The findings of the present study demonstrated that interruption of vasa vasorum flow led to an acute decrease in the distensibility of the ascending aorta. Moreover, structural changes of the aortic wall and further deterioration of the elastic properties of the aorta occurred 15 days after vasa vasorum removal.

Impairment of blood supply to the thoracic aorta leads to abnormal morphology of elastin and collagen fibers of the outer media, resulting in increased aortic stiffness under a wide range of stresses. In the clinical setting, decreased vasa vasorum flow, reportedly occurring in arterial hypertension, may increase the stiffness of the outer media of the thoracic aorta and produce interlaminar shear stresses, contributing to the development of aortic dissection.

Clarithromycin was administered intravenously to 55 rabbits to evaluate its effect on experimental sepsis caused by multidrug-resistant Pseudomonas aeruginosa. Acute pyelonephritis was induced after ligation of the right ureter and injection of 10 8 CFU of the test isolate per kg of body weight into the renal pelvis. The animals were divided into six groups: group A, controls; group B, rabbits that received one intravenous dose of 80 mg of clarithromycin per kg concomitantly with bacterial challenge; group C, rabbits that received two doses of clarithromycin, the second one of which was given 2 h after the first one; group D, rabbits that received 15 mg of amikacin per kg; group E, rabbits that received one dose of clarithromycin and amikacin; and group F, rabbits that received two doses of clarithromycin and amikacin. Serum endotoxin levels were estimated by the QCL-1000 Limulus amoebocyte lysate assay, tumor necrosis factor alpha (TNF-␣) levels were measured by a bioassay, and malondialdehyde (MDA) levels were measured by the thiobarbiturate assay. Viable bacterial counts in various tissue samples were also assessed. The mean survival times of the animals in groups A, B, C, D, E, and F were 4.50, 7.69, 4.07, 4.55, 11.55, and 11.60 days, respectively (P ‫؍‬ 0.033 for group D versus group F, P ‫؍‬ 0.006 for group D versus group E, P ‫؍‬ not significant for group B versus group E, P ‫؍‬ 0.042 for group C versus group F). Serum endotoxin levels were similar between groups at all sampling times; TNF-␣ and MDA levels in groups B, C, E, and F decreased significantly over follow-up. The numbers of viable bacterial cells in the infected kidney were similar among the groups; those in the liver, spleen, lungs, and mesenteral lymph nodes were significantly decreased in groups B, E, and F compared to those in groups A and D. It is concluded that a prolongation of survival in animals with experimental sepsis caused by multidrug-resistant P. aeruginosa was achieved after coadministration of clarithromycin and amikacin and that the increased survival was probably attributable to the immunomodulatory properties of clarithromycin.Clarithromycin is a macrolide classically known to possess an antimicrobial spectrum that includes gram-positive cocci and atypical pathogens (23). However, an increasing body of evidence suggests that clarithromycin possesses considerable antiinflammatory and immunomodulatory properties, recommending its administration for the treatment of chronic inflammatory conditions like diffuse panbronchiolitis and cystic fibrosis (11,21,26). Its immunomodulatory properties are observed in vitro at concentrations close to 10 g/ml (14). On the basis of that finding, intravenous administration of clarithromycin leading to the same levels in blood might be beneficial for the treatment of an acute inflammatory state like sepsis.Pseudomonas aeruginosa is a common pathogen that is involved in nosocomial sepsis and that is often characterized nowadays by multidrug resistance (18). In the present study, intravenous clar...

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