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Hot flashes in the late reproductive years: risk factors for Africa American and Caucasian women.

Hot flashes are a primary reason that midlife women seek medical care, but there is little information about the onset or the predictors of hot flashes in the years before the menopause. This study examines women's experience of hot flashes in the late reproductive years, comparing African American and Caucasian women, and identifies hormonal, behavioral, and environmental risk factors for hot flashes associated with ovarian aging. Data are from a population-based prospective cohort study of ovarian aging in women who were ages 35--47, in general good health, and had regular menstrual cycles at study enrollment. Hot flashes were assessed by subject report in a structured interview at the first follow-up period and correlated highly with previous prospective daily ratings of hot flashes (p = 0.0001). Blood samples were obtained in the first 6 days of the menstrual cycle in two consecutive cycles at enrollment and two consecutive cycles at follow-up. Predictor variables include hormone measures, structured interview, and standard questionnaire data. Thirty-one percent of the sample (n = 375) reported hot flashes (mean age 41 years). In bivariate analysis, more African American than Caucasian women reported hot flashes (38% vs. 25%, p = 0.01). Significant predictors of hot flashes in the final multivariable logistic regression model were higher follicle-stimulating hormone (FSH) levels (odds ratio [OR] 3.19), anxiety (OR 1.06), baseline menopausal symptoms (OR 4.91), alcohol use (OR 1.09), body mass index (BMI) (OR 1.04), and parity (OR 1.20). Race did not predict hot flashes after adjusting for these variables. Hot flashes commonly occur before observable menstrual irregularities in the perimenopause and are associated with both hormonal and behavioral factors. The association of hot flashes with increased body mass (BMI) challenges the current "thin" hypothesis and raises important questions about the role of BMI in hormone dynamics in the late reproductive years.

Adult↗

Predictors of menopausal hot flashes.

There are limited data on the factors associated with menopausal hot flashes, a common and potentially morbid condition. The objective of this study was to identify predictors of menopausal hot flashes. To meet this objective, 233 naturally perimenopausal or post-menopausal women (ages 45-65) attending a large urban hospital center primary care clinic, mammography unit, or women's health practice were enrolled. The women responded to a self-administered questionnaire assessing selected demographic factors, reproductive history, and behavioral factors. Sixty-seven percent of respondents experienced hot flashes, with 63% reporting frequent hot flashes (at least one hot flash per day) and 60% with hot flashes describing the hot flashes as severe. Women with hot flashes were significantly more likely to have mothers who experienced hot flashes (OR = 4.4, CI = 2.0-10.0) or to be smokers (OR = 2.0, CI = 1.2-3.5). There were no statistically significant associations between hot flashes and other selected demographic, reproductive, or behavior characteristics. These results reveal that menopausal hot flashes are associated with a maternal history of hot flashes as well as with cigarette smoking. These results may help physicians to counsel their patients about smoking cessation.

Aged↗

Is sternal skin conductance monitoring a valid measure of hot flash intensity or distress?

OBJECTIVE: To examine the validity of using sternal skin conductance monitoring as a measure of hot flash intensity and hot flash distress. DESIGN: Descriptive, prospective, longitudinal data from the 2-week baseline of a larger hot flash intervention study; 73 breast cancer survivors with daily hot flashes wore a hot flash monitor and completed a hot flash diary during two 24-hour assessment periods that were separated in time by 1 week. RESULTS: Data consisted of 569 diary rated hot flashes; 46.9% had magnitude of less than 2.0 micromhos (insufficient to meet objective hot flash criterion) and 26.3% had magnitude of 0.0 micromho (no change in skin conductance). Results from mixed-linear modeling indicated that, although magnitude significantly predicted hot flash intensity and distress, effect sizes were very small: less than 2% when using all observations, and less than 1% when using only the subset meeting objective hot flash criteria. Even after adjusting for covariates that were associated with intensity or distress, magnitude explained very little variance in intensity or distress (<2.2%). Scatterplots and locally weighted smooth regression curves also revealed very little relationship between magnitude and either intensity or distress. CONCLUSIONS: Findings indicate that objective change in sternal skin conductance, an indicator of sweat gland activity, should not be used as a proxy measure of subjective hot flash intensity or distress. Future research should continue to subjectively measure hot flash intensity and distress when these are important outcome variables to consider.

Female↗

Randomized, double-blind, placebo-controlled, crossover study of sertraline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen.

We observed the relief of hot flashes in breast cancer survivors taking tamoxifen and treated with sertraline for depression. Our objective was to assess the effect of sertraline on the frequency and severity of hot flashes, mood status, and health-related quality of life. We used a randomized, double-blind, placebo-controlled, crossover study using 6 weeks of sertraline (50 mg each morning) versus placebo. Study participants were 62 breast cancer survivors from an oncology clinic in a tertiary care center on adjuvant tamoxifen reporting bothersome hot flashes. Patients were asked to keep a daily hot flash diary to record hot flash frequency and severity, from which hot flash scores (frequency x severity) were calculated. The Center for Epidemiologic Studies depression scale and Functional Assessment of Cancer Therapy--Breast (FACT-B) (at baseline, 6 weeks, and 12 weeks) were used to assess mood and quality of life. Sixty-two women were accrued. Forty-seven women (median age 53.9 years, range 36.6-77.1 years; 89% postmenopausal; 85.5% Caucasian) completed the first 6 weeks and 39 completed 12 weeks. The baseline daily hot flash frequency and score were 5.8 (standard deviation 4.1) and 11.5 (14.0), respectively. At the end of the first 6 weeks, hot flash frequency decreased by 50% in 36% of those taking sertraline compared to 27% taking placebo. In the crossover analysis, sertraline was significantly more effective than placebo: women crossing from placebo to sertraline had a decrease (-0.9 and -1.7) in hot flash frequency and score, whereas those crossing from sertraline to placebo had an increase (1.5 and 3.4) in hot flash frequency and score (p = 0.03 and 0.03). Forty-eight percent preferred the sertraline period, 11% preferred the placebo period, and 41% had no preference (p = 0.006). Measures of depression and quality of life were within normal range and did not change significantly within treatment groups. Sertraline decreases hot flashes in breast cancer survivors taking tamoxifen and women prefer sertraline to placebo. Further study of sertraline for the management of hot flashes is warranted.

Adult↗

Flash kinetics and light intensity dependence of oxygen evolution in the blue-green alga Anacystis nidulans.

Patterns of oxygen evolution in flashing light for the glue-green alga Anacystis nidulans are compared with those for broken spinach chloroplasts and whole cells of the green alga Chlorella pyrenoidosa. The oscillations of oxygen yield with flash number that occur in both Anacystis and Chlorella, display a greater degree of damping than do those of isolated spinach chloroplasts. The increase in damping results from a two- to threefold increase in the fraction (alpha) of reaction centers "missed" by a flash. The increase in alpha cannot be explained by non-saturing flash intensities or by the dark reduction of the oxidized intermediates formed by the flash. Anaerobic conditions markedly increase alpha in Anacystis and Chlorella but have no effect on alpha in broken spinach chloroplasts. The results signify that the mechanism of charge separation and water oxidation involved in all three orgainsms is the same, but that the pool of secondary electron acceptors between Photosystem II and Photosystem I is more reduced in the dark, in the algal cells, than in the isolated spinach chloroplasts. Oxygen evolution in flashing light for Anacystis and Chlorella show light saturation curves for the oxygen yield of the third flash (Y3) that differ markedly from those of the steady-state flashes(YS). In experiments in which all flashes are uniformly attenuated, Y3 requires nearly twice as much light as YS to reach half-saturation. Under these conditions Y3 has a sigmoidal dependence on intensity, while that of YS is hyperbolic. These differences depend on the number of flashes attenuated. When any one of the first three flashes is attenuated, the variation of Y3 with intensity resembles that of YS. When two of the first three flashes are attenuated, Y3 is intermediate in shape between the two extremes. A quantitative interpretation of these results based on the model of Kok et al. (Kik, B., Forbush, B.and McGloin, M. (1970) Photochem. Photobiol. 14, 307-321) fits the experimental data.

Chlorella↗

Climacteric hot flash.

No data are available on either quantitative or qualitative aspects of the climacteric hot flash, yet the phenomenon is widely treated despite unknown aetiology. A basic assumption of this study was that a more complete understanding and description of women with hot flashes would identify alternatives to oestrogens used by women for relief of the hot-flash symptom. An exploratory study was undertaken to answer the question: Who is the woman who has hot flashes and what are the characteristics of the hot flashes? The methodology employed was daily self-report by subjects of hot-flash frequency, duration, trigger, origin, spread, intensity and method of coping with it. Analysis of 20 randomly-selected 2 wk self-report record cards revealed no hot-flash pattern among women. A total of 1041 hot flashes were reported. Mean duration of the hot flash was 3.31 min (range 5 sec to 60 min). Neither hot flash origin nor spread was restricted to the upper body in all subjects. Subjects ranked their hot flash as either mild, moderate or severe. Coping strategies used by subjects (external and internal cooling methods) appeared to be related to both duration and severity of the hot flash.

Adult↗

Effect of fever on menopausal hot flashes.

Some women report that they have fewer hot flashes when they have a fever. This is the first case of physiological monitoring of hot flashes during fever in a subject with a well documented pattern of frequent hot flashes when afebrile. During fever, there were fewer hot flashes than during afebrile periods, and these hot flashes also tended to be less intense. For most of the period of reduced hot flashes, internal (core) temperature was elevated, above 37.5 degrees C. When the fever broke, hot flashes resumed in a pattern similar to that of afebrile periods. Possible explanations for the reduction in hot flashes during a fever include: (1) a hot flash is triggered, but the characteristic physiological changes do not occur due to competing thermoregulatory drives, (2) the febrile core temperature inhibits whatever it is that triggers a hot flash; or (3) some product of the fever process inhibits the hot flash trigger or masks the physiological changes that occur during hot flashes.

Body Temperature↗

Hot flashes: phenomenology, quality of life, and search for treatment options.

Menopausal hot flashes are a significant problem for women. Hot flashes can impact on daily functioning, particularly when they disrupt sleep, leading to fatigue and irritability during the day. However, our knowledge about this primary complaint of menopausal women is far from complete. It is known that a hot flash is associated with thermoregulatory, cardiovascular, and endocrine changes. However, much is unknown about the phenomenology of hot flashes, such as the range of variability in the pattern and longitudinal course of hot flashes. Although estrogen plays a role in the etiology of hot flashes, the mechanism by which its withdrawal precipitates hot flashes and its replacement relieves them is not understood. Nor do we know what it is that triggers individual hot flash episodes. We are beginning to learn about factors, such as ambient temperature, that modulate the frequency of severity of hot flashes. And very new data suggest that the ingestion of certain foods may influence hot flashes via estrogenic substances present in the food plants. Although there is much anecdotal information about herbs and other nonconventional remedies, little or no research had been done to assess the efficacy or safety of these methods for the treatment of hot flashes. An immediate focus on some of the most promising of these therapies could broaden the available treatment options and should provide new insights into the mechanism underlying hot flashes.

Behavior Therapy↗

The nature of rise in threshold produced by contrast-flashes.

1. The rod threshold for seeing a flash on a 2(1/2) degrees square is raised by a nearly simultaneous flash that falls on the surround. When this ;contrast-flash' is held fixed in intensity, it raises the log test threshold by a fixed amount no matter how far that threshold has already been raised by light adaptation owing to background or bleaching.2. This is surprising since fixed backgrounds and bleachings raise the log test threshold much more when the eye is dark than when light adapted.3. When the test flash is held at some fixed supra-threshold value, the contrast flash exhibits a ;critical level', above which the test will no longer be seen. If the surround region upon which the contrast-flash falls is adapted by background or bleaching, its efficacy is reduced so that the ;critical level' is raised.4. Surround adaptation raises the log ;critical level' by the same amount that it raises the log threshold for seeing the contrast-flash itself.5. The way that contrast flashes raise the test threshold is thus entirely different from the way that adaptations by bleachings or backgrounds do. Contrast-flash signals appear to inhibit test-flash signals by interaction at some point central to the site where adaptation occurs.6. This permits the effect of adaptation on signals to be measured. A given state of adaptation attenuates all flash signals in the same proportion. And in any state of adaptation a single flash will reach threshold when the attenuated signal has a fixed size.

Accommodation, Ocular↗

Thermoregulatory physiology of menopausal hot flashes: a review.

Hot flashes during the climacteric years have long been a frequent clinical complaint, generally considered within the realm of the internist, gynecologist, or endocrinologist. Yet the underlying mechanism of hot flashes remains unknown. Only within the past 10 years has there been significant research on hot flashes as a disturbance of thermoregulation. This paper focuses on thermoregulatory aspects of hot flashes, reviewing current knowledge of the thermoregulatory physiology and endocrinology of hot flashes and discussing future avenues for research. Hot flashes are compared with fever in terms of thermoregulatory changes and speculated mechanisms. Although several substances in the peripheral circulation are found in increased concentrations during hot flashes, none is a trigger for a hot flash. The pattern of hot flash occurrence is striking in its regularity, and the possibility of endogenous rhythmicity is discussed. Recently, investigators have begun to explore a primate model of menopausal hot flashes. These studies are summarized. Finally, the multiple effects of estrogen on various systems of the body and their interrelationships are discussed. An understanding of the mechanism of hot flashes would not only be of importance to women suffering with hot flashes but would further our knowledge of thermoregulatory function and the interactions between thermoregulatory and reproductive systems.

Body Temperature↗

Severe hot flashes are associated with chronic insomnia.

BACKGROUND: Because hot flashes can occur during the night, their presence has been frequently associated with insomnia in women with symptoms of menopause. However, many factors other than hot flashes or menopause can be responsible for insomnia, and several factors associated with insomnia in the general population are also commonly observed in perimenopausal and postmenopausal women who have hot flashes. METHODS: A random sample of 3243 subjects (aged > or =18 years) representative of the California population was interviewed by telephone. Included were 982 women aged 35 to 65 years. Women were divided into 3 groups according to menopausal status: premenopause (57.2%), perimenopause (22.3%), and postmenopause (20.5%). Hot flashes were counted if they were present for at least 3 days per week during the last month and were classified as mild, moderate, or severe according to their effect on daily functioning. Chronic insomnia was defined as global sleep dissatisfaction, difficulty initiating sleep, difficulty maintaining sleep, or nonrestorative sleep, for at least 6 months. Diagnoses of insomnia were assessed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, classification. RESULTS: Prevalence of hot flashes was 12.5% in premenopause, 79.0% in perimenopause, and 39.3% in postmenopause. Prevalence of chronic insomnia was reported as 36.5% in premenopause, 56.6% in perimenopause, and 50.7% in postmenopause (P<.001). Prevalence of symptoms of chronic insomnia increased with the severity of hot flashes, reaching more than 80% in perimenopausal women and postmenopausal women who had severe hot flashes. In multivariate analyses, severe hot flashes were significantly associated with symptoms and a diagnosis of chronic insomnia. Poor health, chronic pain, and sleep apnea were other significant factors associated with chronic insomnia. CONCLUSIONS: Severe hot flashes are strongly associated with chronic insomnia in midlife women. The presence of hot flashes should be systematically investigated in women with insomnia. Treating hot flashes could improve sleep quality and minimize the deleterious consequences of chronic insomnia.

Adult↗

Smoking, body mass, and hot flashes in midlife women.

OBJECTIVES: To assess whether lifestyle factors, specifically smoking and body mass index (BMI), are associated with the occurrence of any, moderate to severe, or daily hot flashes. METHODS: A cross-sectional study was conducted among women aged 40-60 years residing in the Baltimore metropolitan area who reported their history of hot flashes through a mailed survey. Logistic regression was used to assess the associations between smoking and BMI with any, moderate to severe, and daily hot flashes. RESULTS: Of the 1,087 women included in the study, 56% reported having hot flashes. Compared with never-smokers, current smokers were at an increased risk for both moderate to severe hot flashes (adjusted odds ratio [OR] = 1.9, 95% confidence interval [CI] 1.3, 2.9) and daily hot flashes (adjusted OR = 2.2, 95% CI 1.4, 3.7). Among current smokers, risk for hot flashes increased with greater amount smoked. High BMI (more than 30 kg/m(2)) was associated with an increased risk for moderate to severe hot flashes compared with low BMI (less than 24.9 kg/m(2)) (adjusted OR = 2.1, 95% CI 1.5, 3.0). An increased risk for any or daily hot flashes with high BMI was present only among premenopausal or perimenopausal women. CONCLUSION: Potentially modifiable factors, such as current smoking and high BMI, may predispose a woman to more severe or frequent hot flashes. This information may be valuable for identifying women at risk for hot flashes and for developing appropriate prevention strategies that may include lifestyle modifications.

Adult↗

Characterization of hot flashes reported by healthy postmenopausal women receiving raloxifene or placebo during osteoporosis prevention trials.

OBJECTIVE: Raloxifene, a selective estrogen receptor modulator, is estrogen-like in the skeleton and cardiovascular system and antiestrogenic in reproductive tissues. In contrast to estrogens, raloxifene is not indicated for the treatment of hot flashes. This study was designed to examine the characteristics of hot flashes among healthy postmenopausal women participating in osteoporosis prevention trials who were receiving raloxifene or placebo. METHODS: Adverse event data from three randomized, double-blind trials (N = 876) comparing raloxifene 60 mg/day with placebo for 30 months were integrated and analyzed. Two of the three trials (one European, two North American) were identically designed and were open to healthy postmenopausal women ages 45 through 60 without regard to prior hysterectomy. The third trial was multinational, was open to women ages 40 through 60, and all enrollees had prior hysterectomy at baseline. Women were questioned in general terms about the occurrence of adverse events at 3-6-month intervals. Treatment-emergent adverse events pertaining to hot flashes were included in the current study. RESULTS: At baseline, 12% of women randomly assigned to placebo and 13% assigned to raloxifene reported prevalent hot flashes. After 30 months, the cumulative incidence of hot flashes was 21% for placebo and 28% for raloxifene (P = 0.022), with the difference in incidence rate confined to the first 6 months of therapy. There was no difference between placebo and raloxifene in reported maximum severity of or early discontinuations as a result of hot flashes (< or = 3% per group for both outcomes). Among women whose hot flashes had stopped completely during the 30-month study period, the median total duration of the event prior to becoming symptom-free was 246 days for placebo and 205 days for raloxifene. Among all women reporting a hot flash, the extrapolated total duration of hot flashes was the same for women treated with either raloxifene or placebo. No subgroup-by-therapy interactions were detected. Multivariable regression analysis revealed several factors that were independently weakly predictive of hot flashes. CONCLUSIONS: Raloxifene slightly affects the incidence but not the natural history of hot flashes in healthy postmenopausal women seeking prevention therapy.

Adult↗

Depomedroxyprogesterone acetate for hot flashes.

To evaluate the efficacy of a long-acting preparation of medroxyprogesterone acetate for hot flash management, 3 men receiving androgen ablation therapy for prostate cancer and 15 women with a history of breast cancer were treated as part of clinical practice with three biweekly intramuscular injections of 500 mg depomedroxyprogesterone. A review of hot flash diaries and patient charts were completed to evaluate the effectiveness and tolerability of these injections for managing hot flashes. Treatment was associated with an approximate 90% decrease in hot flashes (95% CI 82-97%). Daily hot flash frequency decreased from a mean of 10.9 on the first day of treatment (95% CI 8.0-13.8 hot flashes per day) to a mean of 1.1 hot flashes 6 weeks later (95% CI 0.5-1.8 hot flashes) and to a mean of 0.7 hot flashes 12 weeks following therapy initiation (95% CI 0.1-1.2). Improvement in the hot flashes remained for months after discontinuing the injections in many patients. Reported side effects were minimal. This experience suggests that treatment with depomedroxyprogesterone may be an effective and well-tolerated option for the treatment of hot flashes.

Adult↗

Sertraline to treat hot flashes: a randomized controlled, double-blind, crossover trial in a general population.

OBJECTIVE: To evaluate the effectiveness of a selective serotonin reuptake inhibitor (SSRI) (sertraline) in decreasing hot flashes in a general population of women. DESIGN: A double-blind, placebo-controlled, crossover trial was conducted in a southwestern urban setting. A total of 102 women aged 40 to 65 who were experiencing hot flashes and not taking any hormone therapy were recruited. After 1 week of baseline hot flash data collection, study participants were randomized to receive placebo or active drug (sertraline 50 mg) for 4 weeks. This intervention was followed by a 1-week washout and cross over to the opposite treatment for 4 weeks. The number and severity of hot flashes were measured. RESULTS: One hundred two women were enrolled in the study. Five dropped out before providing baseline data. Of the 97 remaining, 52 were randomized to active drug first and 45 to placebo first. Ten dropped out of the study before completing all 10 weeks, leaving 46 in the active drug-first arm and 41 in the placebo-first arm. At baseline, the mean number of hot flashes reported was 45.6 per week (SD = 29.6), ranging from 2 to 148. During the sertraline phase of the study, women experienced five fewer hot flashes per week than they did on the placebo (P = 0.002). The severity of hot flashes was not significantly different; however, the hot flash score (number x average severity) was significantly improved during the sertraline phase. CONCLUSION: Sertraline reduced the number of hot flashes and improved the hot flash score relative to placebo and may be an acceptable alternative treatment for women experiencing hot flashes.

Adult↗

Parenteral medroxyprogesterone for the management of luteinizing hormone releasing hormone induced hot flashes in men with advanced prostate cancer.

PURPOSE: Luteinizing hormone releasing hormone (LHRH) agonist therapy for advanced prostate cancer can manifest significant side effects affecting quality of life, most notably hot flashes. This study evaluated the effectiveness of parenteral medroxyprogesterone acetate (MPA) in reducing the frequency and severity of these hot flashes. MATERIALS AND METHODS: A multi-institutional retrospective review of hot flashes from LHRH therapy for prostate cancer was conducted. The hot flashes were quantified and the severity was graded (3-point analogue scale) before and after treatment with MPA. Two doses of MPA (400 or 150 mg intramuscularly) were administered. Statistical analysis (Student's t test) evaluated the quantity of hot flashes, the quality of hot flashes, and dose effectiveness. RESULTS: A total of 48 men (40 at 400 mg, 8 at 150 mg) with a mean age of 71.4 years (range 54 to 87) from 3 institutions were evaluated. There were 91% with symptomatic improvement with MPA, and half (46%) had a complete response defined as total elimination of hot flashes. The median number of the hot flashes per day decreased from 4 to 1 and the median severity score decreased from 2 to 1 (p <0.05). Significance was not achieved comparing the 2 doses. Complete responders were not noted with the 150 mg dose. Anticipated response to MPA did not correlate with the number or severity of the hot flashes. CONCLUSIONS: This study is the first multi-institutional evaluation of hot flashes demonstrating significant reduction in quantity and severity with MPA. Based on these data we now manage hot flashes associated with LHRH analogues with 400 mg of MPA.

Androgen Antagonists↗

Influence of hot flashes on quality of life in patients with prostate cancer treated with androgen deprivation therapy.

BACKGROUND: We surveyed patients with prostate cancer treated with androgen deprivation therapy to examine the influence of hot flashes on quality of life (QOL). METHODS: Fifty-five outpatients with prostate cancer (M0, 39; M1, 16) treated with androgen deprivation therapy (castration, 15; castration and antiandrogen, 40) were enrolled in this study. Mean duration of androgen deprivation therapy was 21 months (2-91 months). The patients were still being treated with androgen deprivation therapy at the time of the survey. The functional assessment of cancer therapy (FACT) was used as a QOL questionnaire for outpatients with prostate cancer treated with androgen deprivation therapy. Hot flash assessments were used to document the number and severity (mild, moderate, and severe) of daily hot flashes. The patients prescribed fluvoxamine maleate were reassessed for hot flashes 2 weeks after the prescription. RESULTS: Thirty-two of the 55 patients (58.2%) suffered from hot flashes. Hot flashes deteriorated the physical well-being subscale of QOL in patients with prostate cancer treated with androgen deprivation therapy (P = 0.043). There was a significant relationship between the desire to be treated for hot flashes and the hot flash assessments (P = 0.038). Fluvoxamine maleate was significantly effective in reducing hot flashes (P = 0.001). CONCLUSIONS: Hot flashes had adverse effects on the patients' physical status and deteriorated the patients' QOL. New treatment options such as fluvoxamine maleate might help simplify the often difficult management of hot flashes in patients with prostate cancer treated with androgen deprivation therapy.

Aged↗

Static and dynamic actions of cytoplasmic Ca2+ in the adaptation of responses to saturating flashes in salamander rods.

1. In order to study the relative contribution to light adaptation of the various actions of Ca2+ in rod photoreceptors, changes in cytoplasmic calcium concentration ([Ca2+]i) were opposed by manipulating the calcium fluxes across the outer segment membrane at different times during the response to a bright flash. 2. When the outer segment was superfused with 0 Ca2+, 0 Mg2+,0 Na+ solution just before a bright flash, the period of response saturation was greatly prolonged. But if instead the solution change was made at progressively increasing times after the flash, the delay before the response recovered from saturation declined exponentially towards its value in Ringer solution with a time constant of around 1 s. In contrast, recovery time was little affected by stepping to 0 Ca+,0 Mg2+,0 Na+ solution before the flash and returning to Ringer solution shortly before the normal time of recovery from saturation. 3. When a bright flash was delivered just before the extinction of steady light, the response recovered from saturation progressively earlier as this steady intensity was increased. If, instead, the outer segment was transferred to 0 Ca2+,0 Mg2+,0 Na+ solution just before the bright flash then the time spent in saturation by the response was prolonged in darkness, but this additional delay progressively decreased as the steady intensity increased. 4. These results are consistent with the notion that the light-induced reduction of the time spent in saturation by the bright flash response in Ringer solution resulted from the static decrease in [Ca2+]i induced by the background, while the additional delay in the recovery from saturation when further changes in [Ca2+]i were prevented stemmed from the abolition of the dynamic fall in [Ca2+]i during the flash response. 5. Analysis of the effects of steady light on the time spent in saturation by the bright flash response under these conditions suggests that actions of [Ca2+]i at, or soon after, the time of the flash are largely responsible for the graded changes which take place in the bright flash response during light adaptation, while rapid actions of [Ca2+]i at the time of response recovery also play a role in the adaptation of the steady response to background light itself. 6. These data have been interpreted in terms of differential actions of [Ca2+]i on 'early' stages (e.g. events leading to phosphodiesterase activation) and 'late' stages (e.g. guanylyl cyclase) in the transduction mechanism. A quantitative model is presented which suggests that actions of [Ca2+]i on 'late' stages play a proportinately larger role in background adaptation than actions on 'early' stages.

Animals↗