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Combined mitral and aortic valve replacement with the BJORK-Shiley tilting-disc valve prosthesis was performed in 42 patients. Hospital and late mortality rates were both at the 9.5% level. No correlation was seen between mortality and combination of concomitant valve lesions. Morbidity was elevated. No episodes of embolism were observed after surgery, although one patient died of severe haemorrhage. Only one patient showed valvular dysfunction (grade 2/4 leakage), but did not require reoperation. Postoperatively, 75.7% of the patients were asymptomatic for a mean follow-up period of 21.1 months. The Björk-Shiley prosthesis offers a small gradient associated with a low profile, which constitute important advantages in multiple valve replacement.

Prostaglandin-H synthase exists in two isoforms, PGHS-1 and PGHS-2. PGHS-1 is present and is constitutively expressed in most cells and tissues, whereas PGHS-2 is mainly thought to mediate inflammation. Selective prostaglandin-H synthase-2 (or cyclooxygenase-2) inhibitors have been shown to be potent antiinflammatory agents with fewer side effects than currently marketed nonsteroidal antiinflammatory drugs (NSAIDs). This review addresses the main classes of the selective PGHS-2 inhibitors whose selectivity is documented by supporting PGHS-1 and PGHS-2 enzyme data. In addition, we also describe our experience in design, synthesis and pharmacological in vivo evaluation of new 1,2-benzodioxole derivatives as candidate of the selective PGHS-2 inhibitors, with special attention to molecular dynamics simulations of these derivatives attached to the active site of PGHS-2.

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