Abstract-We have shown that leukocytes retract their pseudopods and detach from substrates after exposure to physiological fluid shear stresses (Ϸ1.5 dyn/cm 2 ). In inflammation, however, pseudopod projection during spreading and firm adhesion on endothelium is observed even in microvessels with normal blood flow and fluid shear stresses. Thus, we examined mechanisms that may serve to regulate the shear stress response of circulating leukocytes. In the presence of inflammatory mediators (platelet-activating factor [PAF] f-met-leu-phe), a subgroup of cells ceases to respond to shear stress. cGMP analogs and nitric oxide (NO) donors enhance the shear stress response and reverse the inhibitory effect of inflammatory mediators on the shear stress response, whereas depletion of cGMP leads to cessation of the shear stress response even in unstimulated leukocytes. The ability of cGMP to enhance the shear stress response is not associated with CD18 expression, because cGMP has no effect on CD18 expression in response to shear stress. The shear stress response of leukocytes in endothelial nitric oxide synthase (Ϫ/Ϫ) mice, in which NO level in blood is decreased, is attenuated compared with that in wild-type mice. In rat mesentery venules stimulated by PAF under normal blood flow, a cGMP analog diminishes pseudopod projection of leukocytes, whereas inhibition of NO leads to enhanced pseudopod projection and spreading. The evidence suggests that inflammatory mediators suppress the shear stress response of leukocytes leading to spreading even under normal physiological shear stress, whereas cGMP may serve to maintain shear stress response even in inflammation. The full text of this article is available at http://www.circresaha.org. (Circ Res. 2000;86:e13-e18.) Key Words: leukocyte Ⅲ microcirculation Ⅲ shear stress Ⅲ nitric oxide Ⅲ cGMP T here is now evidence that all cells in the circulation respond to physiological shear stress, including endothelial cells, 1 erythrocytes, 2 platelets, 3 and leukocytes. 4 Human leukocytes (neutrophils, monocytes, and lymphocytes) respond to fluid shear stress by retraction of pseudopods (lamellipodia, filopodia, and other forms) and membrane detachment. 4 The shear stress response of leukocytes serves as the key mechanism to maintain circulatory leukocytes in a spherical shape without pseudopod formation. In the presence of pseudopods, leukocytes become trapped in capillaries with high probability. 5 Pseudopod retraction is a requirement for normal passage of circulating leukocytes through the microcirculation.In inflammation, however, pseudopod projection (change of the cell shape from a spherical shape) of adherent leukocytes is a requirement for migration across the endothelium into the tissue. The adhesion is readily observed even in venules that have essentially normal blood flow. 6 Thus, there may exist a fundamental regulating mechanism for the leukocyte shear stress response in inflammation. Using in vitro experiments on human, rat, and mouse leukocytes and in vivo observations in ...

The present study investigates whether lower-limb dominant exercise training in patients with chronic heart failure (CHF) improves endothelial function primarily in the trained lower extremities or equally in the upper and lower extremities. Twenty-eight patients with CHF were randomized to the exercise or control group. The exercise group underwent cycle ergometer training for 3 months while controls continued an inactive sedentary lifestyle. Exercise capacity (6-min walk test) and flow-mediated vasodilation in the brachial and posterior tibial arteries were evaluated. After 3 months, walking performance increased only in the exercise group (488+/-16 to 501+/-14 m [control]; 497+/-23 to 567+/-39 m [exercise, p<0.05]). The flow-mediated vasodilation in the brachial arteries did not change in either group (4.2+/-0.5 to 4.5+/-0.4% [control]; 4.3+/-0.5 to 4.6+/-0.4% [exercise]), but that in the posterior tibial arteries increased only in the exercise group (4.1+/-0.5 to 4.1+/-0.3% [control]; 3.6+/-0.3 to 6.4+/-0.6% [exercise, p<0.01]). Cycle ergometer training improved flow-mediated vasodilation in the trained lower limbs, but not in the untrained upper limbs. Exercise training appears to correct endothelial dysfunction predominantly by a local effect in the trained extremities.

Abstract-Acute aortic dissection (AAD) is associated with an inflammatory reaction, as evidenced by elevated inflammatory markers, including C-reactive protein (CRP). The association between the peak CRP level and long-term outcomes in type B AAD has not been systematically investigated. The purpose of this study was to investigate whether the peak CRP level during admission predicts long-term outcomes in type B AAD. We conducted a clinical follow-up study of type B AAD. We divided the study population into 4 groups according to the tertiles of peak CRP levels (T1: 0.60 to 9.37 mg/dL; T2: 9.61 to 14.87 mg/dL; T3: 14.90 to 32.60 mg/dL; and unavailable peak CRP group). Multivariate Cox regression analysis was applied to investigate whether the tertiles of peak CRP predict adverse events even after adjusting for other variables. A total of 232 type B AAD patients were included in this analysis. The median follow-up period was 50 months. CRP reached its peak on day 4.5Ϯ1.7. Mean peak CRP values in T1, T2, and T3 were 6.4Ϯ2.

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Return to daily life Early mobilization program Comprehensive CR (disease management program) Discharge from hospital, Return to home Maintain comfortable life, Prevention of recurrence Returning to society-workforce, Establish new healthy lifestyle Inpatient rehabilitation program (CCU/ICU/ward) *Notation of corporation is omitted.