Showing papers by "Peretz Lavie published in 1999"

Interindividual Heterogeneity in the Hypoxic Regulation of VEGF Significance for the Development of the Coronary Artery Collateral Circulation

Abstract: Background—The coronary artery collateral circulation may be beneficial in protecting against myocardial ischemia and necrosis. However, there is a tremendous interindividual variability in the degree of new collateral formation in patients with coronary artery disease. The basis for this interindividual heterogeneity is not understood. In this study we test the hypothesis that failure to generate collateral vessels is associated with a failure to appropriately induce with hypoxia or ischemia the angiogenic factor, vascular endothelial growth factor (VEGF). Methods and Results—We correlated the VEGF response to hypoxia in the monocytes harvested from patients with coronary artery disease with the presence of collaterals visualized during routine angiography. We found that there was a highly significant difference in the hypoxic induction of VEGF in patients with no collaterals compared with patients with some collaterals (mean fold induction 1.9±0.2 versus 3.2±0.3, P<0.0001). After subjecting the data to ...

Periodic, profound peripheral vasoconstriction--a new marker of obstructive sleep apnea.

Abstract: We report a novel approach to the determination of sleep apnea based on measuring the peripheral circulatory responses in a primary condition of disordered breathing. The apparatus is a finger plethysmograph coupled to a constant volume, variable pressure, pneumatic system. The plethysmograph's tip (measurement site) is composed of two parallel opposing longitudinal half thimbles, which is attached to a contiguous annular cuff. Each compartment consists of an internal membrane surrounded by an outer rigid wall. These provide a uniform pressure field and impart a two-point locking action preventing axial and longitudinal motion of the finger. Subdiastolic pressure is applied to prevent venous pooling, engorgement, and stasis, to inhibit retrograde venous shock wave propagation and partially unload arterial wall tension. The annular cuff extends the effective boundary of the pressure field beyond the measuring site. In 42 patients with Obstructive Sleep Apnea Syndrome (OSAS) profound, transient vasoconstriction and tachycardia usually of a periodic nature, were clearly seen with each apneic event, possibly related to transient arousal. Good agreement was found between standard total apnea-hypopnea scoring, 129.5+/-22.4 (Mean +/- SEM), and transient vasoconstriction and tachycardia events, 121.2+/-19.4 (R = .92, p<.0001). We conclude that the finger tip exemplifies the scope of peripheral vascular responsiveness due to its high density of alpha sympathetic innervation, and its high degree of blood flow rate lability. Given that elevated peripheral resistance and tightly linked transient heart rate elevation is a consistent part of the hemodynamic response to arousal and OSAS, we believe that pulsatile finger blood flow patterns can be clearly diagnostic of OSAS and other sleep-disordered breathing conditions.

Relationship between rapid eye movement sleep and testosterone secretion in normal men.

Abstract: The relation between the pituitary-gonadal hormones' rhythm and sleep physiology in men is not fully elucidated. To examine whether the reproductive hormones are correlated with sleep architecture, we determined the nocturnal serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in six healthy young men. Serum hormone levels were obtained every 15 minutes from 1900 to 0700 hours with simultaneous polysomnographic sleep recordings. Hourly testosterone levels were lowest when subjects were awake (1900-2200 hours) than during sleep (2300-0700 hours). Testosterone nocturnal rise antedated the first REM by about 90 minutes. The rise in testosterone levels was slower when REM latency was longer. Mean nocturnal testosterone levels did not correlate with the number of rapid eye movement (REM) episodes. Also, pre-non-REM (NREM) testosterone levels were higher as compared with the pre-REM periods and lower during the first NREM period as compared with other nocturnal NREM periods. Serum LH levels disclosed a nocturnal rise that preceeded a similar rise in testosterone by about an hour. We conclude that in young adult men, testosterone levels begin to rise on falling asleep, peak at about the time of first REM, and remain at the same levels until awakening.

Cardiac autonomic function during sleep in psychogenic and organic erectile dysfunction.

Abstract: The present study investigated the sympathetic/parasympathetic balance during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in patients with psychogenic and organic erectile dysfunction. The cardiac autonomic balance was assessed from the power of the low frequency (LF) and high frequency (HF) spectral components of heart-rate variability in 11 patients with psychogenic erectile dysfunction and 11 patients with organic erectile dysfunction as determined by monitoring sleep-related erections. Spectral analysis of heart-rate variability was calculated for at least four successive 4-min epochs of electrocardiogram recordings during NREM sleep and for all available 4-min epochs during REM sleep. Statistical analysis revealed that organic patients had a significantly higher LF/HF ratio (P < 0.01) during both stages of sleep, which resulted from a significantly lower power in the HF component (P < 0.004) and higher power in the LF component (P < 0.01) in these patients, in both REM and NREM sleep stages. These results demonstrate that patients complaining of daytime sexual dysfunction and found by sleep-related erection monitoring to suffer from organic erectile dysfunction, have altered cardiac autonomic balance during both stages of sleep.

The association between melatonin and sleep stages in normal adults and hypogonadal men.

Abstract: The role of melatonin in normal sleep-wake regulation has been inferred from the temporal relationships between its cycle and the 24 h cycle in sleep propensity. Pharmacological doses of melatonin were reported to have sleep-inducing effects in insomniacs. The current study investigated the relationship between melatonin and sleep stages in groups of hypogonadal men with abnormal melatonin levels. We were also interested in examining what would happen to these relationships during testosterone replacement therapy. Male patients with hypogonadotropic hypogonadism (IGD, n = 6), constitutional delayed puberty (DP, n = 6), and Klinefelter's syndrome (KS, n = 5) before and during testosterone replacement therapy were studied. Six patients with KS and normal testosterone levels were also studied. Results were compared with those obtained in normal controls (n = 6). Serum samples were obtained at 15 min intervals from 1900-0700h in a controlled light-dark environment with simultaneous polysomnographic sleep recordings. Serum melatonin levels were the highest in IGD and DP and lowest in KS patients. A lower percentage of sleep stage 2 and higher percentage of stage 3/4 were observed in IGD and DP groups while KS patients had higher percentage of stage 2 and lower percentage of stage 3/4 as compared to controls. Slow wave sleep was the highest in IGD and the lowest in KS groups. Serum melatonin levels were lowest in KS groups. Serum melatonin levels were lowest in sleep stage 3/4, higher in stage 2 and highest in REM sleep when all groups were combined and averaged together. However, in the IGD group, melatonin levels were actually lowest in REM sleep. Also in the KS group, melatonin levels were lower in REM than during sleep stage 2. Serum melatonin levels were lowest in sleep stage 3/4 in all groups, higher in stage 2, and highest in REM sleep. During waking periods, melatonin levels were the highest in untreated IGD, DP and KS patients. Testosterone treatment given to these patients, although normalized, their melatonin levels did not statistically significantly change these correlations. These data demonstrate that relative melatonin concentrations are associated with sleep stages in hypogonadal and normal men. The results also indicate that the association between melatonin and the reproductive hormones are independent of the synchronizing effects of melatonin on sleep homeostasis.

Melatonin administered in the afternoon decreases next-day luteinizing hormone levels in men: lack of antagonism by flumazenil.

Abstract: The role of melatonin in the regulation of human reproduction remains unclear. In the present study, we examined the influence of exogenous melatonin on pulsatile luteinizing hormone (LH), diurnal rhythm of testosterone, and endogenous melatonin profile in six healthy young adult males. To test the hypothesis that the effect of melatonin on LH or testosterone secretory patterns may be mediated through the benzodiazepine-(BNZ) gamma-amino-butyric acid (GABA) receptor complex, a benzodiazepine receptor antagonist (Flumazenil) was administered. The study design comprised four 10-h (4:00 PM-2:00 AM) testing periods. During each experimental period, subjects were given an oral dose of placebo, or 3 mg melatonin or 10 mg flumazenil, at 5:00 PM, in a randomized, double-blind, partially repeated Latin square design in the following combinations: placebo-placebo, placebo-melatonin, flumazenil-placebo, and flumazenil-melatonin. The following day, serum samples were obtained every 20 min between 4:00 PM and 2:00 AM in a controlled light-dark environment for the determination of LH and melatonin levels. Serum testosterone concentrations were determined every 20 min between 7:00 and 8:00 AM and 7:00 and 8:00 PM. A significant decrease in mean serum LH levels (p < 0.02) was observed in the melatonin-treated groups as compared with placebo-flumazenil groups. There was no change in LH pulse frequency, testosterone levels, or in melatonin onset time and amplitude. No additional effect of flumazenil on LH or testosterone levels was observed. These data indicate that an evening melatonin administration decreases the next-day LH secretion in normal adult males without altering testosterone levels or the endogenous nocturnal melatonin secretory pattern. This effect of melatonin is not mediated through the benzodiazepine-GABA receptor complex.

[Recording nocturnal erections following injuries and insurance claims: cost-effectiveness].

Abstract: Road accidents, work accidents, or other trauma can cause impotence and are frequently followed by insurance claims. During 1990-97 we examined 230 males with such a complaint. All underwent full polysomnographic recordings in the sleep laboratory for 2 nights, during the course of which NPT (nocturnal penile tumescence) was examined with special equipment. It was assessed by an experienced technician following planned awakenings from REM sleep. In 75 of the 230 subjects (33%), satisfactory erections were observed. In 100 (43%), who experienced at least 3 periods of REM sleep, no erections occurred. These patients were categorized as suffering from organic impotence. In the remaining 55 (24%), the results were inconclusive, with only partial erections or not enough REM sleep periods. Since a man recognized as suffering from impotence may be awarded large monthly payments for life, these examinations, in our opinion, are an important tool to prevent unjustified claims, and can save the state unnecessary expenses.