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Biomedical subjects

D B Carr

Publications and source records attributed to D B Carr.

At least 109 records · Page 6Linked to original sources
PubMed1989

Quantitative relationships between plasma beta-endorphin immunoactivity and hemodynamic performance in preoperative cardiac surgical patients.

To quantitate the importance of cardiac dysfunction as a stimulus for plasma immunoactive beta-endorphin (iBE) secretion, we measured iBE and hemodynamic indices in 65 patients prior to anesthetic induction for coronary artery bypass grafting or valve replacement. Linear regression analysis for the group as a whole showed significant correlations between iBE and stroke index (SI), pulmonary artery wedge pressure (PCW), and right atrial pressure (RAP), but not mean arterial pressure (MAP). Two patient subgroups were identified (P less than 0.001 by F-test): those with low SI and high iBE, or those with high SI and low iBE (cutoffs at 40 ml/m2 and 35 pg/ml, respectively). Correlations between hemodynamics and iBE were always stronger within the low-SI than the high-SI subgroups. These correlations were greater for patients with coronary artery than with valvular heart disease. Cardiac output (CO) and cardiac index (CI) correlated with iBE in valve-replacement and coronary-grafting groups. These findings were not an artifact of impaired iBE clearance due to renal dysfunction. Our results quantitate the importance of hemodynamic dysfunction for iBE secretion, and indicate that this relationship is particularly strong when stroke index declines below 40 ml/m2.

Adult↗
PubMed1989

Pituitary-adrenal stress response in the absence of brain-pituitary connections.

To examine whether an acute pituitary-adrenal response to stress may occur in vivo in the absence of hypothalamic-pituitary connections, we measured plasma beta-endorphin (beta-EP) and corticosterone (C) in rats after acute thermal injury. beta-EP rose significantly after thermal injury in normal rats and rats bearing pituitary-to-kidney autotransplants but not in animals with pituitary aspiration without reimplantation. Corticosterone responses paralleled beta-EP but were significant only in normal controls. Propranolol pretreatment did not reduce postburn beta-EP and C rises in autotransplanted animals. Therefore, since circulating factors contribute in vivo to pituitary-adrenal responses, the widespread practice of using "stress hormone" responses to quantitate perioperative stress or pain may in some circumstances be flawed.

Animals↗
PubMed1988

Antifibrillatory action of the narcotic agonist fentanyl.

Morphine, an opiate alkaloid with mixed mu- and delta-agonist properties, raises the ventricular fibrillation threshold in anesthetized dogs by altering autonomic tone. To elucidate further underlying structure-activity relationships, the effect of fentanyl, a nonalkaloid, mu-selective agonist in wide clinical use, was studied. Fentanyl (30 micrograms/kg) was given intravenously to 27 chloralose-anesthetized dogs, and ventricular fibrillation threshold was measured by means of the single-stimulus technique. In the baseline state fentanyl raised the ventricular fibrillation threshold by 14%. When the dogs were subjected to hemorrhagic stress, this effect was amplified to 29% (p less than 0.0001). Bilateral cervical vagotomy abolished fentanyl's antifibrillatory effect, but neither atropine sulfate (0.4 mg/kg/hr) nor atropine methylnitrate (0.5 mg/kg/hr) did so. Fentanyl's influence on the fibrillation threshold during hemorrhage was significantly reduced by bilateral stellate ganglionectomy (p less than 0.005). It is concluded that fentanyl raises the ventricular fibrillation threshold by its known sympathoinhibitory action rather than by its vagal efferent activating effect. The facts that an intact vagus is required and that hemorrhage amplifies the effect suggest that the antifibrillatory effect of fentanyl is mediated through the afferent component of the baroreflex arc.

Animals↗
PubMed1988

Effect of dexamethasone on cortisol and prolactin responses to meals in bulimic and normal women.

In normal individuals, serum cortisol and prolactin concentrations have been shown to rise following a mid-day meal. To determine whether abnormalities of the hypothalamo-pituitary-adrenal axis in bulimics lead to a disrupted hormonal response to eating, cortisol and prolactin responses to meals (600 kcal, 30% protein, 30% fat, 40% carbohydrate) were studied on two consecutive days in six normal weight bulimics and six normal volunteers. Dexamethasone (1 mg orally) was administered at 2330 h after baseline sampling. During baseline sampling, cortisol concentrations were significantly higher in the bulimics (18.2 +/- 0.9 micrograms/dl, mean +/- SEM) than in the normals (12.1 +/- 0.4 micrograms/dl) (p less than 0.001). Post-dexamethasone cortisol concentrations also were higher in the bulimics (5.7 +/- 0.3 micrograms/dl) than in the normals (1.2 +/- 0.2 micrograms/dl) (p less than 0.001). The three bulimics with a major depressive disorder had higher peak post-dexamethasone cortisol concentrations than the nondepressed bulimics. Dexamethasone significantly enhanced the prolactin response to meals among both bulimics (at 90 min post onset of eating) and normals (at 60, 75 and 90 min post onset of eating). This enhancement of the prolactin response to meals by dexamethasone is opposite to the inhibitory effect of dexamethasone on stress-induced prolactin release and suggesting that stress-induced and meal-induced prolactin release involve different neuroendocrine mechanisms.

Adult↗
PubMed1988

Operation, anesthesia, and the endorphin system.

Endogenous opioid peptides regulate a multitude of neuronal pathways and extraneural targets (e.g., white blood cells). Acting in the periphery and at central sites of afferent integration within multiple compartments at multiple levels, they modify the secretion of other hormones yet are themselves secreted during stress to produce important biological effects. Usually quiescent, the opioid system becomes active during a host of stresses to optimize, integrate, and buffer bodily responses. During stress, endorphins act to limit sympathetically driven responses such as tachycardia and vasoconstriction; however, if given to resting subjects, opiates may evoke the very responses they inhibit during stress. As the roles of individual opioid peptides and opiate receptors are studied in increasing depth, an amazing degree of functional heterogeneity and detail has emerged. Such knowledge has barely begun to be exploited in creating the next generation of therapeutics.

Anesthesia↗
PubMed1988

Opioids.

Explore the source record for details and available documents.

Analgesics, Opioid↗
PubMed1988

Urinary catecholamine metabolite and tribulin output during lactate infusion.

Urinary output of homovanillic acid and 4-hydroxy-3-methoxymandelic acid was decreased both in patients with panic attacks and in normal controls during lactate infusion, whereas that of tribulin (an endogenous monoamine oxidase inhibitor and benzodiazepine receptor binding inhibitor) was increased. There was no change in urinary excretion of any of these compounds during saline infusion. These findings provide further evidence of a link between tribulin output and stress and anxiety in man and point to its possible in vivo action as a monoamine oxidase inhibitor.

Anxiety Disorders↗
PubMed1987

Endogenous opioids and ventilatory adaptation to prolonged hypoxia in goats.

To investigate whether endogenous opioid peptides mediate time-dependent changes in ventilatory control during prolonged hypoxia, we studied four adult goats at rest during 14 days at simulated high altitude in a hypobaric chamber (PB approximately 450 Torr). Arterial PCO2 fell during the first several hours of hypoxia, remained stable over the next 7 days, and then rose slightly (but without statistical significance) by day 14. Ventilatory responsiveness to CO2 increased during the first week of hypoxia. By day 14, while still greater than control, the ventilatory response to CO2 was less than that observed on day 7. Immunoactive beta-endorphin levels in plasma and CSF did not change during the 14-day period. Administration of naloxone on day 14 did not restore the ventilatory response to CO2 to the level observed during the first week of acclimatization. We conclude that in adult goats, time-dependent changes in ventilatory response to CO2 during acclimatization to prolonged hypoxia are not primarily attributable to alterations in endogenous opioid peptide activity.

Adaptation, Physiological↗
PubMed1987

Increases in plasma beta-endorphin and tail flick latency in the rat following burn injury.

In children with burn injuries we found, in earlier studies, an inverse association of plasma beta-endorphin immunoactivity (iB-EP) and pain levels. To further explore the effects of burn trauma on the peripheral release of beta-endorphin and the occurrence of centrally mediated stress analgesia, plasma iB-EP levels and tail flick latency (TFL) were measured in rats subjected (while anesthetized) to scald injury. In comparison to sham burn (dip in tepid water), burn injury increased plasma iB-EP and TFL; both the duration and magnitude of these effects were directly proportional to the extent of burns. In rats receiving no treatment, TFLs were unchanged throughout the time of the burn experiments. At 2 days post-burn TFLs were invariably back to pre-burn levels. Administration of the long-acting opioid antagonist naltrexone prior to burn injury prevented the rise in TFL. Thus the trauma of burns appeared to bring about a stress-induced analgesia (SIA). The marked increase in iB-EP during this SIA and its antagonism by naltrexone suggest that it was opioid and hormonal in character.

Analgesia↗
PubMed1987

The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations.

Several lines of evidence indicate that hypothalamic-pituitary-gonadal activity varies among men with idiopathic hypogonadotropic hypogonadism (IHH). To test the hypothesis that a spectrum of abnormalities of GnRH secretion underlies the syndrome of IHH, we characterized the patterns of GnRH-induced gonadotropin secretion during periods of frequent sampling in 50 consecutive men with IHH and contrasted them with those in 20 normal men. The largest group of IHH patients (n = 42) had no detectable LH or FSH pulsations and could be categorized into 2 subsets according to the presence or absence of evidence of spontaneous puberty. The most severely affected subset (n = 32), who recalled no history of puberty, had testes with a mean volume of 3.3 +/- 0.5 (+/- SEM) ml, with a prepubertal appearance on biopsy, and often were anosmic (n = 17). The second subset of apulsatile IHH men (n = 10) had histories of partial or complete spontaneous sexual development with subsequent isolated loss of sexual function, testes with a mean volume of 13.3 +/- 1.9 ml (P less than 0.01 compared to the first subset), a pubertal or adult appearance of the testes on biopsy, and an intact sense of smell. In a second group of IHH patients (n = 3), LH was secreted predominantly in a nighttime pattern similar to that of normal children during early puberty. These men were aged 18-24 yr, had a mean testicular volume of 10.5 +/- 2.3 ml, pubertal changes on testicular biopsy, and an intact sense of smell. A third group of IHH men (n = 4) had LH pulses of abnormally low amplitude. Only one patient in this group had a history of spontaneous sexual development. The mean testicular volume of these patients was 5.6 +/- 1.9 ml, and the testes appeared prepubertal (n = 3) or pubertal (n = 1) on biopsy. In addition to these groups, another patient had apparent LH pulsations and nearly normal amplitude, but the LH was bioinactive and appeared to consist chiefly of alpha-subunit. Testing of other anterior pituitary hormone functions did not distinguish IHH men from normal men. However, those IHH patients with some evidence of endogenous GnRH secretion had higher basal and stimulated serum PRL levels than IHH men without such evidence (P less than 0.05), suggesting an influence of GnRH on PRL secretion.

Adolescent↗
PubMed1986

Reproductive toxicology of inhaled styrene oxide in rats and rabbits.

Experiments were performed to evaluate reproductive and developmental toxicology in rats and rabbits exposed to styrene oxide by inhalation. Female rats were exposed to 100 or 300 ppm styrene oxide or to filtered air for 7 h/day, 5 days/week for 3 weeks. Extensive mortality occurred in rats that received prolonged exposure to 100 ppm styrene oxide while 300 ppm was rapidly lethal. As a result exposures were terminated in this latter group and the group was eliminated from further study. The rats of the 0 and 100 ppm groups were then mated and exposed to 0 or 100 ppm styrene oxide daily through 18 days of gestation (dg). Female rabbits were artificially inseminated and exposed for 7 h daily to 0, 15, or 50 ppm styrene oxide through 24 dg. Both of these lower concentrations used for exposure of the rabbits produced mortality of does. The rats were killed at 20 dg and the rabbits at 30 dg. Pregnant animals were examined for toxic changes including altered tissue weights and histopathologic effects. Litters were evaluated using several measures of embryotoxicity, and live fetuses were examined for external, visceral, and skeletal malformations. Exposure during gestation appeared to increase preimplantation loss in rats, and tended to increase the incidence of resorptions in rabbits. In both species, fetal weights and crown-rump lengths were reduced by gestational exposure. The incidences of ossification defects of the sternebrae aned occipital bones were increased by gestational exposure of rats to styrene oxide. These results indicate that inhalation exposures at these concentrations produce reproductive and development toxicity, as well as maternal toxicity.

Abnormalities, Drug-Induced↗
PubMed1986

Response to low-dose pulsatile cortisol in Addison's disease with suspected corticotropinoma.

A 65 year old woman with long-standing Addison's disease treated with oral glucocorticoid and mineralocorticoid replacement had persistently high ACTH levels, inadequate suppression of ACTH on low-dose dexamethasone, sellar enlargement, and pigmentation, and thus resembled patients alleged to develop corticotropinomas while on oral replacement for adrenal insufficiency. Since animal studies suggested that rapid rises of corticosteroids within the physiologic range can inhibit ACTH release, we administered brief infusions of cortisol every three hours with total daily dose equal to her chronic dose. Prompt suppression of ACTH and immunoreactive beta-endorphin occurred during each cortisol dose profiled, suggesting a role for ultradian cortisol fluctuations in tonic inhibition of ACTH secretion in humans, and a possible therapeutic benefit of mimicking ultradian cortisol rhythms during replacement therapy.

Addison Disease↗
PubMed1986

Neuroendocrine correlates of lactate-induced anxiety and their response to chronic alprazolam therapy.

Lactate infusions are anxiogenic in patients with panic disorder or agoraphobia with panic attacks, but few neuroendocrine profiles of this effect have appeared. The authors measured the number and intensity of panic symptoms and blood hormone levels during double-blind lactate infusions in 25 patients and 10 normal subjects and during placebo infusions in another five patients. Each patient was rechallenged with an identical infusate after chronic double-blind outpatient treatment with alprazolam or placebo. The results confirm the effectiveness of lactate infusions in evoking anxiety, extend previous hormone profiles of this maneuver, and indicate that chronic alprazolam treatment minimizes the neuroendocrine response to lactate challenges in patients with panic disorder or agoraphobia with panic attacks.

Adolescent↗
PubMed1986

Hypercorticosteronuria and diminished pituitary responsiveness to corticotropin-releasing factor in obese Zucker rats.

Metabolic defects in obese (fa/fa) Zucker rats have previously been shown to be reversed by adrenalectomy; however, hypercorticosteronemia has not been demonstrated. We now report that the total daily excretion of corticosterone and urea nitrogen are significantly greater (P less than 0.01) in obese Zucker rats than in age-matched lean Zucker rats. This excessive excretion of corticosterone is not of autonomous adrenal origin, since dexamethasone treatment (20 micrograms/kg X day) for 2 days induced a proportionate reduction in corticosterone excretion (approximately 50%) in both obese and lean Zucker rats. Corticosterone excretion was further suppressed to levels not different from those in lean rats after 2 days of dexamethasone (40 micrograms/kg X day). Both the peak and total pituitary beta-endorphin secretion in response to an iv bolus of corticotropin-releasing factor (CRF) were diminished in obese Zuckers. The response to CRF in obese Zucker rats was dampened and superimposable on that of dexamethasone-treated lean Zucker rats, suggesting the existence of chronic hypercorticosteronemia as a component of this genetic obesity. These observations provide evidence for a compensatory alteration of the pituitary-adrenal axis. We suggest that corticosterone turnover may be increased in obese Zucker rats.

Animals↗
PubMed1986

Neuropeptide investigations with an ovine surgical model.

An ovine surgical model for peptide investigations is presented. Techniques for exteriorization of the carotid artery, catheterization of the sagittal sinus, hypophysectomy via a transnasopharyngeal approach, and ventricular and cisternal cannulation in the sheep are employed within the model. Several experimental applications in neurosurgical research are presented.

Anesthesia↗
PubMed1986

Endotoxic shock elicits greater endorphin secretion than hemorrhage.

Opiopeptides may contribute to the pathophysiology of both endotoxic and hemorrhagic shock. To determine if endorphin secretion is similar in both types of shock, we divided 25 sheep into three groups: a saline control group (n = 10), an endotoxin-treated group (n = 9), and a hemorrhage group (n = 6). Each sheep had baseline determinations of mean arterial pressure (MAP) and plasma levels of beta-endorphin-like immunoreactivity (iB-EP). Experimental animals either received endotoxin (450 ng/kg intravenous) or underwent withdrawal of blood volume sufficient to diminish MAP by approximately one-third of baseline values. MAP and iB-EP levels were determined every 15 minutes thereafter for 5 hours. Individual data were averaged within each group and then compared between groups using analysis of variance. Both the endotoxin- and hemorrhage-treated groups showed a significant fall in MAP, which was significantly lower in the hemorrhage group than the endotoxin group. Endotoxin-treated animals displayed a mean peak iB-EP level 1,550% above baseline as compared to a mean peak iB-EP level of only 201% above baseline in the hemorrhage-treated group, despite a significantly greater degree of hypotension in the latter group; this difference in peak iB-EP response was significant. Mean peak iB-EP levels coincided with mean trough MAP values in the endotoxin-treated group while the mean peak iB-EP lagged the onset of mean trough MAP in the hemorrhage group. These results demonstrate that iB-EP secretory patterns differ in endotoxic versus hemorrhagic shock and suggest that distinct mechanisms of opiopeptide secretion accompany the two shock states.

Animals↗