title: Effects of selective cyclooxygenase-2 and nonselective cyclooxygenase inhibition on myocardial function and perfusion.
abstract: Nonselective nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 (COX-2) inhibitors are purported to increase adverse cardiovascular events. We hypothesized that COX-2 inhibitors would alter myocardial blood flow, microvascular reactivity, oxidative stress, and prostaglandin levels. Adult Yorkshire swine were divided into 3 groups: no drug (control, n = 7), a nonselective COX inhibitor (naproxen 400 mg daily, NAP, n = 7), or a selective COX-2 inhibitor (celecoxib 200 mg daily, CBX, n = 7). After 7 weeks, physiologic measurements were taken and tissue harvested. Animals in the CBX group demonstrated significantly higher blood pressure and rate-pressure product. The NAP and CBX groups demonstrated an increased microvascular contraction response to serotonin. The NAP group showed increased myocardial levels of thromboxane and lower levels of prostacyclin. Levels of protein oxidative stress were increased in the CBX group. Myocardial apoptosis was lowest in the NAP group. Immunoblotting demonstrated decreased vascular endothelial growth factor and phosphorylated endothelial nitric oxide synthase expression in the NAP and CBX groups. Myocardial tumor necrosis factor-α was increased in both treated groups. Immunostaining for thromboxane A2 synthase and receptor demonstrated expression within the vascular smooth muscle and no observable differences between groups. Nonselective and selective COX inhibition does not alter myocardial perfusion but results in altered myocardial and vascular physiology that may have implications regarding cardiovascular risk.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert School of Medicine, Brown University, Providence, RI, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Robich
authors.forename: Louis M
authors.initials: LM
authors.lastname: Chu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Burgess
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Cesario
authors.initials: C
authors.lastname: Bianchi
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D011464:Epoprostenol / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010477:Perfusion / Q000379:methods; D012306:Risk; D013552:Swine; D013556:Swine, Miniature; D013931:Thromboxanes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D013931:Thromboxanes; D014409:Tumor Necrosis Factor-alpha; D011464:Epoprostenol; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2