Leonardo Tocchini

Changes in heart rate variability and QT dispersion in patients with overt hypothyroidism

OBJECTIVE The aim of the present study was to evaluate the effect of clinical hypothyroidism on cardiovascular autonomic function and ventricular repolarization. DESIGN AND METHODS We studied 31 patients (22 females and 9 males; mean age 53.6+/-11.8 years) with overt hypothyroidism (TSH=56.2+/-14.7 microU/ml, low free thyroxine (T4), free tri-iodothyronine (T3)) and 31 euthyroid controls, to investigate the dispersion of the QT interval in electrocardiogram (ECG) (an index of inhomogeneity of repolarization) and heart rate variability (HRV; a measure of cardiac autonomic modulation). The hypothyroid patients and controls underwent a full medical examination, standard 12-lead ECG, and 24-h ambulatory ECG monitoring. The hypothyroid patients were re-examined after 6 months of treatment with L-T4. RESULTS Patients with hypothyroidism showed higher QT dispersion and lower HRV measures than controls (P<0.01 or P<0.001). In hypothyroid patients, standard deviation of all R-R intervals was inversely related (by simple regression) to serum (log)TSH levels (r=-0.47, P=0.008), while QT dispersion (r=0.50, P=0.004) and QTc dispersion (r=0.46, P=0.008) were directly related to (log)TSH. Parameters of HRV improved after 6 months of L-T4 treatment, with the correction of hypothyroidism, becoming comparable with those of the control subjects, whereas the QT and QTc dispersion results were found to be only partially restored, remaining higher than the controls. CONCLUSIONS The results of the study demonstrate that hypothyroidism is associated with a decreased sympatho-vagal modulation of the heart rate and with an increased inhomogeneity of ventricular recovery times. The assessment of HRV and QT dispersion in patients with overt hypothyroidism may represent a useful tool in monitoring the cardiovascular risks.

Cardiac remodeling in patients with primary aldosteronism

Objective: To evaluate the morpho-functional changes of the myocardium in patients with primary aldosteronism (PA). Design: An observational study in a university referral center for blood pressure diseases. Patients: Twenty-three patients with PA, 24 patients with essential hypertension (EH), and 15 normotensive controls (C) underwent conventional echocardiography with integrated backscatter (IBS) and tissue Doppler imaging (TDI) analysis. The corrected IBS (C-IBS) values and the systo-diastolic variation of IBS (CV-IBS) were performed at both interventricular septum and the posterior wall levels. TDI myocardial systolic (Sm), early diastolic (Em), and late diastolic (Am) velocities of both left ventricular walls were also determined. Results: In PA patients, septal and posterior wall CV-IBS were significantly lower than C (p<0.0001) and EH patients (p<0.001). In EH, CV-IBS was significantly lower than C (p<0.001). Patients with PA exhibited lower Sm, lower Em, and higher Am, and a subsequently reduced Em/Am ratio than C (p<0.001 for all) and EH (p<0.01 for all) at interventricular septum and lateral wall levels. In the latter, Sm, Em, and Em/Am ratio were lower and Am was higher than C (p<0.001 for all). In PA and EH patients, CV-IBS at both septum (r=−0.66, p<0.001) and posterior wall levels (r=−0.67, p<0.001) and Sm peak of both septum (r=−0.52, p<0.001) and lateral wall (r=−0.55, p<0.001) were inversely related to plasma aldosterone. Conclusions: Patients with PA showed myocardial wall remodeling characterized by increased myocardial fibrosis and early left ventricular systodiastolic function abnormalities.

In vitro and in vivo study on the antioxidant activity of dexrazoxane.

OBJECTIVES The iron chelator dexrazoxane has been shown to significantly reduce anthracycline-induced cardiac toxicity in several randomized controlled studies. Aim of the present study was to assess the in vitro and in vivo antioxidant effects of dexrazoxane. METHODS The in vitro antioxidant activity of dexrazoxane as its total oxyradical scavenging capacity (TOSC) was assessed and compared to that of some classic antioxidants such as reduced glutathione (GSH), uric acid and trolox. The plasma antioxidant activity of 20 newly-diagnosed non-Hodgkin lymphoma (NHL) patients scheduled to receive anthracycline-containing chemotherapy (ProMECE-CytaBOM) was also evaluated. Results were expressed as TOSC units. RESULTS Dexrazoxane exhibited an in vitro scavenging capacity towards hydroxyl radicals 320% higher than that of GSH (p<0.00001), 20% higher than that of uric acid (p<0.001), and 100% higher than that of trolox (p<0.001). In the clinical study, ProMECE-CytaBOM infusion significantly reduced plasma TOSC in NHL patients (p=0.0001). Dexrazoxane supplementation was able to restore plasma antioxidant activity in two hours from the end of the ProMECE-CytaBOM infusion. CONCLUSIONS Dexrazoxane has in vitro antioxidant capacity. In vivo, it is able to reduce the epirubicin-induced free radical production. The intrinsic antioxidant effect of this compound could explain the reduction of the anthracyclines-induced toxicity in those patients treated with dexrazoxane supplementation.

Changes in autonomic regulation and ventricular repolarization induced by subclinical hyperthyroidism

UNLABELLED The aim of the present study was to evaluate the effect of subclinical hyperthyroidism (SHT) on cardiovascular autonomic function and ventricular repolarization. METHODS Thirty subjects (25 females; mean age 49.6 ± 9.8 years) with SHT, as judged by reduced TSH serum levels and normal free T4 and T3 serum levels, and 30 age and sex-matched control subjects underwent standard 12-lead ECG, and 24h ambulatory ECG monitoring. The dispersion of the QT interval, an index of inhomogeneity of repolarization, and the heart rate variability (HRV), a measure of cardiac autonomic modulation, were studied. RESULTS Patients with SHT showed higher QT dispersion (p<0.001) and lower HRV measures (0.01>p<0.001) than controls. In SHT patients, QT dispersion was inversely related to HRV (r=-0.47, p<0.01). CONCLUSION The results of the present study demonstrated that SHT is associated with a sympathovagal imbalance, characterized by increased sympathetic activity in the presence of diminished vagal tone, and with an increased inhomogeneity of ventricular recovery times. The assessment of HRV and QT dispersion in patients with SHT may represent a useful tool in monitoring the cardiovascular risk of this condition.

Preclinical cardiac involvement in phaeochromocytoma: a study with integrated backscatter

Objective  It is well known that vascular and cardiac structure may be influenced by circulating neurohormonal factors. Our aim was to study the myocardial wall texture by integrated backscatter (IBS) analysis in patients with phaeochromocytoma (PHEO).

Carotid integrated backscatter analysis in patients with subclinical hypothyroidism

Objective  The aim of the present study was to determine whether integrated backscatter (IBS) analysis combined with conventional ultrasonography could differentiate the tissue characteristics of carotid artery intimal hyperplasia in patients with subclinical hypothyroidism (SH).

Effects of recombinant human erythropoietin high mimicking abuse doses on oxidative stress processes in rats

Although many studies highlight how long-term moderate dose of Recombinant Human Erythropoietin (rHuEPO) treatments result in beneficial and antioxidants effects, few studies take into account the effects that short-term high doses of rHuEPO (mimicking abuse conditions) might have on the oxidative stress processes. Thus, the aim of this study was to investigate the in vivo antioxidant activity of rHuEPO, administered for a short time and at high doses to mimic its sports abuse as doping. Male Wistar healthy rats (n=36) were recruited for the study and were treated with three different concentrations of rHuEPO: 7.5, 15, 30μg/kg. Plasma concentrations of erythropoietin, 8-epi Prostaglandin F2α, plasma and urinary concentrations of NOx were evaluated with specific assay kit, while hematocrit levels were analyzed with an automated cell counter. Antioxidant activity of rHuEPO was assessed analyzing the possible variation of the plasma scavenger capacity against hydroxylic and peroxylic radicals by TOSC (Total Oxyradical Scavenging Capacity) assay. Statistical analyses showed higher hematocrit values, confirmed by a statistically significant increase of plasmatic EPO concentration. An increase in plasma scavenging capacity against peroxyl and hydroxyl radicals, in 8-isoprostane plasmatic concentrations and in plasmatic and urinary levels of NOX were also found in all the treated animals, though not always statistically significant. Our results confirm the literature data regarding the antioxidant action of erythropoietin administered at low doses and for short times, whereas they showed an opposite incremental oxidative stress action when erythropoietin is administered at high doses.

The level of physical training modulates cytokine levels through P2X7 receptor in healthy subjects

The P2X7 receptor‐NLRP3 inflammasome complex (P2X7R‐Infl) regulates inflammatory and immune responses. Physical exercise modulates heat‐shock proteins (Hsps), influencing cytokine levels and oxidative stress; Hsp72 triggers P2X7R‐Infl‐dependent responses.

Cardiac involvement in chronic progressive external ophthalmoplegia

Myocardial involvement has not been extensively investigated in mitochondrial myopathies. The aim of the study was to assess the myocardial morpho-functional changes in patients with chronic progressive external ophthalmoplegia (PEO). Twenty patients with PEO and 20 controls underwent standard echocardiography with tissue Doppler imaging (TDI) and integrated backscatter (IBS) analyses. These techniques are capable of providing non-invasively the early, subtle structural and functional changes of the myocardium. TDI myocardial systolic (Sm) and early (Em) and late (Am) diastolic velocities of left ventricular walls were determined. The systo-diastolic variation of IBS was also determined. Patients with PEO exhibited lower Sm, lower Em, and higher Am, and a reduced Em/Am ratio than controls (p<0.001 for all) at interventricular septum and lateral wall levels. In PEO patients, septal and posterior wall cyclic variations of IBS were significantly lower than those in controls (p<0.001). Patients with PEO showed myocardial wall remodeling characterized by increased fibrosis and early left ventricular systo-diastolic function abnormalities. Although cardiac involvement in PEO is generally considered to be limited to the cardiac conduction system, left ventricular dysfunction may be present and should receive more attention in the management of these patients.