Verapamil acutely reduces ventricular-vascular stiffening and improves aerobic exercise performance in elderly individuals.
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OBJECTIVES: We tested the hypothesis that acute intravenous verapamil acutely enhances aerobic exercise performance in healthy older individuals in association with a combined reduction of ventricular systolic and arterial vascular stiffnesses. BACKGROUND: Age-related vascular stiffening coupled with systolic ventricular stiffening may limit cardiovascular reserve and, thus, exercise performance in aged individuals. METHODS: Nineteen healthy volunteers with mean age 70 +/- 10 years underwent maximal-effort upright ergometry tests on two separate days after receiving either 0.15 mg/kg i.v. verapamil or 0.5 N saline in a double-blind, randomized, crossover study. RESULTS: Baseline vascular stiffness, indexed by arterial pulse-wave velocity (Doppler) and augmentation index (carotid tonometry) declined with verapamil (-5.9 +/- 2.1% and -31.7 +/- 12.8%, respectively, both p < 0.05). Preload-adjusted maximal ventricular power, a surrogate for ventricular end-systolic stiffness, also declined by -9.5 +/- 3.6%. Peripheral resistance and peak filling rate were unchanged. With verapamil, exercise duration prior to the anaerobic threshold (AT) increased by nearly 50% (260 +/- 129 to 387 +/- 176 s) with a corresponding 13.4 +/- 4.7% rise in oxygen consumption (VO2) at that time (both p < 0.01). Total exercise duration prolonged by +6 +/- 2.7% (p < 0.05) with no change in maximal VO2. Baseline cardiodepression from verapamil reversed by peak exercise with net increases in stroke volume and cardiac output (p < 0.05). CONCLUSIONS: Acute intravenous verapamil reduces ventriculovascular stiffening and improves aerobic exercise performance in healthy aged individuals. This highlights a role for heart-arterial coupling in modulating exertional capacity in the elderly, suggesting a potentially therapeutic target for aged individuals with exertional limitations. (+info)
Range of tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension.
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OBJECTIVES: The aim of this study was to explore the full range of tricuspid valve regurgitation velocity (TRV) at rest and with exercise in disease free individuals. Additionally we examined the relationship of stroke volume (SV), cardiac output (CO) and TRV to exercise capacity. BACKGROUND: Doppler evaluation of TRV can be used to estimate pulmonary artery systolic pressure (PASP). Most studies have assumed TRV < or = 2.5 m/s as the upper limits of normal. The full range of TRV with exercise has been incompletely defined. METHODS: Highly conditioned athletes (n = 26) and healthy, active, young male volunteers (n = 14) underwent standardized recumbent bicycle exercise. Exercise parameters included: TRV, SV, CO, systolic (SBP) and diastolic (DBP) systemic blood pressure. RESULTS: Tricuspid valve regurgitation, SV, HR and CO were significantly higher in athletes than in nonathletes over all workloads, including rest. Systolic blood pressure and DBP did not show significant differences between the two groups. CONCLUSIONS: This study defines the upper physiologic limits of TRV at rest and during exercise in normals and provides a noninvasive standard for the diagnosis of pulmonary hypertension. (+info)
Combination of calcium channel blockers and beta-adrenoceptor blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. Netherlands Working Group on Cardiovascular Research (WCN).
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AIMS: The combination of calcium channel blockers and beta-adrenoceptor blockers is more effective for the treatment of exercise-induced angina pectoris than beta-adrenoceptor blocker monotherapy. As ischaemia in exercise-induced angina is preceded by increase in heart rate, calcium channel blockers with negative chronotropic properties may perform better for this purpose than nonchronotropic compounds. METHODS: A 335 patient double-blind parallel-group study comparing 14 day treatment with amlodipine 5 and 10 mg, with diltiazem 200 and 300 mg, and mibefradil 50 and 100 mg added to baseline beta-adrenoceptor blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. RESULTS: Although none of the calcium channel blockers improved duration of exercise or amount of workload, all significantly delayed onset of 1 mm ST-segment depression on ETT (P<0.001 for any treatment vs baseline). In addition, mibefradil, both low and high dose treatment, produced the longest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, respectively, P<0. 003 and <0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, respectively, P<0.001 and <0.001). These effects were linearly correlated with the reduction in rate pressure product (RPP). Serious symptoms of dizziness occurred significantly more frequently on mibefradil (P<0.05), and 19 patients on mibefradil withdrew from trial. CONCLUSIONS: Calcium channel blockers with negative chronotropic properties provide greater delay of ischaemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness attenuates this benefit. (+info)
Development of sinus node disease in patients with AV block: implications for single lead VDD pacing.
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OBJECTIVE: To investigate the incidence of sinus node disease after pacemaker implantation for exclusive atrioventricular (AV) block. DESIGN: 441 patients were followed after VDD (n = 219) or DDD pacemaker (n = 222) implantation for AV block over a mean period of 37 months. Sinus node disease and atrial arrhythmias had been excluded by Holter monitoring and treadmill exercise preoperatively in 286 patients (group A). In 155 patients with complete AV block, a sinus rate above 70 beats/min was required for inclusion in the study (group B). Holter monitoring and treadmill exercise were performed two weeks, three months, and every six months after implantation. Sinus bradycardia below 40 beats/min, sinoatrial block, sinus arrest, or subnormal increase of heart rate during treadmill exercise were defined as sinus node dysfunction. RESULTS: Cumulative incidence of sinus node disease was 0.65% per year without differences between groups. Clinical indicators of sinus node dysfunction were sinus bradycardia below 40 beats/min in six patients (1.4%), intermittent sinoatrial block in two (0.5%), and chronotropic incompetence in five patients (1.1%). Only one of these patients (0.2%) was symptomatic. Cumulative incidence of atrial fibrillation was 2.0% per year, independent of the method used for the assessment of sinus node function and of the implanted device. CONCLUSIONS: In patients undergoing pacemaker implantation for isolated AV block, sinus node syndrome rarely occurs during follow up. Thus single lead VDD pacing can safely be performed in these patients. (+info)
Impaired free fatty acid uptake in skeletal muscle but not in myocardium in patients with impaired glucose tolerance: studies with PET and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid.
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Free fatty acids (FFAs) are an important substrate for myocardial and skeletal muscle metabolism, and increased availability and oxidation of FFA are suggested to be associated with insulin resistance. This study was undertaken to assess whether myocardial or muscle uptake of FFA is altered in patients with impaired glucose tolerance (IGT). Eight healthy men (control group; age 48+/-1 years, BMI 25+/-1 kg/m2, mean +/- SE) and eight men with IGT (glucose-intolerant group; age 49+/-1 years, BMI 29+/-1 kg/m2) were studied in the fasting state. Myocardial oxygen consumption and blood flow and myocardial and femoral muscle FFA uptake rates were measured with positron emission tomography (PET) and [15O]O2, [15O]H2O, [15O]CO, and 14(R, S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA), a fatty acid tracer trapped into the cell after undergoing initial steps of beta-oxidation. Serum glucose and insulin concentrations were higher in the glucose-intolerant group during the PET study, but FFA concentrations were comparable between the groups. No differences between the groups were observed in the myocardial blood flow, oxygen consumption, fractional FTHA uptake rates, or FFA uptake indices (5.6+/-0.4 vs. 5.2+/-0.4 pmol x 100 g(-1) x min(-1), glucose-intolerant versus control, NS). In the femoral muscle, fractional FTHA uptake (0.0062+/-0.0003 vs. 0.0072+/-0.0003 min(-1), P = 0.044) and FFA uptake indices (0.30+/-0.02 vs. 0.43+/-0.04 min(-1), P = 0.020) were significantly lower in the glucose-intolerant group than in the control group. In conclusion, when studied at the fasting state and normal serum FFA concentrations, subjects with IGT have similar myocardial but lowered femoral muscle FFA uptake. This finding argues against the hypothesis that an increased oxidation of serum FFA, via the competition of glucose and FFA as fuel sources, is the primary cause for impaired peripheral glucose utilization and insulin resistance commonly observed in IGT. (+info)
Physical performance and associated electrolyte changes after haemoglobin normalization: a comparative study in haemodialysis patients.
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BACKGROUND: To determine the effects of different haemoglobin (Hb) levels on exercise performance and associated electrolyte changes, a prospective, randomized, double-blinded crossover study was completed in 14 haemodialysis patients. METHODS: Performance and changes in arterial [K+] and lactate were compared at rest and during a maximal incremental cycling exercise at a Hb concentration ([Hb]) of 10 g/dl ([Hb]10) and 14 g/dl ([Hb]14) following an initial baseline test (Hb: 8.3 +/- 0.2 g/dl, mean +/- SEM). Ages ranged from 23 to 65 years and patients were divided into younger (age 23-45 years, n = 9) and older (aged 55-65 years, n = 5) groups. RESULTS: Peak work rate and VO2 peak were higher at [Hb]14 than at [Hb]10. 145 +/- 9 vs 134 +/- 9 W, mu +/- SEM, P < 0.01, and 1.90 +/- 0.11 vs 1.61 +/- 0.11 l/min, P < 0.01, respectively. Improvements were demonstrated in both younger and older groups at the higher target [Hb], with an improved aerobic performance evident particularly in younger patients. However, performance remained below that predicted for comparable sedentary controls. Resting plasma [K+] was raised at both [Hb]10 and [Hb]14 compared with baseline (P < 0.01) although the change in [K+] from rest to peak exercise (delta[K+]) was similar at each level. The delta[K+] per unit work performed (used as a marker of K+ regulation) was, however, inversely related to the [Hb] (baseline: 80 +/- 12 micromol/l/kJ vs [Hb]10, 61 +/- 8, P < 0.01, vs [Hb]14. 49 +/- 7, P < 0.05). Exercise induced a significant but similar rise in lactate concentration at both target [Hb] (P < 0.001), which remained markedly elevated for at least 10 min after exercise in both younger and older groups. CONCLUSIONS: These data demonstrate that a physiological [Hb] improves, but does not normalize, exercise performance in end-stage renal failure. Both younger and older patients appear to benefit similarly from the enhanced oxygen transport. Impaired K+ regulation is apparently related to [Hb] and could well contribute to the observed limitations in performance. (+info)
Altered expression of myosin heavy chain in the vastus lateralis muscle in patients with COPD.
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This study was designed to further characterize peripheral skeletal muscle alterations in patients with chronic obstructive pulmonary disease (COPD) and to evaluate the possible relationship between myosin heavy chain (MyoHC) isoform expression and exercise tolerance in these individuals. MyoHC composition from biopsy of the vastus lateralis muscle was examined in 12 COPD patients (forced expiratory volume in one second (FEV1)=31+/-9% predicted, peak oxygen consumption (V'O2)=15+/-4 mL x kg(-1) x min(-1)) and 10 age-matched normal male subjects (peak V'O2=20+/-5 mL x kg(-1) x min(-1)). The proportion of MyoHC type I was smaller in COPD than in normals (27+/-17% versus 41+/-9%, p<0.05) with an increase in MyoHC type IIa (51+/-15% versus 39+/-9%, p<0.05) and the proportion of MyoHC type IIx being comparable between both groups. A significant relationship was found between peak V'Oo2 mL x kg(-1) x min(-1) and FEV1 % pred (r=0.91, p<0.0001) and the percentage of MyoHC type I (r=0.61, p=0.016). In stepwise multiple regression, only FEV1 % pred was found to be a significant determinant of peak V'O2 (p<0.0001). This variable explained 83% of the total variance of peak V'O2. In summary, this study showed considerable modifications in the phenotypic expression of the myosin heavy chain in the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. An independent effect of myosin heavy chain expression on exercise capacity was not found. These results suggest that chronic inactivity and muscle deconditioning may not be the sole factors explaining peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease. (+info)
Influence of immersion on respiratory requirements during 30-min cycling exercise.
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Immersion is considered to facilitate exercise-based rehabilitation. However, the drag effect of moving limbs in water, likely to increase the respiratory requirements at exercise, is not mentioned in many reports. The energetic and ventilatory requirements of 30 min steady state cycling exercise performed by healthy male subjects in air and during immersion up to the xiphoid in 33 degrees C water were compared. In the first experimental series nine subjects exercised at the same 60% maximal oxygen consumption (V'O2,max) in air and water. In the two ambient conditions, ventilatory variables had similar values, but the ergometric setting had to be reduced during water immersion so that the workload rated only 69+/-20 W (mean+/-SD) in water versus 121+/-32 W (p<0.001) in air. In the second experimental series, the same ergometric work load (122 W) was achieved by nine subjects with an average V'O2 of 2,210+/-300 mL x min(-1) in air versus 2,868+/-268 mL x min(-1) in water (p<0.001). Resting water immersion caused a marked trend for decreasing vital capacity (p=0.06), but no modification of other ventilatory variables. During exercise at similar V'O2, the average values of minute ventilation (V'E), tidal volume (VT), respiratory frequency (fR), tidal inspiratory time (VT/tI) were not different between water and air. However, at similar ergometric workload, V'E, VT, fR, VT/tI and plasma lactate levels were significantly higher in water than in air. Such consequences of the drag effect of water upon limb movements have not been reported in previous studies relying on shorter exercise bouts. Thus, maintaining steady exercise levels in water either led to a decrease in the workload or required a 25% higher oxygen consumption than in air. These findings may be relevant to the prescription of water immersion rehabilitation programmes. (+info)