Biomedical subjects

Antonio Sastre

Publications and source records attributed to Antonio Sastre.

9 recordsLinked to original sources

PubMed2006

Effects of omega-3 fatty acids on heart rate in cardiac transplant recipients.

Omega-3 fatty acid (n-3 FA) consumption has been linked to reductions in the risk of death from coronary heart disease and, recently, to lower heart rates (HRs). The investigators previously observed a reduction of 5 beats/min in HR in patients with coronary heart disease given n-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) for 4 months. Reductions in HR may be explained by enhanced vagal tone, influences on cardiac voltage-gated ion channels, or both. The hypothesis that n-3 FAs would affect HR independent of vagal input was investigated by studying the effects of n-3 FA supplementation on HR in patients with denervated hearts after orthotopic heart transplantation. Electrocardiographic data obtained in 2 prospective trials in which 18 heart transplant recipients received n-3 FA supplementation (1 to 3.4 g/day) for 4 to 6 months were collected. Patients were studied 4.4 +/- 2.6 years after transplantation. HR, QRS complex, and QTc duration were determined before and after treatment. Pretreatment HR was reduced from 88 +/- 14 to 83 +/- 13 beats/min after n-3 FA treatment (p = 0.016). QRS duration increased from 107 +/- 24 to 117 +/- 25 ms (p = 0.001). QTc duration remained unchanged from baseline (427 +/- 34 ms) to study end (424 +/- 39 ms). In conclusion, n-3 FA supplementation reduced HR and prolonged QRS duration in heart transplant recipients who were presumably devoid of vagal innervation. These findings suggest that n-3 FAs may modify electrophysiologic properties of the myocardium itself.

Docosahexaenoic Acids↗

PubMed2006

Effects of omega-3 fatty acids on resting heart rate, heart rate recovery after exercise, and heart rate variability in men with healed myocardial infarctions and depressed ejection fractions.

We explored possible mechanisms by which recommended intakes of omega-3 fatty acids may decrease the risk for sudden cardiac death in patients with documented coronary heart disease. The cardioprotective effects of omega-3 fatty acids have been documented in epidemiologic and randomized controlled trials. These fatty acids are presumed to decrease susceptibility to fatal arrhythmias, but whether this is mediated by classic risk factors or direct cardiac mechanisms is not known. Eighteen white men with a history of myocardial infarction and ejection fractions <40% were randomized to placebo or omega-3 fatty acids (585 mg of docosahexaenoic acid and 225 mg of eicosapentaenoic acid) for two 4-month periods in a crossover design. At the end of each period, heart rate (HR), HR variability, and rate of HR recovery after exercise were determined, as were effects on arterial compliance, blood pressure, cardiac function, and fasting serum levels of lipids and inflammatory markers. Omega-3 fatty acids decreased HR at rest from 73 +/- 13 to 68 +/- 13 beats/min (p <0.0001) and improved 1-minute HR recovery after exercise (-27 +/- 10 to -32 +/- 12 beats/min, p <0.01). HR variability in the high-frequency band increased (p <0.02), but no change was noted in overall HR variability. There were no significant effects on blood pressure, arterial compliance, lipids, or inflammatory markers. These changes are consistent with an increase in vagal activity and may in part explain the observed decrease in risk for sudden cardiac death seen with omega-3 fatty acid supplementation.

Aged↗

PubMed2003

Occupational exposure to extremely low frequency magnetic fields and mortality from cardiovascular disease.

The authors evaluated the relation between occupational exposure to extremely low frequency (ELF) magnetic fields and mortality from cardiovascular diseases. The study was based on 27,790 subjects from the Swedish Twin Registry. Exposure to ELF magnetic fields was assessed by linking occupation reported in 1967 or 1973 to a job exposure matrix. Four levels of exposure were related to cause-specific mortality through 1996, and primary and contributing causes of death were considered. The authors estimated relative risks by Cox regression, with adjustment for several cardiovascular disease risk indicators. The authors calculated the synergy index to evaluate potential interaction between exposure to ELF magnetic fields (>0.2 microT) and genetic susceptibility to acute myocardial infarction (AMI). Arrhythmia-related death, ischemic heart disease other than AMI, and atherosclerosis showed no association with ELF magnetic fields. The authors found a low-level increase in AMI risk in the highest exposure group (relative risk=1.3, 95% confidence interval: 0.9, 1.9) and suggestions of an exposure-response relation (p=0.02). A synergy index of 2.7 (95% confidence interval: 1.1, 6.6) in monozygotic twins indicated that the risk of AMI was strengthened among ELF magnetic field-exposed subjects with genetic susceptibility to the disease. The results for AMI corroborate previous findings from the United States. The unusual opportunity to include genetic susceptibility in the present analyses showed that evaluations of effect modification in vulnerable subjects are warranted in ELF magnetic field research.

Adult↗

PubMed2002

Occupational magnetic field exposure and cardiovascular mortality in a cohort of electric utility workers.

In electric utility workers, occupational exposure to magnetic fields has previously been associated with mortality from acute myocardial infarction (AMI) and arrhythmia but not from chronic coronary heart disease (CCHD) or atherosclerosis. To investigate these health endpoints further, the authors examined mortality from AMI (n = 407) and CCHD (n = 369) in a cohort of 35,391 male workers at the Southern California Edison Company between 1960 and 1992. Exposure was estimated according to duration of employment in occupations associated with high levels of magnetic field exposure and was calculated as cumulative exposure to magnetic fields expressed in micro-Tesla-years. Adjustment was made for age, calendar time, socioeconomic status, race, and worker status (active or inactive). The authors found that men working longer in high-exposure occupations or working as electricians, linemen, or power plant operators had no increased risk of dying from either AMI or CCHD compared with men who never worked in high-exposure occupations. For cumulative exposure, no association was observed with mortality from AMI (rate ratio per 1 micro T-year = 1.01, 95% confidence interval: 0.99, 1.02) or CCHD (rate ratio per 1 micro T-year = 1.00, 95% confidence interval: 0.99, 1.02). These results, indicating no exposure-related risk increase for AMI mortality, do not confirm previous results.

Adult↗

PubMed2002

Physiological and performance effects of pyridostigmine bromide in healthy volunteers: a dose-response study.

RATIONALE: Questions have been raised about the role pyridostigmine bromide (PB) plays in the etiology of Gulf War veterans' illnesses. There is a need to understand better the physiological and behavioral effects of this drug, particularly at the 30-mg/8-h regimen recommended by the US Military. OBJECTIVE. To perform a double-blind, cross-over, dose-response study of PB in 67 healthy, young volunteers (31 women, 36 men). METHODS: Volunteers were initially trained on a standardized test battery. Supervised administration of placebo (PL) and PB (every 8 h/5 days) occurred in each of two dosing weeks, separated by a non-dosing week. One group received 30 mg PB and PL, and the other 60 mg PB and PL. In each dosing week, the battery was performed after the first pill and again when steady-state plasma PB levels were achieved. RESULTS: PB was associated with an overall improvement in reaction time on tests of memory and attention, and with a reduction in RMS error on a tracking task. PB slowed heart rate and decreased the high frequency component of heart rate variability (HF HRV). Dose-response effects were found only for HF HRV, and RMS error. The extent of cholinesterase inhibition was directly related to the magnitude of the HF HRV decrease, and was predicted by the weight-normalized PB dose. Cholinesterase inhibition was not related to the extent or severity of reported drug side effects. CONCLUSIONS: PB does not appear to have detrimental physiological or performance consequences at the recommended 30-mg dose, or at twice that dose, when evaluated under non-stressful laboratory conditions.

Administration, Oral↗

PubMed2002

Human EEG responses to controlled alterations of the Earth's magnetic field.

OBJECTIVES: Examine the effects of controlled changes in the Earth's magnetic field on electroencephalogram (EEG) and subjective report. METHODS: Fifty volunteers were exposed double-blind to changes in field magnitude, angle of inclination, and angle of deviation. Volunteers were also exposed to magnetic field conditions found near the North and South Pole. EEG recorded over temporal and occipital sites was compared across 4s baseline, field exposure, and no-change control trials. RESULTS: No EEG spectral differences as a function of gender or recording site were found. Geomagnetic field alterations had no effect on total energy (0.5-42 Hz), energy within traditional EEG analysis bands, or on the 95% spectral edge. Most volunteers reported no sensations; others reported non-specific symptoms unrelated to type of field change. DISCUSSION: Three hypothesized field detection mechanisms were not supported: (1) mechanical reception through torque exerted on the ferromagnetic material magnetite; (2) movement-induced induction of an electric field in the body; and (3) enhanced sensitivity due to alterations in the rates of chemical reactions involving electron spin states. CONCLUSIONS: Humans have little ability to detect brief alterations in the geomagnetic field, even if these alteration are of a large magnitude.

Adult↗

PubMed2002

Candidate sites of action for microdosimetry associated with exposure to extremely-low-frequency magnetic fields, electric fields and contact currents.

Recent advances enable one to apply numerical techniques to anatomically-correct human models to compute current densities and electric fields in tissue due to exposure to electric fields, magnetic fields, or contact currents. These methods have proved to be informative in estimating exceedance of basic restrictions prescribed by exposure guideline organizations. To date, the analyses have been conducted with a resolution on the order of millimeters. However, these techniques have future roles to play at higher levels of resolution at those sites in target tissues suspected of transducing local electric fields into biological responses. Two specific cases in which high resolution "microdosimetry" would yield value involve (a) residential settings and childhood leukemia and (b) worker exposure and cardiovascular disease. Recent research suggests that residential contact currents on the order of microamperes can produce biologically significant dose (expressed as the local electric field) to the bone marrow of a child. Microdosimetry would focus on pluripotent progenitor cells resident in the marrow compartment, as well as anatomic features that distinguish a child's from an adult's marrow. Laboratory and epidemiologic research has suggested that magnetic field exposure may affect heart rate variability, a measure reflective of autonomic nervous system control of cardiac activity. Given the physical attributes of the central nervous system and the sites that could serve as substrates for field interactions, future microdosimetry addressing heart rate variability effects may be well-advised to focus on the electrically excitable dendritic arborizations of neurons. In both cases, microdosimetry will help shed light on primary interactions in tissue.

Adult↗

PubMed2002

Pacemaker interference by magnetic fields at power line frequencies.

Human exposure to external 50/60-Hz electric and magnetic fields induces electric fields within the body. These induced fields can cause interference with implanted pacemakers. In the case of exposure to magnetic fields, the pacemaker leads are subject to induced electromotive forces, with current return paths being provided by the conducting body tissues. Modern computing resources used in conjunction with millimeter-scale human body conductivity models make numerical modeling a viable technique for examining any such interference. In this paper, an existing well-verified scalar-potential finite-difference frequency-domain code is modified to handle thin conducting wires embedded in the body. The effects of each wire can be included numerically by a simple modification to the existing code. Results are computed for two pacemaker lead insertion paths, terminating at either atrial or ventricular electrodes in the heart. Computations are performed for three orthogonal 60-Hz magnetic field orientations. Comparison with simplified estimates from Faraday's law applied directly to extracorporeal loops representing unipolar leads underscores problems associated with this simplified approach. Numerically estimated electromagnetic interference (EMI) levels under the worst case scenarios are about 40 microT for atrial electrodes, and 140 microT for ventricular electrodes. These methods could also be applied to studying EMI with other implanted devices such as cardiac defibrillators.

Electromagnetic Fields↗

PubMed2002

Naturally occurring mutation, Asp70his, in human butyrylcholinesterase.

BACKGROUND: People with genetic variants of butyrylcholinesterase can have hours of prolonged apnoea after a normal dose of succinylcholine or mivacurium. METHODS: Serum samples from 308 persons living in mid-USA were phenotyped to identify the atypical and fluoride variants. 308 samples were analysed for the K variant by DNA amplification, digestion with Mae III and gel electrophoresis. Amplified DNA from 16 samples was sequenced to identify the D70G, T243M and D70H mutations. Values for kcat and Km were determined for the D70H mutant BChE expressed in 293T cells. RESULTS: A new mutation, Asp70His, was identified. This mutation is located in the peripheral anionic site of butyrylcholinesterase, where it causes a 10-fold decrease in binding affinity for positively charged substrates. CONCLUSION: People homozygous for the Asp70His mutation are expected to have prolonged apnoea in response to succinylcholine or mivacurium, similar to people with the Asp70Gly mutation.

Amino Acid Substitution↗