Tlie differential pressure method of Womersley and McDonald was used to measure instantaneous blood flow in the main pulmonary artery in ten human subjects. Three subjects had normal pulmonary arterial pressures and flows, seven had mitral stenosis and pulmonary hypertension. The spectrum of input impedance versus frequency was similar to that previously reported for the dog and rabbit, with the modulus decreasing from relatively high values at zero frequency to a minimum between 2 and 5 cycles/sec. Characteristic impedance and phase velocity were lower in the normal subjects than in those with pulmonary hypertension (averages, 23 dyne sec crrr r ' and 1.68 m/sec in the normals; 46 dyne sec c n r ' and 4.77 m/sec in the hypertensives). Hydraulic energy dissipated per unit time by pulsations in the pulmonary bed was usually higher in the hypertensive than in the normal cases, because of the greater stiffness of the pulmonary arteries in the subjects with pulmonary hypertension. The elasticity of the pulmonary arterial tree appears to be as important as the state of the arterioles and capillaries in determining the energy required for pulsatile pulmonary blood flow. ADDITIONAL KEY WORDS differential pressure hydraulic energy vascular elasticity pulmonary hypertension mitral stenosis blood flow

To determine the systemic input impedance, pulsatile pressure and flow were measured in the ascending aorta in 16 human subjects who were undergoing diagnostic cardiac catheterization. Blood flow was measured with a catheter-tip electromagnetic velocity meter, and pressure with an external transducer connected with the fluid-filled lumen of the catheter. Five subjects were found to have no evidence of cardiovascular disease (group A, mean age 32 +/- 2 years, mean aortic pressure 97 +/- 4 mm Hg). Seven had clinical and angiographic signs of coronary arterial disease, and mean pressures less than 100 mm Hg (group B, mean age 48 +/- 2 years). Four subjects had signs of coronary disease and mean pressures greater than 100 mm Hg (group C, mean age 48 +/- 3 years). The frequency spectra of impedance were qualitatively similar in all three groups and resembled those previously observed in the canine aorta. Characteristic impedance was lower in the normal subjects (group A, average 53 dyn sec cm-5) than in the subjects with coronary artery disease (groups B and C, average 129 dyn sec cm-5). Among the subjects with coronary disease, characteristic impedance was higher in the hypertensive subjects (group C, average 202 dyn sec cm-5) than in those with lower mean pressures (group B, average 95 dyn sec cm-5). External left ventricular work per unit time (hydraulic power) averaged 1715 milliwatts (mW) in group A, 1120 mW in group B, and 2372 mW in group C. Cardiac outputs were within normal limits in all subjects, but tended to be lower in group B than in group C. These results suggest that the subjects of group C were better able to meet the increased energy demands imposed by an abnormally high aortic input impedance. Further investigation is needed to learn whether the high impedances in subjects with coronary disease represent an increase with age and transmural pressure alone, or whether some additional factor is involved. The data on relatively normal subjects permit a tentative definition of the normal limits for aortic input impedance in man: 26-80 dyn sec cm-5.

Background-Mechanisms responsible for anti-ischemic benefits of enhanced external counterpulsation (EECP) remainunknown. This was the first randomized sham-controlled study to investigate the extracardiac effects of EECP on peripheral artery flow-mediated dilation. Methods and Results-Forty-two symptomatic patients with coronary artery disease were randomized (2:1 ratio) to thirty-five 1-hour sessions of either EECP (nϭ28) or sham EECP (nϭ14). Flow-mediated dilation of the brachial and femoral arteries was performed with the use of ultrasound. Plasma levels of nitrate and nitrite, 6-keto-prostaglandin F 1␣ , endothelin-1, asymmetrical dimethylarginine, tumor necrosis factor-␣, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule, high-sensitivity C-reactive protein, and 8-isoprostane were measured. EECP increased brachial (ϩ51% versus ϩ2%) and femoral (ϩ30% versus ϩ3%) artery flow-mediated dilation, the nitric oxide turnover/production markers nitrate and nitrite (ϩ36% versus ϩ2%), and 6-keto-prostaglandin F 1␣ (ϩ71% versus ϩ1%), whereas it decreased endothelin-1 (Ϫ25% versus ϩ5%) and the nitric oxide synthase inhibitor asymmetrical dimethylarginine (Ϫ28% versus ϩ0.2%) in treatment versus sham groups, respectively (all PϽ0.05). EECP decreased the proinflammatory cytokines tumor necrosis factor-␣ (Ϫ16% versus ϩ12%), monocyte chemoattractant protein-1 (Ϫ13% versus ϩ0.2%), soluble vascular cell adhesion molecule-1 (Ϫ6% versus ϩ1%), high-sensitivity C-reactive protein (Ϫ32% versus ϩ5%), and the lipid peroxidation marker 8-isoprostane (Ϫ21% versus ϩ1.3%) in treatment versus sham groups, respectively (all PϽ0.05). EECP reduced angina classification (Ϫ62% versus 0%; PϽ0.001) in treatment versus sham groups, respectively. Conclusions-Our findings provide novel mechanistic evidence that EECP has a beneficial effect on peripheral artery flow-mediated dilation and endothelial-derived vasoactive agents in patients with symptomatic coronary artery disease. (Circulation. 2010;122:1612-1620.)

SUMMARY The input impedance of the systemic circulation was calculated from recordings of pulsatile pressure and flow in the ascending aorta of 20 patients. Ten patients had clinical and hemodynamic evidence of heart failure. The other 10 subjects had no clinical evidence of heart failure and were used as a control group. In the heart failure patients, both input resistance and characteristic impedance (index of aortic distensibility) were significantly increased compared to pressureand age-matched control subjects. Oscillations of impedance moduli, represented by the difference between maximum and minimum moduli, were also significantly increased in the heart failure patients compared with the control subjects. The increased characteristic input impedance in these heart failure patients suggests that the human aorta is stiffer in heart failure, and the larger oscillations in the impedance spectrum indicate an increase in pressure and flow wave reflections. From reflected wave theory in elastic tubes, reflected pressure waves add to the amplitude of incident pressure waves at the entrance of the system, whereas reflected flow waves subtract from the magnitude of the forward flow. Thus, changes in aortic distensibility could have an important influence on the pulsatile function of the failing left ventricle.THE AORTA AND LARGE ARTERIES of the systemic circuit are not rigid pipes, but constitute a distensible elastic buffering chamber. These elastic properties permit a damping mechanism through which pulsatile blood flow waves ejected from the left ventricle are converted to a near-constant blood flow for resistance vessels to distribute to systemic capillaries. Elastic properties of these large vessels can be modified by autonomic nervous effects on vascular smooth muscle cells with only minor changes in vessel dimensions.' Recent studies in our laboratories suggest that age and the presence of atherosclerosis may also be important in modifying the elastic properties of large vessels.2In heart failure, previous studies have emphasized abnormal ventricular and peripheral hemodynamic