frequent clinical presentation of chronic Q fever is endocarditis, although infections of aneurysms and vascular prostheses have also been described. We report seven new cases of Coxiella burnetii infection of aneurysms or vascular grafts. We also review the literature and compare our cases with the six previously reported cases. This study demonstrated the lack of specific symptoms associated with this disease. Moreover, prospectively, in an attempt to reevaluate the incidence of Q fever-associated vascular infection, we systematically searched for C. burnetii infections in 163 patients with aortic aneurysms or vascular grafts who underwent vascular surgery. Microbiological testing included standard culture, Q fever serology, cell culture, and polymerase chain reaction amplification of C. burnetii DNA from biopsy specimens of aneurysms or vascular grafts. A microorganism was isolated from 25 patients, including C. burnetii in two cases; both of these patients had serological titers consistent with chronic Q fever. Both patients had nonspecific clinical features, and thus their infections would have probably remained undiagnosed without our systematic testing. Therefore, since the incidence of C. burnetii vascular infection is probably underestimated, we suggest that C. burnetii serology be routinely carried out in cases of unexplained febrile illness, pain, or weight loss in patients with a history of underlying vascular disease.

Tantalum-Dacron coknit stent for endovascular treatment of aortic aneurysms: A preliminary experimental study

PURPOSE The purpose of this study was to evaluate the efficiency of intraluminal tantalum-Dacron coknit stents for the treatment of artificial aortic aneurysms in minipigs. METHODS Replacement of the infrarenal abdominal aorta with Dacron artificial aneurysm graft was performed in eight minipigs. After 2 weeks, balloon-expandable coknit stents were inserted through the femoral artery to the site of the artificial aneurysm in seven minipigs. One animal was kept as a control. Coknit stent/artificial aneurysm complexes were explanted at various intervals from 24 hours to 12 weeks and underwent gross examination, followed by scanning electron and light microscopy studies. RESULTS Aortography performed at the time of stent placement displayed immediate exclusion of the aneurysm in every case. In follow-up studies, all coknit stents remained patent until the time of explant. Scanning electron microscopy studies revealed apparent endothelialization of the entire coknit stent lumen at and after 6 weeks. CONCLUSION Tantalum-Dacron coknit stents are efficient in the treatment of artificially created aneurysms in minipigs and facilitate the creation of an endothelialized new vascular wall. Clinical application of this coknit stent can be considered but necessitates retaining the same stent structure in diameters greater than 20 mm and the development of a suitable delivery system.

Effects of angiotensin-converting enzyme inhibition with perindopril on hemodynamics, arterial structure, and wall rheology in the hindquarters of atherosclerotic mini-pigs

The effects of ACE inhibition with perindopril on the atherosclerosis-induced impairment of arterial flow were investigated via histopathologic studies, hemodynamics, and vascular rheology of hindlimb arteries in 7 adult Pitman-Moore mini-pigs (7 months of age) fed for 4 months with an atherogenic diet and perindopril (at the daily oral dose of 4 mg, which induced a continuous 70% inhibition of serum ACE activity), versus 7 atherogenic and 7 control animals. Major fibroproliferative fatty lesions with medial intimalization were observed in the abdominal aorta. Atherosclerosis impaired the function of both capacitance and resistance hindlimb arteries. In atherogenic mini-pigs, blood pressure (BP) increased significantly due to increased hindlimb peripheral resistance (HPR) and aortic input impedance, although aortic blood flow was not affected. Altered aortic wall rheology revealed that the stiffness of the aorta was markedly increased due to increased wall tension and reduced viscoelasticity, the viscous component being reduced in the arterial wall. Perindopril significantly opposed these alterations by reducing BP, HPR and input impedance and by returning parietal stiffness to control values by increasing aortic compliance. Angiotensin converting enzyme (ACE) inhibition significantly prevented the development of atherosclerosis in the abdominal aorta by decreasing the cross-sectional area of lesions and the presence of lipid-laden cells, as well as by preventing alteration and fragmentation of elastic laminae. In conclusion, ACE inhibition with perindopril showed a significant preventive action on atherosclerosis-induced deleterious effects on vascular wall function and structure in mini-pig arteries.

Midterm results after endovascular treatment of acute, complicated type B aortic dissection: The Talent Thoracic Registry

OBJECTIVE To assess the efficacy and midterm results of endovascular treatment of acute complicated type B dissection. METHODS From January 1998 to March 2004, 29 patients (7 women and 22 men) with acute complicated aortic type B dissection (mean age, 61 years; range, 22-78), defined as aortic rupture, malperfusion, intractable pain, or uncontrolled hypertension, underwent endovascular stent graft placement with the Medtronic Talent device. Five patients (17%) had undergone previous surgery on the ascending aorta and/or aortic valve. The mean aortic diameter at intervention was 48 ± 13 mm. Follow-up was 100% complete and averaged 53 ± 41 months. RESULTS The technical feasibility and success with deployment proximal to the entry tear was 100%, requiring partial or total coverage of the left subclavian artery in only 1 patient (3%). Hospital mortality was 17% ± 7% (70% confidence limit) with 6 late deaths. The causes of hospital death included multiorgan failure in 2 patients, aortic rupture in 2, and retrograde dissection in 1 patient. Three patients (10%) who survived the procedure developed neurologic complications (2 strokes and 1 transient ischemic attack). One patient required early conversion to surgery because of retrograde type A dissection. Furthermore, 4 patients developed a type Ia endoleak. A postprocedural increase in the distal aortic diameter was observed in 3 patients. The actuarial survival at 1 and 5 years was 79% and 61%, respectively. Freedom from treatment failure at 1 and 5 years (including reintervention, aortic rupture, device-related complications, aortic-related death, or sudden, unexplained late death) was 82% and 77%, respectively. CONCLUSIONS Endovascular stent graft placement in acute complicated type B aortic dissection proves to be a promising alternative therapeutic treatment modality in this relatively difficult patient cohort. Refinements, especially in stent design and application, could further improve the prognosis of patients in this life-threatening situation.

Coxiella burnetii infection of pseudoaneurysm of an aortic bypass graft with contiguous vertebral osteomyelitis

We report the case of a 67-year-old man who had an infection of a pseudoaneurysm of an aortic graft with contiguous vertebral osteomyelitis. The infectious organism was identified as Coxiella burnetii, a strict intracellular pathogen causing Q fever infection in humans. The patient was treated successfully with removal of the infected material in conjunction with extraanatomic bypass and specific antibiotic therapy. He is doing well after more than 3 years, with no evidence of recurrent periaortic infection on successive computed tomographic scans. We suspect that C. burnetii vascular graft infections could be underdiagnosed, because this cause is not frequently evoked. We suggest that extending the etiologic search to C. burnetii could decrease the number of undocumented vascular graft infections.

Conservative Treatment of Spontaneous and Isolated Dissection of Mesenteric Arteries

BACKGROUND Isolated and spontaneous dissection of mesenteric arteries is a rare entity; a little more than 50 cases have been reported in medical literature. There is no therapeutic consensus concerning this type of lesion. METHODS In this study, we report the results of our treatment based on a conservative approach. This retrospective study concerns eight patients with dissection of the celiac trunk and/or of the upper mesenteric artery (UMA) who were treated between 2002 and 2006. Because these patients were not presenting with acute intestinal ischemia diagnosed by clinical examination or paraclinical tests (medical imaging/biology) or with vital complications, they were treated with an efficient anticoagulation (heparin followed by anti-vitamin K) for 3 to 6 months. Endovascular or surgical treatment was used as the first option in patients with obvious intestinal ischemia or likely to have an arterial rupture, and also when medical treatment had failed. Clinical and radiological follow-up was at 1 month, 3 months, 6 months, and 1 year and then every year. Seven men and one woman (mean age, 48.2; age range, 38-53 years) were treated. Six patients presented with isolated dissection (celiac trunk=4, UMA=2). One patient had a celiac trunk and a UMA dissection and one had a celiac trunk and a UMA dissection along with a dissection of his two renal arteries. On entering the hospital, a patient was operated on for mesenteric ischemia related to a stenosis of the upper mesenteric artery (upper aortomesenteric bypass); a covered stent was implanted in the celiac trunk of another patient presenting with a contained rupture. RESULTS Both patients were successfully treated. Six patients were medically treated. One of them required an aortohepatic bypass to treat an aneurysmal evolution of the celiac trunk revealed by a computed tomography scan obtained 1 month after the symptoms had begun. In one patient, the dissection remained stable on imaging. Four patients were cured, with a mean 20.1-month follow-up. CONCLUSION Conservative treatment of spontaneous dissections of mesenteric arteries is possible when there are no complications, and it gives satisfactory results provided regular clinical and radiological checking is performed.

Relevance of the positron emission tomography in the diagnosis of vascular graft infection with Coxiella burnetii.

Coxiella burnetii, the causative agent of Q fever, may cause culture-negative vascular graft infections that can be diagnosed by serology and molecular biology. We present a case of vascular graft infection detected by positron emission tomography (PET) scanner. The presence of C. burnetii was confirmed by high antibody titers and positive polymerase chain reaction specific for C. burnetii. This report emphasizes the relevance of the PET scanner in the diagnosis of infection when used in association with Q fever serology and molecular biology for the etiological identification of C. burnetii.

Efficacy of Local Molsidomine Delivery from a Hydrogel-Coated Angioplasty Balloon Catheter in the Atherosclerotic Porcine Model

Purpose: To evaluate the therapeutic effects of local molsidomine delivery via a hydrogel-coated angioplasty balloon catheter during overstretch angioplasty in atherosclerotic swine iliac vessels. Molsidomine is retained in the arterial wall after local delivery for more than 72 hr and is slowly metabolized into linsidomine, releasing nitric oxide (NO). Methods: A hydrogel-coated angioplasty balloon catheter was used to both deliver drug locally (150 mg molsidomine or placebo in the contralateral vessel) and dilate iliac vessels in nine Pietrin pigs that had been on an atherogenic diet for 5 months. Animals were killed at 3 hr (n = 2), 24 hr (n = 3) and 3 months (n = 3) after treatment. Iliac arteries were examined for wall pulsatility, histomorphometry, cell proliferation and platelet aggregation. Results: No significant therapeutic effects were detected 3 hr after treatment. At 24 hr, wall pulsatility, thromboresistance and vascular cell homeostasis were significantly restored in the molsidomine-treated versus placebo group. At 3 months, molsidomine inhibited restenotic lesion development, except in scarred areas of histologically detectable adventitial/medial dissection. Conclusion: Local delivery of concentrated molsidomine from a hydrogel-coated angioplasty balloon catheter resulted in early NO-dependent vasodilation/stress normalization and antithrombotic and antiproliferative effects. In the medium term, molsidomine inhibited restenosis in the absence of vessel dissection.