Plasma Catecholamine Concentrations Research Articles

Effects of β‐adrenoceptor activation on haemodynamics during hypoxic stress in rats

What is the central question of this study? The acute hypoxic compensatory reaction is based on haemodynamic changes, and β-adrenoceptors are involved in haemodynamic regulation. What is the role of β-adrenoceptors in haemodynamics during hypoxic exposure? What is the main finding and its importance? Activation of β2 -adrenoceptors attenuates the increase in pulmonary artery pressure during hypoxic exposure. This compensatory reaction activated by β2 -adrenoceptors during hypoxic stress is very important to maintain the activities of normal life. The acute hypoxic compensatory reaction is accompanied by haemodynamic changes. We monitored the haemodynamic changes in rats undergoing acute hypoxic stress and applied antagonists of β-adrenoceptor (β-ARs) subtypes to reveal the regulatory role of β-ARs on haemodynamics. Sprague-Dawley rats were randomly divided into control, atenolol (β1 -AR antagonist), ICI118,551 (β2 -AR antagonist) and propranolol (non-selective β-AR antagonist) groups. Rats were continuously recorded for changes in haemodynamic indexes for 10min after administration. Then, a hypoxic ventilation experiment [15% O2 , 2200 m a.sl., 582 mmHg (0.765 Pa), 87.3 mmHg; Xining, China] was conducted, and the indexes were monitored for 5min after induction of hypoxia. Plasma catecholamine concentrations were also measured. We found that, during normoxia, the mean arterial pressure, heart rate, ascending aortic blood flow and pulmonary artery pressure were reduced in the propranolol and atenolol groups. Catecholamine concentrations were increased significantly in the atenolol group compared with the control group. During hypoxia, mean arterial pressure and total peripheral resistance were decreased in the control, propranolol and ICI118,551 groups. Pulmonary arterial pressure and pulmonary vascular resistance were increased in the propranolol and ICI118,551 groups. During hypoxia, catecholamine concentrations were increased significantly in the control group, but decreased in β-AR antagonist groups. In conclusion, the β2 -AR is involved in regulation of pulmonary haemodynamics in the acute hypoxic compensatory reaction, and the activation of β2 -ARs attenuates the increase in pulmonary arterial pressure during hypoxic stress. This compensatory reaction activated by β2 -ARs during hypoxic stress is very important to maintain activities of normal life.

Prophylactic use of intravenous tramadol vs intravenous nalbuphine for control of postspinal shivering after knee arthroscopy: a randomized double-blind placebo controlled trial

Abstract Background Post-anesthetic shivering refers to spontaneous, involuntary, rhythmic, oscillating and tremor-like muscle hyperactivity that increases metabolic heat production up to 600% after general or regional anesthesia. Shivering is not only subjectively unpleasant but is physiologically stressful because it elevates blood pressure, heart rate, oxygen consumption, and plasma catecholamine concentrations. Moreover, shivering may aggravate pain and hinder wound closure by simply stretching surgical incisions. Objective The aim of this work is to compare the efficacy of intravenous tramadol VS nalbuphine for prevention of post spinal shivering during knee arthroscopy. Methods This prospective randomized double blinded study was carried in Ain Shams University hospitals on 90 patients scheduled for knee arthroscopy. Patients were randomized into three groups 30 patients each: Group C: patients received normal saline 0.9%) intravenously. Group T: Patients received Tramadol 0.5 mg/kg intravenously. Group N: Patients received nalbuphine 0.1mg/kg intravenously. All drugs were given immediately after intra thecal injection of the anaesthetic drugs and returning to the supine position. Results The study revealed that the incidence of shivering was less in the tramadol (23.3%) and nalbuphine (26.7%) groups compared to the saline group (56.7%) (P < 0.05) with no significant difference between Nalbuphine and Tramadol groups (p > 0.05). The mean grade of shivering was comparable between the three groups (P > 0.05). Shivering onset was significantly earlier in the saline group (24.1±2.9 min) compared to Nalbuphine (32.3±4.9min) and Tramadol (36.4±4.3min) groups (P < 0.05) with no significant difference between Nalbuphine and Tramadol groups (p > 0.05). There were no significant differences among the three groups as regards hemodynamics (Heart rate and mean blood pressure), respiratory rate, oxygen saturations, body temperature, the incidence of nausea or vomiting (P > 0.05). While sedation grade was significantly highest in Nalbuphine group followed by Tramadol group and least in Saline group (P < 0.001). Conclusion The current study revealed that both tramadol 0.5mg/kg and balbuphine 0.1mg/kg was effective in prevention of post spinal shivering in patients undergoing knee arthroscopy.

КЛИНИЧЕСКОЕ И ПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ЭКСТРАСИСТОЛИЧЕСКОЙ АРИТМИИ У БЕРЕМЕННЫХ БЕЗ СТРУКТУРНЫХ ПОРАЖЕНИЙ СЕРДЦА

Pregnancy is accompanied by physiological hemodynamic changes (an increase in circulating blood volume, stroke volume, cardiac output, heart rate), autonomic (an increase in plasma concentrations of catecholamines, an increase in the sensitivity of adrenergic receptors) and hormonal changes (an increase in the synthesis of estrogen, progesterone, prostaglandins, reninogen, angiotensin) ... All this can contribute to a change in the excitability, automatism and refractoriness of the myocardium, lead to the development and / or an increase in its electrophysiological inhomogeneity and, thus, provoke and / or aggravate the course of an already existing arrhythmia. This article will consider the relevance of the problem of the clinical and prognostic significance of extrasystolic arrhythmia in pregnant women without structural heart damage. The goal of increasing the efficiency of predicting the course of ventricular extrasystole without structural heart lesions in pregnant women at various periods of gestation in terms of thyroid and cardiovascular hormones will be proposed. The study of indicators of pregnancy hormones in pregnant women at different gestational periods with ventricular extrasystole without structural heart damage, the study of indicators of the sinus node, atrioventricular node and refractory periods of the cardiac conduction system in pregnant women is an urgent issue for research at the present time.

Peri-operative management of pheochromocytoma with intravenous urapidil to prevent hemodynamic instability: A 17-year experience.

Background and Aims:Surgery for pheochromocytoma (PCC) can cause excessive catecholamine release with severe hypertension. Alpha blockade is the mainstay of preoperative management. The aim of this study was to evaluate the efficacy and tolerance of intra-venous (IV) urapidil, a competitive short acting α1 receptor antagonist, in the prevention of peri-operative hemodynamic instability of patients with PCC.Material and Methods:This retrospective observational study included 75 patients (79 PCC) for PCC removal surgery from 2001 to 2017 at the Bordeaux University Hospital. They received, 3 days before surgery, continuous intravenous infusion of urapidil with stepwise increase to the maximum tolerated dose. Urapidil was maintained during the procedure and stopped after clamping the adrenal vein. Plasma catecholamine concentrations were measured during surgery. Hypertensive peaks (SAP >160 mmHg) and tachycardia >100 beats/min were treated with boluses of nicardipine 2 mg and esmolol 0.5 mg/kg.Results:We recorded 20/79 (25%) cases with systolic arterial pressure (SAP) >180 mmHg. Only 11/79 (14%) had hypotension with SAP <80 mmHg. Peaks of catecholamine secretions were observed preferentially during peritoneal insufflation and tumor dissection (P < 0.05). A correlation was found between tumor size (mm) and the highest norepinephrine levels [r = 0.288, P = 0.015], and between hypertensive peaks (mmHg) and the highest norepinephrine levels [r = 0.45, P = 0.017]. No mortality was reported. The median [range] postoperative hospital stay was 4 [2–9] days.Conclusion:IV urapidil limits hypertensive and hypotensive peaks during PCC surgery, and corresponds to surgical imperatives allowing a short hospital stay, due to its “on–off” effect.

COULD PHEOCHROMOCYTOMA INDUCED CARDIOMYOPATHY BE INFLUENCED BY AN EXCESSIVE DELAY BEFORE DIAGNOSIS? DISCUSSION ABOUT TWO CASE-REPORTS

Objective: Different types of pheochromocytoma-related cardiomyopathies have been described in literature, but predictive factors of their occurrence and evolution are not yet defined. Here are described two successive clinical cases concerning this issue. Design and method: Case-report 1: A 26 year-old woman was admitted for abdominal pain lasting for ten days. Blood pressure (BP) was 150/100 mmHg. The EKG presented negative T waves on the precordial leads, and the trans-thoracic echocardiography (TTE) revealed a severe left heart dysfunction (Left Ventricular Ejection Fraction (LVEF) 20%). There was no significant coronary artery stenosis but left ventricular apical ballooning resembling Takotsubo cardiomyopathy on the cardiac angiography. Plasma concentration of catecholamines was increased to over 26 times their normal values. A 60x58x58 mm right adrenal mass was detected on computer tomography (CT). A laparoscopic adrenalectomy was performed. The diagnosis was confirmed by histology. Thereafter, BP normalized and TTE control assessed complete recovery. Case-report 2: A 35 years old man presented clinical heart failure, his BP measured at 150/100 mmHg. Medical history revealed high blood pressure, which had been detected for a year, without specific therapy thus far. He also described the classic triad of head-aches, palpitations, and diaphoresis. Hypertrophic cardiomyopathy, evocated by negative T waves on anterior leads on the EKG, was confirmed on TTE with an altered ejection fraction of 30%. Coronary catheterization was normal. Explorations found elevated plasma catecholamines level and a right adrenal tumor of 65X55X50 mm on CT. Pathologic examination of the resection specimen affirmed the diagnosis of pheochromocytoma. The clinical follow-up showed BP normalization, but persistence of an altered LVEF. Results: The severe acute clinical presentation of the first patient led to early diagnosis and treatment, with complete recovery. For the second one, the long term evolution of the disease before treatment may explain the poor improvement of the myocardiopathy. Conclusions: These two case-reports suggest that the form and evolution of pheochromocytoma-related cardiomyopathies depend on duration of catecholamine exposure, possibly in close relation with the length of diagnosis delay. This hypothesis could be tested by a larger follow-up of multiple cases of pheochromocytoma-related cardiomyopathies.

99-OR: Leptin Mediates Postprandial Thermogenesis through a Hypothalamic-Adrenomedullary-BAT Axis

The mechanism by which meal ingestion causes thermogenesis remains unknown. Here we show that refeeding leads to a 10x increase in plasma leptin concentrations associated with a 2.5x increase in plasma catecholamine concentrations in 48h-fasted lean rats. This leptin/catecholamine surge was associated with a 1°C increase in body temperature (BT) (fed 35.9±0.1°C, fasted 35.4±0.0°C, P&amp;lt;0.001; refed 36.4±0.1°C, P&amp;lt;0.001 vs. fasted and P&amp;lt;0.05 vs. fed). Leptin infusion in fasted rats replicated these increases in epinephrine and BT. However, the effect of leptin to increase BT was abrogated in adrenalectomized (ADX) rats following refeeding and leptin infusion. Treatment with a β1-adrenergic antagonist (atenolol) or surgical removal of brown adipose tissue (BAT) also prevented leptin- and refeeding-induced thermogenesis. The effect of refeeding to increase leptin and cause thermogenesis depended on the meal composition: a dextrose meal increased leptin, epinephrine, and BT whereas an isocaloric fat meal did not (AUC P&amp;lt;0.01, 0.05, and 0.01, respectively). Meal thermogenesis was not observed in obese rats, in which fasting plasma leptin failed to fall below the threshold (∼1.8 ng/mL) at which reductions in leptin lowered catecholamine concentrations. In order to examine the potential role for meal thermogenesis to regulate energy balance, we compared rats fed for 10 days with a carbohydrate-rich meal replacement by either two boluses daily or a continuous intragastric infusion. Bolus feeding increased BT and reduced BW gain (bolus feeding 0.1±0.3% weight loss vs. continuous feeding 1.7±0.3% weight gain, P&amp;lt;0.001), an effect abrogated by atenolol. Conclusion: Leptin induces postprandial thermogenesis through stimulation of the hypothalamic-adrenomedullary axis resulting in increased plasma catecholamines, which stimulate BAT through increased β1-adrenergic activity. These results provide a potential mechanism by which time-restricted feeding may improve metabolic health. Disclosure R.J. Perry: Research Support; Self; AstraZeneca. A. Rabin-Court: None. J. Dong: None. K. Lyu: None. X. Li: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research &amp; Development, Merck &amp; Co., Inc. Advisory Panel; Spouse/Partner; Merck &amp; Co., Inc. Board Member; Self; Novo Nordisk A/S. Consultant; Self; Aegerion Pharmaceuticals, IMetabolic BioPharma Corporation, Longitude Capital, Nimbus Discovery, Inc., Staten Biotechnology B.V. Funding National Institutes of Health (R01DK113984, P30DK059635, T32DK101019, K99/R00CA215315, R01NS087568, UL1TR000142, T32DK007058, R01DK075632, R01DK089044, R01DK096010, R01DK111401)

Cinnamaldehyde application decreases tail temperature in ovariectomized rats with and without estradiol administration.

The aim of this study was to examine the effect of estradiol (E2) on the thermoregulatory responses induced by cinnamaldehyde, a component extracted from cinnamon at 16 °C or 27 °C. The thermoneutral and subneutral experiments were performed to evaluate the augmented effect of cinnamaldehyde by cold exposure and the effect of cinnamaldehyde itself. Ovariectomized rats were implanted with a silastic tube with or without E2 (E2(+) and E2(-) groups), and data loggers into the peritoneal cavity. After the application of 30% cinnamaldehyde or vehicle into the skin of the whole trunk of rats, the rats were exposed to 16 °C or 27 °C for 2 h. Body temperature (Tb) and tail temperature (Ttail) were measured using a data logger and thermography. After exposure, blood samples were obtained, and plasma catecholamine concentration were measured by high-performance liquid chromatography. In the E2(-) group exposed to 27 °C, the change in Tb in rats applied cinnamaldehyde was significantly lower than that of rats applied vehicle. The change in Ttail in rats applied cinnamaldehyde was significantly lower than that of rats applied vehicle in both E2(-) and E2(+) groups at 27°C and 16°C. Plasma catecholamine concentration at 27°C was not different among the groups. E2 might not affect thermoregulatory responses induced by cinnamaldehyde application; however, it decreased Ttail in female rats.

Medex 2015: The key role of cardiac mechanics to maintain biventricular function at high altitude.

What is the central question of this study? This study is the first to investigate the effects of high-altitude trekking on biventricular mechanics, including measurements of left ventricular subendocardial and subepicardial function. What is the main finding and its importance? We provide new evidence that an increased contractility and untwisting efficiency, a key element of diastolic function, probably plays a key role in preservation of cardiac function during high-altitude trekking. Persistent increased loading conditions during several weeks at high altitude might have a key role in the appearance of left or right ventricular dysfunction. Cardiac responses to acute hypoxic exposure have been thoroughly investigated. We analysed the effects of high-altitude trekking (i.e. prolonged hypoxic exposure) on biventricular function, including the evaluation of subendocardial and subepicardial function in the left ventricle (LV). Resting evaluations of LV and right ventricular (RV) function and mechanics were assessed by speckle tracking echocardiography on 20 subjects at sea level and at high altitude (5085m, after a 10day ascent). Pulmonary artery systolic pressure was increased at high altitude (sea level, 13.1±5.9mmHg; high altitude, 26.6±10.8mmHg; P<0.001). Left ventricular volumes were decreased, whereas RV volumes were increased at high altitude. Alterations in pulmonary artery systolic pressure and cardiac volumes were correlated with hypoxaemia. We observed neither RV nor LV systolic dysfunction, including analysis of LV subendocardial and subepicardial function. Left ventricular systolic strain rates were enhanced at high altitude. Transmitral and transtricuspid diastolic filling ratios were decreased at high altitude. Diastolic apical rotational rate, untwisting rate and untwisting rate/peak twist ratio (i.e. untwisting efficiency) were enhanced at high altitude. We observed no echocardiographic signs of LV and RV pathological dysfunction at rest at high altitude. In contrast, our data highlighted major changes in the LV mechanics, with an increased LV contractility and a higher untwisting efficiency at high altitude. Biventricular interaction, alterations in loading conditions and an increase in plasma catecholamine concentration might partly explain these modifications. Thus, we demonstrated that LV mechanics (i.e. increased strain rates and untwisting efficiency) have a key role in preservation of cardiac function during high-altitude trekking.

External stress increases sympathoadrenal activity and prolongs the expulsive phase of foaling in pony mares

Mares usually give birth when they perceive their environment as safe and therefore disturbance at foaling may inhibit labor. In this study, foaling mares were transferred to an unfamiliar environment at rupture of the allantochorion (stress, n = 6) or were left undisturbed (control, n = 5). The progress of foaling, heart rate, heart rate variability (HRV) and plasma catecholamine, oxytocin and cortisol concentration were determined. In stressed mares, time from rupture of the allantochorion to appearance of the fetal feet (5.3 ± 1.1 vs. 1.6 ± 0.4 min) and total length of fetal expulsion were longer than in controls (both p < 0.05). Heart rate decreased during the expulsive phase of foaling in control mares (p < 0.01) but increased transiently in stressed mares. Heart rate calculated as percentage of the baseline was higher in stressed than in control mares (p = 0.05). HRV variables SDRR (standard deviation of the beat-to-beat interval) and RMSSD (root mean square of successive beat-to-beat differences) increased during foal expulsion (SDRR p < 0.01 and RMSSD p < 0.05). The increase in HRV was delayed in stressed compared to control mares (SDRR and RMSSD time x group p < 0.05). Plasma epinephrine and norepinephrine concentrations calculated as area under the curve for the expulsive phase of foaling were higher in stressed than control mares (p < 0.05). Concentrations of oxytocin and cortisol were elevated during foal expulsion (both p < 0.001) but not different between groups. In conclusion, disturbance of mares during expulsion of the foal prolonged foaling. This effect is most likely mediated via increased sympathetic activity and not inhibition of oxytocin release.

Dehydration and insulinopenia are necessary and sufficient for\xa0euglycemic ketoacidosis in SGLT2 inhibitor-treated rats

Sodium-glucose transport protein 2 (SGLT2) inhibitors are a class of anti-diabetic agents; however, concerns have been raised about their potential to induce euglycemic ketoacidosis and to increase both glucose production and glucagon secretion. The mechanisms behind these alterations are unknown. Here we show that the SGLT2 inhibitor (SGLT2i) dapagliflozin promotes ketoacidosis in both healthy and type 2 diabetic rats in the setting of insulinopenia through increased plasma catecholamine and corticosterone concentrations secondary to volume depletion. These derangements increase white adipose tissue (WAT) lipolysis and hepatic acetyl-CoA content, rates of hepatic glucose production, and hepatic ketogenesis. Treatment with a loop diuretic, furosemide, under insulinopenic conditions replicates the effect of dapagliflozin and causes ketoacidosis. Furthermore, the effects of SGLT2 inhibition to promote ketoacidosis are independent from hyperglucagonemia. Taken together these data in rats identify the combination of insulinopenia and dehydration as a potential target to prevent euglycemic ketoacidosis associated with SGLT2i.

Mechanism by Which Dapagliflozin Induces Euglycemic Ketoacidosis in Rats

Sodium-glucose transport protein 2 inhibitors (SGLT2i) are the most recent class of antidiabetic agents; however concerns have been raised about their potential to induce euglycemic ketoacidosis by an unknown mechanism. Here we report that dapagliflozin increases rates of hepatic ketogenesis (35±4 vs. 136±8 μmol/[kg-min], p&amp;lt;0.0001) in normal Sprague-Dawley rats by increasing plasma catecholamine (epinephrine 0.5±0.1 vs. 7.3±0.5 nM, p&amp;lt;0.001, norepinephrine 2.5±0.5 vs. 19.8±5.2 nM, p&amp;lt;0.01) and corticosterone (115±15 vs. 233±28 ng/mL, p&amp;lt;0.01) concentrations secondary to volume depletion (weight change -1.9±0.4% vs. -7.1±0.4%), thereby increasing white adipose tissue lipolysis, hepatic acetyl-CoA content, hepatic glucose production and hepatic ketogenesis. Dapagliflozin-induced reductions in plasma insulin concentrations were shown to be necessary but not sufficient to induce these changes since the effects of dapagliflozin to increase hepatic ketogenesis were abrogated when extracellular volume depletion was prevented with saline infusion or free access to water. Furosemide treatment induced similar volume depletion and increases in plasma catecholamine and corticosterone concentrations without any associated changes in WAT lipolysis, hepatic glucose production or hepatic ketogenesis, likely due to its lack of an effect on plasma insulin levels. Furthermore the effects of dapagliflozin to promote increased rates of hepatic ketogenesis and hepatic glucose production were dissociated from changes in plasma glucagon concentrations, which increased (89.5±3.8 vs. 379.2±11.8 ng/mL, p&amp;lt;0.0001) through a central mechanism following ICV injection of dapagliflozin without any alterations in body weight or ketosis, and hepatic malonyl-CoA. Taken together these data identify SGLT2i-induced dehydration as a potential target to prevent SGLT2i-induced euglycemic ketoacidosis. Disclosure R.J. Perry: None.J.D. Song: None.Y. Wang: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research &amp; Development, Merck &amp; Co., Inc., Novo Nordisk Inc.. Research Support; Self; Gilead Sciences, Inc..

Effects of intravenous thyrotropin-releasing hormone on 18F-fluorodeoxyglucose uptake in human brown adipose tissue: a randomized controlled trial.

Brown adipose tissue (BAT) activity in humans is stimulated by cold and by a limited number of pharmacological agents, including β3-adrenergic agonists and bile acids. Although thyrotropin-releasing hormone (TRH) is known to activate BAT in several mammals, this has not been reported in humans. A randomized, placebo-controlled, double-blind, cross-over trial. We investigated the effects of intravenous bolus administration of 400 µg TRH or 2 mL saline on BAT activity in healthy, lean men. BAT activity was measured as standardized 18F-fluorodeoxyglucose (18F-FDG) uptake and glucose metabolic rate (MRglu) using dynamic PET/CT imaging. The first six individuals were studied at room temperature, while subsequently nine were exposed to mild cold (17°C ± 1°C) for 60 min before imaging. During the dynamic scan, blood was withdrawn for measurement of thyroid hormone and catecholamine concentrations. This trial is registered with The Netherlands National Trial Register (number NTR5512). Sixteen participants were recruited. Six men studied at room temperature showed no visible BAT activity during either session. After exposure to mild cold, four of nine men (44.4%) showed clear increase of 18F-FDG uptake after TRH administration compared to placebo. Maximal standardized 18F-FDG uptake showed a trend toward increase after TRH compared to placebo (P = 0.066). MRglu showed a significant increase after TRH administration (P = 0.014). The increase in 18F-FDG uptake was not paralleled by changes in plasma thyroid hormone or catecholamine concentrations. Systemic TRH administration can increase the activity of cold-stimulated BAT in adult men. These findings may assist developing pharmacological strategies for modulating BAT activity in the management of obesity.

Subcutaneously administered dexmedetomidine is efficiently absorbed and is associated with attenuated cardiovascular effects in healthy volunteers.

Palliative care patients often need sedation to alleviate intractable anxiety, stress, and pain. Dexmedetomidine is used for sedation of intensive care patients, but there is no prior information on its subcutaneous (SC) administration, a route that would be favored in palliative care. We compared the pharmacokinetics and cardiovascular, sympatholytic, and sedative effects of SC and intravenously (IV) administered dexmedetomidine in healthy volunteers. An open two-period, cross-over design with balanced randomization was used. Ten male subjects were randomized to receive 1μg/kg dexmedetomidine both IV and SC. Concentrations of dexmedetomidine and catecholamines in plasma were measured. Pharmacokinetic variables were calculated with non-compartmental methods. In addition, cardiovascular and sedative drug effects were monitored. Eight subjects completed both treatment periods. Peak concentrations of dexmedetomidine were observed 15min after SC administration (median; range 15-240). The mean bioavailability of SC dexmedetomidine was 81% (AUC0-∞ ratio × 100%, range 49-97%). The mean (SD) peak concentration of dexmedetomidine in plasma was 0.3 (0.1) ng/ml, and plasma concentrations associated with sedative effects (i.e., > 0.2ng/ml) were maintained for 4h after SC dosing. Plasma noradrenaline concentrations were significantly lower (P< 0.001) within 3h after IV than after SC administration. Subjective scores for vigilance and performance were significantly lower 0-60min after IV than SC dosing (P< 0.001 for both). The onset of the cardiovascular, sympatholytic, and sedative effects of dexmedetomidine was clearly less abrupt after SC than IV administration. Dexmedetomidine is relatively rapidly and efficiently absorbed after SC administration. Subcutaneous dexmedetomidine may be a feasible alternative in palliative sedation, and causes attenuated cardiovascular effects compared to IV administration. CLINICALTRIALS. NCT02724098 . EUDRA CT number 2015-004698-34 .

Differential responses of autonomic function in sea level residents, acclimatized lowlanders at >3500 m and Himalayan high altitude natives at >3500 m: A cross-sectional study

We studied the differential responses of autonomic function in sea level residents (SLR), acclimatized lowlanders (ALH) in high altitude (HA) and HA natives (HAN) at >3500 m. Out of 771 male volunteers included in this cross-sectional study, SLR, ALH and HAN groups were comprised of 351, 307 and 113 volunteers, respectively. Our results showed persistent sympathetic dominance with significantly reduced (p < 0.05) parasympathetic response in ALH as compared to SLR and HAN populations. This may be attributed to significantly increased (p < 0.05) concentration of coronary risk factors and plasma catecholamines in ALH as compared to SLR and HAN. The ALH also showed significantly increased (p < 0.05) level of serum homocysteine as compared to SLR. The HAN exhibited no changes in autonomic function despite significantly elevated (p < 0.05) homocysteine level as compared to SLR. Our findings may have clinical relevance for assessment of susceptibility to cardiovascular risks in HA dwellers, native highlanders and patients with hypoxemia.

Analysis of Stress Indicators for Evaluation of Animal Welfare and Meat Quality in Traditional and Jewish Slaughtering.

Simple SummaryCortisol and catecholamines (dopamine, norepinephrine and epinephrine) are released in response to stress and directly stimulate glycogen mobilization, thus influencing meat acidification. The aim of the study was to estimate and compare these stress indicators to evaluate the welfare of beef cattle, subjected to either traditional slaughtering (with stunning) or to slaughtering with religious Jewish rite (without stunning). Significant differences in plasma cortisol and catecholamine levels were observed during exsanguination by monitoring animals in the pre-slaughtering (before and after transportation) and slaughtering phases. Cortisol, dopamine and norepinephrine, but not epinephrine, were markedly higher in the animals slaughtered by the religious rite. Pursuing animal welfare in the religious slaughtering procedures could produce advantages in terms of hygiene, organoleptic quality and shelf life of meat.Sixty Charolais male beef cattle of eight months of age were divided into two groups according to the slaughtering method, i.e., traditional or Kosher (religious Jewish rite). The aim of the study was to detect and compare the plasma concentrations of cortisol and catecholamines (dopamine, norepinephrine and epinephrine), by Elisa and HPLC test. These four stress indicators were evaluated during three different stages of each animal productive life: on the farm (step 1), after transportation (step 2) and during bleeding (step 3). The patterns of the parameters measured were similar and, interestingly, revealed significant changes throughout the three steps considered. The greatest variation between the two methods of slaughtering was observed in step 3, where we found a statistically significant difference with all the parameters except epinephrine. In the animals slaughtered by the religious rite, cortisol, dopamine, norepinephrine and epinephrine were 68.70 ± 30.61 nmol/L; 868.43 ± 508.52 ng/L; 3776.20 ± 1918.44 ng/L; and 4352.20 ± 3730.15 ng/L, respectively, versus 45.08 ± 14.15 nmol/L; 513.87 ± 286.32 ng/L; 3425.57 ± 1777.39 ng/L; and 3279.97 ± 1954.53 ng/L, respectively, in the other animals. This suggests that the animals slaughtered by the Kosher rite are subjected to higher stress conditions at the exsanguination phase. The animals slaughtered by the religious Jewish rite showed lower cortisol and catecholamine levels on the farm (step 1) and after transportation to the slaughterhouse (step 2). This was likely because the animals selected at the end of step 1 by the Rabbis for the religious rite are usually the most docile and gentle.

Survey on basal blood plasma catecholamine concentrations in Martina Franca donkey (Equus asinus).

Catecholamines are among the most frequently investigated parameters for studying sympathoadrenal activity in response to stress conditions. To evaluate basal plasma concentrations of catecholamines (adrenaline, noradrenaline and dopamine) in healthy donkeys. Cross-sectional study. Catecholamine concentrations from 440 Martina Franca donkeys were determined: 269 females and 171 entire males, aged from 4 months to 24 years. Animals were subdivided into four age categories: under 12 months old (64 males and 54 females), from 13 to 36 months (56 males and 75 females), from 37 to 120 months (49 males and 80 females) and over 120 months (24 males and 38 females). Indwelling jugular catheters were inserted at least 12 h before drawing blood. The data set was subjected to analysis of variance considering age, sex and the two-way interaction between them as independent variables. Pearson's correlation coefficients between the three catecholamines were evaluated. Confidence intervals (CI) for noradrenaline concentration ranged between 239.98 and 255.07 ng/L (mean 247.52 ng/L), for adrenaline between 129.27 and 137.90 ng/L (mean 133.59 ng/L), dopamine concentrations between 149.62 and 160.80 ng/L (mean 155.21 ng/L) and noradrenaline/adrenaline ratio between 1.91 and 2.05 (mean 1.98). Catecholamine plasma concentrations were not influenced by sex. Donkeys older than 37 months had lower adrenaline and noradrenaline plasma concentrations (P<0.001) and higher noradrenaline/adrenaline ratios (P<0.01) than younger animals. Indwelling catheters and blood drawing procedures may have influenced catecholamine levels. Catecholamine concentrations were established within a large group of healthy Martina Franca donkeys.

Facile synthesis of boronic acid-functionalized magnetic metal-organic frameworks for selective extraction and quantification of catecholamines in rat plasma.

Precise determination of the endogenous catecholamines, dopamine (DA), epinephrine (E) and norepinephrine (NE) faces substantial challenges due to their low physiological concentrations in plasma. We synthesized, for the first time, a magnetic metal–organic framework (MIL-100) composite with boronic acid-functionalized pore-walls (denoted as MG@MIL-100-B composite) using a metal–ligand-fragment coassembly (MLFC) strategy. The composites were then applied as an effective magnetic solid-phase extraction (SPE) sorbent for determination of trace catecholamine concentrations in rat plasma through coupling with HPLC-MS/MS. The obtained nano-composites exhibited high magnetic responsivity, uniform mesopores, large specific surface area, and boronic acid-functionalized inner pore-walls. Catecholamines in rat plasma were extracted through interaction between the cis-diol structures and the boronic acid groups in the MG@MIL-100-B composites. Extraction conditions were optimized by studying SPE parameters including adsorption and desorption time, elution solvent type, pH conditions and adsorbent amount. With our approach, the detection limits (S/N = 3) were as low as 0.005 ng mL−1 for DA and E, and 0.02 ng mL−1 for NE. Intra- and inter-day precision ranged from 2.84–6.63% (n = 6) and 5.70–11.44% (n = 6), respectively. Recoveries from spiking experiments also showed satisfactory results of 94.40–109.51%. Finally, the MG@MIL-100-B composites were applied successfully to determine catecholamine concentrations in rat plasma.

Effects of Dexmedetomidine Infusions on Hemodynamic Stability in Patients undergoing Laparoscopic Cholecystectomy

Abstract Objectives: In laparoscopic cholecystectomy, there has been emphasis on maintaining hemodynamic stability by avoiding hypertension, hypotension, or tachycardia. The hemodynamic instability is persistent during the duration of pneumoperitoneum (PNP), namely, CO2 insufflations. This study helps us to find out the efficacy of dexmedetomidine on cardiovascular system stability in patients undergoing laparoscopic cholecystectomy. Materials and methods: Thirty patients were randomized into two groups of 15 members each: group P (placebo group) and group D (dexmedetomidine group). In the former, patients received 0.9% 20 mL normal saline, while in the latter, patients received 0.4 μg/kg/hr of injection dexmedetomidine in 0.9% normal saline. In all patients, age, weight, height, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded. Results: Dexmedetomidine being a highly selective and potent and specific alpha 2 agonist attenuates the hemodynamic response to tracheal intubation, decreases plasma catecholamine concentration during anesthesia, and decreases perioperative requirements of inhaled anesthetics. We found that dexmedetomidine helped in blunting the pressor response during the intubation, kept the HR and mean arterial pressure stable intraoperatively, and there was faster recovery as the requirement of inhalation agent was decreased intraoperatively. Conclusion: The drug dexmedetomidine maintained cardiovascular stability during laparoscopic cholecystectomy. The inhalational agent (isoflurane) requirement was found to be considerably lower. Also, the mean recovery time as indicated by the ability to vocalize following extubation was found to be significantly less. Hence, it can be recommended in laparoscopic cholecystectomy for maintaining cardiovascular system stability.

Oxygénothérapie à haut débit au cours de l’insuffisance respiratoire aiguë : nouvelles avancées physiologiques et cliniques: High-flow oxygen therapy in acute respiratory failure: New physiological and clinical advances

To evaluate the dose-effects of Androctonus australis hector (Aah) venom injected subcutaneously on hemodynamics and neurohormonal secretions, 10 anesthetized and ventilated mongrel dogs, were split in two groups (n = 5/group). Subcutaneous injection was done with either 0.2 mg/kg or 0.125 mg/kg of the purified G50 scorpion toxic fraction. Hemodynamic parameters using right heart catheter were recorded and plasma concentrations of catecholamine, troponin, and serum toxic fraction were measured sequentially from baseline to 120 min.We identified the dose of toxic fraction evoking characteristic hemodynamic perturbation of severe envenomation, the time-lapse to envenomation, and the associated plasma level.The injection of 0.125 mg/kg toxic fraction was not associated with significant variations in hemodynamic parameters, whereas the 0.2 mg/kg dose caused envenomation characterized by significant increase in plasma catecholamines, increased pulmonary artery occluded pressure, mean arterial pressure, and systemic vascular resistance (p < 0.05), in association with sustained decline in cardiac output (p < 0.001). Envenomation occurred by the 30th minute, and the corresponding concentration of toxic fraction was 1.14 ng/ml.The current experiment allowed the identification of the sub-lethal dose (0.2 mg/kg) of the toxic fraction of Aah administered by the subcutaneous route. Two parameters with potential clinical relevance were also uncovered: the time-lapse to envenomation and the corresponding concentration of toxic fraction.

Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency.

Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short- and long-term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β-cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7-day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin-stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants.