Plasma Epinephrine Levels Research Articles

Systemic absorption of epinephrine compared between the intranasal and intramuscular routes of administration in healthy adults.

Epinephrine 5 mg administered via the intranasal (IN) route was shown to be bioequivalent to epinephrine 0.3 mg administered via the intramuscular (IM) route in our preliminary study. To investigate the pharmacokinetics and pharmacodynamics of IN and IM epinephrine absorption in a larger group of healthy adults (n = 12). Each subject was administered IN saline, IN epinephrine (5 mg), and IM epinephrine (0.3 mg) on 3 separate days. Plasma epinephrine levels were determined using liquid chromatography-tandem mass spectrometry. IN epinephrine administration showed significant systemic absorption compared to IN saline control with the areas under the curve (AUC0-180 min) of 4.4 (4.9) ± 4.0 and 0.2 (0.5) ± 0.3 ng.min/mL, respectively; the values are mean (median) ± standard deviation. IN epinephrine absorption was about 0.5-fold that of IM epinephrine (AUC0-180 min 10.0 (9.2) ± 8.6 ng.min/mL), but the difference was not statistically significant (p = 0.16). The mean peak epinephrine concentration and the time to reach it were also not significantly different between the IN and IM routes. The corresponding values were 120 pg/mL and 41 min for IN, and 209 pg/mL and 41 min for IM, respectively. The systemic absorption of IN epinephrine 5 mg was significantly different from the control IN saline and about 0.5-fold that of IM epinephrine 0.3 mg. Although epinephrine administration via the less invasive IN route is safe and feasible, further investigations are necessary to achieve an adequate and consistent systemic absorption comparable to that of the conventional IM injection.

Yokukansan, a traditional Japanese medicine, suppresses stress-induced sympathetic activation and central responses to stress in rats

Stress exposure activates the sympathetic nervous system. We previously reported that restraint stress and stress-related neuropeptides increases plasma catecholamine levels and that brain prostanoids medicate these responses in rats. Yokukansan (YKS), a traditional Japanese medicine, has been used for neurosis, night crying and irritability. Additionally, it has been reported that YKS is also effective against the behavioral and psychological symptoms of dementia in patients with Alzheimer's disease, stress-related anxiety-like behavior and stress-induced increase in plasma corticosterone in rodents. These previous findings raise the possibility that YKS can exert its action in the brain and has suppressive effects on stress responses. In this study, we examined effects of YKS on stress-induced sympathetic activation and stress responses in the brain using rats. Repeated administration with YKS suppressed stress-induced increase in plasma adrenaline level. YKS also suppressed stress-induced elevation of prostaglandin E2 and thromboxane B2 levels in the paraventricular hypothalamic nucleus (PVN). In addition, YKS suppressed stress-induced increases of acetylcholine, GABA and serotonin in the PVN. Our results suggest that YKS can ameliorate stress-induced sympathetic activation via inhibition of stress responses in the brain.

Severe dysautonomia in glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus (PERM): A case report

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder. We report a 59-year-old man who presented with progressive encephalomyelitis causing diplopia, bulbar palsy, severe dysautonomia, followed by stiffness and myoclonic cluster. Laboratory tests showed mild pleocytosis, with markedly elevated plasma levels of norepinephrine, epinephrine, and arginine vasopressin. Glycine-receptor antibodies were identified in both serum and CSF. Despite a poor response to methylprednisolone, immunoglobulins, and plasma exchange, α-blocker stabilized dysautonomia. Dysautonomia is presumed to be due to antibody-mediated disinhibited sympathetic hyperactivity; however, this case suggests that concomitant use of α-blocker with immunotherapy may ameliorate dysautonomia.

Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats.

AimWe evaluated the efficacy of a novel brain permeable “metformin-like” AMP-activated protein kinase activator, R481, in regulating glucose homeostasis.Materials and MethodsWe used glucose sensing hypothalamic GT1-7 neuronal cells and pancreatic αTC1.9 α-cells to examine the effect of R481 on AMPK pathway activation and cellular metabolism. Glucose tolerance tests and hyperinsulinemic-euglycemic and hypoglycemic clamps were used in Sprague-Dawley rats to assess insulin sensitivity and hypoglycemia counterregulation, respectively.Results In vitro, we demonstrate that R481 increased AMPK phosphorylation in GT1-7 and αTC1.9 cells. In Sprague-Dawley rats, R481 increased peak glucose levels during a glucose tolerance test, without altering insulin levels or glucose clearance. The effect of R481 to raise peak glucose levels was attenuated by allosteric brain permeable AMPK inhibitor SBI-0206965. This effect was also completely abolished by blockade of the autonomic nervous system using hexamethonium. During hypoglycemic clamp studies, R481 treated animals had a significantly lower glucose infusion rate compared to vehicle treated controls. Peak plasma glucagon levels were significantly higher in R481 treated rats with no change to plasma adrenaline levels. In vitro, R481 did not alter glucagon release from αTC1.9 cells, but increased glycolysis. Non brain permeable AMPK activator R419 enhanced AMPK activity in vitro in neuronal cells but did not alter glucose excursion in vivo.ConclusionsThese data demonstrate that peripheral administration of the brain permeable “metformin-like” AMPK activator R481 increases blood glucose by activation of the autonomic nervous system and amplifies the glucagon response to hypoglycemia in rats. Taken together, our data suggest that R481 amplifies the counterregulatory response to hypoglycemia by a central rather than a direct effect on the pancreatic α-cell. These data provide proof-of-concept that central AMPK could be a target for future drug development for prevention of hypoglycemia in diabetes.

Clinical and Immune Responses of Peripheral Chemical Sympathectomy in Enterovirus 71 Infection.

The activation of the sympathetic nervous system, release of norepinephrine (NE), and adrenergic receptor signaling participate in and regulate the complicated enterovirus 71 (EV71) brainstem encephalitis (BE). The neurotoxin 6-hydroxydopamine (6-OHDA) selectively ablates sympathetic nerves and markedly depletes NE in innervated organs. Changes in the plasma levels of NE, severity score, cytokine profiles, and percentages of immunophenotype expression in 7-day-old Bltw : CD1 (ICR) mice infected with EV71, with or without 6-OHDA treatment, were compared. The survival rate (76.9%) of EV71-infected and 6-OHDA (30 μg/g)-treated mice was increased significantly. The clinical scores were decreased markedly on days 8-12 in MP4-infected and 6-OHDA-treated mice compared to those without treatment. The results showed that the plasma levels of NE, epinephrine, and dopamine were decreased on days 4–8 after 6-OHDA treatment and at most on day 8. The plasma levels of interleukin (IL)-12p70, tumor necrosis factor, IL-6, and IL-10 did not change significantly after 6-OHDA treatment. Interferon-γ levels decreased evidently on days 4, 6, and 8 after 6-OHDA treatment. The absolute events of CD3+CD4+, CD3+CD8+, and CD3+NK1.1+ cells of peripheral blood mononuclear cells were increased significantly in MP4-infected and 6-OHDA-treated mice compared to those without treatment. In splenocytes, the absolute cells of CD3−NK1.1+, CD3+NK1.1+ and CD11b+Gr-1+ cells of EV71-infected mice were increased significantly after 6-OHDA treatment. These findings suggested that 6-OHDA may be used a probe to explore clinical improvements and immune responses in the complicated EV71 infection. Taken together, peripheral chemical sympathectomy contribute to further understand the immunopathogenesis of EV71 BE with autonomic nervous system dysregulation.

Metoprolol attenuates intracerebral hemorrhage-induced cardiac damage by suppression of sympathetic overactivity in mice

The high rates of mortality and disability resulting from intracerebral hemorrhage (ICH) are closely related to subsequent cardiac complications. The mechanisms underlying ICH-induced cardiac dysfunction are not fully understood. In this study, we investigated the role of sympathetic overactivity in mediating cardiac dysfunction post ICH in mice. Collagenase-injection ICH model was established in adult male C57BL/6J mice. Neurological function was subsequently evaluated at multiple time points after ICH and cardiac function was measured by echocardiography on 3 and 14 days after ICH. Plasma adrenaline, noradrenaline, cortisol and heart β1 adrenergic receptor (β1-AR) levels were assessed to evaluate sympathetic activity. Picro Sirius Red (PSR) staining was performed to evaluate cardiomyocyte hypertrophy and interstitial fibrosis. Monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-6(IL-6), nuclear factor kappa-B(NF-κB), NADPH oxidase-2 (NOX2), matrix metalloprotein (MMP-9) and transforming growth factor-beta (TGF-β) levels were assessed to evaluate inflammation, fibrosis and oxidative stress levels in heart after ICH. Macrophages and neutrophils were assessed to evaluate inflammatory cell infiltration in heart after ICH. ICH induced sympathetic excitability, as identified by increased circulating adrenaline, noradrenaline, cortisol levels and β1-AR expression in heart tissue. Metoprolol-treated ICH mice had improved cardiac and neurological function. The suppression of sympathetic overactivity by metoprolol attenuates cardiac inflammation, fibrosis and oxidative stress after ICH. In conclusion, ICH-induced secondary sympathetic overactivity which mediated inflammatory response may play an important role in post-ICH cardiac dysfunction.

Abstract P192: Orthostatic Tolerance Before And After 60 Days Of Strict Head Down Tilt Bedrest With And Without Daily Artificial Gravity Training

Background: Orthostatic intolerance occurs after space flight, immobilization and in patients with autonomic diseases, so there is a need for more effective countermeasures. We hypothesized that daily artificial gravity elicited through short-arm centrifugation attenuates plasma volume loss and orthostatic intolerance following 60 days of HDTBR, which models cardiovascular responses to weightlessness. Methods: We studied 24 healthy persons (8 women, 33.4±9.3 yr, 24.3±2.1 kg/m2) exposed to 60d HDTBR. Subjects were assigned to 30 min/d continuous short arm centrifugation (cAG), 6x5 min short arm centrifugation (iAG), or a control group (ctr, no countermeasures). Head-up tilt testing (15 min of 80°) followed by incremental lower body negative pressure (-10 mmHg every 3 min) until presyncope was performed before and at the end of HDTBR. Plasma volume was measured (CO rebreathing) 12-2 days before and after 56d of HDTBR. Stroke volume was measured by cMRI. Norepinephrine, epinephrine, aldosterone, and renine plasma levels were measured before and after HDTBR. Results: Time to presyncope decreased in all groups following bedrest (ctr: 22:56 min pre and 9:35 min post, cAG 15:34 min pre and 10:11 min post; iAG 14:56 min pre and 10:00 min post, p<0.001). The significant interaction (p=0.025) between bedrest and intervention was explained by greater baseline orthostatic tolerance time in the ctr. AG Data was pooled analysis. The reduction in stroke volume (ctr, pre: 93±19 ml, HDTBR: 69±13 ml, AG, pre: 88±20 ml, HDTBR: 67±17 ml) and plasma volume was similar (ctr, pre: 4155±1085 ml, HDTBR: 3855±1087 ml, AG, pre: 4114±1250 ml, HDTBR: 3674± 1313 ml). Catechols and aldosterone did not change significantly during bedrest. The increase in renine was similar between groups (ctr pre: 18±12 mE/L, HDTBR: 21±8 mE/L, AG pre: 21±10 mE/L, HDTBR: 31±12 mE/L). Conclusions: 30 min daily AG didn’t prevent a reduction in orthostatic tolerance following 60d HDTBR. Whether numerically smaller reductions in orthostatic tolerance in the AG groups indicate efficacy or result from baseline differences can’t be ascertained. A stronger AG stimulus or combination with other countermeasures might be required to maintain orthostatic tolerance and to attenuate the volume reduction.

Gastric Leiomyoma Misdiagnosed as a Left Cystic Adrenal Tumor

Gastrointestinal leiomyomas often occur in the esophagus, colon, and rectum, but are very rare in the stomach. The patient was referred to Jeju national university medical center for the treatment of a left adrenal tumor diagnosed 5 years ago. She had a long history of repeated left flank pain, nausea, and abdominal distension for the last few years. Annual follow-up computed tomography scan showed a no changed 5×5.5-cm sized multiloculated left adrenal cystic lesion. Laboratory tests revealed that the basal levels of plasma adrenocorticotropin, cortisol, aldosterone, renin, testosterone, adrenaline, noradrenaline, and dopamine were normal findings. The preoperative diagnosis was a left nonfunctioning adrenal neoplasm with symptom of discomfort. However, the tumor revealed as an exophytic growing leiomyoma with cystic changes of a stomach by surgery. The mass was found at the posterior wall of the fundus and about 5-cm-sized mass. Resection of the tumor was performed using laparoscopy. The pathologic diagnosis revealed a gastrointestinal leiomyoma with a benign cystic lesion lined by respiratory epithelium with an old hemorrhage and chronic gastritis. The patient had no evidence of recurrence during the 12-month follow-up. Gastric leiomyoma is unfamiliar to the usual urologists. It needs to take gastric leiomyoma into account if the left adrenal tumor is close to the stomach. Herein, we report the case of a 44-year-old woman with gastrointestinal leiomyoma misdiagnosing as a nonfunctioning adrenal tumor.

Comparison of intraosseous and intravenous epinephrine administration during resuscitation of asphyxiated newborn lambs

ObjectiveIntraosseous access is recommended as a reasonable alternative for vascular access during newborn resuscitation if umbilical access is unavailable, but there are minimal reported data in newborns. We compared intraosseous...

Low Adrenomedullary Function Predicts Acute Illness in Infants With Classical Congenital Adrenal Hyperplasia.

Youth with classical congenital adrenal hyperplasia (CAH) exhibit abnormal adrenomedullary function with decreased epinephrine levels noted in newborns and young infants. Little is known about how this relates to morbidity during the first year of life. This work aimed to study plasma epinephrine levels in infants with classical CAH and examine the clinical significance of epinephrine deficiency in the first year of life. This prospective cohort study comprised participants recruited from a pediatric tertiary care center: 36 infants with classical CAH due to 21-hydroxylase deficiency and 27 age-matched unaffected controls with congenital hypothyroidism. Main outcome measures included plasma epinephrine levels (N = 27), CYP21A2 genotype (N = 15), and incidence of acute illnesses from birth to age 1 year (N = 28). Epinephrine levels in CAH infants independently predicted illness incidence in the first year of life (β = -0.018, R = -0.45, P = .02) and were negatively correlated with 17-hydroxyprogesterone at diagnosis (R = -0.51, P = .007). Infants with salt-wasting CAH exhibited lower epinephrine levels as newborns than simple-virilizing infants (P = .02). CAH patients had lower epinephrine as newborns than did controls (P = .007) and showed decreases in epinephrine from birth to age 1 year (P = .04). Null genotype was associated with lower newborn epinephrine and more illness in the first year of life, compared to less severe mutation categories. Lower epinephrine levels are associated with increased risk of illness among CAH infants. While not currently part of clinical standard of care, measuring epinephrine levels and assessing genotype may help predict acute illness in the first year of life.

Epinephrine to the Rescue: Identifying the Offending Side in Bilateral (B/L) Macronodular Adrenal Hyperplasia (BMAH) With Cushing Syndrome (CS) and Hyperaldosteronism

Management of ACTH-independent CS in the setting of B/L adrenal masses can be challenging. We present a patient with concomitant cortisol and aldosterone hypersecretion and B/L adrenal masses who was treated with unilateral adrenalectomy (UA) based on simultaneous B/L adrenal vein sampling (AVS) results normalized to plasma epinephrine levels, to correct for flow and dilution. A 60-year-old lady presented for evaluation of incidentally discovered B/L adrenal masses. CT abdomen with contrast revealed B/L lobulated adrenal glands measuring 3.4 x 5.5 x 4.1 cm on the right and 3.8 x 4.2 x 2 cm on the left (pre contrast density of 37 and 44 Hounsfield Units respectively). She had a recent diagnosis of HTN and prediabetes. She reported fatigue, easy bruising, and muscle weakness. Family history was notable for a sister with CS and B/L adrenal masses who was successfully treated with UA. On physical examination her BP was 160/94 mm Hg and she did not have an obvious cushingoid appearance. Laboratory testing included an elevated AM serum cortisol level of 16.6 mcg/dL following 1 mg of dexamethasone given at 11 pm the previous night. ACTH was <1.0 pg/mL consistent with ACTH-independent CS. She had a serum aldosterone level of 26.6 ng/dL(4.0 - 31.0 ng/dL),simultaneous plasma renin activity of 0.5 ng/ml/hr (0.5–4 ng/ml/hr) and serum potassium level of 4.4 mmol/l. She underwent B/L simultaneous AVS. Given concomitant hyperaldosteronism, plasma epinephrine levels were measured to determine successful catheter placement and to correct for flow and dilution between the adrenal veins. Right adrenal vein to peripheral vein cortisol ratio was 9.27 (> 6.5) consistent with cortisol hypersecretion. The right to left cortisol ratio was 2.3 (>/= 2.3), consistent with right sided predominance. Right to left ratio of the epinephrine corrected cortisol level was 2.7. She underwent right adrenalectomy, and pathology showed macronodular adrenal hyperplasia. Postoperatively, she had resolution of HTN and normalization of 24 hour urine free cortisol. UA is increasingly becoming recognized as a successful treatment for BMAH due to lower risk of adrenal crisis when compared to B/L adrenalectomy. In a recent publication, remission from CS was seen in 94.4 % of patients with BMAH following UA, with recurrence in 19% of patients. The mean time to recurrence was 5 years. We utilized cutoff values that were previously reported for cortisol lateralization in interpreting AVS. Our patient attained remission of CS 9 months post UA. Epinephrine levels were not significantly different between the adrenal veins, possibly due to simultaneous AVS, so we were also able to calculate epinephrine corrected cortisol ratios. Simultaneous B/L AVS with epinephrine to localize autonomous hypercortisolism in the setting of concomitant hyperaldosteronism can be beneficial in guiding surgical management of patients.

Mixed Corticomedullary Tumors of the Adrenal Gland Harboring Both Medullary and Cortical Properties

Adrenal cortex and medulla are derived from mesoderm and ectoderm, respectively. Mixed corticomedullary tumors (MCMTs), comprising an intimately admixed population of both adrenal cortical cells and pheochromocytes in a single adrenal tumor, are extremely rare and its pathogenesis has remained unknown. Here, we report a case of MCMT whose cells co-expressed cortical and medullary antigens in the same tumor cells.[Case description]A 40-year-old woman was referred to our hospital for investigating Takotsubo cardiomyopathy following resection of uterine fibroids. An abdominal CT scan depicted a 24 mm tumor on her left adrenal gland. Her basal serum ACTH, cortisol levels and urinary cortisol were 13.8 pg/mL, 9.5 μg/dL, and 26.5 μg/day respectively. The cortisol level was normally suppressed by an administration of 1 mg dexamethasone (1.4 μg/dL). Plasma renin activity, aldosterone levels and urinary aldosterone were 15.0 ng/mL/h, 122 pg/mL, and 5.0 μg/day, respectively (with administration history of azosemide). On the other hand, her plasma adrenaline and noradrenaline levels were elevated as high as 177 pg/mL and 536 pg/mL, and urinary metanephrine and normetanephrine were 2.12 mg/day and 1.10 mg/day. A 123I-metaiodobenzylguanidine scan revealed high uptake in the tumor. After adequate adrenergic α-receptor blockage, left adrenalectomy was performed. Her postoperative endocrine and clinical findings were normalized without any further complications.[Pathology] Immunohistochemistry (IHC) revealed the presence of MCMT. Cells morphologically consistent with pheochromocytoma and adrenocortical cells were confirmed by immunostaining of chromogranin A and SF-1, respectively. Chromogranin A-positive medullary-derived and SF-1-positive cortical-derived tumor cells were intermixed in the chimeric fashion. In addition, some tumor cells were positive for both proteins, indicating hybrid nature of the cells. Tumor cells of cortical origin expressed CYP11β1, 3β-HSD, p450c21, and p450c17, but not CYP11β2. Non neoplastic adrenal cortex were atrophic, whereas the glomerulosa was hyperplastic positive for CYP11β2, consistent with diffuse hyperplasia and adrenal medullar unremarkable. [Conclusions:]The adrenal tumor was clinically diagnosed as pheochromocytoma, but the pathological findings did reveal cortisol production in the tumor and aldosterone overproduction in the accompanying cortex. This is the first case of MCMT co-expressing adrenal medullary and cortical antigens in the same tumor cells as hybrid cells.

Cardiac AT 1 Receptor/β‐Arrestin Pathway is a Neonatal‐Specific Druggable Target for Pediatric Heart Failureβ

We recently found a novel neonatal-specific inotropic signaling pathway in murine cardiac myocytes (CMs): strong, long-lasting activation of L-type Ca2+ channels (LTCC) through AT1 receptor (AT1R), β-arrestin 2, and casein kinase 2α’. A peptidyl β-arrestin-biased AT1R agonist (BBA) activates β-arrestin and inhibits G protein after binding to AT1R. Taking our recent above finding into account, its effect was re-analyzed in neonatal mice and human induced pluripotent cell-derived CMs (hiPSC-CMs). BBA caused a significant long-acting positive inotropic but not chronotropic effect in neonatal mice. BBA significantly increased plasma adrenaline (but not serum aldosterone) levels. However, its inotropic effect was mediated by the cardiac AT1R/β-arrestin/LTCC pathway but not adrenaline. BBA significantly increased the peak twitch Ca2+ transients in isolated mouse neonatal ventricular CMs (mNVCMs) as well as hiPSC-CMs exhibiting fetal to neonatal phenotype. It moderately increased unloaded oxygen consumption of spontaneously beating mNVCMs by ~30% but not oxidative stress in the neonatal heart. BBA also significantly enhanced the contractility of the compromised heart of neonatal knock-in mice bearing a point mutation causing human congenital DCM. Therefore, cardiac AT1 receptor /β-arrestin pathway is a neonatal-specific druggable target for pediatric heart failure.

Effects of dietary fiber supplementation in gestation diets on sow performance, physiology and milk composition for successive three parities

The experiment was conducted to evaluate the effects of dietary fiber supplementation in gestation diets on sow performance, physiology and milk composition for three successive parities. Thirty gilts were assigned randomly to two groups, and fed a basal diet [CON group; 1.10 % soluble fiber (SF), 9.14 % insoluble fiber (ISF)] or a basal diet supplemented with 22.60 g/kg inulin and 181.60 g/kg cellulose [high-fiber (HF) group] during gestation period. The gestation diets provided to sows for three successive cycles averaged 2.28 kg/d from 1 to 112 d for the CON group; and corresponding values for the HF group were 2.75 kg. During lactation and empty, all sows were fed ad libitum a standard lactation diet. Sow body weight (BW) and backfat thickness, litter size and weight, parturition progress, placental weight and lactation feed intake were recorded. In parity 3, plasma samples were collected at gestation day 110 and parturition, and colostrum and milk samples were manually collected on lactation d 0 and 14, respectively. Results showed that averaged over three reproductive cycles, sows fed the HF diet farrowed more piglets born alive (P = 0.049) and litter weight (total born, P = 0.001; born alive, P = 0.001), increased placental weight (P < 0.001), lactation feed intake (P = 0.042), and average weaned pig BW (P = 0.014), and shortened parturition progress (P < 0.05); tended to have higher average pig BW total born (P = 0.092). Reproductive cycle had significant effects (P < 0.05) on sow BW, duration of parturition, placental weight, lactation feed intake, litter size and weight, and average pig BW. An interaction between fiber treatment and reproductive cycle was detected for placental weight. Sows fed the HF diet in parities 2 and 3 had greater placental weight than the other sows (P = 0.007). In addition, sows fed the HF diet had lower (P < 0.05) preprandial low-density lipoprotein and endotoxin concentrations, and greater (P < 0.05) plasma estrogen and lutropin concentrations on d 110 of gestation; had higher plasma oxytocin (P < 0.05) and epinephrine (P < 0.10) levels at farrowing compared with sows fed the CON diet. Colostrum and milk compositions were not influenced by the treatment. Above all, when the daily intake of the basal gestation diet was equalized for both treatments, dietary fiber supplementation to the gestation diet with an equal ISF/SF ratio over three reproductive cycles improved sow and litter performance.

Plasma dopamine and catecholamine levels in patients with central serous chorioretinopathy

To evaluate plasma dopamine and catecholamine levels in patients with central serous chorioretinopathy (CSCR). In this prospective study, 32 patients with acute CSCR were included, along with 32 age- and gender-matched healthy controls without CSCR. Complete ophthalmologic examinations were performed. Plasma dopamine, epinephrine, norepinephrine levels were measured in the morning after 8-12hours of fasting. A P-value of less than 0.05 was considered statistically significant. While the mean age of the CSCR group was 40.12±7.96 years, the mean age of the control group was 37.81±7.26 years. There was no statistically significant difference between the groups in terms of age or gender (P=0.229, P=0.740, respectively). The plasma dopamine level was 29.85±9.39pg/ml in the CSCR group and 23.93±7.33pg/ml in the control group (P=0.001). The plasma epinephrine level was 60.73±25.69pg/ml in the CSCR group and 45.77±18.55pg/ml in the control group (P=0.021). The plasma norepinephrine level was 206.68±71.51pg/ml in the CSCR group and 149.33±49.69pg/ml in the control group (P=0.001). Plasma dopamine, epinephrine, and norepinephrine levels were statistically significantly higher in the CSCR group. We concluded that dopamine may be a possible factor in the etiology of CSCR, both through its receptors and by enhancing sympathetic activity.

The Effects of Acute Glucoprivation on Adrenomedullary Function in SHR and WKY Rats

We have shown previously, acute intraperitoneal administration of 2-deoxy-d-glucose (2DG) into Sprague-Dawley rats led to activation of the adrenal medulla chromaffin cells, indicated with increased protein kinase activity and increased tyrosine hydroxylase (TH) phosphorylation, as well as increased plasma adrenaline and glucose levels. Here we have used spontaneous hypertensive (SHR) and Wistar Kyoto (WKY) rats to investigate whether hypertension alters basal adrenal chromaffin cell function, or the response of these cells to acute 2DG treatment. At basal level, we found no differences in adrenal medulla TH protein, TH phosphorylation, TH activity or catecholamine levels between SHR and WKY despite a significant difference in the level of systolic blood pressure; nor were there differences in plasma catecholamine levels or blood glucose (BG). Furthermore, the vehicle animals evoked no significant changes in any parameter measured in SHR, but evoked significant increases in pSer19TH, plasma adrenaline and BG in WKY. Single episode of glucoprivation evoked increases in PKA and CDK/MAPK, pSer40TH, pSer31TH, TH activity, and plasma adrenaline and BG in SHR, and in addition evoked increases in PKC, CAMKII, and pSer19TH in WKY. These findings are significant which indicates hypertension does not impact catecholamine function in the adrenal gland. It also appears that hypertension does not alter the adrenal response to glucoprivation. The findings are also significant as WKY showed greater adrenal activation of protein kinases and TH phosphorylation in response to saline and 2DG when compared to SHR and possible reasons for these findings are further discussed.

Clinical Study of Preemptive Analgesia with Hydromorphine on Postoperative Analgesia in Patients with Laparoscopic Hysterectomy

Pain after laparoscopic hysterectomy can lead to strong stress response, increase blood pressure and heart rate, restless during the awakening period. Preemptive analgesia is one of the methods to relieve postoperative pain. The purpose of this study is to explore the feasibility and safety of hydromorphine hydrochloride in preemptive analgesia, and to provide reference for clinical application. Two hundred American Society of Anesthesiologists I-II patients undergoing laparoscopic hysterectomy under endotracheal intubation general anesthesia from September 2019 to October 2020 were randomly divided into observation group (n=100) and control group (n=100) according to random number table. Patients in both groups were given intravenous rapid induction tracheal intubation combined with general anesthesia. 15 min before skin incision, hydromorphinone hydrochloride 15 μg/kg (diluted to 10 ml with normal saline) was injected intravenously in the observation group, while normal saline 10 ml was injected into the control group. Visual analogue score was used to evaluate the analgesic effect after tracheal extubation. Venous blood samples were taken 5 min before anesthesia and after extubation, and the levels of plasma epinephrine, norepinephrine and dopamine were measured. The mean arterial pressure and heart rate of the two groups were recorded before anesthesia, after operation, immediately after extubation, 10 min after extubation and 30 min after extubation. Ramsay sedation scale was used to evaluate the sedation of patients with 10 min, 30 min and 1 h after endotracheal tube extubation. Riker Sedation-Agitation Scale was used to observe the occurrence of restlessness in the recovery period within 24 h after operation. There was no significant difference in basic characteristics between the two groups (p>0.05). Visual analogue score: compared with the control group, the visual analogue scores at 10 min after extubation, 30 min after extubation, 1 h, 2 h, 4 h, 6 h and 12 h after endotracheal tube extubation in the observation group were significantly lower than those in the control group. There was no significant difference in the levels of plasma epinephrine, norepinephrine and dopamine between the two groups before anesthesia. After extubation, the levels of plasma epinephrine, norepinephrine and dopamine in the 5 min control group were significantly higher than those in the observation group (p<0.05). Hemodynamics (mean arterial pressure and heart rate in the control group were significantly higher than those in the observation group after operation, immediately after extubation, 10 min after extubation and 30 min after extubation in mean arterial pressure and heart rate): groups, and the difference was statistically significant. There was no significant difference in spontaneous respiratory recovery time and extubation time between the two groups (p>0.05). Ramsay sedation score: there was no difference between the two groups. Preemptive analgesia with hydromorphine hydrochloride in patients undergoing laparoscopic hysterectomy under general anesthesia has good analgesic effect, less postoperative adverse reactions, and can effectively inhibit cardiovascular reactions during recovery.

Plasma cerebellin levels in patients with central serous chorioretinopathy

PurposeTo evaluate levels of plasma cerebellin, cortisol, adrenaline and noradrenaline in patients with central serous chorioretinopathy (CSC). Materials and MethodsThis prospective study included 30 patients diagnosed with acute CSC (Group 1) and a control group of 30 age-matched, healthy subjects without CSC (Group 2). Levels of plasma cerebellin, cortisol, adrenaline and noradrenaline were examined in blood samples taken after 8-12hours of fasting. A value of p<0.05 was considered statistically significant in the comparative analyses. ResultsThe mean plasma cerebellin level was found to be 232.56±113.28 pg/ml in Group 1 and 174.07±82.04 pg/ml in Group 2 (p=0.02). Mean plasma cortisol was 13.19±3.87μg/ml in Group 1 and 9.55±2.92μg/ml in Group 2 (p<0.01). Mean plasma adrenaline was 60.62±26.67 pg/ml in Group 1 and 46.17±19.20 pg/ml in Group 2 (p=0.03). Mean plasma noradrenaline was 206.66±73.90 pg/ml in Group 1 and 149.96±51.36 pg/ml in Group 2 (p<0.01). ConclusionIt can be concluded that increased cerebellin may have a role in the etiology of CSC by increasing catecholamine expression from the adrenal medulla and indirectly by increasing cortisol levels via a paracrine effect from the adrenal cortex.

Intraoperative Pain Sensation During Cataract Surgery: Why Does Timing Matter?

ABSTRACT Purpose: To investigate whether timing influences pain perception during cataract surgery and to investigate the possible mechanisms. Methods: Patients scheduled for cataract surgery both in the morning and afternoon were consecutively enrolled. Questionnaires to evaluate anxiety, including the Simplified State–Trait Anxiety Inventory, Amsterdam Preoperative Anxiety and Information Scale, and a visual analogue scale (VAS) for anxiety, were completed preoperatively, whereas a VAS for pain and the Wong–Baker FACES® Pain Rating Scale questionnaire were completed after surgery. Preoperative blood pressure and heart rate were recorded. Blood samples were acquired before surgery, and plasma cortisol, adrenocorticotropic hormone, adrenalin, and noradrenalin were tested. Results: Fifty-five patients underwent uneverntful cataract surgery (28 in the morning and 27 in the afternoon) were included in the final analysis. Greater intraoperative pain perception during cataract surgery was reported in the afternoon than in the morning. Overall anxiety levels were significantly higher in the afternoon. Plasma adrenalin levels were significantly higher in the afternoon. Cortisol levels were higher in the afternoon. Preoperative anxiety levels were closely related to intraoperative pain perception. Both adrenalin and cortisol correlated positively with preoperative anxiety, but only adrenalin correlated significantly with the pain scores. Conclusions: Patients undergoing cataract surgery in the afternoon showed more preoperative anxiety, which may have increased their relevant stress hormones. Both the patient’s emotional state and hormone levels may together aggravate his/her perceived pain in the afternoon. Monitoring preoperative anxiety levels, blood pressure, and heart rate should help to identify patients at higher risk of perceived intraoperative pain. Clinical trial registration : Trial registration number: NCT02182921 Registration site: clinicaltrials.gov

The possible association between COVID-19 and postural tachycardia syndrome

The possible association between COVID-19 and postural tachycardia syndrome