['The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the cardiovascular system remains controversial, especially in patients with cardiovascular comorbidities. We used a swine model of chronic myocardial ischemia to investigate whether hypercholesterolemia alters the cardiovascular effects of the nonselective NSAID naproxen.', 'Yorkshire swine were fed normal chow (NAP; n = 7) or a high-fat diet (HF-NAP; n = 8). Chronic myocardial ischemia was created in all animals by left circumflex ameroid constrictor placement. All swine were started on oral naproxen (440 mg/day) at the time of ameroid placement. After 7 weeks, myocardial perfusion and microvessel reactivity in the ischemic territory were assessed. Tissue levels of prostanoid metabolites 11-dehydrothromboxane B2 (11-d-TXB₂) and 6-keto-prostaglandin F1-α (6-k-PGF(1α)) were measured. Tissue was analyzed for capillary density and protein expression.', "Myocardial perfusion was significantly decreased in the HF-NAP group both at rest and during ventricular pacing. Microvessel relaxation responses to sodium nitroprusside and adenosine 5'-diphosphate were similar between groups. Tissue 11-d-TXB₂ levels were similar between groups, but tissue 6-k-PGF(1α) was significantly decreased in the HF-NAP group (P = .001). Expression of thromboxane synthase was significantly higher in the HF-NAP group (P = .02), while prostacyclin synthase expression was significantly decreased in the HF-NAP group (P = .04). Capillary density was higher in the HF-NAP group (P = .005). Proangiogenic vascular endothelial growth factor (VEGF; P = .0002) and Akt (P = .01) were downregulated in the HF-NAP group."] Does high-fat diet alter prostanoid balance and perfusion in ischemic myocardium of naproxen-treated swine?