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Biomedical subjects

Peretz Lavie

Publications and source records attributed to Peretz Lavie.

At least 19 recordsLinked to original sources
PubMed2006

Ischemic preconditioning as a possible explanation for the age decline relative mortality in sleep apnea.

Breathing disorders in sleep are prevalent phenomena profoundly affecting the cardiovascular system. Mortality studies of sleep apnea patients revealed maximum risk of dying in younger patients and a pronounced age-decline in relative mortality reaching non significant levels in patients older than 50 years. We hypothesize that the age decline mortality risk in sleep apnea can be explained by cardiovascular and cerebrovascular protection conferred by ischemic preconditioning resulting from the nocturnal cycles of hypoxia-reoxygenation. The association of ischemic preconditioning with increase levels of vascular endothelial growth factor, increased production of oxygen reactive species, heat shock proteins, adenosine, and TNF-alpha, all demonstrated in sleep apnea, provide preliminary support to our hypothesis.

Age Factors↗
PubMed2005

Effect of sleep apnea on cognition and mood.

Obstructive sleep apnea syndrome (OSAS) is a common disorder in adults and children, which is characterized by repetitive transient reversible upper airway obstructions during sleep. Due to disrupted sleep architecture and intermittent hypoxemia, OSAS leads to impaired daytime functioning in various neuropsychological and affective domains. The most common abnormalities are executive dysfunction, impaired vigilance, depression, and possibly anxiety and, in children, hyperactivity. Optimal treatment of OSAS with continuous positive airway pressure may reverse the cognitive and affective dysfunction, however, in some patients a residual impairment persists. This persistent deficit, despite effective treatment, raises the possibility of a remaining subtle structural brain damage; such damage has been demonstrated through the use of sensitive functional and other neuroimaging techniques. Prefrontal cortical damage may underlie the cognitive dysfunction in OSAS. Early recognition and treatment may prevent this untoward effect of OSAS.

Cognition Disorders↗
PubMed2005

The effects of sleep loss on medical residents' emotional reactions to work events: a cognitive-energy model.

STUDY OBJECTIVES: This study investigated the relationship between sleep loss and emotional reactivity in medical residents. We hypothesized that this relationship is shaped by the effect of sleep loss on cog-nitive-energy resources required for coping with goal-disruptive events or for capitalizing on new opportunities offered by goal-enhancing events. SETTINGS: 15 medical wards in 4 large hospitals in Israel. PARTICIPANTS: 78 medical residents, 67% men, aged 26 to 39 years. DESIGN: Actigraphic sleep-wake cycles were measured for 5- to 7-day periods, surrounding nightshifts, every 6 months, covering the first 2 years of residency. During each study period, emotional reactivity was investigated using the experience-sampling methodology by which residents received 3 phone calls at random times during their working day for 3 consecutive days. These calls reminded them to fill out brief questionnaires concerning change of circumstances over the previous 15 minutes and to rate their emotional response to these circumstances using the Positive Affect and Negative Affect Scales. Fatigue at those times was measured by a subscale of the Profile of Mood States. MEASUREMENTS AND RESULTS: Multilevel regression analysis was used to determine the influence of sleep duration and sleep fragmentation on the emotional reactions to goal-disruptive and goal-enhancing daytime events. We found that sleep loss intensified negative emotions and fatigue following daytime disruptive events, while positive emotion was mitigated following goal-enhancing events. Sleep loss also resulted in an overall elevated baseline for positive emotion. CONCLUSIONS: Sleep loss amplifies the negative emotive effects of disruptive events while reducing the positive effect of goal-enhancing events. Methodologically, the study highlights the utility and advantages of event-level analysis as opposed to the current practice of random sampling of emotion states during waking hours, disregarding contextual factors associated with purposeful, goal-oriented behavior episodes.

Adult↗
PubMed2005

Endothelial dysfunction in obstructive sleep apnea measured by peripheral arterial tone response in the finger to reactive hyperemia.

STUDY OBJECTIVE: The aim of this study was to investigate endothelial functioning in sleep apnea patients using a novel plethysmographic device that monitors peripheral arterial tone response in the finger to reactive hyperemia induced by forearm ischemia. PARTICIPANTS: Forty-six sleep apnea patients, 74.0% men, mean age 46.8 +/- 9.3 years, and 17 control subjects without sleep apnea, 64.7% men, mean age 47.1 +/- 6.7 years. SETTING: Eight-bed Technion Sleep Medicine Center in Haifa, Israel. DESIGN: Endothelial functioning assessed by the reactive hyperemia peripheral arterial tone index was measured twice, before sleep and after waking from sleep monitored by polysomnography in the laboratory. The reactive hyperemia peripheral arterial tone index was calculated as the average amplitude of the peripheral arterial tone signal after the cuff deflation divided by the average amplitude before the cuff inflation. RESULTS: Morning index of endothelial functioning was significantly lower in patients with moderate to severe sleep apnea (apnea-hypopnea index > or = 30) than in patients with mild sleep apnea (30 < apnea-hypopnea index < or = 10) and in the control group without sleep apnea (apnea-hypopnea index < 10). The morning index was significantly inversely correlated with apnea-hypopnea index. Patients with a history of hypertension or cardiovascular disease had significantly lower morning and evening indexes of endothelial functioning than patients without such a history. Multivariate analysis revealed that apnea-hypopnea index and sleep efficiency were significant predictors of the morning index. CONCLUSION: Measurements of the response of the peripheral arterial tone in the finger to reactive hyperemia can be used as a substitute for the brachial artery ultrasound technique to measure endothelial functioning in patients with sleep apnea.

Adult↗
PubMed2005

Lymphocyte activation as a possible measure of atherosclerotic risk in patients with sleep apnea.

Obstructive sleep apnea (OSA), a breathing disorder in sleep characterized by intermittent hypoxia and sleep fragmentation, constitutes an independent risk factor for cardiovascular morbidity. Investigating how this breathing disorder modulates immune responses may facilitate understanding one of the risk factors for atherosclerosis. T cells play a significant role in atherogenesis and plaque development via cytokine production and by directly contributing to vascular injury. Using flow cytometry and chromium release assays, we found that CD4 and CD8 T cells of OSA patients undergo phenotypic and functional changes and acquire cytotoxic capabilities. Thus, a shift in CD4 and CD8 T cells toward type 2 cytokine dominance with increased IL-4 expression was noted. IL-10 expression in T cells was negatively correlated with the severity of OSA, as determined by the apnea-hypopnea index (AHI), whereas TNF-alpha was positively correlated. CD8 T cells of OSA patients expressed a fourfold increase in TNF-alpha and CD40 ligand (CD40L), and exhibited an increased OSA severity-dependent cytotoxicity against endothelial cells. The percentage of CD4(+)CD28(null) and cytotoxicity of CD4 T lymphocytes were also significantly higher in OSA patients than in controls. Nasal continuous positive airway pressure (nCPAP) treatment, which ameliorated the severity of OSA, significantly lowered TNF-alpha and CD40L expression, and decreased cytotoxicity in CD8 T cells. In conclusion, increased cytotoxicity and cytokine imbalance in CD4 and CD8 T cells may be involved in atherogenesis in OSA. Nasal CPAP treatment ameliorates some lymphocyte dysfunctions and thus may moderate some atherogenic pathways.

Adult↗
PubMed2004

Daily rhythms in plasma levels of homocysteine.

BACKGROUND: There is accumulated evidence that plasma concentration of the sulfur-containing amino-acid homocysteine (Hcy) is a prognostic marker for cardiovascular morbidity and mortality. Both fasting levels of Hcy and post methionine loading levels are used as prognostic markers. The aim of the present study was to investigate the existence of a daily rhythm in plasma Hcy under strictly controlled nutritional and sleep-wake conditions. We also investigated if the time during which methionine loading is performed, i.e., morning or evening, had a different effect on the resultant plasma Hcy concentration. METHODS: Six healthy men aged 23-26 years participated in 4 experiments. In the first and second experiments, the daily rhythm in Hcy as well as in other amino acids was investigated under a normal or an inverse sleep-wake cycle. In the third and fourth, Hcy concentrations were investigated after a morning and evening methionine loading. To standardize food consumption in the first two experiments, subjects received every 3 hours 150 ml of specially designed low-protein liquid food (Ensure(R) formula). RESULTS: In both the first and second experiments there was a significant daily rhythm in Hcy concentrations with a mid-day nadir and a nocturnal peak. Strikingly different 24-h patterns were observed in methionine, leucine, isoleucine and tyrosine. In all, the 24-h curves revealed a strong influence of both the sleep-wake cycle and the feeding schedule. Methionine loading resulted in increased plasma Hcy levels during both morning and evening experiments, which were not significantly different from each other. CONCLUSIONS: There is a daily rhythm in plasma concentration of the amino acid Hcy, and this rhythm is independent of sleep-wake and food consumption. In view of the fact that increased Hcy concentrations may be associated with increased cardiovascular risks, these findings may have clinical implications for the health of rotating shift workers.

Journal Article↗
PubMed2004

Evidence for lipid peroxidation in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSA) is associated with an increased rate of cardiovascular morbidity, which has been suggested to be related to oxidative stress. The present study investigated the concentration of lipid peroxidation biomarkers in patients with OSA in comparison with nonapneic controls and the effects of treatment with nasal continuous positive airway pressure (nCPAP) on these biomarkers. DESIGN: In Experiment 1, morning plasma levels of the oxidative-stress biomarkers, thiobarbituric reactive substances (TBARS) and peroxides (PD), and of the antioxidant protective enzyme paraxonase-1 (PON1), were measured in OSA patients with and without cardiovascular disease (CVD) and in nonapneic controls after an overnight fasting. The concentrations of the biomarkers were compared between patients and controls and were correlated with respiratory disturbance index (RDI). In Experiment 2, TBARS and PD were measured at hourly intervals during sleep in sleep-apnea patients before and after nCPAP treatment as well as in controls. PATIENTS: In the first experiment, 114 consecutive patients with sleep apnea, 55 without (+OSA/-CVD) and 59 with CVD (+OSA/+CVD), and 30 nonapneic controls were investigated. Nine patients and 6 controls participated in Experiment 2. Five of the patients were also studied 9.3 +/- 3.9 months after nCPAP treatment. MEASUREMENTS AND RESULTS: Morning levels of TBARS and PD were found to be significantly higher in both groups of OSA patients than in controls. The PON1 was lower in +OSA/+CVD patients than in controls and +OSA/-CVD patients, but the difference between the 2 OSA groups bordered on statistical significance. The concentrations of TBARS and PD were significantly positively correlated with RDI (.43, P < .0001 and .36, P < .0002, respectively), while a negative correlation was found between RDI and PON1 activity (-.24, P < .01). Stepwise regression analysis revealed that RDI was an independent significant predictor of all 3 lipid-peroxidation biomarkers. In the second experiment, nocturnal levels of TBARS and PD were significantly higher in sleep-apnea patients than in controls and were significantly lowered by nCPAP treatment. CONCLUSIONS: These results support the existence of an increased state of oxidative stress in OSA and its possible involvement in cardiovascular morbidity.

Adult↗
PubMed2004

Effects of task difficulty and invested mental effort on peripheral vasoconstriction.

We ran two experiments to investigate whether peripheral arterial tone reflects changes in mental effort. Finger pulse wave amplitude, interpulse interval, and pulse variability in the mid- and high-frequency bands were recorded by means of a newly developed finger plethysmograph during both rest and cognitive performance. Using a modified version of the Sternberg memory task, we selectively manipulated either the difficulty of the task (Experiment 1) or the subjects' level of engagement in the task (Experiment 2). We found a significant difference in finger pulse wave amplitude between rest and task periods, suggesting that the measure reflects changes in sympathetic activity due to task engagement. In addition, our results suggest that reduced pulse wave amplitude, signaling vasoconstriction, occurs when subjects are investing effort.

Adult↗
PubMed2003

Haptoglobin polymorphism is a risk factor for cardiovascular disease in patients with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Obstructive sleep apnea syndrome is associated with a marked increase in the risk for cardiovascular disease. Increased oxidative stress and leukocyte adhesiveness have been implicated as fundamental pathophysiologic mechanisms underlying the increased susceptibility in these patients. Haptoglobin is an antioxidant and immunomodulatory protein encoded by 2 alleles with profoundly different biophysical and biochemical properties. We therefore sought to determine if the haptoglobin phenotype was a determinant of cardiovascular disease in patients with obstructive sleep apnea syndrome. DESIGN: Haptoglobin phenotype was determined by gel electrophoresis in 465 patients with and 757 individuals without obstructive sleep apnea syndrome. SETTING: Eight-bed Technion Sleep Medicine Center in Haifa, serving the northern part of Israel. PARTICIPANTS: Patients referred for sleep recordings because of suspected breathing disorders in sleep and healthy industry workers. MEASUREMENTS AND RESULTS: Patients with obstructive sleep apnea syndrome and cardiovascular disease had a significantly different distribution of the 3 haptoglobin phenotypes as compared to patients with obstructive sleep apnea syndrome but without cardiovascular disease. No difference in the haptoglobin phenotype frequency was found between controls with and without cardiovascular disease. Log linear analysis revealed a significant interaction effect of haptoglobin phenotype and the presence of sleep apnea on the presence of cardiovascular disease. Logistic regression analysis revealed that the risk of cardiovascular disease in sleep apnea patients younger than 55 years with haptoglobin 2-2 was 2.32-fold higher than in their counterparts with haptoglobin 2-1. CONCLUSIONS: These results suggest that haptoglobin phenotype is an important risk factor in determining susceptibility to cardiovascular disease in obstructive sleep apnea syndrome, which may be mediated by the decreased antioxidant and antiinflammatory actions of the haptoglobin 2 allelic protein product.

Alleles↗
PubMed2003

The KickStrip: a novel testing device for periodic limb movement disorder.

STUDY OBJECTIVES: In light of the ongoing debate over the clinical significance of periodic limb movement disorder (PLMD) and its monitoring in overnight sleep studies, we introduce a novel, portable, low-cost device for PLMD testing. The KickStrip is a disposable device, which includes a movement sensor, a central processing unit with real-time software, and a display. In the present study, the KickStrip final score (Kscore) is validated against the traditional periodic limb movement index (PLMI) based on overnight recordings in the sleep laboratory. DEISGN: Patients underwent full polysomnographic recordings concomitantly with the use of the KickStrip for a single night. SETTING: Sleep Disorders Unit at Loewenstein Rehabilitation Hospital and Sleep Medicine Center at Rambam Medical Center, Israel. PATIENTS: Eighty-two patients referred for overnight sleep recordings due to sleep disturbance of any kind. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The Kscores were collected and the PLMI computed for each leg separately. Pearson correlations between Kscores and PLMI ranged between r = 0.83 to r = 0.88 (p < 0.001). Sensitivity and specificity values of the Kscores for increasing PLMD thresholds showed sensitivity ranging from 50% to 100% and specificity ranging from 83% to 100%. Receiver operating characteristic curves showed area-under-the-curve values ranging from 82% to 92%. Bland-Altman plot showed high agreement between the methods. CONCLUSIONS: Comparisons between the Kscores and the traditional PLMI show increased accuracy with severity level and excellent agreement. The KickStrip is a valuable tool for PLMD testing for both clinical and research purposes.

Adolescent↗
PubMed2003

Phenotypic and functional characterization of blood gammadelta T cells in sleep apnea.

Hypoxia-induced lymphocyte dysfunction may be implicated in endothelial cell damage in obstructive sleep apnea (OSA) syndrome. gammadelta T cells' unique migration, cytotoxic features, and accumulation in atherosclerotic plaques are considered critical in cardiovascular disorders. We characterized the phenotype, cytokine profile, adhesion properties, and cytotoxicity of gammadelta T cells in patients with OSA and control subjects. The following is a summary of our major findings regarding OSA gammadelta T cells: (1) a significant increase in the expression of the inhibitory natural killer B1 receptors was found; (2) the intracellular content of proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin-8 was increased, and the content of the antiinflammatory cytokine interleukin-10 was decreased; (3) gammadelta T cells of patients with OSA adhered significantly more avidly to nonactivated endothelial cells in culture than those of control subjects; (4) L-selectin expression was higher; (5) anti-E/P-selectin antibodies and anti-TNF-alpha antibodies decreased the adhesion index of OSA gammadelta T lymphocytes/endothelial cells but not of control subjects; and (6) cytotoxicity of OSA gammadelta T lymphocytes against endothelial cells in culture was 2.5-fold higher than that of control subjects and could be prevented by pretreatment with anti-TNF-alpha. Collectively these data implicate gammadelta T lymphocyte function in atherogenic sequelae in OSA.

Arteriosclerosis↗