Background and Purpose-Elevated levels of matrix metalloproteinases (MMPs), particularly MMP-1 and MMP-9, have been implicated in plaque rupture. It has been suggested that inhibition of MMPs may stabilize vulnerable atherosclerotic plaques and improve clinical outcome. The aim of the study was to investigate the ability of doxycycline, a nonspecific MMP inhibitor, to reduce MMP concentration in carotid atheroma. Methods-The study design was a prospective, double-blind randomized trial. One hundred patients requiring carotid endarterectomy were randomized to receive 200 mg/d doxycycline or placebo for 2 to 8 weeks before surgery. During endarterectomy, carotid plaques were retrieved. The concentrations of MMPs and doxycycline were determined in the atherosclerotic tissue by enzyme-linked immunosorbent assay and high-performance liquid chromatography, respectively. Clinical events were recorded, as was the rate of preoperative embolization (transcranial Doppler). Results-Analysis of endarterectomized specimens demonstrated a mean doxycycline concentration of 6.0 g/g wet weight in treated patients. Administration of doxycycline significantly reduced the concentration of MMP-1 in carotid plaques from a mean of 14.8 to 10.3 ng/100g wet weight (Pϭ0.038). This difference was due to decreased MMP-1 transcript (PϽ0.001). There was no difference in any other MMP (MMP-2, -3, or -9) or tissue inhibitor of matrix metalloproteinases-1 or -2. Conclusions-Doxycycline penetrated atherosclerotic plaques with acceptable tissue levels. This resulted in a reduction in MMP-1 concentration because of decreased expression.
This case illustrates the potential durability of endoluminal repair of innominate artery lesions and highlights the potential role of this minimally invasive alternative to surgery in these clinical situations.
This case illustrates the potential durability of endoluminal repair of innominate artery lesions and highlights the potential role of this minimally invasive alternative to surgery in these clinical situations.
INTRODUCTION Hypotension is commonly associated with epidural use in postoperative patients and is usually treated with fluid or vasopressor therapy. The former can result in fluid overload, associated with significant morbidity. This study aimed to identify factors increasing the likelihood of fluid overload in elective patients. PATIENTS AND METHODS A prospective audit of fluid therapy in elective, postoperative, epidural patients was carried out over a 6-week period in a teaching hospital in England. Demographic, biochemical, and fluid balance data were collected and analysed to determine which factors had the strongest correlation with fluid overload. Fluid overload was calculated as the percentage of net fluid input relative to pre-operative body weight (%FO). RESULTS Thirty-two patients were included in this study. An overload of 10% of the patients' pre-operative body weight was considered significant. The mean fluid overload incurred by patients in this study was 8.17 l (range, 2.89-14.62 l); %FO was 11.32% (range, 3.67-26.10%). The strongest independently correlating factor to fluid overload was initial, postoperative plasma albumin. Patients with a plasma albumin less than 27 g/l developed significant overload: mean overload 9.75 l (range, 2.89-14.62 l), %FO 15.12% (range, 4.81-26.10%), whilst those with an albumin level greater than 27 g/l did not: mean overload 6.77 l (range, 3.34-11.48 l), %FO 7.96% (range, 3.67-13.93%); P = 0.0001. CONCLUSIONS Patients receiving epidurals with initial, postoperative, plasma albumin levels below 27 g/l are at increased risk of significant fluid overload. Earlier instigation of vasopressor therapy in this subgroup of patients may help prevent this.
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