Bayer AG.

Background: Retrospective and prospective studies have demonstrated that statins have a protective effect in preventing contrast-induced nephropathy (CIN), but there are currently no established guidelines for statin timing or dosage. A systematic review and meta-analysis was performed to determine whether statin administration is protective and the magnitude of their effect. Methods: We searched MEDLINE, EMBASE, Cochrane Library, CNKI and ISI Proceedings for cohort studies comparing the CIN incidence in a chronic statin pretreatment group and a statin-naïve group, as well as for randomized controlled trials (RCTs) comparing short-term high-dose to short-term low-dose statin treatment or placebo. CIN was defined as an increase in serum creatinine >25% or 0.5 mg/dl (44.2 µmol/l). Qualitative analysis of cohort studies and quantitative analysis of RCTs to estimate pooled risk ratios were performed. Results: Among 6 cohort studies, 4 showed chronic statin pretreatment had a preventive effect against CIN. From 6 RCTs, 1,194 patients were included in the meta-analysis. Under the fixed-effects model, a nonsignificant protective trend toward decreased incidence of CIN with periprocedural short-term high-dose statin treatment was seen (RR: 0.70; 95% CI: 0.48–1.02). Conclusion: Current data are not conclusive to whether statins are protective for CIN due to the inherent limitations of the included studies. In the future, large well-designed studies are needed to address the effect of this drug and its longer-term clinical outcomes.

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Objective-The development of a murine model of spontaneous atherosclerotic plaque rupture with luminal thrombus. Methods and Results-Combined partial ligation of the left renal artery and left common carotid artery in 8-week-old apolipoprotein E-deficient mice induced endogenous renovascular hypertension and local low oscillatory shear stress in the left common carotid artery. After 8 weeks, a fresh left common carotid artery lumen thrombus associated with severe plaque burden was found in 50% (10/20) of the mice. Histological analyses indicated that all left common carotid artery lesions had vulnerable features, and 50% (5/10) of the mice showed plaque rupture with a lumen thrombus. Multiple layers with layering discontinuity and intraplaque hemorrhages were found in 80% (8/10) of the mice. Further experiments showed that both increased blood pressure, and angiotensin-II contributed to plaque progression and vulnerability. Decreased intimal collagen associated with increased collagenase activity and matrix metalloproteinase expression also resulted in plaque disruption. Conclusion-We demonstrate a murine model of spontaneous plaque rupture with a high incidence of luminal thrombus.The model not only nicely recapitulates the pathophysiological processes of human plaque rupture but it is also simple, fast, and highly efficient to generate. Therefore, in this study, using the method of partial ligation of left carotid and left renal arteries, we induced local stress change, as well as continuously activated reninangiotensin system in ApoE knockout mice. High incidence of spontaneous plaque rupture associated with lumen thrombosis was successfully generated by combining systematic and local factors. Furthermore, this simple murine model not only nicely recapitulates the pathophysiological processes of human plaque rupture but also has rapid plaque progression. Materials and Methods MiceApoE-deficient (ApoE −/− ) mice on a C57BL/6 background were obtained from the Jackson Laboratory (Bar Harbor, ME). Age-(8-week-old) and sex-matched animals weighing between 20 and 25 g were enrolled in the study. Mice batch 1 was randomly assigned to 5 groups: combined partial ligation of left renal artery and left common carotid artery (LCCA) (R+C), partial ligation of left renal artery (R), partial ligation of LCCA (C), sham control (S), and open control (O). Mice batch 2 was also randomly assigned to 5 groups: combined partial ligation of left renal artery and LCCA + intragastrically administered normal saline (R+C+NS), combined partial ligation of left renal artery and LCCA + intragastrically administered losartan (R+C+LO), partial ligation of LCCA + subcutaneous normal saline infusion (C+NS), partial ligation of LCCA + subcutaneous angiotensin II infusion (C+ANG), and partial ligation of LCCA + subcutaneous phenylephrine infusion (C+PHE). For time series experiment, mice were randomly assigned to 4 groups: sham operation was performed in mice of group 1; mice of other groups underwent partial ligation both of LCCA and left ren...

Endocannabinoid system is reported to be activated during myocardial ischemia-reperfusion (IR) injury and protects against heart injury. We, therefore, observed changes in endocannabinoids levels during acute myocardial infarction (AMI) and myocardial IR injury and evaluated the role of cannabinoid-2 (CB2) receptor in infarct and IR heart injury. In contrast to 16 control patients with normal coronary artery angiogram, the endocannabinoid 2-arachidonoylglycerol level in the infarct-side coronary artery of 23 AMI patients increased significantly, with increased reactive oxygen species and tumor necrosis factor-α levels in both infarct-side coronary artery and radial artery. Then, 35 C57BL/6J mice were made into SHAM, AMI, or IR models. AMI and IR groups were treated with CB2-selective agonist HU308 ((+)-(1aH,3H,5aH)-4-[2,6-dimethoxy-4-(1,1-dimethylheptyl)phenyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbinol), with or without CB2-selective antagonist AM630 [6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone through intraperitoneal injection. Compared with the SHAM, expressions of cannabinoid CB1/CB2 receptor proteins in AMI/IR animals were upregulated; production of 2-arachidonoylglycerol and anandamide and release of reactive oxygen species and tumor necrosis factor-α also increased. HU308 significantly decreased the infarct size and the levels of reactive oxygen species and tumor necrosis factor-α in AMI/IR animals. However, these effects were blocked by AM630. In conclusion, the endocannabinoid system was activated during AMI and IR, and CB2 receptor activation produces a protective role, thus offering a novel pharmaceutical target for treating these diseases.