Intensive cholesterol reduction may be beneficial in the treatment of patients with ISH and normal lipid levels, through a reduction in large artery stiffness.

OBJECTIVE -Diabetic individuals have impaired endothelium-dependent forearm vasodilatory responses to ischemia, acetylcholine, and other endothelium-dependent agonists. The functional significance of impaired endothelium-dependent dilation in diabetic individuals is uncertain but is most likely to be manifest during leg muscle exercise and may have relevance to peripheral vascular disease and leg ischemia, which is prevalent in diabetic individuals. The current study aimed to determine the relationship between leg blood flow (LBF) responses to endothelium-dependent vasodilation and dynamic large muscle exercise. RESEARCH DESIGN AND METHODS -LBF responses (thermodilution)to intrafemoral arterial infusions of an endothelium-dependent (acetylcholine) and endotheliumindependent (sodium nitroprusside) vasodilator and a standardized 25-min cycling bout at 60% VO 2peak were compared in nine male type 2 diabetic subjects and nine age-, sex-, VO 2peak -, and weight-matched control subjects.RESULTS -LBF responses to acetylcholine and exercise but not sodium nitroprusside were significantly (P Ͻ 0.05) attenuated in patients with diabetes compared with healthy control subjects. The percentage increase in LBF in response to exercise and acetylcholine were significantly correlated (r ϭ 0.54, P ϭ 0.02). Furthermore, resting plasma glucose was significantly related to the LBF response to exercise (r ϭ Ϫ0.66, P ϭ 0.003) independently of insulin, HbA 1c , lipids, BMI, and blood pressure.CONCLUSIONS -The increase in LBF during exercise is substantially attenuated in type 2 diabetic compared with matched control subjects. Impaired endothelium-dependent vasodilation secondary to elevated plasma glucose may underlie this observation. This mechanism may be of importance in determining the leg ischemic threshold in diabetic individuals with peripheral vascular disease. Diabetes Care 26:899 -904, 2003

Nitric oxide (NO) synthase inhibition reduces leg glucose uptake during cycling without reducing leg blood flow (LBF) in young, healthy individuals. This study sought to determine the role of NO in glucose uptake during exercise in individuals with type 2 diabetes. Nine men with type 2 diabetes and nine control subjects matched for age, sex, peak pulmonary oxygen uptake (VO 2 peak), and weight completed two 25-min bouts of cycling exercise at 60 ؎ 2% VO 2 peak, separated by 90 min. N G -monomethyl-L-arginine (L-NMMA) (total dose 6 mg/kg) or placebo was administered into the femoral artery for the final 15 min of exercise in a counterbalanced, blinded, crossover design. LBF was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of LBF and femoral arteriovenous glucose difference. During exercise with placebo, glucose uptake was not different between control subjects and individuals with diabetes; however, LBF was lower and arterial plasma glucose and insulin levels were higher in individuals with diabetes. L-NMMA had no effect on LBF or arterial plasma glucose and insulin concentrations during exercise in both groups. L-NMMA significantly reduced leg glucose uptake in both groups, with a significantly greater reduction (P ‫؍‬ 0.04) in the diabetic group (75 ؎ 13%, 5 min after L-NMMA) compared with the control group (34 ؎ 14%, 5 min after L-NMMA). These data suggest a greater reliance on NO for glucose uptake during exercise in individuals with type 2 diabetes compared with control subjects.

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Objectives: To assess whether a collaborative interdepartmental pathway involving emergency department (ED) physicians activating the cardiac catheterisation laboratory (CCL) with immediate patient transfer to the CCL reduces door‐to‐balloon (DTB) times for patients with suspected ST‐elevation myocardial infarction (STEMI). Design, setting and participants: A quasi‐experimental before‐and‐after observational study using a prospective database, supplemented by chart review, of consecutive patients transferred from the ED to the CCL for suspected STEMI, from January 2007 to October 2009, at Sir Charles Gairdner Hospital, an adult tertiary‐care hospital, Western Australia. Main outcomes measures: Median DTB time and proportion of patients with DTB time of < 90 minutes. Secondary outcomes, based on analysis of predefined subgroups, included door‐to‐activation time, activation‐to‐balloon time and false‐positive activations of the CCL. Results: Two hundred and thirty‐four patients underwent emergency coronary angiography for suspected STEMI, with 188 (80%) undergoing percutaneous coronary intervention (118 before and 70 after implementation of the new pathway). Following implementation of the new pathway, median DTB time reduced from 97 to 77 minutes (P < 0.001), median door‐to‐activation time from 28 to 15 minutes (P = 0.002) and median activation‐to‐balloon time from 66 to 53 minutes (P < 0.001). The proportion of patients with recommended DTB time of < 90 minutes increased from 41% to 77% (P < 0.001) with no change in false positive CCL activation rates (12% v 11%; P = 0.38). Conclusion: ED physician activation of CCL with immediate patient transfer is associated with highly significant improvements in DTB time without increased false positive rates.