IMITATION OF THE ADRENO-CORTICAL RESPONSE TO SURGERY BY INTRAVENOUS INFUSION OF SYNTHETIC HUMAN ACTH

1973 ◽  
Vol 72 (1) ◽  
pp. 75-80
Author(s):  
Henrik Kehlet ◽  
Christian Binder ◽  
Christen Engbæk
Keyword(s):  
Intravenous Infusion ◽  
Time Course ◽  
Cortical Response ◽  
Secretion Rate ◽  
Major Surgery ◽  
Acth Secretion ◽  
Dose Rates

ABSTRACT The concentration of plasma corticosteroids was followed during major surgery and during the infusion of synthetic human ACTH at dose rates varying from 2400 ng to 15 000 ng per hour. The results showed that the time course of plasma corticosteroids during major surgery was intermediate between that obtained during the infusion of 7500 and 15 000 ng synthetic human ACTH per hour. This gives an estimated ACTH secretion rate during major surgery of between 7500 ng and 15 000 ng per hour.

ADRENERGIC CONTROL MECHANISM FOR ACTH SECRETION IN MAN

1973 ◽  
Vol 74 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Yoshikatsu Nakai ◽  
Hiroo Imura ◽  
Teruya Yoshimi ◽  
Shigeru Matsukura
Keyword(s):  
Intravenous Infusion ◽  
Human Subjects ◽  
Blocking Agent ◽  
Inhibitory Effect ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Glucose Levels ◽  
Alpha Receptors ◽  
Normal Human ◽  
Adrenergic Blocking

ABSTRACT In order to determine if an adrenergic mechanism is involved in the secretion of corticotrophin (ACTH), the effect of adrenergic-blocking or -stimulating agent on plasma ACTH, cortisol and glucose levels was studied in normal human subjects. The intravenous infusion of methoxamine, an alpha adrenergic-stimulating agent, caused a rise in plasma ACTH and cortisol. This increase in plasma ACTH and cortisol was significantly inhibited by the simultaneous administration of phentolamine, an alpha adrenergic-blocking agent, in combination with methoxamine. The intravenous infusion of propranolol, a beta adrenergic-blocking agent, caused no significant change in plasma ACTH and cortisol, although it enhanced the plasma ACTH response to insulin-induced hypoglycaemia. On the other hand, alpha adrenergicblockade by intravenous infusion of phentolamine significantly suppressed the plasma ACTH response to insulin-induced hypoglycaemia. These studies suggest a stimulatory effect of alpha receptors and a possible inhibitory effect of beta receptors on ACTH secretion in man.

Infused salbutamol accentuates acid-induced lung injury in the rat

1986 ◽  
Vol 71 (2) ◽  
pp. 205-209 ◽  
Author(s):  
Stanley Braude ◽  
David Royston
Keyword(s):  
Lung Injury ◽  
Intravenous Infusion ◽  
Time Course ◽  
Weight Ratio ◽  
Dry Weight ◽  
Adrenergic Agonist ◽  
Lung Water ◽  
Significant Difference ◽  
And Control ◽  
Control Infusion

1. The effect in the rat of salbutamol infusion (1 μg min−1 kg−1) on acid-induced lung injury has been determined. Severity of lung injury was assessed by two techniques: the pulmonary clearance of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and the lung wet/dry weight ratio, giving indices of alveolar epithelial permeability and transendothelial water filtration respectively. 2. Mean half-time of clearance of 99mTc-DTPA was increased significantly in rats who had intratracheal acid-induced injury and control (saline) intravenous infusion (19.4 ± 2.6 min) compared with non-acid-treated rats (98.1 ± 7.2) (P < 0.0001). However, those animals who had intratracheal acid injury and subsequent salbutamol intravenous infusion had significantly faster clearance (11.5 ± 1.9) than the acid and control infusion group (P < 0.05). 3. Gravimetric lung water in the acid-only rats (expressed as wet/dry weight ratio) was increased significantly (6.4 ± 0.3) compared with the non-acid-treated controls (5.4 ± 0.2) (P < 0.01). Acid-treated rats who had salbutamol infused had dramatically increased lung water (10.0 ± 0.6) (P < 0.001 vs acid and control infusion). 4. Intravenous salbutamol infusion itself produced no significant difference in the results for both techniques, compared with the non-acid-treated time-course controls. 5. Infused salbutamol accentuates acid-induced lung injury in the rat. Possible factors responsible for these findings include β2-adrenergic agonist mediated inhibition of hypoxic pulmonary vasoconstriction (HPV) and a predominant β1-adrenergic agonist inotropic effect of salbutamol with resultant rise in pulmonary artery pressure.

scholarly journals Perioperative metabolic acidosis: The Bradford Anaesthetic Department Acidosis Study

2018 ◽  
Vol 20 (1) ◽  
pp. 11-17 ◽  
Author(s):  
TO Lawton ◽  
A Quinn ◽  
SJ Fletcher
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Metabolic Acidosis ◽  
Early Phase ◽  
Time Course ◽  
Late Phase ◽  
Common Finding ◽  
Major Surgery ◽  
Arterial Blood ◽  
Early Fluid

Metabolic acidosis is considered deleterious but is common in post-surgical patients admitted to intensive care unit. We evaluated the prevalence and time course of metabolic acidosis in elective major surgery, and generated hypotheses about causes, by hourly arterial blood sampling in 92 patients. Metabolic acidosis began before incision and most had occurred by the next hour. Seventy-eight per cent of patients had a significant metabolic acidosis post-operatively. Two overlapping phases were observed. The early phase started before incision, characterised by a rising chloride and falling anion gap, unrelated to saline use. The late phase was partly associated with lactate, related to surgery type, and early fluids appeared protective. There was a trend towards longer intensive care unit (+1.3 days) and hospital (+3.2 days) stay with metabolic acidosis. This is the first large study of the evolution of this common finding, demonstrating a pre-incision component. The early phase appears unavoidable or unpredictable, but the late phase might be modified by early fluid administration. It remains unclear whether acidosis of this type should be avoided.

scholarly journals Prediction of Human Pharmacokinetics of Bendamustine from Preclinical Species Pharmacokinetics Based on Normalizing Time Course Profiles

Drug Research ◽  
2018 ◽  
Vol 69 (01) ◽  
pp. 32-39 ◽  
Author(s):  
Nuggehally Srinivas ◽  
Ravi Jairam ◽  
Sadanand Mallurwar ◽  
Suresh Sulochana ◽  
Devaraj Chandrasekar ◽  
...  
Keyword(s):  
Intravenous Infusion ◽  
Time Course ◽  
Animal Species ◽  
Anticancer Agent ◽  
Time Profile ◽  
Lymphocytic Leukemia ◽  
Human Pharmacokinetics ◽  
Correction Factors ◽  
Preclinical Pharmacokinetics ◽  
Preclinical Species

AbstractBendamustine, an alkylating anticancer agent, is used to treat chronic lymphocytic leukemia by intravenous infusion alone or in combination. The work aimed to develop a method to predict time vs. concentration profile for humans based on preclinical pharmacokinetics using the assumption of superimposability of normalized time course profiles of animals and humans. Standard allometric equations with/without correction factors (CF) were also used in prediction. The Vss was predicted by simple allometry of 0.312W0.871 (r2=0.987), where W is body weight; predicted Vss (19.71 L) was similar to the reported value (20.10 L). However, CL prediction involved both simple and CF allometry. Best proximity CL (543 vs. 598 mL/min) was obtained with maximum life span correction (MLP) [2.46W1.215 (r2=0.988)]. Normalized curves were obtained by normalizing the time (with mean residence time) vs. concentration (with dose/Vss) in animal species. The concentration vs. time profile in humans after intravenous infusion was then simulated using normalized curve for each animal species and the values of CL and Vss were predicted for humans. In summary the findings indicate that normalized time course approach could predict the bendamustine human pharmacokinetics and such an approach could be prospectively applied for analog drugs of this class.

Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion

1978 ◽  
Vol 234 (1) ◽  
pp. R66-R71 ◽  
Author(s):  
D. J. Ramsay ◽  
L. C. Keil ◽  
M. C. Sharpe ◽  
J. Shinsako
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Concentration ◽  
Plasma Renin Activity ◽  
Plasma Levels ◽  
Intravenous Infusion ◽  
Plasma Renin ◽  
Acth Secretion ◽  
Plasma Vasopressin ◽  
Bilateral Carotid

The effects of intravenous infusion of Asp1. Ile5-angiotensin II on blood pressure, plasma vasopressin, ACTH and 11-hydroxycorticosteroid levels and on plasma renin activity were studied in five trained, conscious dogs. The dogs were prepared with bilateral carotid loops. Infusion of angiotensin II at rates of 5, 10, and 20 ng/kg.min raised its plasma concentration from 23 +/- 7 to 48 +/- 8, 125 +/- 8, and 187 +/- 21 pg/ml, respectively. The lowest rate of infusion was mildly pressor, the two higher rates more so. All rates of infusion promptly increased vasopressin levels and depressed renin levels. The two higher rates also stimulated ACTH, although with a latency of 30-45 min. Since the rates of infusion of angiotensin II employed produced plasma levels within the physiological range, it is suggested that peripherally generated angiotensin II may play an important role in the regulation of vasopressin, and ACTH secretion.

scholarly journals Time course of salinity adaptation in a strongly euryhaline estuarine teleost, fundulus heteroclitus: a multivariable approach

1999 ◽  
Vol 202 (11) ◽  
pp. 1535-1544 ◽  
Author(s):  
W.S. Marshall ◽  
T.R. Emberley ◽  
T.D. Singer ◽  
S.E. Bryson ◽  
S.D. Mccormick
Keyword(s):  
Fresh Water ◽  
Plasma Cortisol ◽  
Time Course ◽  
Fundulus Heteroclitus ◽  
Citrate Synthase ◽  
Sea Water ◽  
Short Circuit ◽  
Secretion Rate ◽  
Ion Secretion ◽  
Cortisol Levels

Freshwater-adapted killifish (Fundulus heteroclitus) were transferred directly from soft fresh water to full-strength sea water for periods of 1 h, 3 h, 8 h and 1, 2, 7, 14 and 30 days. Controls were transferred to fresh water for 24 h. Measured variables included: blood [Na+], osmolality, glucose and cortisol levels, basal and stimulated rates of ion transport and permeability of in vitro opercular epithelium, gill Na+/K+-ATPase and citrate synthase activity and chloride cell ultrastructure. These data were compared with previously published killifish cystic fibrosis transmembrane conductance regulator (kfCFTR) expression in the gills measured over a similar time course. Plasma cortisol levels peaked at 1 h, coincident with a rise in plasma [Na+]. At 8 h after transfer to sea water, a time at which previous work has shown kfCFTR expression to be elevated, blood osmolality and [Na+] were high, and cortisol levels and opercular membrane short-circuit current (Isc; a measure of Cl- secretion rate) were low. The 24 h group, which showed the highest level of kfCFTR expression, had the highest plasma [Na+] and osmolality, elevated plasma cortisol levels, significantly lower opercular membrane resistance, an increased opercular membrane ion secretion rate and collapsed tubule inclusions in mitochondria-rich cells, but no change in gill Na+/K+-ATPase and citrate synthase activity or plasma glucose levels. Apparently, killifish have a rapid (&lt;1 h) cortisol response to salinity coupled to subsequent (8–48 h) expression of kfCFTR anion channel proteins in existing mitochondria-rich cells that convert transport from ion uptake to ion secretion.

The effect of route of administration on the enantioselective pharmacokinetics of ketamine and norketamine in rats

2018 ◽  
Vol 32 (10) ◽  
pp. 1127-1132 ◽  
Author(s):  
Martin Le Nedelec ◽  
Paul Glue ◽  
Helen Winter ◽  
Chelsea Goulton ◽  
Natalie J Medlicott
Keyword(s):  
Intravenous Infusion ◽  
Time Course ◽  
Drug Exposure ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Drug Efficacy ◽  
Route Of Administration ◽  
Routes Of Administration ◽  
Similar Drug ◽  
Treatment Of Depression

Background: Ketamine has been shown to produce a rapid and potent antidepressant response in patients with treatment-resistant depression. Currently ketamine is most commonly administered as a 40-minute intravenous infusion, though it is unknown whether this is the optimal route of administration. Aims: To determine the plasma concentration time course of the R- and S-enantiomers of ketamine and norketamine following administration of ketamine by four different routes of administration. Methods: Plasma from conscious non-anaesthetised rats was collected following administration of ketamine by either subcutaneous (SC), intramuscular (IM), intravenous infusion (IVI) or intravenous bolus (IVB) routes of administration. Concentrations of the enantiomers of ketamine and norketamine were determined by LC/MS. Results: Administration by the SC, IM and IVI routes produced an overall similar drug exposure. In contrast, administration by the IVB route produced approximately 15-fold higher peak plasma concentrations for the enantiomers of ketamine and an approximately four-fold lower AUC for the enantiomers of norketamine. Conclusions: Route of administration can significantly influence ketamine and norketamine exposures. These differences may influence safety and tolerability, and potentially drug efficacy in humans. This knowledge adds to current research into the optimisation of the use of ketamine for the treatment of depression.

scholarly journals Acute-Onset Panhypopituitarism Nearly Missed by Initial Cosyntropin Testing

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Claudine A. Blum ◽  
Daniel Schneeberger ◽  
Matthias Lang ◽  
Janko Rakic ◽  
Marc Philippe Michot ◽  
...  
Keyword(s):  
Septic Shock ◽  
Diabetes Insipidus ◽  
Time Course ◽  
Low Dose ◽  
Adrenal Glands ◽  
Acute Onset ◽  
Adrenal Crisis ◽  
Acth Secretion ◽  
Basal Cortisol ◽  
History Of

Introduction. Diagnosis of adrenal crisis and panhypopituitarism in patients with septic shock is difficult but crucial for outcome. Case. A 66-year-old woman with metastasized breast cancer presented to the ED with respiratory insufficiency and septic shock after a 2-day history of the flu. After transfer to the ICU, corticosteroids were started in addition to antibiotics, as the patient was vasopressor-nonresponsive. Diabetes insipidus was diagnosed due to polyuria and treated with 4 mg desmopressin. Thereafter, norepinephrine could be tapered rapidly. On day 2, basal cortisol was 136 nmol/L with an increase to 579 nmol/L in low-dose cosyntropin testing. Polyuria had not developed again. Therefore, corticosteroids were stopped. On day 3, the patient developed again nausea, vomiting, and polyuria. Adrenal crisis and diabetes insipidus were postulated. Corticosteroids and desmopressin were restarted. Further testing confirmed panhypopituitarism. MRI showed a new sellar metastasis. After 2 weeks, stimulated cortisol in cosyntropin testing reached only 219 nmol/l, confirming adrenal insufficiency. Discussion. The time course showed that the adrenal glands took 2 weeks to atrophy after loss of pituitary ACTH secretion. Therefore, a misleading result of the cosyntropin test in the initial phase with low basal cortisol and allegedly normal response to exogenous ACTH may be seen. Cosyntropin testing in the critically ill should be interpreted with caution and in the corresponding clinical setting.

Effects of variations in renal hemodynamics on the time course of renin secretion rate

1983 ◽  
Vol 245 (6) ◽  
pp. F784-F791
Author(s):  
S. Simchon ◽  
S. Chien
Keyword(s):  
Time Constant ◽  
Time Course ◽  
Renal Perfusion ◽  
Renal Hemodynamics ◽  
Secretion Rate ◽  
Renin Secretion ◽  
Renin Release ◽  
Pump System ◽  
Renal Vasoconstriction ◽  
Nitroprusside Infusion

The effects of variations in renal hemodynamics on the time course of renin secretion were studied in dogs anesthetized with pentobarbital-chloralose. Hemodynamic changes were induced either locally in kidneys perfused in situ via an extracorporeal circuit (with or without a pump system) or systemically by hemorrhage or nitroprusside infusion. In the autoperfused kidney the reduction of renal perfusion pressure to approximately one-half of the arterial pressure by inflow occlusion caused an increase in renal conductance (renal vasodilation) and an increase in renin secretion rate (RSR). In the pump-perfused kidney, a step increase in renal blood flow (RBF) caused renal vasoconstriction and a decrease in RSR; a step decrease in RBF caused renal vasodilation and an increase in RSR. Following step changes in RBF, the time constant of the alterations of renal conductance was 56.5 s, and the time constant of the RSR responses was 80.1 s. The total time required to reach a steady state for RSR lagged behind that for renal conductance by approximately 5 min. These differences reflect the time needed for the kidney to release renin in response to changes in renal vascular caliber. The results suggest that renin release occurs in response to the autoregulatory dilation of the renal arterioles. When systemic hypotension was induced by nitroprusside infusion, RSR also increased together with the renal conductance. Following hemorrhage, however, RSR increased despite a decrease in renal conductance, reflecting the role of neurohumoral factors in causing renin release in this case. The comparison of renin secretion following different types of hemodynamic alterations serves to elucidate the mechanisms of renin secretion.

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