Matrix metalloproteinases. Their role in degenerative chronic diseases of abdominal aorta.

BACKGROUND: The main chronic degenerative diseases of the abdominal aorta, namely aneurysmatic and steno-obstructive pathologies, have a common denominator: atherosclerosis. Both pathologies are characterised by the destruction of the structural integrity of the extracellular protein matrix (ME). A number of studies have shown the presence and involvement of a group of enzymes with proteolytic activity towards one or more ME components, the matrix metalloproteinases (MMPs), in the pathogenesis of aneurysms of the abdominal aorta. Other authors have underlined the role of MMPs in the proliferation and migration process of smooth muscle cells into the intima in the pathogenesis of atheromasic plaque. The aim of this study was to evaluate the possible role of these enzymes in the pathogenesis of chronic degenerative diseases of the aorta. METHODS: Fragments of aortic wall were removed from patients undergoing elective aortic surgery for aneurysms (14 patients) or aortic steno-obstruction (4 patients). The samples obtained were treated appropriately and then subject to immunohistochemical analysis. The preparations were incubated with specific anti-MMP antibodies and were also incubated with substrate and chromogen, forming a pigmented precipitate on the site of the antigen, before being observed using an optic microscopic at an enlargement of 250x. Nuclear positivity linked to the presence of the antigen testified the validity of staining. Lastly, the MMP INDEX, or in other words the number of positive cells out of 100, was stained in the adventitia and in the tunica media in each preparation. RESULTS: MMPs were divided into three main groups: interstitial collagenase (MMP1) which degrade type I and III native collagen; gelatinases (MMP9, MMP2) which act on elastin and type IV collagen; stromelysins (MMP3) with specific proteolytic action towards proteoglycans, fibronectin and laminine. In our experience, those preparations obtained from aorta affected by steno-obstructive pathologies (4 patients) revealed the presence of MMPs with a preferential localisation on the intimal side of the tunica media. In particular, the increased activity of gelatinases MMP9 in atherosclerotic aorta might be responsible for destroying the internal elastic lamina and fostering the proliferation and migration of smooth muscle cells and the formation of atheromasic plaque. On the other hand, preparations obtained from aneurysmatic aorta (14 patients) showed an opposite situation with a preferential localisation within the adventitia and on the adventitial side of the media. Above all, the loss of elastin represents an essential stage in the formation of aortic aneurysms. CONCLUSIONS: This study concords with numerous authors who have demonstrated the involvement of proteinase MMPs in the development of aortic aneurysms and their possible role in the pathogenesis of atheromasic plaque. The different origin of these enzymes (inflammatory cells and macrophages or endothelial cells) may be the result of different pathogenetic mechanisms. Although they present different pathogenetic features, aortic aneurysms and steno-obstructions have a common denominator in atherosclerosis. The mechanisms responsible for their evolution towards one or other form are not known. The different expression of MMPs in the context of the aortic wall represents a field for future research.

Intraoperative assessment of cerebral ischaemia during carotid surgery.

BACKGROUND: This study aimed to evaluate the reliability of somatosensory evoked potentials (SEPs) in identifying clamping ischaemia during carotid surgery under general anaesthesia. METHODS: We reviewed the records of 196 consecutive carotid endarterectomies (CEA) performed under general anaesthesia, out of 1550 patients operated on between 1975 and 1993. SEPs were monitored after contralateral median nerve stimulation at the wrist in all patients. Moreover they received an intravenous bolus of 2500 IU of heparin and the stump pressure was measured. A completion angiography was performed in all patients. An intraluminal shunt was inserted when the amplitude of the N20-P25 SEPs complex decreased by more than 50% of pre-clamping value (pathologic SEPs) or when a preoperative CT-scan showed an ischaemic area in the contralateral hemisphere. In some patients the shunt was not inserted because of technical difficulties or because the pathological SEP complex decrease developed when the suture of the arteriotomy was almost complete. RESULTS AND CONCLUSIONS: As the preclamping amplitude (Ab) of N20-P25 was extremely variable, ranging from 0.9 and 7.5 microV, we adopted the ratio: deltaA=(At-Ab)/Ab (At=amplitude measured during clamping every 2 min at time t). Mean decrease of deltaA measured in the whole group ranged between 15% and 20%, but mean deltaA values in patients with pathological SEPs were around 60%. Even patients with positive CT-scans or with a back-pressure lower than 50 mmHg developed a mean deltaA decrease of about 20%. A pathological SEP was present in 50 patients, but developed in only 12 during the clamping trial. An intraluminal shunt was inserted in 22 cases; the other patients received pharmacological treatment with anaesthetic or vasoactive drugs. Among the patients with pathological SEPs, 3 presented postoperative symptoms related to carotid cross-clamping; only 1 of these was shunted but without SEPs normalisation. No patients with normal SEPs developed a postoperative neurological deficit, giving a reliability of 86.7%, a sensitivity of 100% and a specificity of 86.5%.

Natural history of patients with carotid stenosis waiting for surgical treatment.

BACKGROUND AND PURPOSE: The natural history of carotid lesions has generally been evaluated in anedoctal series or in clinical trials. The purpose of this study was to evaluate clinical and pathological modifications linked to an increasing waiting list in our region and the related medico-legal implications. METHODS: Neurological symptoms that occurred during the waiting period were evaluated in 282 out of 491 patients placed on the waiting list for a carotid stenosis less than 80% or without an unstable plaque. The other 202 patients cancelled their booking. Progression of carotid disease was evaluated by duplex scanning in 116 patients who had a duplex evaluation in our Department both at booking and at the time of operation. RESULTS: The incidence of stroke in a mean waiting period of 8.9 months was 2.6% in symptomatic patients and 1.5% in asymptomatic, respectively; 39 (13.8%) patients experienced an ipsilateral TIA and 4.2% a carotid thrombosis (25% of which symptomatic). The crude mortality-rate was 2.4% with a 1% of related deaths. The cumulative actuarial hard end points rate (stroke, carotid thrombosis and related death) was 7.8% at 12 months and 19.8% at 18 months. CONCLUSIONS: This study gives us data about the natural history of carotid stenosis in our country. The high morbidity and mortality-rate related to this lesion and particularly their occurrence within the first 3 months stress the urgency of treatment, and of the planning of specialized Departments in relation to the real incidence of the pathology in order to avoid medico-legal consequences.

Morbidity and mortality following carotid surgery.

The records of 920 patients who underwent carotid endarterectomy by the same surgeon (M. D'A) between 1976 and 1989 were reviewed. Particular attention was paid to both the neurological and general complications and to how and when the neurological symptoms appeared. Among these patients, a cumulative stroke plus death rate of 3.1% was observed. Complications were classified as clamping ischemia (2.2%), postoperative embolism (1.5%), postoperative thrombosis (2.4%), and cerebral haemorrhage (0.3%). Two patients (0.2%) died from myocardial infarction. In 3.5% of patients, neurological symptoms were transient. The incidence of clamping ischemia was higher when 40 mmHg was considered as the safety limit of the back-pressure; this incidence fell by raising this limit to 50 mmHg, and introducing, in recent years, SEPs monitoring. Intraoperative monitoring of SEPs, in fact, reduced the neurological complications to 1.4%, while intraoperative angiography reduced the need for intraoperative reoperation from 10% to 2%. The use of antiplatelet drugs and an accurate surgical technique are useful steps in the prevention of postoperative embolism or thrombosis.

Endothelial injury in human atherosclerosis.

A light and electron microscopic investigation (scanning and transmission electron microscopy) was performed on 51 human atherosclerotic carotid lesions. The purpose of this study was to establish whether features of endothelial injury such as those described in animals occur in man and whether these features can be related to specific stages of human atherosclerosis. Irrespective of their histological appearance the atherosclerotic lesions were covered with endothelium which showed non-specific changes in cell shape and size. However, all complicated lesions appeared denuded. Moreover, a peculiar interaction of endothelium with monocytes and lymphocytes as well as blood components (e.g., fibrin and lipoproteins) was observed in intimal thickenings, fatty streaks and uncomplicated plaques. The surface exposure of macrophage-derived foam cells was seen on florid fatty lesions. Large areas of the arterial surface lacking any endothelial coverage were characteristic of complicated plaques. They appeared to be a consequence of the arterial wall degeneration with an associated failure in endothelial repair.

Elastic modulus in young diabetic patients (ultrasound measurements of pulse wave velocity).

Aim of this study is to confirm the validity of non-invasive evaluation with Doppler C.W. in the study of arterial diseases and in the identification of pre-clinical arterial lesions. We studied twenty-eight children suffering from diabetes mellitus, and dependent on insulin and a control group composed of twenty-eight healthy persons. All subjects were studied using the methodology of the transit time for the determination of the elastic modulus of the lower limb arterial wall and results were analysed according to a statistical method. Although the groups were small, an increase in pulse wave velocity was noted in diabetic children and a significative correlation was found between the elastic modulus and duration of diabetes.