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Biomedical subjects

Ferdinando Franzoni

Publications and source records attributed to Ferdinando Franzoni.

At least 19 recordsLinked to original sources
PubMed2006

Identification of a cytochrome P450 2C9-derived endothelium-derived hyperpolarizing factor in essential hypertensive patients.

OBJECTIVES: We assessed the role of cytochrome P450 2C9 (CYP 2C9)-derived endothelium-derived hyperpolarizing factor (EDHF) in the forearm microcirculation of essential hypertensive patients (EH) by utilizing sulfaphenazole (SUL), a selective CYP 2C9 inhibitor. BACKGROUND: In EH patients, EDHF acts as a compensatory pathway when nitric oxide (NO) availability is reduced. Cytochrome P450 2C9 is a possible source of EDHF. METHODS: In 36 healthy subjects (normotensive [NT]) and 32 hypertensive patients (HT), we studied forearm blood flow (strain-gauge plethysmography) changes induced by intraarterial acetylcholine (ACH) and bradykinin (BDK), repeated during N(G)-monomethyl-L-arginine (L-NMMA) (100 mug/100 ml/min) or SUL (0.03 mg/100 ml/min). In HT, the effect of SUL on ACH and BDK was repeated during vitamin C (8 mg/100 ml/min). Sodium nitroprusside (SNP) was utilized as control. RESULTS: In NT, vasodilation to ACH and BDK was blunted by L-NMMA and not changed by SUL. In contrast, in HT responses to ACH and BDK, reduced compared with NT, were resistant to L-NMMA. In these patients, SUL blunted vasodilation to ACH and to a greater extent the response to BDK. When retested with vitamin C, SUL was no longer effective on both endothelial agonists. In 2 final groups of normotensive control subjects, vasodilation to ACH or BDK residual to cyclooxygenase and L-NMMA blockade was further inhibited by simultaneous SUL infusion. Response to SNP, similar between NT and HT, was unaffected by SUL. CONCLUSIONS: Cytochrome P450 epoxygenase-derived EDHF acts as a partial compensatory mechanism to sustain endothelium-dependent vasodilation in HT, particularly the BDK-mediated response, when NO activity is impaired because of oxidative stress.

Acetylcholine↗
PubMed2006

Carotid vascular remodeling in patients with pheochromocytoma.

CONTEXT: The influence of catecholamines on vascular remodeling in humans was investigated. OBJECTIVE: The objective was to study the carotid vascular wall in patients with pheochromocytoma (PHEO). DESIGN AND SETTING: An observational study was conducted in a university referral center for blood pressure diseases. PATIENTS: Fourteen patients with PHEO, 15 matched high-normal essential hypertensives, 15 mild essential hypertensives, and 15 controls underwent two-dimensional conventional ultrasonography and ultrasonic tissue characterization of the carotid wall. MAIN OUTCOME MEASURES: Intimal media thickness (IMT), diameter, and corrected ultrasonic integrated backscatter signal (C-IBS) of carotid arteries were evaluated. RESULTS: IMT in PHEOs (0.844 +/- 0.18 mm, mean +/- sd) was greater than not only controls (0.596 +/- 0.09 mm, P < 0.0002) but also high-normal (0.710 +/- 0.17 mm, P < 0.03), and even mild (0.727 +/- 0.20 mm, P = 0.06) hypertensives. IMT in the latter was higher than in controls (P < 0.03), without difference in comparison with high-normal hypertensives. C-IBS values in PHEOs (-21.71 +/- 2.0 dB, mean +/- sd) were greater than in controls (-26.20 +/- 1.73 dB, P < 0.0001) but also than in high-normal (-23.84 +/- 1.16 dB, P < 0.002) and mild (-23.37 +/- 1.99 dB, P < 0.01) hypertensives. C-IBS values in controls were lower than in high-normal (P < 0.0005) and mild (P < 0.0001) hypertensives. Carotid diameter was not significantly different in the four groups. In PHEOs, C-IBS was associated with urinary noradrenaline (r = 0.640, P < 0.01) and normethanephrine (r = 0.737, P < 0.009). CONCLUSIONS: Carotid IMT of PHEOs is higher than in controls and matched groups of hypertensives with comparable or even higher blood pressure. This vascular rearrangement is characterized by increased IBS values due to collagen deposition and vascular fibrosis. Therefore, our data show that abnormal catecholamine levels take part per se in carotid wall remodeling of patients with PHEO.

Adrenal Gland Neoplasms↗
PubMed2005

Acute effects of hemodialysis on left ventricular function evaluated by tissue Doppler imaging.

Evidence exists that left ventricular function is impaired in chronic uremic patients. During hemodialysis (HD) treatment, myocardium undergoes electrolyte, hemodynamic and neuro-humoral stress; however, data about the acute changes on ventricular function are controversial. Aim of the present study was to evaluate the effect of a single hemodialysis session on left ventricular (LV) systolic and diastolic function using pulsed tissue Doppler imaging (TDI) sampled by echocardiography. The study group included 20 uremic patients (17 males, aged 51+/-13 yrs) on maintenance HD, free from clinically overt cardiac dysfunction who underwent echocardiography with pulsed TDI 30 min prior and 30 min after a HD session. TDI was performed by placing the sample volume in the center of the basal lateral segment and the basal interventricular septum in the apical four-chamber view. Myocardial systolic wave (S(m)) and early (E(m)) and atrial (A(m)) diastolic waves were measured. On standard sonography examination, no significant changes in LV systolic function parameters were observed after HD, but the indices for LV diastolic function deteriorated significantly (peak E, 75.4+/-11.2 vs. 58.8+/-12.5 cm/s, P<0.01; E/A ratio, 1.0+/-0.3 vs. 0.8+/-0.2, P<0.01). However, regarding TDI measures following HD, the patients exhibited a lower S(m) peak (septum: 7.6+/-1.1 vs. 5.9+/-0.8 cm/s; lateral wall: 7.7+/-1.7 vs. 6.8+/-1.2 cm/s, P<0.001), a lower E(m) peak (septum: 8.3+/-1.6 vs. 6.3+/-1.7 cm/s; lateral wall: 10.2+/-2.4 vs. 7.1+/-1.9 cm/s, P<0.001), and a reduced E(m)/A(m) ratio (septum: 1.0+/-0.4 vs. 0.7+/-0.2; lateral wall: 1.2+/-0.5 vs. 0.7+/-0.2, P<0.001, respectively), as compared to pre-HD parameters. Of interest, peak E(m), and E(m)/A(m) ratio of the lateral wall were negatively related to ultrafiltration rate (r = -0.60, P<0.05 and -0.69, P<0.01, respectively). Our data indicate that a single hemodialysis session is associated with acute deterioration of diastolic and systolic parameters of myocardial function, as assessed by TDI. These reversible changes could be considered as a cardiac stunning that seems to be related to the ultrafiltration rate and then to the interdialysis weight gain. These findings suggest that low ultrafiltration volume and/or limited interdialytic weight gain are cardioprotective measures in hemodialysis patients.

Echocardiography, Doppler↗
PubMed2005

In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients.

BACKGROUND: The beneficial effects of statins in reducing cardiovascular events have been attributed predominantly to their lipid-lowering effects, recent studies suggest that these effects might be due to their anti-inflammatory properties. We here investigate the in vivo and in vitro effects of simvastatin on cytokine production in pre-dialysis chronic renal failure patients. METHODS: Our clinical study has been designed as a randomized double-blind placebo controlled study. A total of 55 chronic kidney disease (CKD) patients at stages 3 and 4 (mean creatinine clearance 45 ml/min, range 15-60) were randomly assigned to receive simvastatin 40 mg/day or placebo, added to their ongoing treatment, for 6 months. Blood samples were obtained at baseline, and after 3 and 6 months of observation for the determination of lipids, inflammatory markers and renal function. For the in vitro studies, the effect of increasing doses of simvastatin on cytokine production [namely interleukin (IL)-6 and IL-8] in human cultured monocytes from 10 healthy subjects (HS) and 15 CKD patients stimulated by lipopolysaccharide (LPS) was investigated. RESULTS: A significant reduction in total cholesterol from 221+/-44 mg/dl to 184+/-41 mg/dl (3 months) and to 186+/-39 mg/dl (6 months) (P<0.02) and low-density lipoprotein cholesterol from 139+/-40 mg/dl to 104+/-29 mg/dl (3 months) and to 100+/-31 mg/dl (6 months) (P<0.001) was observed in the 28 patients treated with simvastatin. In this group, C-reactive protein (CRP) levels significantly decreased from 2.6 mg/l [interquartile range (IQR 4.9)] to 2.0 mg/l (IQR 1.9) (P = 0.03) at 6 months (P<0.05). A parallel reduction of IL-6 levels from 5.1 pg/ml (IQR 3.8) to 3.5 pg/ml (IQR 3.1) (P = 0.001) at 6 months was also observed. No significant reduction in inflammatory markers [CRP from 5.1 mg/l (IQR 1.9) to 5.4 mg/l (IQR 1.3) (P = NS) at 6 months] or plasma lipids [LDL-cholesterol from 127+/-32 mg/dl to 131+/-21 mg/dl (6 months)] was observed in the 27 patients of the placebo group. In the in vitro studies, the average value for cell-associated IL-6 and IL-8 was higher in CKD (155+/-95 pg/ml monocytes for IL-6 and 722+/-921 pg/ml monocytes for IL-8) vs HS (137+/-87 pg/ml monocytes and 186+/-125 pg/ml monocytes) (P<0.01) and was not affected by simvastatin alone. LPS resulted in a significant increase in cytokine production (IL-6: 1954+/-321 pg/ml monocytes for CKD and 1451+/-237 pg/ml monocytes for HS; P<0.001); the simultaneous addition of increasing doses of simvastatin to these cultures induced a dose-dependent inhibition of IL-6 and IL-8 production in stimulated peripheral blood mononuclear cells in all groups. CONCLUSIONS: These results indicate that simvastatin in commonly used doses has an in vitro and in vivo anti-inflammatory effect in CKD patients, and may play an important role in counteracting the mechanisms involved on the pathogenesis of cardiovascular disease.

Biomarkers↗
PubMed2005

Effect of epirubicin-based chemotherapy and dexrazoxane supplementation on QT dispersion in non-Hodgkin lymphoma patients.

BACKGROUND AND OBJECTIVE: Aim of the present study was to assess the effect of epirubicin-based chemotherapy on QT interval dispersion in patients with aggressive non-Hodgkin lymphoma (NHL), and the effect of dexrazoxane supplementation. Prolongation of QT dispersion may not only represent a sensitive tool in identifying the first sign of anthracycline-induced cardiotoxicity, but it may serve also in identifying patients who are at risk of arrhythmic events. METHODS: Twenty untreated patients, <or=60 years of age with newly-diagnosed aggressive NHL, eligible for a treatment with epirubicin-based chemotherapy were selected for the study. The patients were randomly allocated in two subgroups (N=10) to receive or not dexrazoxane hydrochloride (400 mg/m(2)) after epirubicin infusion. The patients underwent 12-lead electrocardiogram (ECG) before and after epirubicin infusion and after dexrazoxane supplementation. QT dispersion was defined as the difference between the maximum and the minimum QT interval occurring in any of the 12 ECG leads, corrected (QTc) for heart rate. RESULTS: All the 20 patients showed increased QT dispersion (44.3 +/- 8.4 vs. 68.4+/-11.4 ms, P<0.001) and QTc dispersion (46.2 +/- 6.2 vs. 72.2 +/- 8.4, P<0.001) after chemotherapy infusion. The 10 patients who underwent supplementation with dexrazoxane exhibited a significant reduction of QT dispersion (67.4 +/- 8.1 vs. 49.5 +/- 4.2 ms, P<0.001) and QTc dispersion (71.2 +/- .7 vs. 51.4 +/- 4.3 ms, P<0.001), while the 10 patients not supplemented with dexrazoxane did not (QT dispersion: 69.3 +/- 7.6 vs. 64.2 +/- 6.9 ms; QTc dispersion: 72.8 +/- 8.1 vs. 67.3 +/- 7.2 ms, ns). CONCLUSIONS: Epirubicin-based chemotherapy causes an early increase of the QT and QTc dispersion, which is attenuated by dexrazoxane supplementation. Therefore, dexrazoxane can reduce the arrhythmic risk in patients treated with epirubicin.

Antibiotics, Antineoplastic↗
PubMed2005

Endothelium-dependent vasodilation and carotid artery wall remodeling in athletes and sedentary subjects.

In this study, the relationship between age, carotid artery remodeling, and endothelium-dependent vasodilation is investigated in sedentary subjects and athletes. Thirty-two young and old healthy sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring intima-media thickness (IMT) and corrected integrated backscatter (C-IBS), two early indicators of the atherosclerosis process. Endothelium-dependent vasodilation was assessed by intra-brachial acetylcholine (strain-gauge plethysmography), at baseline and during NO sythase inhibitor NG-monomethyl-L-arginine (L-NMMA), and the antioxidant Vitamin C. Response to sodium nitroprusside (SNP) was also evaluated. Independently of trained status, IMT and C-IBS were higher in older than in young individuals (p<0.0001), while response to acetylcholine, but not to SNP, was lower (p<0.0001). Older athletes showed lower IMT, lower C-IBS (p<0.0001), greater response to acetylcholine (p<0.0001), and greater inhibition of acetylcholine by L-NMMA (p<0.001) than older controls. Only in older sedentary individuals, Vitamin C increased response to acetylcholine (p<0.001) and restored the inhibiting effect of L-NMMA (p<0.01). In the whole population maximal acetylcholine-induced vasodilation was inversely related to IMT (r=-0.60, p<0.0001) and to C-IBS (r=-0.56, p<0.0001). In conclusion, regular physical training can attenuate the age-related impairment of endothelium-dependent vasodilation, which is related to an attenuation of the age-induced remodeling of the carotid wall.

Acetylcholine↗
PubMed2005

Early detection of cardiac dysfunction in patients with anorexia nervosa by tissue Doppler imaging.

BACKGROUND: Cardiac damage is a major complication of chronic starvation. The aim of this study was to evaluate the changes of left ventricular function in patients with anorexia nervosa by means of pulsed tissue Doppler imaging. METHODS: A total of 20 females (age 22.4+/-4.3 years) with overt anorexia nervosa, 20 matched healthy thin females with body mass index < 19 kg/m2 and 20 matched healthy normal-weight females underwent both standard echocardiography and tissue Doppler imaging. Myocardial systolic wave (Sm) and early (Em) and atrial (Am) diastolic waves were measured on the basal lateral segment and the basal interventricular septum from the apical four-chamber view. RESULTS: When compared with control groups, the anorexia nervosa group showed lower left ventricular mass (p < 0.0001), lower Sm peak of both lateral wall (6.5+/-0.9 vs. 9.4+/-2.1 and vs. 9.5+/-1.9 cm/sec, p < 0.001) and septum (5.6+/-1.5 vs. 8.6+/-1.6 and vs. 8.8+/-1.5 cm/sec, p < 0.001), and comparable Em, Am and Em/Am ratio. The ratio between transmitral peak E and Em was significantly greater in anorexic patients than in controls (lateral wall: 8.1+/-0.1 vs. 6.8+/-0.2 and vs. 6.9+/-0.2, p < 0.001; septum: 10.8+/-0.4 vs. 8.8+/-0.5 and vs. 8.8+/-0.3, p < 0.001). No differences were observed between thin and normal-weight females. In the anorexia nervosa group, S(m) peak was significantly related to left ventricular mass indexed, at both septum (r = 0.55, p < 0.02) and lateral wall (r = 0.49, p < 0.03) levels. CONCLUSIONS: These results show that anorexia nervosa is associated with left ventricular systolic dysfunction, which is related with the reduction of cardiac mass. Tissue Doppler imaging can give useful information in the identification of regional left ventricular dysfunction, in addition to traditional parameters.

Adult↗
PubMed2005

Subclinical cardiac involvement in patients with facioscapulohumeral muscular dystrophy.

Myocardial involvement is a common finding in certain myopathies, while it has not been extensively investigated in facioscapulohumeral muscular dystrophy (FSHD1A). Aim of this study was to assess in FSHD1A patients the electrical and functional properties of the myocardium. Twenty-four patients with FSHD1A (mean age 41.2+/-14.5 years) and 24 matched healthy subjects were studied. Standard- and signal-averaged electrocardiography were recorded to determine QT dispersion and the presence of ventricular late potentials (VLPs). Standard echocardiography with systo-diastolic variations of integrated backscatter signal (CV-IBS) were performed to assess functional properties of the myocardium. Compared with control subjects, patients with FSHD1A had significantly lower CV-IBS and higher QT dispersion. Nine patients had positive VLPs. QT and QTc dispersion were inversely related to CV-IBS at both septum and posterior wall levels. Moreover, septal CV-IBS was inversely related to the Kpnl-BinI4q fragment size. These results suggest a subclinical cardiac involvement in FSHD1A patients, which can represent a substrate for ventricular arrhythmias and heart failure.

Adult↗
PubMed2005

Physical activity, plasma antioxidant capacity, and endothelium-dependent vasodilation in young and older men.

BACKGROUND: Sedentary aging is associated with oxidative stress and endothelial dysfunction. The aim of this study was to evaluate the relationship between long-term physical activity, plasma antioxidant status, and conduit artery endothelial function in young and older healthy men. METHODS: In young (n = 16) and older athletes (n = 16) and in matched healthy sedentary subjects, endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent response to glyceryl trinitrate (GTN), 400 microg, were measured in the brachial artery from high-resolution ultrasonography. Plasma malondialdehyde (MDA) and antioxidant capacity as total oxyradical scavenging capacity (TOSC) were also evaluated. RESULTS: We found that FMD was lower (< or =0.01) in sedentary older subjects (2.3% +/- 1.0%) as compared with older athletes (5.3% +/- 3.2%) and both sedentary (5.4% +/- 2.0%) and athletically trained (6.1% +/- 3.2%) young subjects. Sedentary older subjects showed higher (P < or = .05) MDA levels and lower (P < .0001) plasma antioxidant capacity as compared with the other subgroups, whereas in older athletes MDA levels and antioxidant capacity were similar to those observed in the young subgroups. In the whole group, FMD, but not GTN, was negatively related to age (r = -0.31, P < .05) and directly related (P < or = .01) to VO2max (r = 0.49) and TOSC against peroxyl (r = 0.69) and hydroxyl radicals (r = 0.53). In the multivariate analysis, TOSC against peroxyl radicals resulted as the most significant predictor of FMD (R2 = 0.60; P = .003). CONCLUSIONS: These results suggest that regular physical activity is associated with preserved antioxidant defenses and endothelial function in older individuals.

Adult↗
PubMed2004

An in vitro study of the peroxyl and hydroxyl radical scavenging capacity of the calcium antagonist amlodipine.

Amlodipine has been reported to improve endothelial function in patients with arterial hypertension and to significantly limit the progression of carotid atherosclerosis. The aim of this study was to assess the total antioxidant activity of amlodipine. We measured the in vitro antioxidant activity of amlodipine as its ability to antagonize the oxidation of alpha-keto-gamma-methiolbutyric acid by both hydroxyl and peroxyl radicals. The results are expressed as Total Oxyradical Scavenging Capacity (TOSC) units. Reduced glutathione, uric acid and trolox were used as the reference antioxidants. Amlodipine showed an efficiency as scavenger of peroxyl radicals (TOSC: 5945 +/- 544 units/mg) significantly higher (>50%, P <0.001) than that of GSH (2733 +/- 636 units/mg), and 70% lower (P < 0.0001) than the value obtained with uric acid (18144 +/- 696 units/mg) and trolox (17522 +/- 734 units/mg). Of interest, the scavenging capacity of amlodipine towards hydroxyl radicals (1455 +/- 154 units/mg) was 320% higher (P < 0.00001) than that of GSH (358 +/- 112 units/mg), 20% higher than that of uric acid (1198 +/- 121 units/mg), and 100% higher than that of trolox (759 +/- 143 units/mg). Amlodipine has intrinsic antioxidant activity with both anti-hydroxyl and anti-peroxyl radicals activity.

Amlodipine↗
PubMed2004

Responses to Tilt test in young and elderly patients with syncope of unknown origin.

The aim of the present study was to assess the cardiovascular autonomic function and responses to tilt test in young and elderly patients with syncope of unknown origin. We evaluated two groups of patients with previous unexplained syncope: 192 older subjects (112 males, 80 females, mean age 67.2 +/- 6.8 years) and 188 young subjects (102 males, 86 females, mean age 25 +/- 9 years). All patients underwent ambulatory electrocardiogram (ECG) monitoring, to evaluate time domain indices of heart rate variability (HRV), and head-up tilt test in the morning after an overnight fast. The responses of positive tilt test were classified using the VAsovagal Syncope International Study (VASIS) criteria: mixed (VASIS-1), cardioinhibition (VASIS-2A), severe cardioinhibition/asystole (VASIS-2B), pure vasodepression (VASIS-3). All the time-domain HRV indexes were lower in the older than in young subjects. The rate of positive responses was not different in the two groups. In elderly group the positive head-up tilt test responses showed: a pure vasodepressive response (VASIS 3) in 126 patients (65%), a mixed (VASIS-1) response in 25 patients (13%), a cardioinhibitory (VASIS-2A) response in 13 patients (7%). Only 28 (14.6%) of elderly group patients had negative head-up tilt test response. In contrast, in young group the positive head-up tilt test responses showed: 114 patients (61.2%) a mixed (VASIS-1) vasovagal response, 40 patients (22.3%) a cardioinhibitory (VASIS-2A) response, four (2.1%) patients a severe cardioinhibitory (VASIS-2B) and four (2.1%) patients a pure vasodepression (VASIS-3) response, respectively. The tilt test was negative in response in 26 young patients (12.2%). Our results confirm that the head-up tilt test may be useful in assessing unexplained syncope, since it is seen to be positive in 85% of elderly patients and 86% in young patients. In our subjects, vasodepressive response was the most frequent cause of syncope in older subjects, while vasovagal response is the commonest cause of syncope of young patients. This different behaviour in the elderly may be is explained with physiological aging, which is associated with a reduction of sympathetic-parasympathetic control on the cardiac rhythm, demonstrated by reduction in all the time domain HRV indices.

Adult↗
PubMed2004

Left ventricular diastolic function and carotid artery wall in elderly athletes and sedentary controls.

Advancing age is characterized by structural and functional change of left ventricle (LV) and large elastic arteries. Recent advances in tissue Doppler imaging (TDI) and integrated backscatter (IBS), new ultrasound tools, have allowed non-invasive assessment of structural and functional characterization of myocardium and artery wall. Our aim was to compare LV diastolic function and carotid artery remodeling in elderly athletes and sedentary controls. Twenty-five elderly athletes (males, aged 68.6 +/- 4.2 years) were compared to 25 age-sex-matched sedentary controls. All the subjects underwent either conventional Doppler echocardiography with pulsed TDI to evaluate LV diastolic function, and conventional ultrasonography and integrated backscatter (IBS) analysis to evaluate the carotid wall. Corrected IBS values (C-IBS) were obtained by subtracting the IBS value of the adventitia. Body mass index and blood pressure were not different in the two groups; athletes showed lower heart rate (P < 0.0001) and, as expected, higher LV mass than sedentary subjects (P < 0.0001). Transmitral Doppler analysis showed in trained subjects a significantly lower peak A and a higher E/A ratio (P < 0.001). On regards to TDI measurements, athletes exhibited a higher Em, a lower Am, and, subsequently, an increased Em/Am ratio of both lateral wall and septum (P < 0.0001). The IVRTm was shorter in trained subjects (P < 0.001). Athletes showed a lower C-IBS (-26.8 +/- 2.9 vs. -23.4 +/- 3.8 dB, P < 0.001) and a smaller intima-media thickness (IMT: 0.66 +/- 0.14 vs. 0.80 +/- 0.18 mm, P < 0.001) respect to sedentary controls. Moreover, a significant direct correlation was found between Em/Am of LV septal and lateral wall and C-IBS values (respectively, r = 0.62 and r = 0.56, P < 0.001). Thus the aging heart manifests structural and functional changes in response to physical activity. The expected pattern of cardiac and arterial alterations normally seen in response to age is modified in the older athletes, suggesting the exercise training is an effective stimulus in shaping arterial structure and left ventricular function in older heart. It would appear that pulsed TDI and IBS analysis may play an important role in detecting training-induced LV and carotid artery structural and functional modifications.

Adult↗
PubMed2004

Plasma antioxidant activity and cutaneous microvascular endothelial function in athletes and sedentary controls.

Aging is associated with endothelial dysfunction in both conduit arteries and peripheral microcirculation. Furthermore, aging is associated with an increased susceptibility to free radical mediated tissue damage. The aim of this study was to assess the relationship between age, regular aerobic-endurance training, plasma antioxidant activity and microcirculatory skin blood flow in healthy individuals. Thirty-six male athletes (range: 22-74 years; VO2max 54.3 +/- 5.2 ml/kg/min) and 36 age-sex-matched sedentary controls (range: 20-75 years; VO2max 34.2 +/- 3.4 ml/kg/min) were studied. Each group was divided into a younger (<30 years) and an older (>60 years) subgroup. Hand and foot baseline and stimulated skin blood flow (SBF) was measured by laser-Doppler flowmetry. Plasma free radicals antioxidant capacity against both peroxyl and hydroxyl radicals was also evaluated as Total Oxyradical Scavenging Capacity (TOSC) units. Baseline SBFs were not significantly different between athletes and sedentary groups, while plasma TOSC values against peroxyl radicals (18.4 +/- 3.1 vs. 13.8.0 +/- 3.4 units/ml, P < 0.001) and hydroxyl radicals (8.7 +/- 2.5 vs 4.9 +/- 2.3 units/ml, P <0.001) was higher in athletes. Hand SBF after heating and ischemia and foot SBF after heating were higher in athletes (P <0.0001) than in the sedentary group. In the sedentary groups, the lowest tertile of age had higher plasma TOSC values than the highest tertile of age (ROO- 18.2 +/- 2.2 vs 8.8 +/- 1.4 units/ml; HO- 9.2 +/- 1.3 vs 3.7 +/- 0.5 units/ml, P < 0.001). Among athletes, the lowest and the highest tertile of age did not show significantly different plasma TOSC (young: ROO- 20.3 +/- 1.5 and HO-: 9.7 +/- 1.4 units/ml; older: ROO-: 17.1 +/- 1.3 and HO-: 9.0 +/- 0.8 units/ml, n.s.). Resting SBF was similar in all the subgroups; stimulated SBFs were lower in both subgroups of untrained respect to trained individuals (P <0.001). In the sedentary subjects, SBF was inversely related to age (r = -0.63; P <0.0001) and directly related to TOSC against peroxyl (r = 0.59, P <0.001) and hydroxyl radicals (r = 0.47, P <0.01). In athletes SBF was related only to VO2max (r = 0.36; P <0.05) and TOSC vs ROO. (r = 0.41, P <0.01). In conclusion, these results suggest that regular physical activity is associated with a better microvascular endothelial function in older athletes probably due to increased antioxidant defenses.

Adult↗
PubMed2004

Abnormal ventricular repolarization in hypertensive patients: role of sympatho-vagal imbalance and left ventricular hypertrophy.

BACKGROUND: An increased risk for life-threatening arrhythmias and sudden death has been observed in hypertensive patients, associated with either left ventricular hypertrophy (LVH) or prolonged QT interval. To investigate the influence of autonomic imbalance and LVH on QT interval in hypertensive patients, we compared two different models of LVH: hypertension and endurance physical training. METHODS: Forty-seven untreated subjects affected by essential hypertension and 35 endurance runners, with a similar degree of LVH, were enrolled into the study. All subjects underwent 24-h ambulatory ECG recording and morning blood sampling for catecholamines. Heart rate variability was evaluated by spectral analysis and a computerized algorithm was used to measure the QT interval; QTc was then computed by the Bazett's formula. Left ventricular mass index (LVMI) was assessed by echocardiogram. RESULTS: No difference in LVMI was found between hypertensive patients and athletes. Athletes showed lower heart rate (64 +/- 1 vs. 75 +/- 1 bpm, p<0.001, mean +/- S.E.M.) and shorter QTc (401 +/- 3 vs. 434 +/- 4 ms, p<0.001) than hypertensive patients throughout the 24-h period. Athletes showed a higher vagal drive compared to hypertensive patients as suggested by bradycardia and higher values of vagal indices, which negatively correlated with QTc. Plasma norepinephrine was significantly lower in athletes than in hypertensive patients (p<0.05) and positively correlated with QTc. CONCLUSION: Despite similar degrees of LVH, hypertensive patients show QTc lengthening, as compared to athletes. Heart rate variability and plasma norepinephrine levels suggest sympathetic predominance in hypertensive patients, which could contribute to abnormal ventricular repolarization, thus identifying patients with an increased arrhythmic risk.

Autonomic Nervous System↗
PubMed2004

Effects of age and physical fitness on microcirculatory function.

Sedentary aging is associated with endothelial dysfunction and nitric oxide (NO) impairment. The aim of the present study was to assess the effects of regular physical exercise on nitrite/nitrate (NOx) concentrations and microcirculatory function in older men compared with young individuals. We measured NOx plasma concentrations and baseline and stimulated skin blood flow (SBF) by laser Doppler flowmetry in 39 male athletes [range, 22-72 years; maximal oxygen consumption (VO2max), 60.0 +/- 4.7 ml.min(-1).kg of body weight(-1) (mean +/- S.D.)] and 45 age- and sex-matched sedentary controls (VO2max, 38.0 +/- 7.1 ml.min(-1).kg of body weight(-1)). NOx concentrations were higher in athletes than in controls (50.4 +/- 16.3 compared with 39.0 +/- 15.4 micromol/l; P<0.005), whereas baseline SBF was comparable. Hand SBF after heating and ischaemia and foot SBF after heating were higher in athletes (P<0.0001) than in controls. By comparing the lowest and the highest tertile of age, sedentary young subjects had higher NOx concentrations than sedentary older subjects (43.3 +/- 13.4 compared with 31.8 +/- 12.2 micromol/l respectively; P<0.05). Exercise abolished this difference (49.1 +/- 9.6 micromol/l for young subjects and 52.1 +/- 11.5 micromol/l for older subjects; not significant). Resting SBF was similar in all the subgroups, but stimulated SBFs were lower in both subgroups of untrained compared with trained subjects. NOx concentrations were positively correlated with VO2max (r=0.46, P<0.001). Stimulated SBFs were correlated with NOx (r>0.30, P<0.05). These findings show that chronic exercise may improve endothelial function in older (and young) men, probably by increasing NO availability.

Adult↗
PubMed2004

Nutritional status and dietary manipulation in predialysis chronic renal failure patients.

OBJECTIVE: A properly implemented dietary treatment for patients with chronic renal failure (CRF) can correct several metabolic and endocrine disturbances and delay initiation of dialysis, but concerns exist about the risk of malnutrition and protein depletion. The goal of this study is to evaluate nutritional status and its relation to the dietary treatment in patients with advanced CRF. DESIGN: Cross-sectional survey. SETTING: Predialysis outpatient clinic. PATIENTS: Seventy patients (43 males, 27 females, 50 +/- 12 years) with severe CRF (glomerular filtration rate [GFR] <15 mL/min) being treated with a low-protein (0.6 g/kg/day) diet (LPD) or a very-low-protein (0.3 g/kg/day) diet supplemented with essential amino acids and ketoacids (KAD). Fifty-two healthy subjects with comparable age and sex served as controls. MAIN OUTCOME MEASURES: In all patients and controls, we performed biochemistry, anthropometry, bioelectrical impedance vector analysis (BIVA), and subjective global assessment (SGA), and the patients' outcomes were also assessed. RESULTS: Values of anthropometry and BIVA were similar in patients and controls. SGA scores showed a normal nutritional status (SGA-0) in 50 patients (71.4%) and mild to moderate SGA abnormalities (SGA-1) in 20 patients (28.6%); none had severe malnutrition. The SGA-1 patients differed from the SGA-0 patients by having higher serum urea, lower bicarbonate, and lower renal function (87% of SGA-1 patients had GFR <10 mL/min.). At the same GFR values (6.6 +/- 2.3 versus 6.6 +/- 2.3 mL/min) SGA-1 patients had lower bicarbonate (21.9 +/- 4.3 versus 25.3 +/- 2.7 mM, P <.01) and higher serum urea (115 +/- 29 versus 82 +/- 38 mg/dL, P =.01) and protein intake than SGA-0 patients; SGA-1 score was more prevalent with LPD compared with KAD treatment (45% versus 27%, P <.05). BIVA and anthropometry, serum levels of albumin, prealbumin, insulin-like growth factor-1, hematocrit, and lymphocyte count did not differ between SGA-1 and SGA-0 patients, but the number entering dialysis was higher in the group scoring as SGA-1 compared with SGA-0 (82% versus 47%, P <.05). CONCLUSIONS: With a planned dietary regimen, severe or overt malnutrition does not occur in predialysis CRF without other serious illnesses. However, some mild to moderate SGA abnormalities were detected in association with a more severe renal insufficiency, a lower serum bicarbonate, a higher serum urea and dietary protein levels and were predictive of poor renal outcome. This study emphasizes the role of proper dietary implementation, correction of metabolic acidosis, and clinical monitoring including SGA in the predialysis conservative care of CRF patients.

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