Low anaerobic threshold and increased skeletal muscle lactate production in subjects with Huntington's disease.

Mitochondrial defects that affect cellular energy metabolism have long been implicated in the etiology of Huntington's disease (HD). Indeed, several studies have found defects in the mitochondrial functions of the central nervous system and peripheral tissues of HD patients. In this study, we investigated the in vivo oxidative metabolism of exercising muscle in HD patients. Ventilatory and cardiometabolic parameters and plasma lactate concentrations were monitored during incremental cardiopulmonary exercise in twenty-five HD subjects and twenty-five healthy subjects. The total exercise capacity was normal in HD subjects but notably the HD patients and presymptomatic mutation carriers had a lower anaerobic threshold than the control subjects. The low anaerobic threshold of HD patients was associated with an increase in the concentration of plasma lactate. We also analyzed in vitro muscular cell cultures and found that HD cells produce more lactate than the cells of healthy subjects. Finally, we analyzed skeletal muscle samples by electron microscopy and we observed striking mitochondrial structural abnormalities in two out of seven HD subjects. Our findings confirm mitochondrial abnormalities in HD patients' skeletal muscle and suggest that the mitochondrial dysfunction is reflected functionally in a low anaerobic threshold and an increased lactate synthesis during intense physical exercise.

[What underlies NYHA class in elderly patients with heart failure? Role of diastolic dysfunction, functional mitral regurgitation and abnormal ventilation during exercise]. / Determinanti della classe NYHA nel paziente anziano con scompenso cardiaco: ruolo della disfunzione diastolica, dell'insufficienza mitralica funzionale e dell'alterata ventilazione durante esercizio.

BACKGROUND: Color-Doppler ecocardiography and cardiopulmonary stress test are pivotal in the evaluation of patients with heart failure. Besides determining systolic function through left ventricular ejection fraction (EF), color-Doppler ecocardiography evaluates the presence and degree of functional mitral regurgitation and the severity of diastolic dysfunction. Moreover, in addition to the aerobic capacity indicated by peak O2 consumption, other parameters of cardiopulmonary stress have proven useful for diagnostic purposes, such as the peak VE/VCO2 ratio or ventilatory efficiency. Since in elderly patients with heart failure the functional impairment often is a combination of the effects of aging with those of disease, the relationship between symptoms, i.e. the NYHA class, ventricular pump function and aerobic performance is sometimes difficult to estabilish. MATERIALS AND METHODS: In 60 elderly with systolic heart failure (75 +/- 3 years, EF 30 +/- 6%), we correlated symptoms (i.e. NYHA class) with [1] degree of functional mitral regurgitation (FMR) determined by color-Doppler echocardiography; [2] degree of left ventricular diastolic dysfunction, measured by Doppler analysis of transmitralic and pulmonary veins flow; [3] VO2 and VE/VCO2 at peak exercise at cardiopulmonary test. RESULTS: In all patients, NYHA class was only weakly related with EF and peak VO2, with wide overlap of individual values among patients with different NYHA class. Instead, we observed a tight relationship between NYHA class, FMR degree, and severity of diastolic dysfunction and VE/VCO2 ratio at peak exercise (p<0.001), with a more evident partition among patients in different NYHA classes. CONCLUSIONS: In elderly heart failure patients, the reduced effort tolerance expressed by the NYHA classification is only weakly associated with reduced aerobic capacity and pump function, but rather is related with the presence of mitral regurgitation, left ventricular diastolic dysfunction, and a poor ventilatory efficiency during exercise.

Different ventricular remodelling and autonomic modulation after long-term beta-blocker treatment in hypertensive, ischaemic and idiopathic dilated cardiomyopathy.

OBJECTIVE: In this retrospective analysis, we investigated the influence of aetiology on autonomic modulation and reverse ventricular remodelling induced by beta-blockade in heart failure. METHODS: Twenty-three heart failure patients without comorbidities (mean age 61 +/- 4 years, New York Heart Association class 3.1 +/- 0.1, treated with angiotensin-converting enzyme inhibitors and diuretics) were divided into three groups according to aetiology: hypertensive (group 1, n = 7), ischaemic (group 2, n = 6), and idiopathic (group 3, n = 10). Before and after 6 months of carvedilol (53 +/- 10 mg/day), patients underwent cardiopulmonary test, echocardiography and autonomic evaluation with spectral analysis of RR variability (10 min of rest plus 10 min of standing: the low frequency/high frequency ratio between low and high frequency components of each spectrum was the index of sympathovagal balance). RESULTS: Carvedilol improved New York Heart Association class and exercise performance. In group 1, ejection fraction and left ventricular end-diastolic volume normalised, and interventricular septum thickness increased. No remodelling occurred in group 2. In group 3, interventricular septum thickness was unchanged, ejection fraction and left ventricular end-diastolic volume improved. Also autonomic modulation differed. At baseline, adrenergic activation was observed either at rest or during standing. After carvedilol treatment, group 1 did not show any change in the low frequency/high frequency ratio in both conditions, whereas groups 2 and 3 showed reduced adrenergic activation at rest and normal response to standing. CONCLUSIONS: Despite favourable ventricular remodelling, the poor autonomic modulation observed with beta-blockade indicates a persistent central adrenergic activation in hypertensive heart failure patients.

Original articles primary coronary angioplasty and subsequent cardiovascular rehabilitation are linked to a favorable sympathovagal balance after a first anterior myocardial infarction.

BACKGROUND: Modulation of the autonomic tone may contribute to the positive clinical effects of reperfusion of the ischemic zone after acute myocardial infarction (AMI). Little information exists about the effects on the sympathovagal balance of the early reopening of the vessel achieved by means of primary coronary angioplasty (PTCA). Even less is known on the autonomic effects of rehabilitation in patients undergoing PTCA. METHODS: We performed spectral analysis of the RR interval variability during 15 min of ECG in resting conditions in 51 patients (47 males, 4 females, mean age 55 +/- 6 years) 2-3 weeks after a first anterior AMI, and after 8 weeks of rehabilitation with physical training. The ratio between the low- and high-frequency (LF/HF) components of each autospectrum was used to describe the sympathovagal balance. Patients were divided into three groups: group 1 (n = 26, primary PTCA/stenting); group 2 (n = 11, recombinant tissue-type plasminogen activator); group 3 (n = 14, no reperfusion). Treatment was similar in the three groups and was maintained during the whole rehabilitation period. Results. Before rehabilitation, group 1 showed an adrenergic activation that was more blunted than that observed in groups 2 and 3. This activation was maximal in those patients with the shortest delay before the procedure. Cardiovascular rehabilitation modulated the LF/HF ratio in all groups. CONCLUSIONS: Early and effective reperfusion of the infarct-related artery is associated with a better sympathovagal tone shortly after AMI; this is followed by the known benefits of cardiovascular rehabilitation on autonomic tone.

[Favourable effects of cardiovascular rehabilitation on funcional capacity and autonomic balance in elderly patients with heart failure]. / Effetti favorevoli della riabilitazione cardiovascolare su capacità funzionale ed equilibrio autonomico in pazienti anziani con insufficienza cardiaca.

In 42 patients with chronic heart failure we evaluated left ventricular function, exercise capability and autonomic control before and 3 months after a program of cardiovascular rehabilitation. The results were analyzed separately for younger (Group 1, n=18, age 51 +/- 6 years) and older patients (Group 2, n=24, age 68 +/- 4 years), with comparable clinical characteristics and therapy. Before rehabilitation, compared to younger patients, Group 2 patients showed a lower exercise capability, a comparable left ventricular ejection fraction and similar high sympathetic activity at rest, with no response to regular breathing (= stimulation of cardiopulmonary receptors, i.e. parasympathetic challenge) and active standing (= sympathetic stimulation). After rehabilitation, in both groups a 20% improvement of exercise tolerance and aerobic performance was observed, as well as a slightly increase of left ventricular ejection fraction (about 10%), and a recovery in vagal and sympathetic responsiveness. Thus, in heart failure patients age does not hinder the favorable clinical and autonomic modulation induced by cardiovascular rehabilitation.

Patterns of QT dispersion in athletic and hypertensive left ventricular hypertrophy.

OBJECTIVE: The objective of this article is to assess whether left ventricular hypertrophy (LVH) due to physical training or of hypertensive patients shows similarities in QT length and QT dispersion. METHODS: A total of 51 subjects were studied: 17 essential hypertensive patients (27.7 +/- 5.6 years), 17 athletes involved in agonistic activity (canoeing) (24.8 +/- 6.1 years), and 17 normotensive healthy subjects as control group (24.8 +/- 3.6 years). The testing protocol consisted of (1) clinic BP measurement, (2) echocardiography, (3) 12-lead electrocardiographic examination (QT max, QTc max, QT min, QTc min, DeltaQT, DeltaQTc). RESULTS: There were no significant differences between the body surface area, height, and age of the three groups. Clinic blood pressure was higher in hypertensives (146.5 +/- 45.2/93.5 +/- 4.9 mmHg) versus athletes (120.9 +/- 10.8/77.1 +/- 6.0 mmHg) and controls (123.5 +/- 4.8/78.8 +/- 2.9 mmHg) by definition. Indexed left ventricular mass (LVM/BSA) was significantly greater in both athletes (148.9 +/- 21.1 g/m2) and hypertensives (117.1 +/- 15.2 g/m2) versus controls (81.1 +/- 14.5 g/m2; P < 0.01), there being no statistical difference among them. LVH (LVMI > 125 g/m2) was observed in all athletes, while the prevalence in hypertensives was 50%. In spite of this large difference in cardiac structure there were no significant differences in QT parameters between athletes and the control group, while hypertensive patients showed a significant increase in QT dispersion versus the two other groups (DeltaQT 82 +/- 2.1, 48 +/- 1.3, 49 +/- 2.3 ms; P < 0.01; DeltaQTc 88 +/- 2.0, 47 +/- 1.4, 54 +/- 2.7; P < 0.01). CONCLUSIONS: LVH induced by physical training activity is not associated with an increase in QT dispersion, whereas pathological increase in LVM secondary to hypertension is accompanied by an increased QT dispersion.