Increase In Plasma Catecholamine Concentrations Research Articles

COMPARISON OF DEXMEDETOMIDINE VERSUS FENTANYL IN ATTENUATING PRESSOR RESPONSE DURING LARYNGOSCOPY AND ENDOTRACHEAL INTUBATION

Background and objectives: Laryngoscopy and intubation is associated with a sympathetic response that results in a rapid increase in blood pressure and heart rate. The mechanisms underlying these hemodynamic changes are incompletely understood. They may be caused by a reex sympathetic discharge due to stimulation of the upper respiratory tract. It has been observed that hemodynamic responses to tracheal intubation are associated with an increase in plasma catecholamine concentrations and are attenuated by β-adrenergic blockade. This study was conducted to compare the efcacy of dexmedetomidine and fentanyl for attenuation of pressor response during laryngoscopy and intubation. Materials and methods Following approval by ethical committee, 60 ASA grade I and II patients of either sex undergoing general anaesthesia for elective surgery were included in this study. Patients were randomly divided into two groups of 30 patients each. Dexmedetomidine in a dose of 1μg/kg i.v was given to Group A patients and Fentanyl 2 μg/kg i.v was given to Group B patients. Both the drugs were diluted with normal saline solution to make 10ml and were administered slow intravenous 10 min before induction. The hemodynamic parameters were recorded, demographic data was analyzed using unpaired t-test and hemodynamic variables were analyzed by using unpaired and paired t-test. Side effects were analyzed using chi square test. Result: The two groups were comparable in their demographic proles. Dexmedetomidine proved itself to be an excellent drug when given intravenously in dose of 1μg/kg to attenuate hemodynamic response to laryngoscopy and intubation. It blunted the hemodynamic response to laryngoscopy and intubation to a greater magnitude than fentanyl in a dose of 2μg/kg intravenously as a premedication. Conclusion: We conclude that fentanyl 2μg/kg i.v. given ten minutes prior to airway instrumentation shows an inconsistent response to laryngoscopy and intubation. Between the two drugs under study, the use of dexmedetomidine 1μg/kg i.v. is satisfactory and produces a more favorable hemodynamic prole while fentanyl 2μg/kg is found to be non- dependable and less effective for the attenuation of the pressor response to laryngoscopy and endotracheal intubation.

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<0.001; refed 36.4±0.1°C, P<0.001 vs. fasted and P<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<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<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 & Development, Merck & Co., Inc. Advisory Panel; Spouse/Partner; Merck & 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)

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.

Comparative Evaluation of Lightwand (Lighted Stylet) with Direct Laryngoscopy on Hemodynamic Response- A Prospective Study

Background:Laryngoscopy and tracheal intubation are often associated with hypertension, tachycardia, and an increase in plasma catecholamine concentrations. The present study was done to compare the hemodynamic response during tracheal intubation, guided by either Lightwand or Direct laryngoscopy. Method and patients: Seventy adult consented patients of ASA I or II aged 18-58 years of either sex scheduled for elective surgeries from September 2011 to March 2013 were randomized according to sealed envelopes into two groups of 35 patients each. The patients of Group LWI were intubated with lighted stylet (Lightwand, GE) and patients of Group DLI were intubated using direct laryngoscope (Macintosh). Any patient with history of systemic hypertension and cardiopulmonary disease, hepatic, renal or endocrine disorder, difficult airway or MP Grade III & IV, history of previous difficult tracheal intubation or patient who required more than 30 seconds or more than one attempt for intubation were excluded. The anesthetic induction technique was standardized. The hemodynamic parameters of heart rate, blood pressure and ECG were recorded, at baseline, after induction, after tracheal intubation and then at regular interval of 1 min for 5 min after tracheal intubation. Intubation time was noted by stopwatch. Results: There was no significant difference in demographic profile, in terms of changes in blood pressure and heart rate during laryngoscopy and after tracheal intubation between groups. Post intubation dysphasia, hoarseness, sore throat were also comparable between the groups. Conclusion: The effects of Lightwand technique on hemodynamic response to tracheal intubation were similar to those of direct laryngoscopy.

Role of salsolinol in the regulation of pituitary prolactin and peripheral dopamine release.

(R)-Salsolinol (SAL), a dopamine (DA)-related tetrahydroisoquinoline, has been found in extracts of the neuro-intermediate lobes (NIL) of pituitary glands and in the median eminence of the hypothalamus obtained from intact male rats and from ovariectomized and lactating female rats. Moreover, analysis of SAL concentrations in NIL revealed parallel increases with plasma prolactin (PRL) in lactating rats exposed to a brief (10 min) suckling stimulus after 4-h separation. SAL is sufficiently potent in vivo to account for the massive discharge of PRL that occurs after physiological stimuli (i.e. suckling). At the same time, it was without effect on the secretion of other pituitary hormones. It has been also shown that another isoquinoline derivative, 1-methyldihydroisoquinoline (1MeDIQ), which is a structural analogue of SAL, can dose-dependently inhibit the in-vivo PRL-releasing effect of SAL. Moreover, 1MeDIQ can inhibit the elevation of plasma PRL induced by physiological stimuli, for example suckling, or in different stressful situations also. 1MeDIQ also has a psycho-stimulant action, which is fairly similar to the effect of amphetamine, i.e. it induces an increase in plasma catecholamine concentrations. It is clear from these data that this newly discovered endogenous compound could be involved in regulation of pituitary PRL secretion. It has also been observed that SAL is present in peripheral, sympathetically innervated organs, for example the atrium, spleen, liver, ovaries, vas deferens, and salivary gland. Furthermore, SAL treatment of rats results in dose-dependent and time-dependent depletion of the DA content of the organs listed above without having any effect on the concentration of norepinephrine. More importantly, this effect of SAL can be completely prevented by amphetamine and by 1MeDIQ pretreatment. It is clear there is a mutual interaction between SAL, 1MeDIQ, and amphetamine or alcohol, not only on PRL release; their interaction with catecholamine "synthesis/metabolism" of sympathetic nerve terminals is also obvious.

Marked increases in plasma catecholamine concentrations precede hypotension and bradycardia caused by 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in conscious rats

Plasma noradrenaline and adrenaline responses to 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a selective putative 5-HT1A receptor agonist, have been studied in conscious, freely moving rats. Intravenously administered 8-OH-DPAT caused dose-related and sustained increases in plasma noradrenaline (2-fold) and adrenaline (11-fold) concentrations. Neither metergoline pretreatment (0.5 mg kg-1 i.v.) nor splanchnicectomy had any effect on the noradrenaline and adrenaline elevation caused by 8-OH-DPAT (250 micrograms kg-1 i.v.). The catecholamine responses peaked early but were still present during nadirs in blood pressure and heart rate. The discrepancy between plasma catecholamine and cardiovascular changes raises further questions about the mechanism of action of 8-OH-DPAT and supports other evidence suggesting a role for vagus stimulation in the cardiovascular effects caused by this drug.

Effects induced by exercise on lymphocyte β-adrenergic receptors and plasma catecholamine levels in performance horses

The effect of dynamic exercise on complete blood cell count, lymphocyte β-adrenergic receptor and plasma catecholamine (adrenaline and noradrenaline) levels in horses performing different disciplines were investigated during rest and after exercise. Blood samples were collected from jumping horses ( n = 6), Arabian Endurance horses ( n = 6) and Standardbred trotters ( n = 6) before and immediately after competition. Dynamic exercise caused a significant increase in red blood cell count (Standardbred trotters: P = 0.0012), haemoglobin concentration (jumping horses: P = 0.001; Standardbred trotters: P = 0.01), haematocrit percentage (Standardbred trotters: P = 0.005), neutrophil percentage (jumping horses: P = 0.0003), lymphocyte percentage (jumping horses: P = 0.0003), monocyte percentage (Standardbred trotters: P = 0.0008), lymphocyte β-AR numbers (jumping horses: P = 0.01; Arabian Endurance horses: P = 0.016; Standardbred trotters: P = 0.05), plasma adrenaline concentration (Standardbred trotters: P = 0.0001) and plasma noradrenaline levels (Standardbred trotters: P = 0.003). It is concluded that acute increases in plasma catecholamine concentrations depended on the exercise performed and may induce up-regulation of β-AR in equine lymphocytes. However, the exact mechanism of β-AR up-regulation still remains unclear.

Maternal Separation and Lesion of Adtn Alters Anxiety And Adrenal Activity in Male Rats

The present study investigated the effect of early maternal separation on anxiety and hypophyso-adrenal system activity to anterodorsal thalamic nuclei (ADTN) lesion in male rats as adults in order to compare this with previous results with female rats. During the first 3 weeks of life, male rats were isolated 4.5 hr daily and tested as adults. Thirty days after ADTN lesion we found that adrenocorticotropic hormone (ACTH) plasma levels were affected neither by maternal separation nor by ADTN lesion. Plasma corticosterone (CORT) concentration was increased with lesion of the ADTN in maternally separated rats. A significant increase in plasma catecholamine concentration was induced by early maternal separation. In ADTN-lesioned rats, plasma norepinephrine (NE) concentration was significantly lower than in the respective sham-lesioned groups. In terms of anxiety, there were no significant effects of early experience. However, the ADTN lesion tended to decrease anxiety-related behavior.

Anaesthetic management of Wolff Parkinson White syndrome for caesarean section

We present two cases of WPW syndrome in pregnancy. Risk factors for development of supraventricular tachycardia and the anaesthetic management during caesarean section are discussed. We recommend that regional anaesthesia can be given in patients with WPW syndrome; Phenylephrine is the best vasopressor for treatment of hypotension during spinal blockage and Adenosine is the first line therapy for the acute termination of PSVT. In women of reproductive age, the commonest arrhythmia seen is paroxysmal supraventricular tachycardia (SVT).1 Wolf Parkinson White syndrome accounts for the majority of supraventricular tachycardia in this population; with an incidence of 1.2 per 1000 people. Over half of these patients are asymptomatic.2Patients may complain of palpitation, dizziness, syncope or shortness of breath. The diagnosis is confirmed by E.C.G. The incidence and severity of tachyarrhythmia in these patients may increase during pregnancy. Although reasons for this observation are unclear, some explanations have been proposed. Increased awareness, hemodynamic, hormonal, autonomic and emotional changes related to pregnancy, which may include increase in plasma catecholamine concentrations and adrenergic receptor sensitivity, atrial stretch and increased end diastolic volumes due to intravascular volume expansion have been implicated as some of the reasons.3 We present two cases of Wolf Parkinson White syndrome who underwent caesarean section under regional anaesthesia. A 28 year old female, primigravida, was planned for caesarean section for cephalopelvic disproportion. The patient gave history of palpitations occasionally before pregnancy. But her symptoms increased during pregnancy. The patient did not give any history of syncope, dizziness or chest pain. In preanaesthetic check up, ECG showed features of WPW syndrome. The patient was advised cardiological consultation who confirmed the diagnosis. She was not put on any medication except anxiolytics. She was planned for caesarean section under spinal anaesthesia. Her preoperative heart rate and blood pressure was normal. She was preloaded with 500 ml of normal saline. Routine monitoring included ECG, NIBP and pulse oximetry. Spinal anaesthesia was achieved with 2.5 ml hyperbaric Bupivacaine (12.5 mgs) using 25 G pencil point needle in sitting position. The patient was given a left lateral tilt of 15-20 degrees to prevent supine hypotensive syndrome. A live healthy baby was delivered. Soon after the delivery of the baby, syntocinon 5 units were given as bolus and an infusion of 15 units in 500 ml of normal saline commenced. At this moment patient complained of palpitations and dizziness. Her heart rate increased from 84 to 180 beats / min and her blood pressure dropped to 80 mm Hg. Initially vagal manoeuvres were tried but without any improvement. Injection Phenylephrine 10 μg iv bolus was given which was repeated to treat hypotension. Adenosine 6 mg iv push was given which terminated arrhythmia and sinus rhythm was restored. There were no further episodes of PSVT and post operative period was uneventful. She was discharged after four days and was advised to follow cardiology department. Anaesthetic management of Wolff Parkinson White syndrome for caesarean section

In vivo evaluation of α2-adrenoceptors in cats with idiopathic cystitis

To evaluate the in vivo response of alpha(2)-adrenoceptors to medetomidine administration in cats with feline idiopathic cystitis (FIC) during periods of stress and after environmental enrichment. 13 cats with FIC and 12 healthy cats. Procedures-Cats were subjected to an acute-onset moderate stressor for 8 days. After stress, 20 microg of medetomidine/kg was administered IM on days 1, 3, and 8. Heart rate, blood pressure, pupil diameter, respiratory rate, and level of sedation were evaluated before and after administration of the drug. After day 8, cats were moved to an enriched environment, and tests were repeated on day 35. Heart rate decreased and pupil diameter increased significantly after medetomidine administration in healthy cats, compared with cats with FIC. Cats with FIC had significantly lower respiratory rates. No significant differences in blood pressure or sedation level were found. Increased plasma catecholamine concentrations during the enrichment phase, which have been reported elsewhere, may have contributed to the differences in alpha(2)-adrenoceptor responses detected in cats with FIC.

Treatment by n-acetylcysteine and melatonin increases cardiac baroreflex and improves antioxidant reserve

The aims of this study were to investigate the effects of melatonin and n-acetylcysteine on the baroreflex sensitivity and to verify whether those effects were correlated with their antioxidant capacity in Wistar-Kyoto and spontaneously hypertensive rats (SHR). Rats were treated with 30 mg/kg/day of melatonin or 4 g/kg/day of n-acetylcysteine for 4 weeks. Changes in mean arterial pressure, heart rate, plasma norepinephrine, and epinephrine were measured in conscious rats after an intravenous injection of phenylephrine or sodium nitroprusside. The SHR were characterized by decreased reflex chronotropic responses to phenylephrine and sodium nitroprusside (P < .001 and P < .001), as well as by an enhanced increase in plasma catecholamine concentrations in response to sodium nitroprusside (P < .001). Melatonin and n-acetylcysteine produced a significant reduction in mean arterial pressure and heart rate in SHR (P < .001). Melatonin and n-acetylcysteine improved bradycardic (P < .001) and tachycardic (P < .001) baroreflex responses in SHR without modifying catecholamine responses. The antioxidant reserve, which was reduced in SHR as reflected by the lower glutathione peroxidase activity in plasma (P < .05), was normalized by n-acetylcysteine and melatonin (P < .05). n-acetylcysteine (P < .001) and melatonin (P < .05) increased glutathione peroxidase activity in erythrocytes from SHR. The results of the present study suggest that melatonin and n-acetylcysteine improve the baroreflex response in SHR in correlation with the antioxidant effects of these substances.

Aerobic training improves exercise-induced lipolysis in SCAT and lipid utilization in overweight men.

The aim of this study was to investigate whether endurance training improves lipid mobilization and oxidation in overweight subjects. Eleven young men (25.6 +/- 1.4 yr and body mass index 27.7 +/- 0.2) performed a 4-mo training program consisting of practicing aerobic exercise 5 days/wk. Before and after the training period, lipid oxidation was explored during a 60-min exercise at 50% of peak O2 consumption by use of indirect calorimetry. Lipid mobilization and antilipolytic alpha2-adrenoceptor effect were also studied using the microdialysis method in abdominal subcutaneous adipose tissue (SCAT). After training, plasma nonesterified fatty acid (NEFA) levels, at rest and during exercise, were significantly lower than before (P < 0.001). Lipolysis in SCAT was significantly higher after than before training. An antilipolytic alpha2-adrenoceptor effect in SCAT was underlined during exercise before training and disappeared after. The respiratory exchange ratio was lower after training, i.e., the percentage of lipid oxidation was higher only at rest. The amount of lipid oxidized was higher after training, at rest, and during exercise. Although exercise power was higher after training, the relative intensity was equivalent, as suggested by a similar increase in plasma catecholamine concentrations before and after training. In conclusion, 4-mo training in overweight men improved lipid mobilization through a decrease of antilipolytic alpha2-adrenoceptor effect in SCAT and lipid oxidation during moderate exercise. Training induced a decrease of blood NEFA, predicting better prevention of obesity.

Energy expenditure and plasma catecholamines in preterm infants with mild chronic lung disease.

The present study examined the hypothesis that the energy expenditure (EE) increases during the development of chronic lung disease (CLD) together with serum catecholamines as indicator of stress. Sixteen spontaneously breathing infants with gestational age of 28-34 weeks and birth weight of 870-1920 g were studied. Eight patients were at risk for CLD, eight were healthy controls. Measurements of indirect calorimetry were done weekly at postnatal ages of 2, 3, 4 and 5 weeks. Serum concentrations of adrenaline and noradrenaline were measured by means of a high-pressure liquid chromatography (HPLC) method. The eight CLD risk infants developed mild CLD with FiO(2) of 0.27-0.31 and characteristic radiographic signs at 28 days. Compared to the healthy controls, preterm infants with mild CLD showed increases in EE from week 3 (+67%) to week 5 (+46%). Plasma noradrenaline was increased significantly in the CLD infants when compared to the controls at week 3 (0.7+/-0.3 vs. 0.5+/-0.1 ng/ml; P<0.05) and more pronounced at week 4 (1.4+/-0.2 vs. 0.6+/-0.2 ng/ml; P<0.001) and 5 (1.1+/-0.3 vs. 0.7+/-0.2 ng/ml; P<0.01). Plasma adrenaline was markedly higher in the CLD risk group (mean overall value: 0.64+/-0.1 ng/ml) than in the controls (<0.1 ng/ml in all controls) from week 2 to 5. Regression analysis for the combined values of the infants with and without CLD showed that EE was directly correlated with heart rate, noradrenaline and adrenaline concentration at each of the four study weeks and with respiratory rate at weeks 2 and 3. Increased plasma catecholamine concentrations in preterm infants with CLD suggest that these infants experienced marked stress during the early stages of the disease. Increased EE may in part be a result of this stress.

Nitric oxide plays a role in the regulation of adrenal blood flow and adrenocorticomedullary functions in the llama fetus.

The hypothesis that nitric oxide plays a key role in the regulation of adrenal blood flow and plasma concentrations of cortisol and catecholamines under basal and hypoxaemic conditions in the llama fetus was tested. At 0.6-0.8 of gestation, 11 llama fetuses were surgically prepared for long-term recording under anaesthesia with vascular and amniotic catheters. Following recovery all fetuses underwent an experimental protocol based on 1 h of normoxaemia, 1 h of hypoxaemia and 1 h of recovery. In nine fetuses, the protocol occurred during fetal I.V. infusion with saline and in five fetuses during fetal I.V. treatment with the nitric oxide synthase inhibitor L-NAME. Adrenal blood flow was determined by the radiolabelled microsphere method during each of the experimental periods during saline infusion and treatment with L-NAME. Treatment with L-NAME during normoxaemia led to a marked fall in adrenal blood flow and a pronounced increase in plasma catecholamine concentrations, but it did not affect plasma ACTH or cortisol levels. In saline-infused fetuses, acute hypoxaemia elicited an increase in adrenal blood flow and in plasma ACTH, cortisol, adrenaline and noradrenaline concentrations. Treatment with L-NAME did not affect the increase in fetal plasma ACTH, but prevented the increments in adrenal blood flow and in plasma cortisol and adrenaline concentrations during hypoxaemia in the llama fetus. In contrast, L-NAME further enhanced the increase in fetal plasma noradrenaline. These data support the hypothesis that nitric oxide has important roles in the regulation of adrenal blood flow and adrenal corticomedullary functions during normoxaemia and hypoxaemia functions in the late gestation llama fetus.

Glucose and lactate turnover in adults with falciparum malaria: effect of complications and antimalarial therapy

Hypoglycaemia and lactic acidosis are potentially life-threatening, poorly understood sequelae of Plasmodium falciparum infections. We investigated relationships between clinical status, treatment, and glucose and lactate kinetics during management of falciparum malaria in 14 Vietnamese adults. Nine had severe malaria, of whom 4 were administered quinine (Group 1a) and 5 artesunate (Group 1b). Five uncomplicated cases received artesunate (Group 2). Glucose and lactate turnover were studied on 3 occasions: (i) immediately after initial antimalarial treatment, (ii) at parasite clearance a median of 3 days later, and (iii) at discharge from hospital a median of 9 days post-admission. Steady-state glucose and lactate kinetics were derived from plasma isotopic enrichment during a primed-continuous infusion of d-[6,6-D 2]glucose and a parallel infusion of l-[1- 13C]lactate. Group 1a patients had the lowest plasma glucose concentrations in the admission study (median [range] 3.9 [3.6–5.1] vs 6.3 [4.9–7.1] and 4.5 [4.3–5.5] mmol/L in Groups 1b and 2 respectively; P < 0.05 vs Group 1b), but glucose production rates and serum insulin concentrations that were similar to those in the other groups ( P > 0.17). This was also the case at parasite clearance and suggested an inappropriate beta cell response. Group 1a patients had the highest admission lactate production (60 [36–77] vs 26 [21–47] and 22 [4–31] μmol/kg.min in Groups 1b and 2 respectively; P < 0.05 vs Group 2). Amongst the 9 severe cases, there was an inverse association between plasma glucose and lactate production at admission and parasite clearance ( P < 0.05), but no correlation between admission lactate production and serum bicarbonate ( P = 0.73). The present data confirm previous studies showing that quinine depresses plasma glucose through stimulation of insulin secretion. It is hypothesized that the low plasma glucose activates Na +, K +-ATPase through increased plasma catecholamine concentrations, leading to accelerated glycolysis and increased lactate production in well-oxygenated tissues. In some severely ill patients with falciparum malaria, a raised plasma lactate on its own may, therefore, be an unreliable index of a developing acidosis.

Sympathetic control of the cardiovascular response to acute hypoxemia in the chick embryo.

In response to an acute hypoxemic insult, the mammalian fetus shows a redistribution of the cardiac output in favor of the heart and brain. Peripheral vasoconstriction contributes to this response and is partly mediated by the release of catecholamines. Two mechanisms of catecholamine release in the fetus are reported: 1) neurogenic sympathetic stimulation and 2) a nonneurogenic mechanism via a direct effect of hypoxemia on chromaffin tissues. In the present study, the effects of sympathetic blockade on plasma catecholamine release and cardiac output distribution in response to acute hypoxemia were studied in the chick embryo at different stages of incubation. Only at the end of the incubation period, sympathetic blockade markedly attenuated the increase in plasma catecholamine concentrations and resulted in a greater fraction of the cardiac output distributed to the carcass. However, these effects did not prevent a significant increase in cardiac output to the brain and heart during acute hypoxemia. These data imply that in the chick embryo the contribution of neurogenic mechanisms to the catecholaminergic response to acute hypoxemia becomes greater by the end of the incubation period.

Perioperative shivering: physiology and pharmacology.

IN homeothermic species, a thermoregulatory system coordinates defenses against cold and heat to maintain internal body temperature within a narrow range, thus optimizing normal physiologic and metabolic function. The combination of anesthetic-induced thermoregulatory impairment and exposure to a cool environment makes most unwarmed surgical patients hypothermic. Although shivering is but one consequence of perioperative hypothermia, and rarely the most serious, it occurs frequently (i.e., 40–60% after volatile anesthetics), and it remains poorly understood. While coldinduced thermoregulatory shivering remains an obvious etiology, the phenomenon has also been attributed to numerous other causes. Our first goal is to review the organization of the thermoregulatory system, and particularly the physiology of postanesthetic shivering. We then discuss the pharmacology of thermoregulation and review the putative mechanisms and sites of action of various antishivering drugs.

Treatment of tachyarrhythmias during pregnancy and lactation.

The incidence and severity of tachyarrhythmias, both supraventricular tachycardia and ventricular tachycardia may increase during pregnancy. Although the reasons for this observation are unclear, some explanations have been proposed: increased awareness, haemodynamic, hormonal, autonomic, and emotional changes related to pregnancy, which may include: increases in plasma catecholamine concentrations and adrenergic receptor sensitivity, atrial stretch and increased end-diastolic volumes due to intravascular volume expansion. Treatment of tachyarrhythmias during pregnancy and lactation is complicated by concerns regarding safety and tolerability for the fetus or infant. All commonly used antiarrhythmic drugs cross the placenta and are excreted in breast milk. Their plasma concentration in the fetus and infant are partly determined by differences in pH between their serum and that of the mother (most antiarrhythmic drugs are alkalic compounds and accumulate in acidic environments). Teratogenic risk is greatest during the period of organogenesis, i.e. during the first 8 weeks. However, other adverse effects may still occur during the latter periods of pregnancy, e.g. uterine perfusion and contractility may be affected by antiarrhythmic drugs, influencing fetal growth and labour. However, quinidine, procainamide, lidocaine, flecainide, propranolol, amiodarone, verapamil, and digoxin do not reduce human placental blood flow (but adenosine does). Physiological changes in the mother may alter the effective plasma concentration of antiarrhythmic drugs. The increased intravascular

High-dose S(+)-ketamine improves neurological outcome following incomplete cerebral ischemia in rats.

To determine the effects of the non-competitive NMDA-receptor antagonist S(+)-ketamine on neurological outcome in a rat model of incomplete cerebral ischemia. Thirty rats were anesthetized, intubated and mechanically ventilated with isoflurane, O2 30% and nitrous oxide 70%. Following surgery animals were randomly assigned to one of the following treatment groups: Rats in group 1 (n = 10,OFF control) received fentanyl (bolus: 10 microg x kg(-1) i.v.; infusion 25 microg x kg(-1) x h(-1)) and N2O 70% / O2. Rats in group 2 (n = 10) received O2 30% in air and low-dose S(+)-ketamine (infusion: 0.25 mg x kg(-1) x min(-1)). Rats in group 3 (n = 10) received O2 30% in air and high-dose S(+)-ketamine (infusion: 1.0 mg x kg(-1) min(-1)). Following 30 min equilibration period ischemia was induced by combined unilateral common carotid artery ligation and hemorrhagic hypotension to 35 mm Hg for 30 min. Plasma catecholamines were assayed before and at the end of ischemia. Neurological deficit was evaluated for three postischemic days. Neurological outcome was improved with high-dose S(+)-ketamine when compared to fentanyl / N2O -anesthetized controls (9 vs. 1 stroke related deaths, P<0.05). Increases in plasma catecholamine concentrations were higher in fentanyl / N2O -anesthetized (adrenaline baseline 105.5+/-92.1 pg x ml(-1), during ischemia 948+/-602.8 pg x ml(-1), P<0.05; noradrenaline baseline 407+/-120.2 pg x ml(-1), ischemia 1267+/-422.2 pg x ml(-1), P <0.05) than in high-dose S(+)-ketamine-treated animals (adrenaline baseline 71+/-79.5 pg x ml(-1), ischemia 237 +/-131.9; noradrenaline baseline 317.9+/-310.5 pg x ml(-1), ischemia 310.5+/-85.7 pg x ml(-1)). Neurological outcome is improved following incomplete cerebral ischemia with S(+)-ketamine. Decreases in neuronal injury may be related to suppression of sympathetic discharge.

Splanchnic organ blood flow during calcitonin gene-related peptide-induced hypotension with or without propranolol in dogs.

Propranolol has been used to attenuate reflex tachycardia during induced hypotension. The purpose of the current study was to determine whether propranolol can modify splanchnic organ blood flow during calcitonin gene-related peptide (CGRP)-induced hypotension in dogs anesthetized with 1.3% isoflurane in oxygen. After surgical preparation and hemodynamic stabilization, saline as a control, 0.5 mg/kg and 2.0 mg/kg propranolol (n = 10, each) were administered in a bolus injection 20 min before hypotension was induced. Mean arterial pressure was reduced to 60 mm Hg during 60 min of CGRP infusion. Renal blood flow (RBF), hepatic blood flow (HBF), and pancreatic blood flow (PBF) were measured using the hydrogen clearance method. Cardiac index did not change in all three groups, and heart rate in the control group remained unchanged. In the propranolol groups, however, heart rate decreased (P < 0.01). Plasma norepinephrine (NE), but not epinephrine (E), increased (P < 0.05) after propranolol administration. The NE and E increased (P < 0.01) during induced hypotension in all three groups. NE was higher in the 0.5 mg/kg propranolol group than in the control group. RBF in the control group remained unchanged throughout observation. RBF, HBF, and PBF decreased (P < 0.01) after propranolol and remained decreased during and after induced hypotension. The degrees of decreased HBF and PBF in the control group were less than those in the 2.0 mg/kg propranolol group. In conclusion, pretreatment with propranolol decreases splanchnic organ blood flow further during CGRP-induced hypotension, due in part to increased plasma catecholamine concentrations. The reductions in splanchnic organ blood flows during CGRP-induced hypotension with propranolol are due to a reflex augmentation in sympathetic vasoconstrictor tone caused by an increase in plasma catecholamine concentrations. These findings suggest that propranolol may impair splanchnic organ blood flow during CGRP-induced hypotension.