Background— Elevated heart rate is associated with increased cardiovascular morbidity. We hypothesized that selective heart rate reduction may influence endothelial function and atherogenesis and tested the effects of the I (f) current inhibitor ivabradine in apolipoprotein E–deficient mice. Methods and Results— Male apolipoprotein E–deficient mice fed a high-cholesterol diet were treated with ivabradine (10 mg · kg −1 · d −1 ) or vehicle for 6 weeks (n=10 per group). Ivabradine reduced heart rate by 13.4% (472±9 versus 545±11 bpm; P <0.01) but did not alter blood pressure or lipid levels. Endothelium-dependent relaxation of aortic rings was significantly improved in ivabradine-fed animals ( P <0.01). Ivabradine decreased atherosclerotic plaque size in the aortic root by >40% and in the ascending aorta by >70% ( P <0.05). Heart rate reduction by ivabradine had no effect on the number of endothelial progenitor cells and did not alter aortic endothelial nitric oxide synthase, phosphorylated Akt, vascular cell adhesion molecule-1, or intercellular adhesion molecule-1 expression but decreased monocyte chemotactic protein-1 mRNA and exerted potent antioxidative effects. Ivabradine reduced vascular NADPH oxidase activity to 48±6% and decreased markers of superoxide production and lipid peroxidation in the aortic wall ( P <0.05). The in vivo effects of ivabradine were absent at a dose that did not lower heart rate, in aortic rings treated ex vivo, and in cultured vascular cells. In contrast to ivabradine, treatment with hydralazine (25 mg · kg −1 · d −1 for 6 weeks) reduced blood pressure (−15%) but increased heart rate (37%) and did not improve endothelial function, atherosclerosis, or oxidative stress. Conclusions— Selective heart rate reduction with ivabradine decreases markers of vascular oxidative stress, improves endothelial function, and reduces atherosclerotic plaque formation in apolipoprotein E–deficient mice.

Food supplementation with PSE impairs endothelial function, aggravates ischemic brain injury, effects atherogenesis in mice, and leads to increased tissue sterol concentrations in humans. Therefore, prospective studies are warranted that evaluate not only effects on cholesterol reduction, but also on clinical endpoints.

Regional anesthesia is the most effective procedure for acute pain therapy. Whether neuraxial and peripheral blocks in patients with pre-existing infectious conditions, immune deficits or other risk factors increase the risk of additional infections is unclear. Analyzing the available literature currently seems to indicate that the incidence of severe infectious complications is generally low. Diabetes, steroid therapy or malignant diseases are apparently present in many cases in which infections associated with regional anesthesia and analgesia have been described. A strict contraindication in patients with pre-existing systemic or local infections seems unjustifiable. A clear and documented risk-benefit ratio in these patients is mandatory.

The presence of diabetes is associated with an increased risk for catheter-related infections in lower limb and lumbar epidural. Specific care should be taken to avoid and detect infections in this population.

We showed a preemptive effect with ketoprofen, which was expressed significantly both in terms of the time to first analgesic request and by the lower analgesic consumption in the first 24 hours after surgery.