Background-Both statins and thiazolidinediones have antiinflammatory properties. However, the exact mechanisms underlying these effects are unknown. We investigated whether atorvastatin (ATV) and pioglitazone (PIO) increase the myocardial content of lipoxin-A 4 and 15(R)-epi-lipoxin-A 4 (15-epi-LXA 4 ), both arachidonic acid products with strong antiinflammatory properties. Methods and Results-In experiment 1, rats received 3-day pretreatment with water; PIO 2, 5, or 10 mg · kg Ϫ1 · d Ϫ1 ; ATV 2, 5, or 10 mg · kg Ϫ1 · d

Ye Y, Martinez JD, Perez-Polo RJ, Lin Y, Uretsky BF, Birnbaum Y. The role of eNOS, iNOS, and NF-B in upregulation and activation of cyclooxygenase-2 and infarct size reduction by atorvastatin. Am J Physiol Heart Circ Physiol 295: H343-H351, 2008. First published May 9, 2008 doi:10.1152/ajpheart.01350.2007.-Pretreatment with atorvastatin (ATV) reduces infarct size (IS) and increases myocardial expression of phosphorylated endothelial nitric oxide synthase (p-eNOS), inducible NOS (iNOS), and cyclooxygenase-2 (COX2) in the rat. Inhibiting COX2 abolished the ATV-induced IS limitation without affecting p-eNOS and iNOS expression. We investigated 1) whether 3-day ATV pretreatment limits IS in eNOS Ϫ/Ϫ and iNOS Ϫ/Ϫ mice and 2) whether COX2 expression and/or activation by ATV is eNOS, iNOS, and/or NF-B dependent. Male C57BL/6 wild-type (WT), University of North Carolina eNOS Ϫ/Ϫ and iNOS Ϫ/Ϫ mice received ATV (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ; ATV ϩ ) or water alone (ATV Ϫ ) for 3 days. Mice underwent 30 min of coronary artery occlusion and 4 h of reperfusion, or hearts were harvested and subjected to ELISA, immunoblotting, biotin switch, and electrophoretic mobility shift assay. As a result, ATV reduced IS only in the WT mice. ATV increased eNOS, p-eNOS, iNOS, and COX2 levels and activated NF-B in WT mice. It also increased myocardial COX2 activity. In eNOS Ϫ/Ϫ mice, ATV increased COX2 expression but not COX2 activity or iNOS expression. NF-B was not activated by ATV in the eNOS Ϫ/Ϫ mice. In the iNOS Ϫ/Ϫ mice, eNOS and p-eNOS levels were increased but not iNOS and COX2 levels; however, NF-B was activated. In conclusion, both eNOS and iNOS are essential for the IS-limiting effect of ATV. The expression of COX2 by ATV is iNOS, but not eNOS or NF-B, dependent. Activation of COX2 is dependent on iNOS. endothelial nitric oxide synthase; inducible nitric oxide synthase; nuclear factor-B THE 3-HYDROXY-3-METHYLGLUTARYL coenzyme A (HMG-CoA) reductase inhibitors (statins) protect against ischemia-reperfusion injury and, when administered before ischemia (2, 5, 7, 25, 26, 34 -36, 43, 44, 46 -48, 52, 53) or immediately upon reperfusion (4, 17, 47), limit myocardial infarct size (IS) in various animal models. Several investigators have shown that the activation of endothelial nitric oxide synthase (eNOS) is essential for this protective effect, since nonspecific nitric oxide synthase (NOS) inhibitors blunt the IS-limiting effect of statins (5, 48) and since statins do not reduce IS in eNOS Ϫ/Ϫ mice (1, 4, 18, 25, 52). However, most of these studies used a particular eNOS Ϫ/Ϫ line (Harvard). As reported by Sharp et al. (37), there are two distinct lines of eNOS Ϫ/Ϫ mice: the Harvard line lacks compensatory increases in inducible NOS (iNOS) and has an IS bigger than the corresponding wild-type (WT) mice, and the University of North Carolina line, which has compensatory increases in iNOS expression and an IS smaller than the corresponding WT mice. It has been suggested that iNOS can be protective and compensate for the lack in eNOS and that ...

We assessed whether aspirin (acetylsalicylic acid, ASA), administered before reperfusion, abrogates the infarct size (IS)-limiting effect of atorvastatin (ATV). Statins reduce IS. This dose-dependent effect is mediated by upregulation of cycloxygenase-2 (COX2) and PGI(2) production. Administration of selective COX2-inhibitors either with ATV for 3 days or immediately before coronary occlusion blocks the IS-limiting effect of ATV. Sprague-Dawley rats received 3-day ATV (10 mg x kg(-1) x day(-1)) or water alone. Rats underwent 30 min coronary artery occlusion and 4 h reperfusion (IS protocol, n=8 in each group), or rats underwent 30 min coronary artery occlusion and 10 min reperfusion (enzyme expression and activity protocol, n=4 in each group). Immediately before reperfusion rats received intravenous ASA (5, 10, or 20 mg/kg) or saline. Area-at-risk (AR) was assessed by blue dye and IS by triphenyltetrazolium chloride. ATV reduced IS (10.1 +/- 1.4% of the AR) compared with controls (31.0 +/- 2.2%). Intravenous ASA alone did not affect IS (29.0 +/- 2.6%); however, ASA dose dependently (5, 10, and 20 mg/kg) attenuated the protective effect of ATV on IS (15.8 +/- 0.9%, 22.0 +/- 1.6%, and 23.7 +/- 3.8%, respectively). ASA dose dependently blocked the upregulation of COX2 by ATV. COX2 activity was as follows: control, 8.93 +/- 0.90 pg/mg; ATV, 75.85 +/- 1.08 pg/mg; ATV + ASA5, 34.39 +/- 1.48 pg/mg; ATV + ASA10, 19.87 +/- 1.10 pg/mg; and ATV + ASA20, 9.36 +/- 0.94 pg/mg. ASA, administered before reperfusion in doses comparable to those used in the clinical setting, abrogates the IS-limiting effect of ATV in a model with mechanical occlusion of the coronary artery. This potential adverse interaction should be further investigated in the clinical setting of acute coronary syndromes.

Elevated cardiac biomarkers in conjunction with electrocardiographic (ECG) changes are valuable in diagnosing acute coronary syndrome (ACS). Elevated troponin I (TnI), while commonly seen in ACS, can also occur in entities such as sepsis and pulmonary thromboembolic disease. Raised TnI levels in patients with sepsis result from various mechanisms, including hypoperfusion or direct extension of infection to cardiac tissue, and can also serve as an important prognostic indicator. Electrocardiographic changes in sepsis are not as well described. Some of the ECG findings associated with septic shock include loss of QRS amplitude, increase in QTc interval, bundle branch blocks, and development of narrowed QRS intervals with deformed, positively deflected J waves (commonly known as Osborn waves). ST-segment elevations in sepsis are rare and have only previously been noted in a handful of case reports involving patients with septic shock. We present a case of a 59-year-old woman with ST-segment elevations and increased levels of cardiac troponin from Escherichia coli septic shock in the setting of normal coronary angiography.

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Crude protein and amino acid ( AA ) content in rearing diets affect body composition and reproductive performance. This study evaluated the effects of 4 dietary AA levels during rearing on BW, egg production and composition, fertility, hatchability, and embryo mortality up to 65 wk of age on Cobb 500 slow-feathering ( SF ) broiler breeders. The treatments consisted in 80% (low-AA), 90% (moderate-AA), 100% (standard-AA), and 110% (high-AA) of the AA recommendations for Cobb 500 SF pullets from 5 to 24 wk. AA was guided by an ideal protein profile based on digestible Lys. A total of 1,360 pullets and 288 Cobb MV cockerels were randomly placed in 16 pullets and 16 cockerel floor-pens. At 22 wk, 1,040 females and 112 males were transferred into 16-floor pens in a laying house. BW increased linearly ( P < 0.01) as AA augmented at 25, 36, and 40 wk. No effects ( P > 0.05) at the onset of lay were observed. Moderate-AA and standard-AA resulted in the best hen-housed egg production ( HHEP ) at 65 wk with 174.3 and 176.5 eggs, respectively. The optimum level of AA for HHEP at 65 wk was estimated ( P < 0.001) in 96.7% and 94.7% by the quadratic and broken line models, respectively. Overall, the lightest egg weight ( P = 0.022) was obtained with 89%AA during rearing, and the heaviest eggs ( P < 0.001) were found at 54 wk. Response surface regression indicated linear effects on albumen and yolk percentages ( P < 0.01) increasing and decreasing, respectively, as AA levels augmented; consequently, AA had a negative linear effect on Y:A ratio ( P = 0.004) with quadratic effects ( P < 0.01) of age (R 2 = 0.92). No statistical effect of treatments was observed in fertility ( P > 0.05), but AA had a quadratic effect ( P = 0.046) on hatchability up to 50 wk of age with 97% as optimum, and decreased linearly ( P = 0.004) from 51 to 65 wk. A few effects of treatments ( P < 0.05) on embryo mortality were observed. In conclusion, AA levels during rearing affect broiler breeder reproductive performance.

Drying temperature ( DT ) of corn can influence its nutritional quality, but whether this is influenced by endosperm hardness is not clear. Two parallel experiments were conducted to investigate the effects of 2 yellow dent corn hybrids with average and hard kernel hardness, dried at 3 temperatures (35, 80, and 120°C), and 2 supplementation levels of an exogenous amylase (0, 133 g/ton of feed) on live performance, starch and protein digestibility, and energy utilization of Ross 708 male broilers. Twelve dietary treatments consisting of a 2 × 3 × 2 factorial arrangement were evaluated using 3-way ANOVA in a randomized complete block design. In Experiment 1, a total of 1,920 male-chicks were randomly allocated to 96 floor pens, whereas 480 day-old chicks were distributed among 96 cages for Experiment 2. At 40 d, interaction effects ( P < 0.05) were detected on BWG, FCR, and flock uniformity. Supplementation with exogenous amylase resulted in heavier broilers, better FCR and flock uniformity, only in the diets based on corn dried at 35°C. Additionally, interaction effects were observed on FCR due to kernel hardness and DT ( P < 0.01), kernel hardness and amylase supplementation ( P < 0.001), and DT and amylase supplementation ( P < 0.05). Exogenous amylase addition to the diets based on corn with an average hardness improved FCR up to 2 points (1.49 vs. 1.51 g:g) whereas there was no effect of amylase on FCR of broilers fed diets based on corn with hard endosperm. Total tract retention of starch was increased ( P < 0.05) in broilers fed diets based on corn with average kernel hardness compared to hard kernel. Corn dried at 80 and 120°C had up to 1.21% points less starch total tract retention than the one dried at 35°C. Supplementing alpha-amylase resulted in beneficial effects for broiler live performance, energy utilization, and starch total tract digestibility results. Treatment effects on starch characteristics were explored. Corn endosperm hardness, DT and exogenous amylase can influence the live performance of broilers. However, these factors are not independent and so must be manipulated strategically to improve broiler performance.