Cardiovascular responses during free-diving in the sea.

Cardiac output has never been assessed during free-diving diving in the sea. Knowledge of human diving response in this setting is therefore scarce. 3 immersions were performed by 7 divers: at depths of 10 m, 20 m and 30 m. Each test consisted of 3 apnea phases: descent, static and ascent. An impedance cardiograph provided data on stroke volume, heart rate and cardiac output. Mean blood pressure, arterial O2 saturation and blood lactate values were also collected. Starting from a resting value of 4.5±1.6 L∙min(-1), cardiac output at 10 m showed an increase up to 7.1±2.2 L∙min(-1) (p<0.01) during the descent, while conditions during the static and ascent phases remained unchanged. At 20 m cardiac output values were 7.3±2.4 L∙min(-1) and 6.7(±1).2 L∙min(-1) during ascent and descent, respectively (p<0.01), and 4.3±0.9 L∙min(-1) during static phase. At 30 m cardiac output values were 6.5±1.8 L∙min(-1) and 7.5±2 L∙min(-1) during descent and ascent, respectively (p<0.01), and 4.7±2.1 L∙min(-1) during static phase. Arterial O2 saturation decreased with increasing dive depth, reaching 91.1±3.4% (p<0.001 vs. rest) upon emergence from a depth of 30 m. Blood lactate values increased to 4.1±1.2 mmol∙L(-1) at the end of the 30 m dive (p<0.001 vs. rest). Results seem to suggest that simultaneous activation of exercise and diving response could lead to an absence of cardiac output reduction aimed at an oxygen-conserving effect.

Muscle ischemic preconditioning does not improve performance during self-paced exercise.

Muscle ischemic preconditioning (IP) has been found to improve exercise performance in laboratory tests. This investigation aims at verifying whether performance is improved by IP during self-paced exercise (SPE) in the field. 11 well-trained male runners performed 3 randomly assigned 5 000 m self-paced running tests on an outdoor track. One was the reference (RT) test, while the others were performed following muscle IP (IPT) and a control sham test (ST). Average speeds were measured during each test. Mean values in oxygen uptake (VO2), aerobic energy cost (AEC) during race and post-race blood lactate (BLa) were gathered. Data showed that none of the studied variables were affected by IPT or ST with respect to the RT test. Average speeds were 4.63±0.31, 4.62±0.31 and 4.60±0.25 m·s(-1) for the RT, the ST and the IPT tests, respectively. Moreover, there was no difference among tests in speed reached during each lap. VO2 was 3.5±0.69, 3.74±0.85 and 3.62±1.19 l·min(-1). AEC was 1.04±0.15, 1.08±0.1 and 1.09±0.15 kcal·kg(-1)·km(-1). Finally, post-race BLa levels reached 12.85±3.54, 11.88±4.74 and 12.82±3.6 mmol·l(-1). These findings indicate that performance during SPE is not ameliorated by ischemic preconditioning, thereby indicating that IP is not suitable as an ergogenic aid.

Measurement of pulmonary gas exchange variables and lactic anaerobic capacity during field testing in elite indoor football players.

AIM: The aims of this study were: 1) to examine the gas exchange responses of elite indoor football players to a repeated sprint ability (RSA) test; and 2) to verify whether or not the excess of carbon dioxide production (CO2excess) correlates with blood lactate accumulation during RSA field testing. METHODS: Eleven elite male indoor football players were recruited. A preliminary incremental exercise test on a treadmill was performed to elicit V'O2max. Then, participants underwent an RSA test consisting in a shuttle running through a course with various changes of direction while wearing a portable gas analyzer able to provide values of oxygen uptake, carbon dioxide production, and CO2excess. BLa concentrations during recovery were also measured. RESULTS: The main results were that: 1) during the RSA test subjects did not reached the V'O2max level achieved in the preliminary test; 2) during the RSA test BLa levels were higher compared with the preliminary test; 3) the peak BLa concentration during recovery was significantly correlated with the average CO2excess CONCLUSION: It was concluded that the RSA test did not appear to be useful to elicit V'O2max. Rather, it seemed suitable to recruit subjects' lactic anaerobic capacity. Moreover, CO2excess appeared suitable for qualitatively estimate BLa accumulation during field testing.

Assessment of circulatory adjustments during underwater apnoea in elite divers by means of a portable device.

AIM: Considering that sympathetic activation is induced by exercise, it is reasonable to assume that hemodynamic adjustments to exercise act in opposition to those elicited by the diving response. However, cardiovascular measurements have never been performed during underwater dynamic apnoea (DA), and this hypothesis remains speculative. METHODS: Data concerning heart rate (HR), stroke volume (SV) and cardiac output (CO) during static apnoea (SA) and DA were collected from 12 elite divers by means of an impedance cardiograph adapted to the underwater environment. Mean arterial pressure (MBP), systemic vascular resistance (SVR) and arterial oxygen saturation (SaO(2)) were also assessed. Five trials were performed by the divers: head-out immersion during normal breathing (test A); 3 min of SA immersed at the surface (B) and at 3 m depth (C); DA till exhaustion immersed at the surface (D) and at 3 m depth (E). RESULTS: Both B and C conditions led to bradycardia (-17%) compared to A and also induced a decrement in SV (-8%) and in CO (-25%), while MBP was maintained because of an increase in SVR. A significant MBP increment (+11%) was detected only during tests D and E, when a SaO(2) drop was also present, whereas HR, SV and CO remained unchanged. CONCLUSION: We concluded that typical diving response was present only during SA, while sympathetic activation was induced by exercise during DA, which partially obscured the effects of the diving response.

Quantification of Spinning bike performance during a standard 50-minute class.

Spinning is a type of indoor fitness activity performed on stationary bikes by participants who pedal together to the rhythm of music and the motivating words of an instructor. Despite worldwide popularity of this type of recreational activity, to date there have been few, mainly non-scientific, studies of the impact of spinning on metabolic, respiratory, and cardiovascular functions. The main aim of this study was to evaluate a number of metabolic and cardiovascular variables during a standard 50-min class performed by Spinning instructors of both sexes: six males (age 30 +/- 4.8 years, body mass index 24 +/- 2.5 kg x m(-2); mean +/- s) and six females (age 34 +/- 6.3 years, body mass index 21 +/- 1.9 kg x m(-2)). The mean power output, heart rate, and oxygen uptake during the performance were 120 +/- 4 W, 136 +/- 13 beats x min(-1), and 32.8 +/- 5.4 ml x kg(-1) x min(-1) respectively for males, and 73 +/- 43 W, 143 +/- 25 beats x min(-1), and 30 +/- 9.9 ml x kg(-1) x min(-1) respectively for females. Analysis of individual performances showed that they were compatible with physical exercise that ranged from moderate-to-heavy to very heavy, the latter conditions prevailing. The results show that this type of fitness activity has a high impact on cardiovascular function and suggest that it is not suitable for unfit or sedentary individuals, especially the middle aged or elderly, who are willing to begin a recreational physical activity programme.

Poor reliability of heart rate monitoring to assess oxygen uptake during field training.

The aim of this study was to quantify the error associated with the assessment of oxygen uptake (VO2) by heart rate (HR) monitoring in 15 athletes freely performing their training session. A laboratory-derived equation was used on the running track to calculate VO2 (VO2est) from HR. Oxygen uptake was also assessed by means of a portable gas analyzer (VO2real). Bland and Altman statistics were carried out in order to evaluate agreement between VO2real and VO2est. The excess in carbon dioxide production (CO2excess) was measured to test the hypothesis that the subject with the highest CO2excess had the highest VO2est - VO2real difference. VO 2real was on average 0.14 l x min (-1) below VO2est. The limits of agreement of this difference were between + 0.77 and - 0.48 l x min (-1). Thus, on average VO2real was overestimated by VO2est. Spearman non-parametric statistics found a significant correlation between CO2excess and VO2est - VO2real difference (R = 0.55, p = 0.031). This study demonstrates that the use of HR monitoring to assess VO2 during field training overestimates VO2real, especially when a substantial increase in CO2excess occurs. Therefore, this method should be used with care when an excessive amount of CO2 is produced as occurs in activities that involve the lactic acid anaerobic source of energy production.

Osteoprotegerin and bone mineral density in hemodiafiltration patients.

A newly identified cytokine, osteoprotegerin (OPG) appears to be involved in the regulation of bone remodeling. In vitro studies suggest that OPG, a soluble member of the TNF receptor family of proteins, inhibits osteoclastogenesis by interrupting the intercellular signaling between osteoblastic stromal cells and osteoclast progenitors. As patients with chronic renal failure (CRF) often have renal osteodystrophy (ROD), we investigated the role of osteoprotegerin (OPG) in ROD, and investigated whether there was any relationship between serum OPG, intact parathyroid (PTH) (iPTH), vitamin D, and trabecular bone. Serum OPG combined with iPTH might be a useful tool in the noninvasive diagnosis of ROD, at least in cases in which the range of PTH values compromises reliable diagnosis. Thirty-six patients on maintenance hemodiafiltration (HDF) and a control group of 36 age and sex matched healthy subjects with no known metabolic bone disease were studied. The following assays were made on serum: iPTH, osteocalcin (BGP), bone alkaline phosphatase, 25(OH)-cholecalciferol, calcium, phosphate, OPG, IGF-1, estradiol, and free testosterone. Serum Ca++, P, B-ALP, BGP, IGF-1, iPTH, and OPG levels were significantly higher in HDF patients than in controls, while DXA measurements and quantitative ultrasound (QUS) parameters were significantly lower. On grouping patients according to their mean OPG levels, we observed significantly lower serum IGF-1, vitamin D3 concentrations, and lumbar spine and hip bone mineral density in the high OPG groups. No correlation was found between OPG and bone turnover markers, whereas a negative correlation was found between serum OPG and IGF-1 levels (r=-0.64, p=0.032). Serum iPTH concentrations were positively correlated with bone alkaline phosphatase (B-ALP) (r=0.69, p=0.038) and BGP (r=0.92, p<0.001). The findings made suggest that an increase in OPG levels may be a compensatory response to elevated bone loss. The low bone mineral density (BMD) levels found in the high OPG group might have been due to the significant decrease in serum IGF-1 and vitamin D3 observed. In conclusion, the findings made in the present study demonstrate that increased OPG in hemodiafiltration patients is only partly due to decreased renal clearance. As it may partly reflect a compensatory response to increased bone loss, this parameter might be helpful in the identification of patients with a marked reduction in trabecular BMD.

Endothelial cytochrome P450 contributes to the acetylcholine-induced cardiodepression in isolated rat hearts.

AIMS: Acetylcholine (ACh) is known to reduce the contractility of the heart by acting on myocardial muscarinic M2 receptors. ACh induces also an endothelial-dependent vasodilatation by causing the release of nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factors from the vascular endothelium. It has been proposed that ACh elicits a hyperpolarization of the coronary endothelial cells which may be accompanied by the activation of cytochrome P450 (CYP) and the resulting release of epoxyeicosatrienoic acids (EETs). The study aims at investigating whether endothelial CYP is involved in the cardiodepression by ACh. METHODS AND RESULTS: In isolated rat hearts, cardiodepression by ACh (i.e. 25-30% reduction of developed left ventricular pressure) was partially attenuated either by inhibition of CYP with 1-aminobenzotriazole (ABT) or by endothelial dysfunction obtained with Triton X-100. No attenuation of cardiodepression was seen after nitric oxide synthase and cyclooxygenase inhibition by L-nitro-arginine methyl ester and indomethacin, respectively. CONCLUSION: The results suggest that the negative inotropic effect of ACh depends not only on a direct myocardial effect but also on the endothelial CYP activation.

Does reduction of blood prolactin levels reveal the activation of central dopaminergic pathways conveying reward in top athletes?

Prolactin blood levels are modulated directly by CNS via the known tubero-infundibular dopaminergic neurons which exert an inhibitory action on lactotrope cells in the hypophysis. Prolactin is devoid of peripheral negative feedback and via lesser known central pathways (e.g., mesolimbic and mesocortical) might be further tuned by means of appropriate stimuli (e.g., addictive drugs, gambling, exercise and so forth). Therefore, a prolactin test can be utilised to obtain an objective index to assess the compliance to exercise in men. This index may be used to identify the most suitable athlete for a given sport and mainly to survey exercise as rewarding behaviour in trained people. Prolactin was assessed in male top world windsurfers (WS) and in a control group of non-windsurfer trained subjects (CS) during an exercise simulating marine windsurfing. The result was that prolactin levels decreased significantly in WS with respect to CS when compared with pre-test levels (WS: -22.7%; P<0.05).

External mechanical work versus oxidative energy consumption ratio during a basketball field test.

BACKGROUND: A field test consisting of 5 continuous runs at the maximum speed possible, playing the ball, starting from the centre line to the basket with a final shot, was studied in order to obtain an index of mechanical work efficiency in basketball players (micro-index=Jmec/Joxy) and evaluate the correlation between micro-index and velocity, acceleration, mechanical power and lactacid anaerobic capacity, respectively. METHODS: Eight male basketball players were studied; Jmec was the external mechanical work output obtained by means of a video image analysis software which gave the potential and the kinetic translational energies of athletes running and jumping and their velocity, acceleration and mechanical power. By means of a telemetric device (Kosmed K4), for measuring O2 consumption ( VO2), we obtained oxidative work (Joxy). By using this device we also assessed the excess of CO2, which was considered an index of lactacid anaerobic capacity. RESULTS: Non-parametric Spearman statistics revealed a significant correlation between mu index and mean velocity (p<0.01, r=0.90), acceleration (p<0.05, r=0.78), mechanical power (p<0.05 r=0.76) and CO2 excess (p<0.01, r=0.95). Consequently athletes who had the best index of mechanical efficiency also had the best biomechanical quality and the greatest lactacid anaerobic capacity. CONCLUSIONS: This study strongly supports the hypothesis that in basketball anaerobic capacity is important in achieving high values of speed, acceleration, mechanical power and endurance velocity.

Bisphosphonates in the treatment of thalassemia-induced osteoporosis.

The aim of our randomized, placebo-controlled study was to investigate the effects of 2 years' daily oral administration of alendronate or intramuscular administration of clodronate every 10 days, on bone remodeling parameters and bone mineral density (BMD), safety and tolerability in a group of osteoporotic thalassemic patients. Twenty-five young patients (mean age 26.6 +/- 7.1 years) with beta-thalassemia major were randomly divided to receive placebo or 100 mg of clodronate intramuscularly every 10 days or 10 mg of alendronate per os daily. All patients took 500 mg of elemental calcium and 400 IU cholecalciferol in the evening at meal time. After 2 years, pyridinium crosslinks, which are bone resorption markers, did not differ significantly from baseline values in the placebo group, whereas they had decreased significantly in the clodronate and alendronate groups. Osteocalcin, a bone formation marker, did not change significantly in the placebo group, whereas it decreased slightly, but not significantly, in the clodronate and alendronate groups after 12 and 24 months. At the end of the study, the lumbar spine BMD had decreased significantly in the placebo group; it did not change significantly in the clodronate group; in the alendronate group it had increased but not significantly, whereas the increase was significant with respect to the placebo group. Femoral neck BMD decreased significantly in the placebo group; it did not change significantly in the clodronate group, but increased significantly in the alendronate group. No relevant side effects were recorded during our study. In conclusion, in patients with thalassemia-induced osteoporosis, the daily administration of alendronate significantly increases BMD, the most important predictor of the risk of fracture at several sites. Clodronate treatment at our dosage is ineffective in this pathology in spite of the good compliance of patients.

Osteoporosis and beta-thalassemia major: role of the IGF-I/IGFBP-III axis.

Patients with beta-thalassaemia major are susceptible to osteopenia due to several factors which interfere with bone remodeling. It is known that bone metabolism and skeletal consolidation result from a complex sequence of hormonal changes, where the concerted actions of GH, IGF-I and sex hormones and their receptors, are responsible for the timing and attainment of skeletal consolidation. IGF-I and the corresponding binding protein (IGFBP-III), markers of bone metabolism and lumbar and femoral neck BMD were measured in 28 adult patients, undergoing hormonal replacement and chelation therapy and a hypertransfusion program, with beta-thalassaemia major (12 males with mean age 22.5+/-3.1 and 16 females with mean age 27.5+/-8.2), and in 28 healthy volunteers matched for age, anthropometric features and sex to the patients. BMD values, both at lumbar and femoral neck level were significantly lower (p<0.001 and p<0.05) by 18.7 and 4.2% respectively, in patients than in the controls. Markers of bone resorption [pyridinoline (Pyr) 78.1+/-15.7 vs 47.5+/-11.2 pmol/pmol urinary creatinine, p<0.001 and deoxypyridinoline (D-Pyr) 21.9+/-3.5 vs 14.5+/-5.4 pmol/ micromol urinary creatinine, p<0.001] were higher in patients than in controls, whereas the marker of bone formation was slightly lower [osteocalcin (BGP) 3.8+/-0.6 vs 4.6+/-1.7 pmol/ml, p<0.05]. Plasma levels of IGF-I (21.07+/-5.12 vs 35.25+/-8.33 nmol/ml, p<0.001) and IGF binding protein III (IGFBP-III) (1.9+/-0.4 vs 2.5+/-0.1 mg/ml, p<0.001) were lower in patients than in controls and positively correlated with BMD L2-L4 (r=0.57, p<0.05 and r=0.47, p<0.05 respectively), BMD neck (r=0.40, p<0.05 and r=0.34, p<0.05 respectively) and BGP (r=0.52, p<0.05 and r=0.34, p<0.05 respectively). Our beta-thalassaemic patients, in spite of normalizing hemoglobin levels, adequate hormone replacement and chelation therapies, showed osteopenia and an unbalanced bone turnover with an increased resorptive phase and a decreased formation phase probably correlated to low levels of IGF-I and IGFBP-III observed in our study.

Haemodynamics during a complete exercise induced atrioventricular block.

The case is reported of an athlete who, during an exercise test, had a complete atrioventricular block without symptoms of cardiac output failure. Heart rate, stroke index, cardiac index, and myocardial contractility were monitored during the episode by an impedance cardiograph. The most important findings of this report are the continuous increase in stroke index, which compensated for the lack of heart rate response, and the normal cardiac index values achieved during the exercise. This stroke index response was mainly due to an increase in myocardial contractility.

Hemodynamic during a postexertional asystolia in a healthy athlete: a case study.

Hemodynamic events leading to spontaneous postexertional vasovagal syncope are not completely understood because of the lack of beat-to-beat data. We report a case study of a young athlete who undergoes a syncopal episode during the recovery period following a maximal cycle-ergometer test. The episode was monitored by an impedance cardiograph which can gather noninvasively beat-to-beat the flow of heart rate (HR), stroke volume (SV), cardiac output (CO), diastolic filling rate (SV/DT), and myocardial contractility index (PEP/LVET). The most important findings of this report are the dramatic reduction of SV/DT preceding the syncope, the increment of SV together with the reduction of HR preceding and following the syncope, the prompt recovery of CO values after the syncopal episode despite the bradycardia, and the reduction of PEP/LVET after the syncope. This report confirms the importance of active recovery immediately after strenuous exercise and supports the hypothesis that the reduction of SV/DT in the presence of an inotropic stimulation can trigger the vasovagal reaction.

Oscillations in stroke volume and cardiac output arising from oscillatory ventilation in humans.

Oscillations in the cardiovascular system have been observed in patients with periodic breathing. It is not clear whether these are driven by primary oscillations in the respiratory system or whether an intrinsic cardiovascular instability is required, as previous studies with subjects performing voluntary periodic breathing have failed to produce the cardiovascular oscillations. We investigated whether cardiovascular oscillations occurred in healthy controls performing voluntary periodic breathing. Six healthy subjects performed voluntary periodic breathing with guidance from a real-time computer display. We measured ventilation, end-tidal partial pressures of O2 (PO2) and CO2 (PCO2), heart rate, blood pressure (BP), arterial oxygen saturation and stroke volume and cardiac output by transthoracic impedance cardiography. Fourier analysis was used to quantify the size and phase of the periodic breathing-induced oscillations in these parameters. Periodic breathing (amplitude 30% of mean ventilation) induced oscillations in end-tidal PO2 (amplitude 0.8 kPa), end-tidal PCO2 (amplitude 0.3 kPa), R-R interval (amplitude 32.6 ms), systolic BP (amplitude 3 mmHg), diastolic BP (amplitude 3 mmHg), stroke volume (amplitude 8.0 ml, mean 79.5 ml) and cardiac output (amplitude 0.6 1, mean 5.9 l x min(-1)). The oscillations in stroke volume and cardiac output were nearly in phase with ventilation, with their peaks occurring 5.6 and 6.1 s, respectively, after the peak in ventilation. An oscillatory ventilatory pattern entrains the cardiovascular system in healthy controls into fluctuations, not only in heart rate and BP, but also in stroke volume and cardiac output.

Field test for mechanical efficiency evaluation in matching volleyball players.

Field tests were performed in 10 volleyball (VB) players (4 females and 6 males) in order to obtain an index of mechanical work efficiency (mu' = Wmec/Woxy) while athletes played a game. Wmec was the mechanical work output, obtained by means of home made video image analysis software, by summing potential, kinetic translational and kinetic rotational energies of running and jumping athletes. Woxy was the oxidative energy consumption obtained from O2 consumption (VO2) by a telemetry device (Cosmed K2) that also gave values of pulmonary ventilation (VE) and heart rate (HR). VB were studied at rest before a game (R), during attacking phases (A) and during defensive phases (D). At R were found: VE = 11 +/- 1 l x min(-1), HR = 78 +/- 7b x min(-1), VO2 = 3.71 +/- 1.1 ml x kg(-1) x min(-1), Woxy = 75.1 +/- 22.3 J x kg(-1) x min(-1). During A all variables increased: VE = 49 +/- 6l x min(-1), HR = 149 +/- 15 b x min(-1), VO2 = 23.1 +/- 3.3ml x kg(-1) x min(-1), Woxy = 482.8 +/- 69.0 J x kg(-1) x min(-1), and Wmec 275.5 +/- 57.0 J x kg(-1) x min(-1) with mu'=0.57 +/- 0.09. In D HR (-9%), VE, VO2 and Woxy (-18%) were reduced when compared to A, decreasing mu' to 0.21 +/- 0.05. On the other hand mu' was found higher than 0.25 during A indicating an anaerobic contribution to energy expenditure; in D the mu' lower than 0.25 indicated a restoration of anaerobic energy sources. It might be proposed that a greater difference in mu' values between A and D also means a higher anaerobic energy contribution to the volleyball game.

Cognitive assessment of infants with West syndrome: how useful is it for diagnosis and prognosis?

Thirty-one infants with West syndrome were followed up. Their cognitive competence was assessed before the onset of the disease, and during and after the acute stage. Two kinds of cognitive impairment were identified: the first was transitory, linked to the acute stage and mainly consisting of arousal disturbances; the second was the well known long-term sequela. It is not possible to exclude the aetiological role of a persistent, severe epileptic change: however, this study emphasizes the prognostic value of previous mental impairment. In serial cognitive assessment during the acute stage, the progression of the developmental quotient was the best indicator of a good mental outcome, and vice versa.

Marital discord and child behavior problems: a meta-analysis.

The relation of marital discord to the behavior problems of children was examined through a meta-analysis of the results of prior research. The sample comprised all published studies through 1988 that met criteria for the meta-analysis and that could be located through a combined computer and hand search of the literature. Marital discord included conflict, disharmony, and lack of agreement between currently married parents. Child behavior problems were defined as conduct problems, excluding internalized difficulties, such as anxiety. Four hypotheses were drawn from recent reviews of studies on this topic: The relation between marital conflict and child behavior problems will be (1) positive overall and will be stronger (2) for boys than for girls, (3) for cases based entirely on parent self-report data than for cases involving external sources of data, (4) for clinic than for nonclinic families. Results supported the first three hypotheses. Little evidence was found for an association between marital conflict and the behavior problems of girls. Findings are discussed in terms of their methodological and theoretical implications and in relation to a recent review of research on sex differences in children's reactions to divorce.

Functional hyperthermia due to central dopaminergic impairment.

The clinical cases described are characterized by rigidity, mutism and hyperthermia, with cutaneous pallor and diaphoresis. This symptomatology marks the "malignant neuroleptic syndrome" and can be found, at times, in parkinsonians on "drug holiday". The cases described, which comprehend patients with both disorders, lead us to a single pathogenetic hypothesis: a central dopaminergic impairment. Hyperthermia, secondary to functional hypothalamic deficiency, is maintained by defective heat dispersion due to the lack of cutaneous vasodilation.

Parkinson-like side effects during prolonged treatment with flunarizine.

Forty-two elderly patients affected by a generic cerebrovascular disease developed a parkinsonian syndrome after prolonged treatment with flunarizine. Following flunarizine withdrawal the extrapyramidal symptomatology remitted slowly and progressively for 12 weeks, leading to the belief that the observed parkinsonian syndrome is directly linked to the chronic use of this compound. Similar side effects are not described in young populations, however. A periodic flunarizine discontinuation in chronically treated subjects aged 65 or more is suggested.