Rapamycin suppresses experimental aortic aneurysm growth.

OBJECTIVE: Inflammatory modulators are important in the pathogenesis of aneurysmal disease. Gene expression profiling of experimental abdominal aortic aneurysm (AAA) tissue demonstrated upregulation of the FK506BP12 (rapamycin binding protein) gene product. Rapamycin is a potent immunosuppressor that prevents recurrent stenosis. However, its effect on aneurysm formation has not been studied. We therefore examined the effect of rapamycin in an experimental rat AAA model. METHODS: Adult male Wistar rats underwent elastase infusion into isolated infrarenal aortas to create experimental aneurysms. Rats were randomized to receive either rapamycin or placebo via gastric lavage daily starting on the day of surgery. On postoperative day 7 the aneurysm was measured, the infrarenal aorta was harvested, and the rats were euthanized. NF kappa B was measured with Western blotting as a marker of inflammation. Matrix metalloproteinase (MMP)-9 protein levels were measured. Hematoxylin-eosin and elastin staining were used to examine tissue inflammation and elastin preservation. RESULTS: Aneurysms were significantly smaller in diameter in the rapamycin-treated group (3.3 +/- 0.7 mm vs 4.5 +/- 0.5 mm; P <.0001). NF kappa B levels were significantly reduced by 64% +/- 14% in rapamycin-treated aortas (P =.023). MMP-9 was reduced in rapamycin-treated aortas by 54% +/- 22% (P =.043). Hematoxylin-eosin and elastin staining showed no changes in inflammatory infiltrate or degradation of elastin fibers in elastase-infused aortic segments in rapamycin-treated rats. CONCLUSION: Rapamycin significantly reduces the rate of aneurysm expansion in the experimental AAA rat model by 40%. Biochemical evidence suggests that this is related to suppression of inflammatory signaling and decreased MMP-9 levels. Rapamycin could provide a new treatment for small aneurysms. CLINICAL RELEVANCE: Human aortic aneurysms are characterized histologically by an inflammatory infiltrate with severe proteolytic destruction. Rapamycin is an immunosuppressive agent commonly used to control transplant rejection and intimal hyperplasia by modulating the inflammatory cascade. In this experimental model rapamycin suppressed aneurysm expansion, decreased NF kappa B activation (a marker of inflammation), and decreased matrix metalloproteinase-9 levels. It is hoped that rapamycin or other similar anti-inflammatory drugs will one day be able to control aneurysm expansion in patients

Type B aortic dissection with rupture of the left common iliac artery: a case report.

Type B aortic dissection involves the appearance of a false lumen distal to the left subclavian artery and extending distally into the descending thoracic aorta and into the abdominal aorta. Complications of the dissection include rupture of the thoracic aorta, leg ischemia, visceral ischemia, and renal failure. A 37-year-old man presented with complaints of sudden onset of chest pain, left leg pain, and numbness. Examination revealed no femoral, popliteal, or distal pulses with decreased sensory and motor function on the left lower extremity. A CT scan revealed an aortic dissection at the proximal descending aorta extending into the iliac arteries with a left retroperitoneal hematoma at the iliac bifurcation. An MRI confirmed the dissection distal to the left subclavian artery into the iliac artery with a distal occlusion. Exploration revealed rupture of the left iliac artery dissection with arterial occlusion and a contained hematoma. The common iliac artery was ligated and an 8-mm Dacron bypass graft from the right common femoral artery to the left femoral artery was performed. Type B aortic dissection can present as rupture of the common iliac artery. Revascularization of the extremity with a femoral-femoral crossover graft is the recommended procedure in the absence of visceral ischemia. The surgeon should have a keen suspicion of this rare complication and its management.