Enhanced external counterpulsation (EECP) decreases advanced glycation end products and proinflammatory cytokines in patients with non-insulin-dependent type II diabetes mellitus for up to 6 months following treatment.

AIMS: Enhanced external counterpulsation (EECP) is a noninvasive, non-pharmacologic intervention proven to increase nitric oxide bioavailability in patients with coronary artery disease. The purpose of the present study was to evaluate the potential clinical benefits of EECP on advanced glycation end products (AGEs) and proinflammatory cytokine concentrations in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). METHODS: Thirty subjects (60.7 ± 1.9 years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n = 20) or time-matched standard care (n = 10). AGEs, receptors for AGEs (RAGEs), soluble vascular cell adhesion molecules-1 (sVCAM-1), and 8-iso-prostaglandin 2α (8-iso-PGF2α) were evaluated before and at 48 h, 2 weeks, 3, and 6 months following EECP treatment or time-matched control. RESULTS: EECP significantly decreased AGEs and RAGEs at all follow-up measurement time points. AGEs and RAGEs were decreased at 48 h (-75 and -16 %), 2 weeks (-87 and -28 %), 3 months (-89 and -29 %), and 6 months (-92 and -20 %) following EECP treatment, respectively. sVCAM-1 and 8-iso-PGF2α were significantly decreased at 48 h (-30 and -49 %) and 2 weeks (-22 and -27 %) following EECP, respectively. sVCAM-1 (-27 %) remained significantly reduced at 3 months following EECP. Nitrite/nitrate (NOx) was significantly increased at 48 h (+48.4 %) and 2 weeks (+51.9 %) following EECP treatment. CONCLUSIONS: Our findings provide novel evidence that EECP decreases AGE/RAGE concentrations, inflammation, and oxidative stress in patients with T2DM that persist for up to 6 months following treatment.

Enhanced external counterpulsation (EECP) improves biomarkers of glycemic control in patients with non-insulin-dependent type II diabetes mellitus for up to 3 months following treatment.

AIMS: The purpose of the present study was to evaluate the potential clinical benefits of EECP on glycemic parameters [fasting plasma glucose (FPG), postprandial glucose (PPG120), glycosylated hemoglobin (HbA1c)] in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). METHODS: Thirty subjects (60.7 ± 1.9 years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n = 20) or time-matched control of standard care (n = 10). FPG, PPG120, and HbA1c were evaluated before and at 48 h, 2 weeks, 3 and 6 months following EECP treatment or time-matched control. RESULTS: EECP significantly decreased FPG (-14.6 and -12.0 %), PPG120 (-14.6 and -13.5 %), and HbA1c (-11.5 and -19.6 %) 48 h following EECP and 2 weeks following EECP, respectively. HbA1c remained significantly reduced at 3 months following EECP (-14.3 %). The homeostasis model assessment of insulin resistance (-31.1 %) and whole-body composite insulin sensitivity index (+54.2 %) were significantly improved 48 h following EECP. Nitrite/nitrate (NO x ) was significantly increased 48 h following EECP (+48.4 %) and 2 weeks (+51.9 %) following EECP treatment. CONCLUSIONS: Our findings provide novel evidence that EECP improves glycemic control in patients with T2DM that persist for up to 3 months following treatment.

Enhanced external counterpulsation reduces indices of central blood pressure and myocardial oxygen demand in patients with left ventricular dysfunction.

Enhanced external counterpulsation (EECP) therapy decreases angina episodes and improves quality of life in patients with left ventricular (LV) dysfunction. However, the underlying mechanisms relative to the benefits of EECP therapy in patients with LV dysfunction have not been fully elucidated. The purpose of this study was to investigate the effects of EECP on indices of central haemodynamics, aortic pressure wave reflection characteristics, and estimates of LV load and myocardial oxygen demand in patients with LV dysfunction. Patients with chronic stable angina and LV ejection fraction < 40% but > 30%, were randomized to either an EECP group (LV ejection fraction = 35.1 ± 4.6%; n = 10) or sham-EECP group (LV ejection fraction = 34.3 ± 4.2%; n = 7). Pulse wave analysis of the central aortic pressure waveform and LV function were evaluated by applanation tonometry before and after 35 1-h sessions of EECP or sham-EECP. Enhanced external counterpulsation therapy was effective in reducing indices of LV wasted energy and myocardial oxygen demand by 25% and 19%, respectively. In addition, indices of coronary perfusion pressure and subendocardial perfusion were increased by 9% and 30%, respectively, after EECP. Our data indicate that EECP may be useful as adjuvant therapy for improving functional classification in heart failure patients through reductions in central blood pressure, aortic pulse pressure, wasted LV energy, and myocardial oxygen demand, which also suggests improvements in ventricular-vascular interactions.

Flow-mediated dilation is associated with endothelial oxidative stress in human venous endothelial cells.

Flow-mediated dilation (FMD) is recognized as a non-invasive endothelial function bioassay. However, FMD's relationship with endothelial cell oxidative stress in humans is yet to be determined. Here, we sought to determine if FMD was associated with endothelial nitric oxide synthase (eNOS) and endothelial oxidative stress in humans. Twenty-seven apparently healthy young men (26.5±5.9 years) underwent brachial artery FMD testing and endothelial cell biopsy from a forearm vein. Non-normalized FMD (%) and three different brachial artery FMD normalizations were performed: (1) peak shear rate (%/SR); (2) area under the SR curve until peak dilation (%/AUC); and (3) AUC 30 seconds before peak dilation (%/AUC30). Immunofluorescence quantification was used to assess eNOS expression and nitrotyrosine (NT), a criterion marker of endothelial oxidative stress. Values for eNOS and NT expression were reported as a ratio of endothelial cell to human umbilical vein endothelial cell average pixel intensity. NT expression was significantly correlated with FMD normalized by AUC30 (r = -0.402, p<0.05). Other FMD normalizations and non-normalized FMD were not significantly correlated with NT expression (r range = -0.364 to -0.142, all p>0.05). There were no significant correlations between eNOS expression and normalized and non-normalized FMD (r range = -0.168 to -0.066, all p>0.05). In conclusion, brachial artery FMD is associated with venous endothelial cell oxidative stress. However, this association is observed only when FMD is normalized by AUC30.

Enhanced external counterpulsation improves endothelial function and exercise capacity in patients with ischaemic left ventricular dysfunction.

Enhanced external counterpulsation (EECP) therapy decreases angina episodes and improves quality of life in patients with left ventricular (LV) dysfunction (LVD). However, studies have not elucidated the mechanisms of action and overall effects of EECP in patients with LVD. The purpose of the present study was to investigate the effects of EECP on endothelial function in peripheral conduit arteries and exercise capacity (peak Vo2 ) in patients with LVD. Patients with ischaemic LVD (ejection fraction (EF) 34.5 ± 4.2%; n = 9) and patients with symptomatic coronary artery disease (CAD) and preserved LV function (EF 53.5 ± 6.6%; n = 15) were studied before and after 35 sessions (1 h) of EECP. Brachial and femoral artery flow-mediated dilation (bFMD and fFMD, respectively) were evaluated using high-resolution ultrasound. Enhanced external counterpulsation elicited similar significant improvements in the following FMD parameters in the CAD and LVD groups (P ≥ 0.05 between groups for all): absolute bFMD (+53% and +70%, respectively), relative bFMD (+50% and +74%, respectively), bFMD normalized for shear rate (+70% and +61%, respectively), absolute fFMD (+33% and +21%, respectively) and relative fFMD (+32% and +17%, respectively). In addition, EECP significantly improved plasma levels of nitrate/nitrite (+55% and +28%) and prostacyclin (+50% and +70%), as well as peak Vo2 (+36% and +21%), similarly in both the CAD and LVD groups (P ≥ 0.05 between groups for all). Despite reduced LV function, EECP therapy significantly improves peripheral vascular function and functional capacity in CAD patients with ischaemic LVD to a similar degree to that seen in CAD patients with preserved LV function.

Peripheral resistance artery blood flow in subjects with abnormal glucose tolerance is improved following enhanced external counterpulsation therapy.

Enhanced external counterpulsation (EECP) improves resistance artery function in coronary artery disease patients. However, whether EECP elicits similar effects in persons with abnormal glucose tolerance (AGT) is unknown. Here we provide novel evidence that EECP significantly improves resistance arterial function in the forearm of persons with AGT, whereas the calf only approached significance (P ≤ 0.10). These improvements were coincident with greater glycemic control, providing further insight into the potential mechanisms of EECP-mediated alterations in glycemia.

Enhanced external counterpulsation improves peripheral resistance artery blood flow in patients with coronary artery disease.

Enhanced external counterpulsation (EECP) increases coronary artery perfusion and improves endothelium-dependent vasodilation in peripheral muscular conduit arteries. It is unknown whether vasodilatory capacity is improved in the peripheral resistance vasculature. Here we provide novel evidence from the first randomized, sham-controlled study that EECP increases peak limb blood flow and improves endothelium-dependent vasodilation in both calf and forearm resistance arteries in patients with coronary artery disease.

Validity of a novel wristband tonometer for measuring central hemodynamics and augmentation index.

BACKGROUND: Central hemodynamic and augmentation indices are independent predictors of cardiovascular events and all-cause mortality that can be estimated noninvasively by pulse wave analysis. The purpose of this study was to assess the reliability and validity of a newly engineered wristband tonometer for acquiring radial artery pressure waveforms. METHODS: Radial artery pulse pressure waveforms were evaluated with an established pencil-type and a novel wristband tonometer in 31 participants (aged 30.2±9.5 years) resting in a supine position. Pulse wave analysis was executed using the same validated generalized transfer function (SphygmoCor) for both tonometers. RESULTS: A significant difference in time to data acquisition between tonometers was observed (-70.2±147.7 s; P < 0.05; wristband faster). The wristband tonometer had significantly lower within-subject coefficients of variation (CV) compared with the pencil-type tonometer in aortic pulse wave height (-2.67% ± 5.51%; P < 0.05) and time to reflection (-2.26% ± 6.16%; P < 0.01). No other differences in CV were observed. Slight but statistically significant mean differences between tonometers were observed in aortic systolic blood pressure (ASBP; 0.43±1.08 mm Hg; P < 0.05; wristband lower), aortic pulse pressure (APP; 0.43±0.96 mm Hg; P < 0.05; wristband lower), and round-trip travel time of the reflected pressure wave (Δtp; 3.58±12.86 ms; P < 0.05; wristband higher). However, ASBP, APP, and Δtp measurements were highly correlated (r = 0.9970, r = 0.9953, and r = 0.8838, respectively, P <0.0001) between tonometers; within-subject and between tonometer significant mean differences were within clinical ranges. CONCLUSIONS: This novel, hands-free platform may be interchangeable with the commonly used pencil-type tonometer, heralding new directions in noninvasive in vivo vascular research and clinical application.

Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial.

Testosterone acts directly at androgen receptors and also exerts potent actions following 5α-reduction to dihydrotestosterone (DHT). Finasteride (type II 5α-reductase inhibitor) lowers DHT and is used to treat benign prostatic hyperplasia. However, it is unknown whether elevated DHT mediates either beneficial musculoskeletal effects or prostate enlargement resulting from higher-than-replacement doses of testosterone. Our purpose was to determine whether administration of testosterone plus finasteride to older hypogonadal men could produce musculoskeletal benefits without prostate enlargement. Sixty men aged ≥60 yr with a serum testosterone concentration of ≤300 ng/dl or bioavailable testosterone ≤70 ng/dl received 52 wk of treatment with testosterone enanthate (TE; 125 mg/wk) vs. vehicle, paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased upper and lower body muscle strength by 8-14% (P = 0.015 to <0.001), fat-free mass 4.04 kg (P = 0.032), lumbar spine bone mineral density (BMD) 4.19% (P < 0.001), and total hip BMD 1.96% (P = 0.024) while reducing total body fat -3.87 kg (P < 0.001) and trunk fat -1.88 kg (P = 0.0051). In the first 3 mo, testosterone increased hematocrit 4.13% (P < 0.001). Coadministration of finasteride did not alter any of these effects. Over 12 mo, testosterone also increased prostate volume 11.4 cm(3) (P = 0.0051), an effect that was completely prevented by finasteride (P = 0.0027). We conclude that a higher-than-replacement TE combined with finasteride significantly increases muscle strength and BMD and reduces body fat without causing prostate enlargement. These results demonstrate that elevated DHT mediates testosterone-induced prostate enlargement but is not required for benefits in musculoskeletal or adipose tissue.

Exercise training improves endothelial function in young prehypertensives.

Prehypertensives exhibit marked endothelial dysfunction, a risk factor for future cardiovascular morbidity and mortality. However, the ability of exercise to ameliorate endothelial dysfunction in prehypertensives is grossly underinvestigated. This prospective randomized and controlled study examined the separate effects of resistance and endurance training on conduit artery endothelial function in young prehypertensives. Forty-three unmedicated prehypertensive (systolic blood pressure [SBP]=120-139 mmHg; diastolic blood pressure [DBP]=80-89 mmHg) but otherwise healthy men and women and 15 normotensive matched time-controls (NMTC); n = 15) between 18 and 35 y of age met screening requirements and participated in the study. Prehypertensive subjects were randomly assigned to either a resistance exercise training (PHRT; n = 15), endurance exercise training (PHET; n = 13) or time-control group (PHTC; n = 15). The treatment groups performed exercise training three days per week for eight weeks. The control groups did not initiate exercise programs throughout the study. Flow mediated dilation (FMD) of the brachial artery, biomarkers of enodothelial function and peripheral blood pressure were evaluated before and after exercise intervention or time-matched control. PHRT and PHET reduced resting SBP (9.6 ± 3.6 and 11.9 ± 3.4 mmHg, respectively; P < 0.05) and DBP (8.0 ± 5.1 and 7.2 ± 3.4 mmHg, respectively; P < 0.05). Exercise training improved brachial artery FMD absolute diameter, percent dilation and normalized percent dilation by 30%, 34% and 19% for PHRT, P < 0.05; and by 54%, 63% and 75% for PHET, P < 0.05; respectively. PHRT and PHET increased plasma concentrations of 6-keto prostaglandin F1α (19% and 22%, respectively; P < 0.05), NO x (19% and 23%, respectively; P < 0.05), and reduced endothelin-1 by (16% and 24%, respectively; P < 0.01). This study provides novel evidence that resistance and endurance exercise separately have beneficial effects on resting peripheral blood pressure, brachial artery FMD and endothelial-derived vasoactive agents in young prehypertensives.

Exercise training reduces peripheral arterial stiffness and myocardial oxygen demand in young prehypertensive subjects.

BACKGROUND: Large artery stiffness is a major risk factor for the development of hypertension and cardiovascular disease. Persistent prehypertension accelerates the progression of arterial stiffness. METHODS: Forty-three unmedicated prehypertensive (systolic blood pressure (SBP) = 120-139 mm Hg or diastolic blood pressure (DBP) = 80-89 mm Hg) men and women and 15 normotensive time-matched control subjects (NMTCs; n = 15) aged 18-35 years of age met screening requirements and participated in the study. Prehypertensive subjects were randomly assigned to a resistance exercise training (PHRT; n = 15), endurance exercise training (PHET; n = 13) or time-control group (PHTC; n = 15). Treatment groups performed exercise training 3 days per week for 8 weeks. Pulse wave analysis, pulse wave velocity (PWV), and central and peripheral blood pressures were evaluated before and after exercise intervention or time-matched control. RESULTS: PHRT and PHET reduced resting SBP by 9.6±3.6mm Hg and 11.9±3.4mm Hg, respectively, and DBP by 8.0±5.1mm Hg and 7.2±3.4mm Hg, respectively (P < 0.05). PHRT and PHET decreased augmentation index (AIx) by 7.5% ± 2.8% and 8.1% ± 3.2% (P < 0.05), AIx@75 by 8.0% ± 3.2% and 9.2% ± 3.8% (P < 0.05), and left ventricular wasted pressure energy, an index of extra left ventricular myocardial oxygen requirement due to early systolic wave reflection, by 573±161 dynes s/cm(2) and 612±167 dynes s/cm(2) (P < 0.05), respectively. PHRT and PHET reduced carotid-radial PWV by 1.02±0.32 m/sec and 0.92±0.36 m/sec (P < 0.05) and femoral-distal PWV by 1.04±0.31 m/sec and 1.34±0.33 m/sec (P < 0.05), respectively. No significant changes were observed in the time-control groups. CONCLUSIONS: This study suggests that both resistance and endurance exercise alone effectively reduce peripheral arterial stiffness, central blood pressures, augmentation index, and myocardial oxygen demand in young prehypertensive subjects.

Enhanced external counterpulsation creates acute blood flow patterns responsible for improved flow-mediated dilation in humans.

Enhanced external counterpulsation (EECP) is a FDA-approved treatment for patients with coronary artery disease and unstable angina. Although beneficial effects of EECP have been linked to central/cardiac adaptations, recent findings have shown peripheral/vascular effects. Here, we sought to determine EECP-induced blood flow patterns and their association with vascular function. The present study was designed to investigate endothelium-mediated arterial vasodilation changes after one 45-min session of either EECP or Sham EECP in 18 randomly assigned apparently healthy, young men (25±4 years). Brachial (b) and femoral (f) flow-mediated dilation (FMD) were assessed before and within 10 min after completing EECP or Sham. After 20 min of EECP, peak blood flow velocity (V) and brachial and femoral artery diameters (D) were recorded live for 2 min. In addition, a blood sample was drawn from the earlobe to determine hematocrit and then to calculate blood viscosity (µ) and density (ρ), Reynolds number (Re=V*D*ρ/µ), and endothelial shear stress (ESS=2µ*V/D). EECP increased retrograde shear stress and retrograde-turbulent blood flow in the femoral artery and antegrade-laminar shear stress in the brachial artery. fFMD was increased after EECP compared with Sham and baseline (fFMD=13.1±3.7 vs. 7.9±4.6% and 7.8±4.5%, respectively, P<0.05) and bFMD was increased after EECP compared with baseline (bFMD=10.6±4.8 vs. 7.0±3.5%, P<0.05), despite different blood flow patterns. These results provide novel evidence that a single session of EECP-induced blood flow patterns improve endothelial function in peripheral muscular conduit arteries.

Anti-inflammatory effects of enhanced external counterpulsation in subjects with abnormal glucose tolerance.

Elevated markers of systemic inflammation are associated with impaired glucose tolerance and type 2 diabetes mellitus. Enhanced external counterpulsation (EECP) has been shown to decrease circulating concentrations of pro-inflammatory markers in coronary artery disease patients. Here we provide novel evidence that EECP intervention also has a beneficial effect on circulating markers of systemic inflammation coincident with improvements in glycemic control in subjects with abnormal glucose tolerance.

Limb blood flow after class 4 laser therapy.

CONTEXT: Laser therapy is purported to improve blood flow in soft tissues. Modulating circulation would promote healing by controlling postinjury ischemia, hypoxia, edema, and secondary tissue damage. However, no studies have quantified these responses to laser therapy. OBJECTIVE: To determine a therapeutic dose range for laser therapy for increasing blood flow to the forearm. DESIGN: Crossover study. SETTING: Controlled laboratory setting. PATIENTS OR OTHER PARTICIPANTS: Ten healthy, college-aged men (age = 20.80 ± 2.16 years, height = 177.93 ± 3.38 cm, weight = 73.64 ± 9.10 kg) with no current history of injury to the upper extremity or cardiovascular conditions. INTERVENTION(S): A class 4 laser device was used to treat the biceps brachii muscle. Each grid point was treated for 3 to 4 seconds, for a total of 4 minutes. Each participant received 4 doses of laser therapy: sham, 1 W, 3 W, and 6 W. MAIN OUTCOME MEASURE(S): The dependent variables were changes in blood flow, measured using venous occlusion plethysmography. We used a repeated-measures analysis of variance to analyze changes in blood flow for each dose at 2, 3, and 4 minutes and at 1, 2, 3, 4, and 5 minutes after treatment. The Huynh-Feldt test was conducted to examine differences over time. RESULTS: Compared with baseline, blood flow increased over time with the 3-W treatment (F(3,9) = 3.468, P < .011) at minute 4 of treatment (2.417 ± 0.342 versus 2.794 ± 0.351 mL/min per 100 mL tissue, P = .032), and at 1 minute (2.767 ± 0.358 mL/min per 100 mL tissue, P < .01) and 2 minutes (2.657 ± 0.369 mL/min per 100 mL tissue, P = .022) after treatment. The sham, 1-W, and 6-W treatment doses did not change blood flow from baseline at any time point. CONCLUSIONS: Laser therapy at the 3-W (360-J) dose level was an effective treatment modality to increase blood flow in the soft tissues.

Enhanced external counterpulsation for ischemic heart disease: a look behind the curtain.

Enhanced external counterpulsation (EECP) is a noninvasive treatment for patients with coronary artery disease who have angina pectoris that is refractory to pharmacotherapy and revascularization. The popular concept is that EECP may promote collateral development and improve myocardial perfusion. We hypothesize that improvements in peripheral arterial function are responsible for the clinical benefits of EECP.

Analysis of both pulsatile and streamline blood flow patterns during aerobic and resistance exercise.

Blood flow-induced endothelial shear stress (ESS) during aerobic (AX) and resistance (RX) exercise can regulate endothelial function. However, non-invasive in vivo ESS estimation is normally obtained only according to Poiseuille's laws for streamline flow, rather than using Womersley's approximation for pulsatile flows. Here, we sought to determine brachial and femoral artery blood flow patterns, based on ESS, flow direction, and flow turbulence, using both pulsatile and streamline flow approximations during low- and moderate-intensity AX and RX. We performed high-resolution ultrasound imaging and Doppler peak blood flow velocity (V) measurements of the brachial and femoral arteries in eight young, healthy men during rest and two intensities of AX and RX at 40 and 70% of VO2max and 1-RM, respectively. Microhematocrit measurement was used to determine blood density (ρ) and viscosity (µ). ESS was calculated using Poiseuille's law, ESS = 2µ × SR (V/artery diameter), and Womersley's approximation, ESS = 2 Kµ × SR, where K is a function of Womersley's parameter α. Turbulence was determined using Reynolds number (Re). Re was calculated using Re = V × artery diameter × ρ/µ and normalized to resting steady-state values (nRe). ESS increases in a dose-dependent manner in the femoral and brachial arteries during both AX and RX when using either streamline or pulsatile approximations. However, our findings indicate that ESS is underestimated when using Poiseuille's law. Secondly, turbulence increases in conduit arteries with exercise intensity in a dose-dependent manner in both retrograde and antegrade flows during both AX and RX.

Effects of enhanced external counterpulsation on arterial stiffness and myocardial oxygen demand in patients with chronic angina pectoris.

Enhanced external counterpulsation (EECP) is a noninvasive technique for treatment of symptomatic coronary artery disease in patients not amenable to revascularization procedures. However, the mechanisms underlying the benefits of EECP remain unknown. We hypothesized that decreases in arterial stiffness and aortic wave reflection are a therapeutic target for EECP. Patients with coronary artery disease and chronic angina pectoris were randomized (2:1 ratio) to 35 1-hour sessions of EECP (n = 28) or sham EECP (n = 14). Central and peripheral arterial pulse-wave velocity and aortic wave reflection (augmentation index) were measured using applanation tonometry before, and after 17 and 35 1-hour treatment sessions. Wasted left ventricular pressure energy and aortic systolic tension-time index, markers of left-ventricular myocardial oxygen demand, were derived from the synthesized aortic pressure wave. Exercise duration, anginal threshold, and peak oxygen consumption were measured using a graded treadmill test. Central arterial stiffness and augmentation index were decreased after 17 and 35 sessions in the treatment group. Measurements of peripheral arterial stiffness were decreased after 35 sessions in the treatment group. Changes in aortic pressure wave reflection resulted in decreased measurements of myocardial oxygen demand and wasted left ventricular energy. No changes in central or peripheral arterial stiffness were observed in the sham group. Furthermore, measurements of exercise capacity were improved in the EECP group but unchanged in the sham group. In conclusion, EECP therapy decreases central and peripheral arterial stiffness, which may explain improvements in myocardial oxygen demand in patients with chronic angina pectoris after treatment.

Association of age with timing and amplitude of reflected pressure waves during exercise in men.

BACKGROUND: Increased elastic conduit artery stiffness with aging is associated with early wave reflection and increased wasted left ventricular pressure energy (LVE(W)). The effects of aging on central hemodynamics during exercise have not been well characterized. This study sought to investigate changes in central hemodynamics during cycle exercise in young, middle-aged, and older men. METHODS: Central blood pressure and wave reflection characteristics were measured noninvasively using radial artery applanation tonometry at rest and during cycling exercise (45, 55, and 65% of predicted maximum heart rate (HR(max))) in 14 young (24 ± 1 years), 16 middle-aged (49 ± 2 years) and 13 older (73 ± 2 years) men. RESULTS: Repeated measures analysis of variance revealed significant group-by-time interactions for heart rate, central diastolic blood pressure (DBP), central pulse pressure (PP), PP amplification (PPA), central aortic pressure augmentation (AP), aortic augmentation index (AI(X)), and LVE(W). Magnitude of change from baseline was significantly different in the older group compared to young and middle-aged groups in response to exercise at 65% of predicted HR(max) for AP (+3 ± 1 mm Hg vs. -7 ± 1, P < 0.001 and -3 ± 1 mm Hg, P < 0.001) and LVE(W) (+724 ± 215 dynes s/cm(2)·min vs. -494 ± 199, P < 0.001 and -315 ± 192, P < 0.001). CONCLUSIONS: This study suggests that changes in the timing and amplitude of reflected pressure waves during exercise alter the hemodynamic response to exercise with aging. In response to exercise, AP and LVE(W) increased in older subjects while young and middle-aged subjects exhibited a decline in AP and no change in LVE(W).

Enhanced external counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic angina: a randomized sham-controlled study.

BACKGROUND: Mechanisms responsible for anti-ischemic benefits of enhanced external counterpulsation (EECP) remain unknown. 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 (n=28) or sham EECP (n=14). 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(1α), endothelin-1, asymmetrical dimethylarginine, tumor necrosis factor-α, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule, high-sensitivity C-reactive protein, and 8-isoprostane were measured. EECP increased brachial (+51% versus +2%) and femoral (+30% versus +3%) artery flow-mediated dilation, the nitric oxide turnover/production markers nitrate and nitrite (+36% versus +2%), and 6-keto-prostaglandin F(1α) (+71% versus +1%), whereas it decreased endothelin-1 (-25% versus +5%) and the nitric oxide synthase inhibitor asymmetrical dimethylarginine (-28% versus +0.2%) in treatment versus sham groups, respectively (all P<0.05). EECP decreased the proinflammatory cytokines tumor necrosis factor-α (-16% versus +12%), monocyte chemoattractant protein-1 (-13% versus +0.2%), soluble vascular cell adhesion molecule-1 (-6% versus +1%), high-sensitivity C-reactive protein (-32% versus +5%), and the lipid peroxidation marker 8-isoprostane (-21% versus +1.3%) in treatment versus sham groups, respectively (all P<0.05). EECP reduced angina classification (-62% versus 0%; P<0.001) 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.