Differences in cardiorespiratory responses of young and senior male endurance athletes to maximal graded exercise test.

Within recent years the popularity of sportive activities amongst older people, particularly competitive activities within certain age groups has increased. The purpose of this study was to assess the differences in the cardiorespiratory output at anaerobic threshold and at maximal power, output during an incremental exercise, among senior and young athletes. Ten elderly male subjects [mean (SD) age: 68.45 ± 9.32 years] and eight young male subjects [mean (SD) age: 25.87 ± 5.87 years] performed an incremental exercise test on a treadmill ergometer. No significant differences in body size were evident; however, the differences between the groups for peak power (451.62 ± 49 vs. 172.4 ± 32.2 W), aerobic capacity (57.97 ± 7.5 vs. 40.36 ± 8.6 mL kg-1 min-1), maximal heart rate (190.87 ± 9.2 vs. 158.5 ± 9.1 beats min-1), peak blood lactate (11 ± 1.7 vs. 7.3 ± 1.4 mmol L-1), and % VO2max at ventilatory thresholds (93.18 ± 4.3 vs. 79.29 ± 9.9%) were significantly lower in the senior athletes. The power output at anaerobic threshold was also higher (392 ± 48 vs. 151 ± 23 W) in the young athletes, explaining the significant difference in terms of performance between these groups. We have observed an evident deterioration in some of the cardiovascular parameters; however, the submaximal exercise economy seems to be preserved with aging. Exercise economy (i.e. metabolic cost of sustained submaximal exercise) was not different considerably with age in endurance-trained adults.

Influence of body height on aortic systolic pressure augmentation and wave reflection in childhood.

The enhanced wave reflection in small children is a well-known phenomenon. It is explained on the basis of differences in the body height and the timing of wave reflection. This hypothesis still has not been proved directly. The aim of our study was to determine the reference values of aortic augmentation index (Aix(ao)) and the simultaneously measured return time of the systolic pulse wave (RT) in relation to the body height to test this hypothesis. Aix(ao) and RT were measured by Arteriograph in a healthy population aged 3-18 years (n = 4619, 2489 males). The Aix(ao) decreased with increasing age in boys from 18.6 ± 8.4% to 4.7 ± 4.3% and in girls from 22.3 ± 9.2% to 8.1 ± 5.1%, whereas the RT increased from 115.5 ± 16.3 ms to 166.7 ± 20.8 ms in boys and from 106.7 ± 21.9 ms to 158.1 ± 15.5 ms in girls. These changes were constant during childhood, but they slowed down after the onset of puberty. Because aortic pulse wave velocity (PWV(ao)) measured in the same population was unchanged during childhood, the increase of RT can only be explained by the increase of aortic length due to growth. In the puberty PWV(ao) starts increasing indicating that RT (Aix(ao)) does not follow the increase (decrease) of aortic length proportionally.

Comparison of arterial stiffness parameters in patients with coronary artery disease and diabetes mellitus using Arteriograph.

Recently an expert consensus document advised to standardize user procedures and a new cut-off value for carotid-femoral pulse wave velocity in daily practice. Our aim was to observe aortic pulse wave velocity (PWVao) and augmentation index (AIXao) in two high cardiovascular risk groups: patients with verified coronary artery disease (CAD) or with type 2 diabetes mellitus (T2DM). We also aimed to determine the cut-off values for PWVao, AIXao in CAD and T2DM patients using oscillometric device (Arteriograph). We investigated 186 CAD and 152 T2DM patients. PWVao and AIXao increased significantly in the CAD group compared to the age-, gender-, blood pressure-, and heart rate-matched control group (10.2+/-2.3 vs. 9.3+/-1.5 m/s; p<0.001 and 34.9+/-14.6 vs. 31.9+/-12.8 %; p<0.05, respectively). When compared to the apparently healthy control subjects, T2DM patients had significantly elevated PWVao (9.7+/-1.7 vs. 9.3+/-1.5 m/s; p<0.05, respectively), however the AIXao did not differ significantly. The ROC-curves of CAD and healthy control subjects explored cut-off values of 10.2 m/s for PWVao and 33.23 % for AIXao. Our data provide supporting evidence about impaired arterial stiffness parameters in CAD and T2DM. Our findings encourage the implementation of arterial stiffness measurements by oscillometric method in daily clinical routine.

Physiological regulation of cardiac contractility by endogenous reactive oxygen species.

Increased production of reactive oxygen species (ROS) has been linked to the pathogenesis of congestive heart failure. However, emerging evidence suggests the involvement of ROS in the regulation of various physiological cellular processes in the myocardium. In this review, we summarize the latest findings regarding the role of ROS in the acute regulation of cardiac contractility. We discuss ROS-dependent modulation of the inotropic responses to G protein-coupled receptor agonists (e.g. ß-adrenergic receptor agonists and endothelin-1), the potential cellular sources of ROS (e.g. NAD(P)H oxidases and mitochondria) and the proposed end-targets and signalling pathways by which ROS affect contractility. Accumulating new data supports the fundamental role of endogenously generated ROS to regulate cardiac function under physiological conditions.

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients.

According to previous studies endogenous ouabain (EO) closely correlates with high blood pressure, congestive heart failure and kidney disease in humans. Our aims were to analyse associations between plasma, urinary EO level and various markers of cardiovascular damage in treated hypertensive patients. Forty-one adult patients with hypertension and/or diabetes mellitus (DM) and/or chronic kidney disease (CKD) were studied. We assessed plasma and urinary EO, pro-brain natriuretic peptide and catecholamines, profile of ambulatory blood pressure monitor and cardiovascular status by echocardiography and echo-tracking. The highest level of plasma EO (19.7±9.5 pmol l⁻¹) was measured in hypertensive patients with DM and CKD. The nighttime mean arterial blood pressure independently correlated with the level of plasma EO (P=0.004), while independent predictor of the ß-stiffness of carotid artery was the urinary EO (P=0.011). Elevated level of EO was associated with nighttime blood pressure and subclinical organ damage in treated hypertensive patients, suggesting possible role of EO in the pathogenesis of impaired diurnal blood pressure rhythm and arterial stiffness.

Structure and giant magnetoresistance behaviour of Co-Cu/Cu multilayers electrodeposited under various deposition conditions.

Electrodeposited Co-Cu/Cu multilayers were prepared under a variety of deposition conditions on either a polycrystalline Ti foil or on a silicon wafer covered by a Ta buffer and a Cu seed layer. X-ray diffraction (XRD) revealed a strong (111) texture for all multilayers with clear satellite peaks for the multilayers on Si/Ta/Cu substrates, in some cases for up to three reflections. Cross-sectional transmission electron microscopy investigations indicated a much more uniform multilayer structure on the Si/Ta/Cu substrates. The bilayer periods from XRD satellite reflections were in reasonable agreement with nominal values. An analysis of the overall chemical composition of the multilayers gave estimates of the sublayer thickness changes due to the Co-dissolution process during the Cu deposition pulse. The XRD lattice spacing data indicated a behaviour close to a simple "multilayer" Vegard's law which was, however, further refined by taking into account elastic strains as well. In agreement with the structural studies, magnetoresistance data also indicated the formation of more perfect multilayers on the smooth Si/Ta/Cu substrates. An analysis of the magnetoresistance behaviour revealed the presence of superparamagnetic (SPM) regions in the magnetic layers. The contribution of these SPM regions to the total observed giant magnetoresistance was found to be dominating under certain deposition conditions, e.g., for magnetic layer thicknesses less than 1 nm (about 5 monolayers).

Suppression of poly (ADP-ribose) polymerase activation by 3-aminobenzamide in a rat model of myocardial infarction: long-term morphological and functional consequences.

1. Recent studies demonstrated that inhibition or genetic inactivation of the enzyme poly (ADP-ribose) polymerase (PARP) is beneficial in myocardial reperfusion injury. PARP activation in the reperfused myocardium has been assumed, but not directly demonstrated. Furthermore, the issue whether pharmacological PARP inhibition affords long-term functional benefit in the reperfused myocardium has not been explored. These questions were addressed in the present study. 2. In a rat model of myocardial ischemia (1 h) and reperfusion (up to 24 h), there was a marked and significant activation of PARP in the ischemic borderzone, as determined by poly(ADP-ribose) (PAR) immunohistochemistry. PAR localized to the nuclei of myocytes and infiltrating mononuclear cells. In the core of the infarction, necrotic tissues and diffuse PAR staining were observed. PARP activation remained markedly detectable 24 h after reperfusion. The PARP inhibitor 3-aminobenzamide (20 mg kg(-1) intraperitoneally 10 min before reperfusion, and every 2 h thereafter for 6 h) markedly reduced the activation of the enzyme in myocytes. 3. 3-aminobenzamide significantly protected against myocardial morphological and functional alterations at 24 h post-reperfusion. Notably, infarct size was reduced, circulating creatine kinase activity was attenuated, and myocardial contractility (dP dt(-1)) was restored by 3-aminobenzamide. 4. Our results demonstrate a significant and prolonged activation of PARP in the reperfused myocardium, localizing to the necrotic area and the ischaemic borderzone. Furthermore, the studies demonstrate that PARP inhibition affords long-term beneficial morphological and functional effects in the reperfused myocardium. These data strengthen the notion that pharmacological PARP inhibition is a viable novel experimental approach for protection against myocardial reperfusion injury.

Formation of nanocrystalline phases during thermal decomposition of amorphous Ni-P alloys by isothermal annealing.

The microstructure and the average grain size were investigated by x-ray diffraction and transmission electron microscopy for nanocrystalline (n) Ni-P alloys with 18, 19, and 22 at.% P. A detailed study of the nanocrystalline states obtained along different heat treatment routes has been performed: (1) a-->ni by isothermal annealing of the melt-quenched amorphous (a) Ni-P alloys; (2) ni-->nii by isothermal annealing of the nanocrystalline ni state; (3) ni-->nii by linear heating of the ni state. The heats evolved during the structural transformations were determined by differential scanning calorimetry. From these studies, a scheme of the structural transformations and their energetics was constructed, which also includes previous results on phases obtained by linear heating of the as-quenched amorphous state of the same alloys. Grain boundary energies also have been estimated. In some cases it was necessary to assume a variation of the specific grain boundary energy during the phase transformation to understand the enthalpy and microstructure changes during the different heat treatments.

Quantification of pulmonary capillary endothelium-bound angiotensin converting enzyme inhibition in man.

Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal ectoenzyme expressed abundantly on the pulmonary capillary endothelium and recognized as the site for the conversion of circulating angiotensin I to II. In the present study, we have applied recently developed methodologies for assaying pulmonary capillary endothelium-bound (PCEB) ACE activity in man, to estimate the interaction of an ACE inhibitor (enalaprilat) with PCEB ACE in human subjects. Trace amounts of the specific ACE substrate, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP; 40 Ci or 2 nmol), was injected as a bolus into the subclavian vein and immediately blood was withdrawn from a radial arterial catheter. Plasma concentrations of surviving substrate and product (3H-benzoyl-Phe) were estimated and BPAP utilization was calculated during a single transpulmonary passage, at baseline (T(0)) and at 15 min (T(15)) and 2 h (T(120)) after intravenous administration of 1.5 g/kg enalaprilat in 12 normotensive subjects. This treatment had no significant effect on mean arterial pressure (91+/- 6 vs. 84 +/- 7 vs. 88 +/- 6 mm Hg for T(0), T(15) and T(120), respectively), but significantly decreased serum and PCEB ACE activities. When normalized to predrug (T(0)) activity levels, enalaprilat inhibited PCEB and serum ACE activities at T(15) 74 +/- 6% and 68 +/- 6%, respectively. However, 2 h after enalaprilat (T(120)), PCEB ACE inhibition was maintained at 66 +/- 7%, whereas serum ACE inhibition was reduced to 46 +/- 8% (P<.01 from PCEB ACE), suggesting a preferential PCEB ACE inhibitory effect of enalaprilat.

[Beneficial effect of the ACE inhibitor captopril in normotensive patients with insulin-dependent diabetes]. / Az ACE-gátló captopril kedvezö hatása normotenziós, inzulindependens cukorbetegekben.

The increase of glomerular filtration can often be observed in patients with insulin dependent diabetes mellitus, even in the early stage of the disease and it does not require the presence of microalbuminuria. This phenomenon can be explained by vasoconstriction occurring in the efferent arterioles. Eighteen normotensive, diabetic patients (aged: 28-42) who developed increased glomerular filtration were recruited in this study. The specific objectives were: 1. to study the beneficial effect of angiotensin converting enzyme inhibitor on the glomerular filtration, 2. to evaluate the effect of this treatment on blood pressure and hemodynamic parameters in normotensive, diabetic subjects. After a placebo period of one week, patients were treated orally a daily dose of 3 x 6.25 mg of captopril for twelve weeks. Glomerular filtration was assessed by the isotopic clearance method and blood pressure recordings were taken every 30 minutes throughout a day using an automatic programmable device. Preload, afterload and linear ejection fraction were estimated by echocardiograph, whereas cardiac index was measured by isotopic first pass technique. At the end of the treatment period a significant decrease of glomerular filtration was observed (from 141.9 +/- 10 ml/min to 98.9 +/- 12 ml/min; p < 0.01. Similarly, the afterload exhibited a significant drop due to drug treatment (45.6 +/- 5.8 x 10(3) dyn/cm2 vs. 55.4 +/- 4.7 x 10(3) dyn/cm2 at the end of the placebo period (p < 0.01). However, preload, linear ejection fraction, and cardiac index did not significantly change during the treatment. According to the results obtained from this study a beneficial effect of captopril on the early development of the glomerular hyperfiltration was demonstrated in normotensive diabetic patients who did not develop microalbuminuria. This issue needs to be investigated further in a large scale clinical trial.

Effect of acute coronary occlusion on the size of the dynamically perfused coronary capillary bed in the dog.

The aim of the present study was to investigate the influence of reduced left anterior descending (LAD) coronary arterial blood flow on the size of the perfused coronary capillary surface area (CCSA) in dogs. The transcoronary hydrolysis (v) of the specific ACE substrate, [3H]benzoyl-Phe-Ala-Pro, was estimated and the parameter Amax/Km (proportional to the size of the perfused CCSA) was calculated. By means of a ligature placed around the LAD, LAD blood flow was transiently reduced to 36.0 +/- 4.1 (E1) and 17.4 +/- 4.3% (E2) of control; in a separate maneuver the first diagonal branch of the LAD was ligated to achieve 40.0 +/- 6.7% (E3) of control flow. The v values remained unchanged at around 0.7 for E1, E2, and E3 determinations, suggesting unaltered substrate transit time through the coronary capillary bed. Amax/Km values decreased to 36 +/- 5, 17 +/- 4, and 47 +/- 10% of control for E1, E2, and E3 determinations, respectively, reflecting a flow-proportional decrease in CCSA. Values of the transpulmonary measures of v and Amax/Km performed at the beginning and end of the protocol were unchanged. These results support the hypothesis that reduction in coronary blood flow will produce proportional decreases in the size of the CCSA. This new procedure can thus serve as a useful tool for investigating alterations in the size of the CCSA in different species and under various pathophysiologic challenges.

Unaltered pulmonary capillary surface area in the presence of changing arterial resistance.

We hypothesized that capillary recruitment may not be solely dependent on extracapillary factors. To test this hypothesis, rabbits were anesthetized and placed on total cardiac bypass at a constant, physiological pulmonary blood flow. Vascular occlusion techniques were combined with measurement of the transpulmonary metabolism of an angiotensin-converting enzyme substrate, allowing the concomitant assessment of changes in segmental resistances and dynamically perfused capillary surface area. Intra-arterial serotonin infusion increased upstream pulmonary vascular resistances without affecting dynamically perfused capillary surface area. Intra-arterial isoproterenol infusion diminished serotonin-induced increased upstream resistances, also without affecting capillary surface area. These findings support the hypothesis that pulmonary capillary recruitment may not be solely dependent on extracapillary factors.

cGMP accumulation and gene expression of soluble guanylate cyclase in human vascular tissue.

Gene expression of soluble guanylate cyclase (sGC) and cGMP accumulation in response to sodium nitroprusside (SNP) were studied in cultured human vascular cells and freshly harvested vascular tissue. As revealed by reverse transcriptase-polymerase chain reaction, cultured smooth muscle and endothelial cells, as well as freshly isolated human vascular tissue, express mRNA for the alpha 3 and beta 3 subunits but not for the alpha 2 and beta 3 subunits is evident even in the absence of increased cGMP accumulation in response to SNP. cGMP accumulation in human cells cultured from different vascular beds typically increased two- to five-fold (maximum of 11.4-fold) over baseline following stimulation with 100 microM SNP. Bovine, murine, canine, and avian vascular smooth muscle cells accumulated similar or lower amounts of cGMP than human cells, whereas porcine, rat, and rabbit smooth muscle cells accumulated greater amounts of cGMP. In freshly harvested human vessels, cGMP accumulation in response to SNP was found to increase fifteen-fold over baseline. In contrast to the SNP-induced cGMP accumulation, cGMP levels in response to particulate guanylate cyclase activator atriopeptin II were equal to or greater in cultured human cells than in fresh human vascular tissue. We conclude that human vascular cells (fresh and cultured) express the mRNA for both a large (alpha 3) and a small (beta 3) sGC subunit and that fresh human cells are more sensitive to SNP stimulation.