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1.
Effect of intravenous infusion of adrenaline on the cardiovascular responses to distal body subatmospheric pressure in man 总被引:1,自引:0,他引:1
I W Fellows I A MacDonald T Bennett D P O'Donoghue 《Clinical science (London, England : 1979)》1988,75(4):389-394
1. On two separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline [0.27 nmol (50 ng) min-1 kg-1] or saline (154 mmol/l NaCl), plus ascorbic acid (5.68 mmol/l), over 30 min. 2. On each occasion, the subjects were exposed to distal body subatmospheric pressure (DBSP), 0 to 50 mmHg (0 to 6.65 kPa) in 10 mmHg (1.33 kPa) steps, before infusion, during the final 15 min of the infusion, and at 15 min and 30 min after the cessation of the infusion. 3. Venous adrenaline concentrations of 2.85 +/- 0.22 nmol/l were achieved during the adrenaline infusion, compared with 0.49 +/- 0.07 nmol/l during the saline infusion (P less than 0.001). At 15 min and at 30 min after cessation of the adrenaline infusion, venous adrenaline concentrations had fallen to levels similar to those achieved after the cessation of the saline infusion. 4. Heart rate rose significantly from 58 +/- 4 beats/min to 67 +/- 4 beats/min during the adrenaline infusion (P less than 0.05), but there was no further significant change in response to 50 mmHg (6.65 kPa) DBSP. At 30 min after the cessation of the adrenaline infusion, heart rate rose from 60 +/- 4 beats/min to 78 +/- 7 beats/min in response to 50 mmHg DBSP. This increase was significantly greater than that observed before the adrenaline infusion [58 +/- 4 beats/min to 69 +/- 7 beats/min during 50 mmHg (6.65 kPa) DBSP; P less than 0.01].(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
2.
Elevated plasma noradrenaline concentrations in patients with low-output cardiac failure: dependence on increased noradrenaline secretion rates 总被引:1,自引:0,他引:1
1. Plasma noradrenaline concentrations are elevated in patients with congestive heart failure; however, the pathogenesis of these elevated noradrenaline levels is controversial. 2. Possible mechanisms for elevated noradrenaline concentrations in patients with congestive heart failure include increased noradrenaline secretion, decreased clearance of noradrenaline, and a combination of increased secretion and decreased clearance. 3. In the present study, plasma noradrenaline clearance and apparent secretion rates were determined using a whole-body steady-state radionuclide tracer method in six otherwise healthy patients with moderate degrees of low-output cardiac failure and in six normal control subjects. 4. The venous plasma noradrenaline level was elevated in the patients with congestive heart failure as compared with the control subjects (4.18 +/- 1.34 versus 1.54 +/- 0.16 nmol/l, P less than 0.05). There was no stimulation of the adrenal medulla as evident by normal plasma adrenaline levels in both groups (0.19 +/- 0.04 versus 0.18 +/- 0.02 nmol/l, not significant). The apparent secretion rate of noradrenaline was elevated in the patients with congestive heart failure (4.75 +/- 1.95 versus 1.78 +/- 0.18 nmol min-1 m-2, P less than 0.05), whereas the clearance rate of noradrenaline was similar in the two groups (1.26 +/- 0.27 versus 1.16 +/- 0.02 l min-1 m-2, not significant). 5. We conclude that the high peripheral venous plasma noradrenaline concentrations in patients with mildly decompensated low-output cardiac failure are initially due to increased secretion, rather than to decreased metabolic clearance, perhaps in response to diminished effective arterial blood volume. 相似文献
3.
On three separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline, 50 ng min-1 kg-1 (high A), adrenaline, 10 ng min-1 kg-1 (low A) or sodium chloride solution (saline: 154 mmol of NaCl/l) plus ascorbic acid, 1 mg/ml (control), over 30 min. Venous adrenaline concentrations of 2.19 +/- 0.15 nmol/l, 0.73 +/- 0.08 nmol/l and 0.15 +/- 0.03 nmol/l were achieved during the high A, low A and control infusions respectively. Heart rate rose significantly by 19 +/- 3 beats/min (high A) and by 6 +/- 1 beats/min (low A). Heart rate remained significantly elevated 30 min after cessation of the high A infusion, despite venous plasma adrenaline concentration having fallen to control levels. The diastolic blood pressure fell during the high A and low A infusions, but the systolic blood pressure rose only during the high A infusion. Vasodilatation occurred in the calf vascular bed during both high A and low A infusions. The changes in hand blood flow and hand vascular resistance were not statistically significant, although there was a tendency to vasoconstriction during the infusion of adrenaline. Metabolic rate rose significantly by 23.5 +/- 1.8% (high A) and by 11.8 +/- 1.6% (low A). Metabolic rate remained elevated between 15 and 30 min after termination of the high A infusion. There was an initial transient increase in respiratory exchange ratio (RER) during the adrenaline infusions. During the later stages of the adrenaline infusions and after their cessation, RER fell, probably reflecting increased fat oxidation.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
4.
Effects of vasopressin on adrenal gland regional perfusion during experimental cardiopulmonary resuscitation 总被引:4,自引:0,他引:4
Krismer AC Wenzel V Voelckel WG Stadlbauer KH Wagner-Berger H Schaefer A Lindner KH 《Resuscitation》2003,56(2):223-228
OBJECTIVE: Despite the important role of the adrenal gland during cardiac arrest, little is known about changes in the adrenal medullary or cortical blood flow in this setting. This study was designed to assess regional adrenal gland perfusion in the medulla and cortex during cardiopulmonary resuscitation (CPR), and after administration of adrenaline (epinephrine) versus vasopressin versus saline placebo. METHODS: After 4 min of untreated ventricular fibrillation, and 3 min of basic life support CPR, 19 animals were randomly assigned to receive either vasopressin (0.4 U/kg; n=7), adrenaline (45 microg/kg; n=6) or saline placebo (n=6), respectively. Haemodynamic variables, adrenal, and renal blood flow were measured after 90 s of CPR, and 90 s and 5 min after drug administration. RESULTS: All values are given as mean+/-S.E.M. Blood flow in the adrenal medulla was significantly higher 90 s after adrenaline when compared with saline placebo in the right adrenal medulla (210+/-14 vs. 102+/-5 ml/min per 100 mg), and in the left adrenal medulla (218+/-14 vs. 96+/-3 ml/min per 100 mg). Blood flow in the adrenal medulla was significantly higher 90 s and 5 min after vasopressin when compared with adrenaline in the right (326+/-22 mg vs. 210+/-14 ml/min per 100 mg, and 297+/-17 vs. 103+/-5 ml/min per 100 mg), and in the left medulla (333+/-25 vs. 218+/-14 ml/min per 100 mg, and 295+/-14 vs. 111+/-7 ml/min per 100 mg). Ninety seconds and five minutes after vasopressin, and 90 s after adrenaline, adrenal cortex blood flow was significantly higher when compared with saline placebo. After 12 min of cardiac arrest, including 8 min of CPR, seven of seven pigs in the vasopressin group, one of six pigs in the adrenaline group, but none of six placebo were successfully defibrillated. CONCLUSION: Both vasopressin and adrenaline produced significantly higher medullary and cortical adrenal gland perfusion during CPR than did a saline placebo; but vasopressin resulted in significantly higher medullary adrenal gland blood flow when compared with adrenaline. 相似文献
5.
G C Inglis C J Kenyon J A Hannah J M Connell S G Ball 《Clinical science (London, England : 1979)》1987,73(1):93-97
This study investigated the role of dopamine in the control of adrenal steroidogenesis. Adrenaline, noradrenaline and dopamine have been measured in plasma and in the adrenal zona glomerulosa and medulla of rats fed low, normal and high sodium diets and in zona glomerulosa tissue of rats with adrenal regeneration hypertension (ARH). Adrenal concentrations (means +/- SE) of adrenaline, noradrenaline and dopamine in rats fed a normal diet were 1471 +/- 335, 527 +/- 75 and 51 +/- 12 nmol/g in the medulla, and 66 +/- 17, 18 +/- 9 and 6 +/- 1 nmol/g in the zona glomerulosa. The dopamine content of the zona glomerulosa was greater than could be accounted for by simple contamination from the medullary catecholamines and is commensurate with that of tissue with dopaminergic innervation. Adrenal noradrenaline and adrenaline concentrations and plasma catecholamine and corticosterone concentrations were not affected by dietary sodium intake. Plasma aldosterone concentrations were greater than 3030.4, 339.8 +/- 41.5 and 55.2 +/- 11.0 pmol/l in rats fed low, normal and high sodium diets respectively. Five weeks after right adrenalectomy and nephrectomy and left adrenal enucleation, ARH rat systolic blood pressure had increased by 47 mmHg. In the regenerated gland, the concentrations of noradrenaline and adrenaline were negligible but dopamine was present in amounts similar to that of a normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
Circulating adrenaline and blood pressure: the metabolic effects and kinetics of infused adrenaline in man 总被引:2,自引:0,他引:2
G A Fitzgerald P Barnes C A Hamilton C T Dollery 《European journal of clinical investigation》1980,10(5):401-406
Abstract. Six normotensive volunteers were infused with L-adrenaline at 001, 003, 005, 0075 and 010 μg/kg-1 min-1 , each increment lasted 10 min. Plasma adrenaline rose from 0–27 to 4–61 nmol/1, and there were dose-related increases in plasma renin activity, blood glucose, plasma cyclic AMP and plasma free fatty acids, but not in plasma noradrenaline and cyclic GMP. Levels of circulating adrenaline previously noted in essential hypertensives had minimal cardiovascular effects. The secretion rate of adrenaline and its rate of clearance from the circulation were calculated from plasma samples taken during an hour-long infusion (0–083 ± 0006 μg kg-1 min-1 ) of L-adrenaline in the same individuals. The secretion rate ranged from 1 40 to 601 nmol/min with a mean (±SEM, 6) of 2–82 ±0–76 nmol/min. Mean clearance (±SEM, 6) was 9–41 ± 1 -37 1/min and ranged from 4–86 to 14.611/min. The decline of plasma adrenaline following the infusion was biexponential.
Plasma adrenaline is unlikely to be of primary importance in the elevation of blood pressure, either directly, via renin release or by noradrenaline release via presynaptic beta receptors. However, variation in clearance between subjects limits the use of plasma levels as an interindividual index of adrenal release of adrenaline. The relationship between sympathoadrenal activity and plasma adrenaline may be further perturbed by equilibration between the circulation and sites of tissue uptake. The lower levels of plasma adrenaline than of noradrenaline appear to result from both a slower rate of secretion and a higher rate of clearance from the circulation. 相似文献
Plasma adrenaline is unlikely to be of primary importance in the elevation of blood pressure, either directly, via renin release or by noradrenaline release via presynaptic beta receptors. However, variation in clearance between subjects limits the use of plasma levels as an interindividual index of adrenal release of adrenaline. The relationship between sympathoadrenal activity and plasma adrenaline may be further perturbed by equilibration between the circulation and sites of tissue uptake. The lower levels of plasma adrenaline than of noradrenaline appear to result from both a slower rate of secretion and a higher rate of clearance from the circulation. 相似文献
7.
R A Linton M Lim C B Wolff P Wilmshurst D M Band 《Clinical science (London, England : 1979)》1984,67(4):427-431
Five continuous records of arterial plasma potassium were obtained from three normal subjects during brief periods (5-7 min) of exercise (100 W). In two of these subjects hepatic venous blood samples were withdrawn at 0.5-1.0 min intervals and analysed in vitro for plasma potassium. Arterial plasma potassium rose rapidly at the start of exercise from 3.8 +/- 0.3 mmol/l (mean +/- SD) to plateau levels of 5.4 +/- 0.1 mmol/l. One of the above subjects and a further subject were studied after beta-blockade with propranolol. This resulted in an exaggerated rise in arterial plasma potassium during exercise. Hepatic venous potassium measurements indicated that the liver probably had little effect on potassium changes during exercise. The changes in arterial plasma potassium during exercise are rapid and substantial. If transmitted to the extracellular fluid these changes would alter cell transmembrane potential and might as a result alter receptor sensitivity. 相似文献
8.
1. The metabolic clearance rate of arginine vasopressin was determined using a constant infusion technique in normal subjects and patients with chronic renal failure immediately before commencing dialysis. Endogenous arginine vasopressin was suppressed in all subjects before the infusion with a water load. 2. Plasma arginine vasopressin concentrations were determined using a sensitive and specific radioimmunoassay after Florisil extraction. The detection limit of the assay was 0.3 pmol/l, and intra- and inter-assay coefficients of variation at 2 pmol/l were 9.7% and 15.3%, respectively. 3. In normal subjects, the metabolic clearance rate was determined at two infusion rates producing steady-state concentrations of arginine vasopressin of 1.3 and 4.4 pmol/l. In the patients with renal failure, a single infusion rate was used, producing a steady-state concentration of 1.5 pmol/l. 4. At comparable plasma arginine vasopressin concentrations, metabolic clearance rate was significantly reduced in patients with renal failure (normal 1168 +/- 235 ml/min versus renal failure 584 +/- 169 ml/min; means +/- SD; P < 0.001). 5. Free water clearance was significantly reduced in normal subjects during the arginine vasopressin infusion from 8.19 +/- 2.61 to -1.41 +/- 0.51 ml/min (P < 0.001), but was unchanged in the patients with renal failure after attaining comparable plasma arginine vasopressin concentrations. 6. In normal subjects there was a small but significant fall in metabolic clearance rate at the higher steady-state arginine vasopressin concentration (1168 +/- 235 ml/min at 1.3 pmol/l versus 1059 +/- 269 ml/min at 4.4 pmol/l; P = 0.016).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
The metabolic effects of moderate exercise in the fasting state were examined in 12 insulin-dependent diabetic adolescents treated with continuous subcutaneous insulin infusion (CSII) or intensive conventional therapy (ICT). Six patients received their usual afternoon dose the evening before the study and six received their usual infusion rate during exercise. Insulin was injected subcutaneously in the abdominal wall. Exercise was performed on a bicycle ergometer for 45 min at 50% maximum oxygen consumption. Resting plasma glucose values during both CSII (114 +/- 18 mg/dl, P less than 0.02) and ICT (136 +/- 30 mg/dl, P less than 0.01) were higher than normal (77 +/- 11 mg/dl). Diabetic patients receiving CSII showed a sharp decrease in glycemia after 45 min of exercise (77 +/- 18 mg/dl, P less than 0.02). In contrast, in patients receiving ICT and in control subjects plasma glucose did not change during exercise or recovery. Insulin levels decreased significantly during exercise in the control subjects while there was no change in plasma free insulin levels during exercise in the diabetic subjects. Profiles of intermediary metabolites in response to exercise were similar in all groups with no significant differences in resting values between diabetic subjects and controls. Continuous subcutaneous insulin infusion provides near-normoglycemia in the insulin-dependent diabetic adolescent. However, with the basal insulin infusion rate necessary to achieve near-normal fasting blood glucose levels, moderate exercise in the postabsorptive state may result in hypoglycemia with CSII. 相似文献
10.
A Wennmalm E Karwatowska-Prokopczuk M Wennmalm 《Clinical science (London, England : 1979)》1989,76(3):255-260
1. Methylxanthines have been shown to elevate the basal plasma level and/or urinary excretion of noradrenaline (NA) and adrenaline (ADR) in healthy subjects. The present study addressed the hypothesis that the methylxanthine aminophylline also augments plasma and urinary catecholamines during increased sympathoadrenal activity. 2. Eleven healthy young men performed a maximal 2 h bicycle exercise twice, after double-blind intravenous administration of placebo or aminophylline. Femoral venous plasma and urinary concentrations of NA and ADR were analysed in samples representing basal state, exercise and recovery, using liquid chromatography with electrochemical detection. 3. Leg exercise induced eight- and six-fold increases in the plasma concentrations of NA and ADR, respectively, and seven- and four-fold increases in the urinary concentrations of NA and ADR, respectively, indicating that sympathoadrenal activity was considerably elevated. 4. After aminophylline (mean plasma concentration 20-35 mumol/l), the plasma concentrations of NA (P less than 0.001) and ADR (P less than 0.05) were independently higher at rest, during exercise and during recovery, in comparison to after placebo; the mean exercise plasma level of NA was increased by the drug from 13 +/- 1 to 21 +/- 2 nmol/l and the corresponding level of ADR from 2.1 +/- 0.4 to 2.9 +/- 0.5 nmol/l. Also urinary NA (P less than 0.01) and ADR (P less than 0.05) were elevated by aminophylline; the exercise concentrations of NA in the urine were 75 +/- 8 and 97 +/- 10 mumol/mol of creatinine after placebo and aminophylline, respectively, and the corresponding levels of ADR were 12 +/- 3 and 16 +/- 3 mumol/mol of creatinine, respectively. 相似文献
11.
P T Larsson P Hjemdahl G Olsson N Egberg G Hornstra 《Clinical science (London, England : 1979)》1989,76(4):369-376
1.The effects of mental stress induced by a colour word conflict test (CWT; n = 9) or 3 h infusions of placebo or adrenaline (0.4 nmol min-1 kg-1; n = 9) on platelet function in vivo were studied in 16 healthy male volunteers. 2. Platelet function was assessed by a filtragometry technique, which reflects aggregability in vivo, and by measurements of the plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4). 3. Adrenaline and CWT induced marked cardiovascular responses as expected. Venous plasma adrenaline increased from 0.1-0.2 nmol/l at rest to 4.87 +/- 0.42 nmol/l during adrenaline infusion and to 0.46 +/- 0.10 nmol/l during CWT. 4. Filtragometry measurements were reproducible within individuals with coefficients of variation of 7.9% during placebo infusion and 5.4% for resting measurements between days. 5. Platelet aggregability, as measured by filtragometry, was similarly increased during both adrenaline infusion (P less than 0.05) and CWT (P less than 0.01). 6. The coefficients of variation for beta-TG and PF4 levels were 17.3% for log beta-TG and 27.9% for log PF4 between days, but could not be calculated for within-day variability. Both beta-TG (P less than 0.05) and PF4 (P less than 0.01) levels decreased time-dependently during placebo infusion, indicating that long resting periods (hours) are needed to attain basal levels. Artefactual results could not be identified by evaluating beta TG/PF4 ratios. 7. beta-TG and PF4 levels did not decrease time-dependently during adrenaline infusion. There were no significant changes of beta-TG or PF4 during CWT.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
12.
A A Connacher W M Bennet R T Jung D M Bier C C Smith C M Scrimgeour M J Rennie 《Clinical science (London, England : 1979)》1991,81(5):635-644
1. Energy expenditure, plasma glucose and palmitate kinetics and leg glycerol release were determined simultaneously both before and during adrenaline infusion in lean and obese human subjects. Seven lean subjects (mean 96.5% of ideal body weight) were studied in the post-absorptive state and also during mixed nutrient liquid feeding, eight obese subjects (mean 165% of ideal body weight) were studied in the post-absorptive state and six obese subjects (mean 174% of ideal body weight) were studied during feeding. 2. Resting energy expenditure was higher in the obese subjects, but the thermic response to adrenaline, both in absolute and percentage terms, was similar in lean and obese subjects. Plasma adrenaline concentrations attained (3 nmol/l) were comparable in all groups and the infusion had no differential effects on the plasma insulin concentration. Before adrenaline infusion the plasma glucose flux was higher in the obese than in the lean subjects in the fed state only (45.8 +/- 3.8 versus 36.6 +/- 1.0 mmol/h, P less than 0.05); it increased to the same extent in both groups with the adrenaline infusion. 3. Before the adrenaline infusion plasma palmitate flux was higher in the obese than in the lean subjects (by 51%, P less than 0.01, in the post-absorptive state and by 78%, P less than 0.05, in the fed state). However, there was no significant change during adrenaline infusion in the obese subjects (from 13.5 +/- 1.00 to 15.0 +/- 1.84 mmol/h, not significant, in the post-absorptive state and from 14.4 +/- 2.13 to 15.7 +/- 1.74 mmol/h, not significant, in the fed state), whereas there were increases in the lean subjects (from 8.93 +/- 1.10 to 11.2 +/- 1.19 mmol/h, P less than 0.05, in the post-absorptive state, and from 8.06 +/- 1.19 to 9.86 +/- 0.93 mmol/h, P less than 0.05, in the fed state). 4. Before adrenaline infusion the palmitate oxidation rate was also higher in the obese than in the lean subjects (1.86 +/- 0.14 versus 1.22 +/- 0.09 mmol/h, P less than 0.01, in the post-absorptive state and 1.73 +/- 0.25 versus 1.12 +/- 0.12 mmol/h, P less than 0.05, in the fed state). However, in response to adrenaline the fractional oxidation rate (% of flux) increased less in the obese than in the lean subjects, especially in the post-absorptive state (from 13.8 +/- 1.02 to 14.9 +/- 1.39%, not significant, versus from 13.7 +/- 0.98 to 19.3 +/- 1.92%, P less than 0.05). These effects were independent of feeding.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
13.
S E Kjeldsen A Westheim I Aakesson I Eide P Leren 《Scandinavian journal of clinical and laboratory investigation》1986,46(5):397-401
Plasma adrenaline and noradrenaline were measured in arterial blood and in forearm venous blood during supine rest and after 30 min standing in normotensive, healthy 50-year-old men (n = 16). After 30 min standing, venous noradrenaline had increased from 1.61 +/- 0.11 to 4.22 +/- 0.30 nmol/l and arterial from 1.43 +/- 0.06 to 2.93 +/- 0.15 nmol/l. Orthostasis induced a seven-fold increment in the forearm arterial-venous difference of noradrenaline from -0.18 +/- 0.08 to -1.29 +/- 0.25 nmol/l (p less than 0.001). Orthostasis more than doubled the forearm arterial-venous difference of adrenaline from 0.15 +/- 0.03 to 0.31 +/- 0.05 nmol/l (p less than 0.001) since arterial adrenaline increased from 0.31 +/- 0.03 to 0.53 +/- 0.05 nmol/l and venous from 0.16 +/- 0.02 to 0.22 +/- 0.02 nmol/l. Arterial adrenaline correlated significantly with venous in the supine (r = 0.64, p less than 0.01) but not in the standing position (r = 0.34, NS). The results indicate that arterial concentrations of adrenaline are a much better indicator of sympatho-adrenal activity during orthostasis than peripheral venous concentrations. For noradrenaline, measurements of arterial concentrations during the orthostatic manoeuvre seem to provide information about the total noradrenergic sympathetic reactivity, while the corresponding measurements in peripheral venous blood represent the forearm locally. 相似文献
14.
Cardiac and whole-body [3H]noradrenaline kinetics during adrenaline infusion in man. 总被引:1,自引:0,他引:1
1. To investigate the possible role of adrenaline as a modulator of noradrenaline release from the sympathetic nervous system, the responses of cardiac and whole-body noradrenaline kinetics to intravenous infusions of adrenaline (30 ng min-1 kg-1) and matching saline placebo were determined at rest and during supine bicycle exercise in 16 patients undergoing cardiac catheterization, in whom beta-adrenoceptor antagonists had been discontinued for 72 h. 2. At rest and compared with placebo, infusion of adrenaline was associated with a small increase in arterial plasma noradrenaline from 211 +/- 29 pg/ml to 245 +/- 29 pg/ml (P less than 0.05). Increases in whole-body noradrenaline spillover to arterial plasma were larger (from 282 +/- 40 ng min-1 m-2 to 358 +/- 41 ng min-1 m-2, P less than 0.01) and there was a trend towards an increase in whole-body noradrenaline clearance. Cardiac noradrenaline clearance was modestly increased during adrenaline infusion, but cardiac noradrenaline spillover was not altered despite increases in heart rate and coronary sinus plasma flow. Adrenaline infusion was associated with symptomatic myocardial ischaemia in four of 14 patients with coronary heart disease. 3. Supine bicycle exercise was associated with significant increases in peripheral noradrenaline concentrations and in cardiac and whole-body noradrenaline spillover. The increases on exercise were not significantly different for these variables during saline and adrenaline infusions. 4. Infusion of adrenaline to produce 'physiological' increases in plasma adrenaline concentration was associated with an increase in total noradrenaline release, as assessed by whole-body noradrenaline spillover to plasma.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
15.
Kemme MJ Burggraaf J Schoemaker RC Paulson S Karim A Lentjes EG Childs A Braeckman RA Cohen AF 《Clinical pharmacology and therapeutics》2000,67(5):504-511
OBJECTIVES: Recombinant tissue factor pathway inhibitor (rTFPI) has been shown to be an effective treatment in animal models of sepsis and is under investigation for human use. Reduced liver blood flow during septic shock may substantially alter the pharmacokinetics of rTFPI because clearance of rTFPI approaches liver blood flow. The aim of this study was to examine the effect of exercise-induced reduction in liver blood flow on the pharmacokinetics and pharmacodynamics of rTFPI. METHODS: This was a two-way, open-label, randomized crossover study in eight healthy male volunteers. The subjects in both treatment groups received a continuous intravenous infusion of rTFPI (0.2 mg/kg/h) concurrently with intravenous sorbitol (50 mg/min) for 4 hours. Sorbitol was used as a biomarker for liver blood flow. The subjects were randomized to remain supine or to exercise on a bicycle ergometer for 30 minutes starting at the beginning of the third hour of the infusion. RESULTS: Exercise reduced liver blood flow (mean +/- SEM) from 1.44 +/- 0.06 L/min to 0.40 +/- 0.03 L/min. The average clearance of rTFPI decreased from 0.73 +/- 0.04 L/min in the supine position to 0.25 +/- 0.02 L/min during exercise. This decrease in rTFPI clearance resulted in an 80% (95% confidence interval [CI], 60% to 102%) increase in plasma rTFPI levels during exercise. The average maximal prothrombin time and activated partial thromboplastin time values during exercise were 1.4 (95% CI, 0.4 to 2.5) and 4.4 (95% CI, 2.7 to 6.1) seconds higher compared with the supine steady-state level. CONCLUSIONS: Reduction in liver blood flow by exercise markedly increased rTFPI concentrations and induced a slight but variable prothrombin time and activated partial thromboplastin time increase at the rTFPI dose studied. 相似文献
16.
P I Mansell I W Fellows A T Birmingham I A Macdonald 《Clinical science (London, England : 1979)》1988,75(3):285-291
1. The cardiovascular and metabolic responses to low doses of isoprenaline (15 and 5 ng min-1 kg-1 body weight infused over 30 min) were determined in six healthy males. The study was performed to investigate whether there were sustained effects after the termination of the isoprenaline infusion, as has been observed previously after the infusion of adrenaline. 2. The isoprenaline infusions produced dose-dependent increases in heart rate, systolic blood pressure and metabolic rate, but similar increases in calf blood flow and decreases in diastolic blood pressure for the two infusion rates. Finger tremor was increased in amplitude by the 15 ng min-1 kg-1 infusion only. The changes in each of these physiological variables largely resolved within a few minutes of discontinuing the isoprenaline infusions. 3. There were no changes in arterialized venous plasma adrenaline or noradrenaline levels during the isoprenaline infusions. Mean peak plasma isoprenaline levels were 0.16 +/- 0.02 nmol/l during the 5 ng min-1 kg-1 infusion and 0.71 +/- 0.05 nmol/l during the 15 ng min-1 kg-1 infusion. 4. Plasma insulin levels increased with isoprenaline but blood glucose concentrations were unchanged, consistent with a direct effect of isoprenaline on beta 2-adrenoceptors mediating insulin release from pancreatic beta-cells. Blood glycerol concentration also increased with isoprenaline but blood lactate concentration was unaltered. 5. The present study demonstrates pronounced cardiovascular and metabolic effects of low dose isoprenaline infusions. Differences in the rate of resolution of the changes induced by isoprenaline and by adrenaline seen in previous studies may result from a significant difference in their metabolism. 相似文献
17.
A Grossman P Bouloux P Price P L Drury K S Lam T Turner J Thomas G M Besser J Sutton 《Clinical science (London, England : 1979)》1984,67(5):483-491
Opioid involvement in the physiological and hormonal responses to acute exercise was investigated in six normal male subjects. Each was exercised to 40% (mild exercise) and 80% (severe exercise) of his previously determined maximal oxygen consumption on two occasions, with and without an infusion of high-dose naloxone. The exercise task was a bicycle ergometer; mild and severe exercise were performed for 20 min each, followed by a recovery period. Exercise produced the expected increases in heart rate, blood pressure, ventilation, tidal volume, respiratory rate, oxygen consumption and carbon dioxide production. After severe exercise, naloxone infusion increased ventilation from 94.8 +/- 4.9 litres/min to 105.7 +/- 5.0 litres/min (P less than 0.05), but had no effect on any of the other physiological variables. Exercise-induced changes in several hormones and metabolites were noted, including elevations in circulating lactate, growth hormone (GH), prolactin, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenaline noradrenaline, plasma renin activity (PRA) and aldosterone. There was no change in plasma met-enkephalin. Naloxone infusion produced the expected increases in LH and cortisol, but also significantly enhanced the elevations in prolactin, adrenaline, noradrenaline, plasma renin activity and aldosterone (P less than 0.05). Psychological questionnaires revealed minor mood changes after exercise, but no evidence was found for the suggested 'high' or euphoria of exercise. Effort was perceived as greater during the naloxone infusion than the saline infusion in every subject.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
18.
ANG II (angiotensin II) facilitates catecholamine release from the adrenal medulla and neuronal NE (noradrenaline) release. Since animal experiments point to specific sympatho-inhibitory properties of the AT1 (ANG II type 1)-receptor blocker EPRO (eprosartan), the primary aim of this study was to clarify if EPRO inhibits sympathetic reactivity in humans as determined by the effect of EPRO on insulin-induced catecholamine release. Sixteen healthy male volunteers were randomized in a double-blind cross-over study to receive a single dose of EPRO (600 mg) compared with placebo, followed by insulin-induced hypoglycaemia [0.15 IU (international unit)/kg of body weight; intravenous bolus] on two study days 1 week apart. From baseline to the end of hypoglycaemia (170 min), the sympatho-adrenal reactivity was mapped by invasive continuous blood pressure monitoring and repeated measurements of FBF (forearm blood flow), arterial and venous concentrations of glucose, catecholamines [EPI (adrenaline) and NE (noradrenaline)], renin, ANG II and aldosterone. EPRO induced an 8-10-fold increase in plasma renin and ANG II concentrations compared with placebo. Plasma glucose decreased equally during placebo and EPRO from baseline 5.9 mmol/l to 1.9 mmol/l and 2.1 mmol/l respectively, inducing a 17-fold increase in arterial EPI concentration at peak. The AUC (area under the curve) during hypoglycaemia for arterial EPI concentrations was 314+/-48 nmol.min.l-1 in placebo compared with 254+/-26 nmol.min.l-1 following EPRO treatment (P=0.14). EPRO attenuated the corresponding AUC for the EPI-induced pulse pressure response (4670+/-219 mmHg.min in EPRO compared with 5004+/-266 mmHg.min in placebo; P=0.02). Moreover, EPRO caused a less pronounced increase in FBF compared with placebo (402+/-30 compared with 479+/-46 ml.100 g-1 of body weight; P=0.04). Musculocutaneous NE release was not affected by EPRO and the AUC for NE release was 51.69+/-15.5 pmol.min-1.100 g-1 of body weight in placebo compared with 39.35+/-18.2 pmol.min-1.100 g-1 of body weight after EPRO treatment (P=0.57). In conclusion, EPRO did not significantly inhibit sympathetic reactivity compared with placebo; however, it blunted the haemodynamic responses elicited by the sympatho-adrenal stimulation which only tended to be attenuated by this drug. 相似文献
19.
S A Amiel H R Archibald G Chusney A J Williams E A Gale 《Clinical science (London, England : 1979)》1991,81(2):189-194
1. The effect of hyperketonaemia on counter-regulatory hormone responses to hypoglycaemia has been examined in six healthy subjects. 2. A controlled, step-wise reduction in blood glucose concentration was achieved by adjusting the rate of glucose infusion during a primed-continuous infusion of soluble insulin (1.5 m-units min-1 kg-1 body weight, plasma insulin concentration approximately 90 m-units/l). Simultaneous infusion of either saline or beta-hydroxybutyrate (3 mg min-1 kg-1 body weight) was administered in a single-blind fashion, in random order. Despite a need for 40% more glucose during the ketone infusion, an identical fall in blood glucose concentration was achieved in each study. 3. The glycaemic threshold for stimulating an adrenaline response of 0.41 nmol/l was reduced from 3.1 to 2.8 mmol/l (P less than 0.05) during ketone infusion, and that for stimulating a response of more than 50% of basal from 3.6 to 3.1 mmol/l (P less than 0.001). The peak adrenaline response fell from 7.97 to 2.6 nmol/l (P less than 0.04). Peak noradrenaline, cortisol and growth hormone responses were also significantly lower during ketone infusion (P = 0.04, 0.001 and 0.006, respectively). Glucagon responses alone were unaffected by hyperketonaemia. 4. The provision of an alternate metabolic fuel thus produced immediate changes in the neurohumoral responses to hypoglycaemia. This is consistent with the hypothesis that human nervous tissue can metabolize ketones acutely. 相似文献
20.
Alpha-adrenoceptor blockade by phentolamine inhibits adrenaline-induced platelet activation in vivo without affecting resting measurements. 总被引:2,自引:0,他引:2
P T Larsson N H Wallén N Egberg P Hjemdahl 《Clinical science (London, England : 1979)》1992,82(4):369-376
1. The effects of phentolamine (500 micrograms/min) on platelet aggregability in vivo at rest and during adrenaline infusion were assessed by ex vivo filtragometry and measurements of plasma beta-thromboglobulin levels in 10 healthy male subjects. Plasma levels of von Willebrand factor antigen and free fatty acids were also measured. 2. Adrenaline induced marked and expected increases in heart rate and systolic blood pressure and decreased diastolic blood pressure when venous plasma adrenaline levels were elevated from 0.12 +/- 0.02 to 2.9 +/- 0.3 nmol/l (P less than 0.01). 3. Adrenaline caused platelet activation in vivo. Ex vivo filtragometry readings were shortened by 58 +/- 9% (P less than 0.01), plasma beta-thromboglobulin levels increased by 99 +/- 44% (P less than 0.01) and platelet counts increased by 26 +/- 6% (P less than 0.01). Plasma levels of von Willebrand factor antigen and free fatty acids increased by 53 +/- 5% and 475 +/- 113% (both P less than 0.01), respectively. 4. Phentolamine enhanced the beta-adrenergic vasodilator responses to adrenaline, as both the decrease in diastolic blood pressure and the reflexogenic increase in heart rate were enhanced (both P less than 0.01). Marked elevations in plasma noradrenaline levels were found during infusions of phentolamine and adrenaline (P less than 0.001). 5. Phentolamine did not alter platelet indices at rest, but abolished adrenaline-induced platelet activation, as filtragometry readings, plasma beta-thromboglobulin levels and platelet counts remained at, or below, resting levels. Responses of plasma levels of von Willebrand factor antigen and free fatty acids to adrenaline were not influenced by phentolamine and did not seem to influence platelet responses.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献