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.

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.

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.

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.

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.

Relationship between endogenous concentrations of vasoactive substances and measures of peripheral vasodilator function in patients with coronary artery disease.

1. The aim of the present study was to determine the relationship between plasma concentrations of nitrite/nitrate (NO(x)) and endothelin (ET)-1 and non-invasive measures of peripheral vasodilator function in patients with coronary artery disease (CAD). 2. Twenty-two patients with angiographic CAD underwent non-invasive measurement of peripheral vasodilator function in the brachial conduit artery (flow-mediated dilation (FMD) testing via ultrasound) and in the forearm resistance arteries (via venous occlusion plethysmography) during reactive hyperaemia after 5 min ischaemia. In addition, plasma NO(x) and ET-1 concentrations were determined. 3. The plasma concentration of NO(x) was related to the peak brachial FMD response when expressed as either the relative (%) or absolute (mm) change in diameter (r = 0.73, P < 0.001; and r = 0.64, P < 0.01, respectively). Moreover, plasma concentrations of NO(x) demonstrated a relationship with forearm vasodilation estimated by total forearm blood flow following 5 min ischaemia (r = 0.63, P < 0.01) and the flow debt repayment of the forearm (r = 0.54, P < 0.01). Finally, ET-1 concentrations were inversely related to FMD% (r = -0.45, P < 0.05). 4. The findings of the present study demonstrate a relationship between the plasma concentrations of NO(x) and measures of vascular reactivity in conduit and resistance arteries in patients with CAD. Therefore, measurement of plasma NO(x) may serve as a reliable marker for peripheral vasodilator dysfunction in patients with CAD.

Effect of enhanced external counterpulsation on inflammatory cytokines and adhesion molecules in patients with angina pectoris and angiographic coronary artery disease.

Cardiovascular disease is associated with chronic low-level inflammation, as evidenced by elevated circulating proinflammatory cytokines. Experimental evidence suggests that inflammation can be suppressed under conditions of high shear stress. This study was conducted to examine the effects of enhanced external counterpulsation (EECP), a noninvasive therapy that increases endothelial shear stress, on circulating levels of inflammatory biomarkers and adhesion molecules in patients with angina pectoris. Twenty-one patients were randomly assigned to either 35 1-hour treatments at cuff pressures of 300 mm Hg (EECP; n=12) or 75 mm Hg (sham; n=9). Plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and soluble vascular cell adhesion molecule-1 were measured before and after 35 1-hour sessions of treatment or sham. Patients in the EECP group demonstrated reductions in tumor necrosis factor-alpha (6.9+/-2.7 vs 4.9+/-2.5 pg/ml, p<0.01; -29%) and monocyte chemoattractant protein-1 (254.9+/-55.9 vs 190.4+/-47.6 pg/ml, p<0.01; -19%) after treatment, whereas there was no change in the sham group. Changes in soluble vascular cell adhesion molecule-1 were not observed in either group. In conclusion, 35 sessions of EECP decreased circulating levels of proinflammatory biomarkers in patients with symptomatic coronary artery disease.

Impact of aging on central pressure wave reflection characteristics during exercise.

BACKGROUND: Age is associated with increases in elastic artery stiffness and pulse wave velocity, which cause profound changes in arterial pressure waves, including increases in the augmentation index (AIx) and wasted left ventricular (LV) energy. We examined the impact of aging on the central blood pressure (BP) waveform and wave reflection responses during exercise. METHODS: Central BP and wave reflection characteristics were measured non-invasively using radial artery applanation tonometry at rest and during cycling exercise (45-65% of age predicted maximal heart rate (HR)) in 16 older (48 +/- 2 years) and 14 younger (24 +/- 1 years) men. RESULTS: Older men had increased central pressure values and AIx (26 +/- 2% vs. 12 +/- 2%) and lower pulse pressure amplification (PPA; 1.29 +/- 0.03 vs. 1.50 +/- 0.04) than their younger counterparts at rest (P < 0.05). Central pressure values and AIx (10 +/- 3% vs. -8 +/- 3%) continued to be greater, while PPA (1.61 +/- 0.04 vs. 1.85 +/- 0.03) was lower in the older group compared with the younger group during exercise (P < 0.05). However, the relative changes from baseline for central pressure values, AIx (-15 +/- 2 vs. -19 +/- 3), and PPA (0.32 +/- 0.03 vs. 0.35 +/- 0.04) were similar for both groups (P > 0.05). CONCLUSIONS: The findings of this study suggest that older men have a greater central BP and AIx and lower PPA during exercise. However, the magnitude of the central hemodynamic responses (i.e., change from baseline) during exercise does not differ between older and younger men.

Role of heart failure etiology on arterial wave reflection in heart transplant recipients: relation with C-reactive protein.

OBJECTIVES: Aortic augmentation index (AIa), a measure of arterial pressure wave reflection related to central and peripheral arterial stiffness, is elevated in many heart transplant recipients. We investigated whether the increase in wave reflection observed in some heart transplant recipients is influenced by the etiology of antecedent heart failure and circulating pro-inflammatory proteins early in the post-transplantation period. METHODS: Two months after heart transplantation, 20 heart transplant recipients underwent noninvasive measurement of aortic pressure and wave reflection properties and measurement of plasma pro-inflammatory proteins. RESULTS: AIa adjusted to a heart rate of 75 beats/min (AIaHR75) was higher in heart transplant recipients with ischemic (n = 12) compared with nonischemic (n = 8) heart failure (P < 0.01). Similarly, circulating C-reactive protein, a marker of systemic inflammation and an independent predictor of allograft vasculopathy and death in heart transplant recipients, was higher in heart transplant recipients with ischemic than with nonischemic heart failure (log-transformed, P < 0.05). Moreover, there was a significant relation between log C-reactive protein and AIaHR75 (r = 0.68, P < 0.05), augmented pressure (r = 0.60, P < 0.01), roundtrip time of the reflected wave to the peripheral reflecting sites and back (r = -0.62; P < 0.01), and left ventricular wasted energy (r = 0.55, P < 0.01). Multiple regression analysis revealed that log C-reactive protein explained 43% of the variance in AIaHR75 and the difference in AIaHR75 between groups was abolished when adjusted for log C-reactive protein. CONCLUSIONS: Heart transplant recipients with antecedent ischemic heart failure demonstrated increased AIaHR75 compared with nonischemic heart transplant recipients and AIaHR75 was associated with higher circulating C-reactive protein concentration. Whether elevated arterial wave reflection and associated systemic low-grade inflammation early after transplantation have clinical implications in ischemic heart transplant recipients requires further investigation.

Arterial-wave reflections are increased in heart failure patients with a left-ventricular assist device.

BACKGROUND: Chronic heart failure (HF) is associated with increased central arterial pulse-wave reflections, which may contribute to increased myocardial oxygen demand. Although the treatment of HF via left-ventricular assist device (LVAD) placement has recently become widespread, the effects of LVAD therapy on central arterial pulse-wave reflections are unknown. METHODS: Central aortic pulse-wave analysis was performed on patients with end-stage HF awaiting cardiac transplantation and on healthy age-matched controls using the SphygmoCor (Akor Medical, Sydney, Australia) system. Arterial pulse-wave data were compared between patients receiving LVAD support versus those receiving intravenous inotropic drugs and healthy control patients. RESULTS: Five patients on LVAD support were compared with 10 patients on inotropic drugs and 10 healthy control patients. Aortic augmented pressure and the aortic augmentation index (AI(a)) were higher in LVAD patients compared with inotrope and control patients, despite similar brachial and aortic blood pressures between groups. The AI(a) was significantly higher in LVAD patients than in patients on inotropic drugs (28.2% +/- 10% v 7.9% +/- 9%, P < or = .01). Additionally, there was a significantly higher aortic systolic tension time index, an index of left-ventricular myocardial oxygen demand, in the LVAD group compared with the inotrope group (2655 +/- 298 mm Hg/sec/min v 1748 +/- 303 mm Hg/sec/min, P < .01). CONCLUSIONS: Central arterial pressure-wave reflection is increased in end-stage HF patients on LVAD support compared with those on inotropic drugs, leading to an increase in aortic augmented pressure, AI(a), and systolic tension time index. The AI(a) is also higher in LVAD patients than in healthy controls. This increased central arterial-wave reflection places an additional hemodynamic load on the LVAD device and may have relevance to the medical management of patients after LVAD placement and to the longevity of the LVAD device itself.

Progressive resistance training without volume increases does not alter arterial stiffness and aortic wave reflection.

Endurance exercise is efficacious in reducing arterial stiffness. However, the effect of resistance training (RT) on arterial stiffening is controversial. High-intensity, high-volume RT has been shown to increase arterial stiffness in young adults. We tested the hypothesis that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume would not elicit increases in either central or peripheral arterial stiffness or alter aortic pressure wave reflection in young men and women. The RT group (n = 24; 21 +/- 1 years) performed two sets of 8-12 repetitions to volitional fatigue on seven exercise machines on 3 days/week for 12 weeks, whereas the control group (n = 18; 22 +/- 1 years) did not perform RT. Central and peripheral arterial pulse wave velocity (PWV), aortic pressure wave reflection (augmentation index; AIx), brachial flow-mediated dilation (FMD), and plasma levels of nitrate/nitrite (NOx) and norepinephrine (NE) were measured before and after RT. RT increased the one-repetition maximum for the chest press and the leg extension (P < 0.001). RT also increased lean body mass (P < 0.01) and reduced body fat (%; P < 0.01). However, RT did not affect carotid-radial, carotid-femoral, and femoral-distal PWV (8.4 +/- 0.2 vs. 8.0 +/- 0.2 m/sec; 6.5 +/- 0.1 vs. 6.3 +/- 0.2 m/sec; 9.5 +/- 0.3 vs. 9.5 +/- 0.3 m/sec, respectively) or AIx (2.5% +/- 2.3% vs. 4.8% +/- 1.8 %, respectively). Additionally, no changes were observed in brachial FMD, NOx, NE, or blood pressures. These results suggest that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume does not increase central or peripheral arterial stiffness or alter aortic pressure wave characteristics in young subjects.

Comparison of calcitonin versus calcitonin + resistance exercise as prophylaxis for osteoporosis in heart transplant recipients.

BACKGROUND: Rapid bone loss occurs early after heart transplantation. There is no standard therapeutic intervention to prevent osteoporosis in heart transplant recipients (HTR). The purpose of this study was to determine the effectiveness of a regimen combining the antiresorptive properties of nasal calcitonin with the osteogenic stimulus of resistance exercise. METHODS: Eighteen candidates for heart transplantation were randomly assigned either to a group that received calcitonin and participated in 6 months of resistance exercise (n=10) or to a group that received only calcitonin (n=8). Calcitonin therapy (200 IU daily for 8 months) was initiated 48 hr after transplantation. Resistance exercise was initiated 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck, and lumbar vertebra (L2-3) were assessed before, and at 2 and 8 months after transplantation. RESULTS: Total body and femur neck BMD did not decrease (P>or=0.05) below pretransplantation values at 2 months after transplantation in either group. BMD of the lumbar spine was significantly (P

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.

High-dose angiotensin-converting enzyme inhibition restores body fluid homeostasis in heart-transplant recipients.

OBJECTIVES: We tested the hypothesis that salt and fluid retention in heart-transplant recipients (HTRs) is caused by a failure to reflexively suppress the renin-angiotensin-aldosterone system (RAAS). BACKGROUND: It is known that extracellular fluid volume is expanded (12% to 15%) in HTRs who develop hypertension. METHODS: Responses to volume expansion were measured in eight HTRs (ages 57 +/- 6 years) and six liver-transplant recipients (LTRs) (ages 52 +/- 2 years) both before and after treatment with captopril (225 mg/day). After three days of a standardized diet, 0.154 mol/l saline was infused at 8 ml/kg/h for 4 h. Blood pressure, hormones, and renal function were monitored for 48 h. After four months, the same subjects received captopril (225 mg/day), and the protocol was repeated. RESULTS: Before captopril, saline infusion suppressed the RAAS in LTRs but not in HTRs, resulting in elimination of 86 +/- 12% versus 50 +/- 11% of the sodium load by 48-h postinfusion. Blood pressure increased only in the HTRs (+16 +/- 5/9 +/- 3 mm Hg) and remained elevated for 48 h (p < or = 0.05). After captopril, sodium elimination was comparable in the liver (87 +/- 13%) and heart groups (86 +/- 12%) and blood pressure did not change in either group. CONCLUSIONS; Heart transplant recipients have blunted diuretic and natriuretic responses to volume expansion that is mediated by their inability to suppress the RAAS. Pharmacologic suppression of the RAAS normalized defects in blood pressure and fluid homeostasis. These findings indicate that hypertension in HTRs is caused, in part, by a failure to reflexively suppress the RAAS when these patients become hypervolemic.

Effect of resistance exercise on skeletal muscle myopathy in heart transplant recipients.

The purpose of this study was to determine the efficacy of resistance exercise in reversing skeletal muscle myopathy in heart transplant recipients. Myopathy, engendered by both heart failure and immunosuppression with glucocorticoids, is a post-transplant complication. The sequelae of myopathic disease includes fiber-type shifts and deficits in aerobic metabolic capability. We randomly assigned patients to either 6 months of resistance exercise (training group; n = 8) or a control (control group; n = 7) group. Exercise was initiated at 2 months after transplant. Biopsy of the right vastus lateralis was performed before and after the 6-month intervention. Myosin heavy chain (MHC) composition was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Biochemical assays were performed to determine citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and lactate dehydrogenase activity. There were no group differences (p >or=0.05) in MHC composition and enzymatic reserve at baseline. Improvements in the training group for citrate cynthase (+40%), 3-hydroxyacyl-CoA-dehydrogenase (+10%), and lactate dehydrogenase activity (+48%) were significantly greater (p

Obesity and postexercise oxidative stress in older women.

PURPOSE: This study compared lipid peroxidation values in nonobese and obese postmenopausal women before and after acute maximal aerobic exercise (AX). METHODS: Blood samples were collected in nonobese (22.1 +/- 0.9% body fat) and obese (40.8 +/- 0.9% body fat) women (61-75 yr, N = 34) before and immediately after a maximal graded treadmill test. Lipid hydroperoxides (PEROX), cholesterol, and thiol profiles were measured. Oxygen consumption (V(O2), respiratory exchange ratios (RER), and minute ventilation (VE) values were determined before and during exercise. RESULTS: PEROX levels were not different between the nonobese and obese groups at baseline (2.4 vs 2.8 nmol.mL(-1), respectively) or post-AX (2.8 vs 3.2 nmol.mL(-1), respectively) (P > 0.05). When expressed as DeltaPEROX (nmol.mL(-1))/DeltaVO(2) (mL.kg(-1).min(-1)), to account for different exercise durations, the obese group had a greater lipid peroxidation response compared with the nonobese group (0.13 vs 0.02 (nmol.mL(-1)).mL(-1).kg(-1).min(-1), respectively; P < 0.05). Regression analysis revealed that when baseline PEROX and body fat values were controlled, age, exercise intensity, and duration were significant contributors to the DeltaPEROX/DeltaV(O2) after AX (R(2) = 0.536 P < 0.05). CONCLUSION: For a given oxidative challenge (exercise-associated oxygen utilization), older, obese women were at a greater risk for oxidative stress compared with nonobese counterparts.

Improved cardiorespiratory endurance following 6 months of resistance exercise in elderly men and women.

OBJECTIVE: To examine the effect of 6 months of high- or low-intensity resistance exercise on aerobic capacity and treadmill time to exhaustion in adults aged 60 to 83 years. METHODS: Sixty-two men and women completed the study protocol. Subjects were matched for strength and randomly assigned to a control (n = 16), low-intensity exercise (LEX, n = 24), or high-intensity exercise (HEX, n = 22) group. Subjects trained at either 50% of their one repetition maximum (1-RM) for 13 repetitions (LEX) or 80% of 1-RM for 8 repetitions (HEX) 3 times per week for 24 weeks. One set each of 12 exercises was performed. Strength was measured for the leg press, chest press, leg curl, leg extension, overhead press, biceps curl, seated row, and triceps dip. Muscular endurance was measured for the leg press and chest press. Aerobic capacity (peak oxygen consumption [VO(2)peak]) was measured during an incremental treadmill test (Naughton). Treadmill time to exhaustion was measured as the time to exhaustion during the incremental exercise test. RESULTS: The 1-RM significantly increased (P< or =.05) for all exercises tested for both the HEX and LEX groups. Aerobic capacity increased (P< or =.05) by 23.5% (20.2 to 24.7 mL x kg(-1) x min(-1)) and by 20.1% (20.9 to 24.4 mL x kg(-1) x min(-1)) for the LEX and HEX groups, respectively. Treadmill time increased (P< or =.05) by 26.4% and 23.3% for the LEX and HEX groups, respectively. CONCLUSIONS: Significant improvements in aerobic capacity and treadmill time to exhaustion can be obtained in older adults as a consequence of either high- or low-intensity resistance exercise. These findings suggest that increased strength, as a consequence of resistance exercise training, may allow older adults to reach and/or improve their aerobic capacity.