Comparative Effects of Ethacrynic Acid, Furosemide, and Diazoxide in the Perfused Dog Hindlimb

1971 ◽  
Vol 49 (12) ◽  
pp. 1038-1043 ◽  
Author(s):  
R. I. Ogilvie ◽  
E. Schlieper
Keyword(s):  
Dose Response ◽  
Time Course ◽  
Ethacrynic Acid ◽  
Maximal Effect ◽  
Vasodilator Effect ◽  
Arterial Blood ◽  
The Mean ◽  
Mean Time ◽  
Higher Doses ◽  
Vasodilating Effect

The vasodilator effects of intravenous ethacrynic acid (EA), furosemide (F), and diazoxide (DZ) were compared in the hindlimb of anesthetized anephric dogs, perfused with a constant inflow of arterial blood. A dose-response relationship was demonstrated for all three agents. The curves for EA and F were parallel and relatively flat, with EA being 10 times more potent than F in producing vasodilatation of the perfused limb. The dose–response for DZ was steep and the maximal vasodilator response observed at the lowest dose of DZ (5 mg/kg) did not differ from that at the highest doses of EA (10 mg/kg) or F (100 mg/kg). The maximal vasodilator effect of DZ in the perfused hindlimb occurred within 2 min after intravenous administration. After the higher doses of F there was a transitory vasodilator effect within 2 min but the maximal and more persistent effect was not observed until much later. The mean time for maximal effect was 40 min for EA, 46 min for F, and 2 min for DZ. The time course of vasodilator effect and maximal observed effect for EA and F was not altered by intraarterial administration nor by sympathetic decentralization of the perfused hindlimb. We conclude that F, like EA, has a direct vasodilating effect on peripheral arterioles and both EA and F probably act by a different mechanism than DZ.

Effects of Isoproterenol, Diazoxide, Ethacrynic Acid, and Furosemide on Skeletal Muscle Vascular Resistance

1973 ◽  
Vol 51 (3) ◽  
pp. 183-189 ◽  
Author(s):  
P. Larochelle ◽  
E. Mikulic ◽  
R. I. Ogilvie
Keyword(s):  
Skeletal Muscle ◽  
Ethacrynic Acid ◽  
Perfusion Pressure ◽  
Gracilis Muscle ◽  
Maximal Effect ◽  
Vasodilator Response ◽  
Arterial Blood ◽  
Constant Rate ◽  
The Mean ◽  
The Right

The vasodilator properties of isoproterenol, diazoxide, ethacrynic acid, and furosemide were compared in the isolated canine gracilis muscle perfused with arterial blood at a constant rate. Isoproterenol was the most potent agent with a steep vasodilator response to 10−8–10−6 M infusions and a maximal decrease in perfusion pressure of 45.5 ± 2.9% at the 10−6 M concentration. The dose – vasodilator responses for diazoxide and ethacrynic acid were parallel to that for isoproterenol but shifted three log doses to the right. The dose–response for furosemide was almost flat with a maximal vasodilator response of 15.5 ± 2.3% at the 10−2 M concentration. The maximal effect of isoproterenol was noted within 5 min of starting the infusion whereas for diazoxide and furosemide it was noted after 10 min and for ethacrynic acid after 20 min. The mean ratio of venous to arterial resistance was unaltered during isoproterenol infusions, decreased with 10−3 M diazoxide, and increased with 10−3 M ethacrynic acid; however, none of these changes were statistically significant. Capillary hydrostatic pressure was significantly decreased only with higher concentrations of isoproterenol and diazoxide, an average of 6 mm Hg with 10−7 M isoproterenol, 8 mm Hg with 10−6 M isoproterenol, and 9 mm Hg with 10−3 M diazoxide. No significant changes in capillary pressure were noted during infusion of ethacrynic acid or furosemide. The results clearly differentiate these agents on the basis of potency, onset, and characteristics of vasodilator effect on sequential segments of a skeletal muscle vascular bed.

The Comparative Pharmacodynamics of Remifentanil and Its Metabolite, GR90291, in a Rat Electroencephalographic Model 

1999 ◽  
Vol 90 (2) ◽  
pp. 535-544 ◽  
Author(s):  
Eugene H. Cox ◽  
Mariska W. E. Langemeijer ◽  
Josy M. Gubbens-Stibbe ◽  
Keith T. Muir ◽  
Meindert Danhof
Keyword(s):  
Steady State ◽  
Time Course ◽  
Parent Drug ◽  
Volume Of Distribution ◽  
Pharmacodynamic Model ◽  
Pharmacokinetic Parameters ◽  
Maximal Effect ◽  
Total Blood ◽  
The Mean

Background The purpose of this study was to investigate the in vivo pharmacodynamics and the pharmacodynamic interactions of remifentanil and its major metabolite, GR90291, in a rat electroencephalographic model. Methods Remifentanil and GR90291 were administered according to a stepwise infusion scheme. The time course of the electroencephalographic effect (0.5-4.5 Hz) was determined in conjunction with concentrations of the parent drug and the metabolite in blood. Results Administration of remifentanil resulted in concentrations of remifentanil and GR90291 in the ranges 0-120 ng/ml and 0-850 ng/ml, respectively. When the metabolite was administered, concentrations of the metabolite in the range 0-220 microg/ml and no measurable concentrations of remifentanil were observed. The mean +/- SE values of the pharmacokinetic parameters clearance and volume of distribution at steady state were 920+/-110 ml x min(-1) x kg(-1) and 1.00+/-0.93 l/kg for remifentanil and 15+/-2 ml x min(-1) x kg(-1) and 0.56+/-0.08 l/kg for GR90291. The relative free concentrations in the brain, as determined on the basis of the cerebrospinal fluid/total blood concentration ratio at steady state, were 25+/-5% and 0.30+/-0.11% for remifentanil and GR90291, respectively. Concentration-electroencephalographic effect relations were characterized on the basis of the sigmoidal Emax pharmacodynamic model. The mean +/- SE values for the maximal effect (Emax), the concentration at which 50% of the maximal effect is obtained (EC50), and Hill factor for remifentanil were 109+/-12 microV, 9.4+/-0.9 ng/ml, and 2.2+/-0.3, respectively (n = 8). For GR90291, the mean +/- SE values for EC50 and the Hill factor were 103,000+/-9,000 microg/ml and 2.5+/-0.4, respectively (n = 6). Conclusions Analysis of the data on the basis of a previously postulated, mechanism-based pharmacokinetic-pharmacodynamic model for synthetic opioids revealed that the low in vivo potency of GR90291 can be explained by a low affinity to the mu-opioid receptor in combination with a poor brain penetration.

Metabolic control of Argyropelecus hemigymnus photophores: effects of glucose and pyruvate

1991 ◽  
Vol 69 (9) ◽  
pp. 2410-2413 ◽  
Author(s):  
J. Mallefet ◽  
F. Baguet
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Uptake ◽  
Metabolic Control ◽  
Time Course ◽  
Light Emission ◽  
Mesopelagic Fish ◽  
Fresh Weight ◽  
Hypometabolic State ◽  
The Mean ◽  
Mean Time

Modifications in oxygen consumption and luminescence of isolated luminescent organs of the mesopelagic fish Argyropelecus hemigymnus following glucose and pyruvate administration were studied before and during light emission triggered by adrenaline. Isolated photophores (mean fresh weight 13.5 ± 0.9 mg) at rest, i.e., in the absence of light emission, in saline (20 °C) exhibit a respiration rate of 1.045 ± 0.082 (SE) nmol O2/min (n = 35). A significant decrease (p = 0.05) in oxygen consumption was observed after the addition of 5.5 mM glucose. Instead of the oxygen decrease usually observed as a result of control stimulations using adrenaline, photophores pretreated with glucose increased their oxygen uptake in response to adrenaline, and maximal light emission was reduced by 85% (p = 0.01). The addition of 5.5 mM pyruvate induced a significant transient increase (p = 0.05) in oxygen uptake of isolated photophores, though this treatment did not statistically modify the mean time course of oxygen consumption and light emission in response to adrenaline. The hypothesis of a hypometabolic state of the isolated photophores of A. hemigymnus during light emission is discussed.

Evaluation of a method for noninvasive intracranial pressure assessment during infusion studies in patients with hydrocephalus

2000 ◽  
Vol 92 (5) ◽  
pp. 793-800 ◽  
Author(s):  
Bernhard Schmidt ◽  
Marek Czosnyka ◽  
Jens Jürgen Schwarze ◽  
Dirk Sander ◽  
Werner Gerstner ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Intracranial Pressure ◽  
Time Course ◽  
Cerebral Blood Flow Velocity ◽  
Absolute Error ◽  
Content Type ◽  
Arterial Blood ◽  
Potential Clinical Benefit ◽  
The Mean ◽  
Fine Print

Object. A mathematical model previously introduced by the authors allowed noninvasive intracranial pressure (nICP) assessment. In the present study the authors investigated this model as an aid in predicting the time course of raised ICP during infusion tests in patients with hydrocephalus and its suitability for estimating the resistance to outflow of cerebrospinal fluid (Rcsf).Methods. Twenty-one patients with hydrocephalus were studied. The nICP was calculated from the arterial blood pressure (ABP) waveform by using a linear signal transformation, which was dynamically modified by the relationship between ABP and cerebral blood flow velocity. This model was verified by comparison of nICP with “real” ICP measured during lumbar infusion tests. In all simulations, parallel increases in real ICP and nICP were evident. The simulated Rcsf was computed using nICP and then compared with Rcsf computed from real ICP. The mean absolute error between real and simulated Rcsf was 4.1 ± 2.2 mm Hg minute/ml. By the construction of simulations specific to different subtypes of hydrocephalus arising from various causes, the mean error decreased to 2.7 ± 1.7 mm Hg minute/ml, whereas the correlation between real and simulated Rcsf increased from R = 0.73 to R = 0.89 (p < 0.001).Conclusions. The validity of the mathematical model was confirmed in this study. The creation of type-specific simulations resulted in substantial improvements in the accuracy of ICP assessment. Improvement strategies could be important because of a potential clinical benefit from this method.

CYCLIC AMP AND CYCLIC GMP ACCUMULATION IN HAMSTER PRE-OVULATORY FOLLICLES STIMULATED WITH LH AND FSH

1978 ◽  
Vol 87 (1) ◽  
pp. 158-163 ◽  
Author(s):  
Anastasia Makris ◽  
Kenneth J. Ryan
Keyword(s):  
Cyclic Amp ◽  
Dose Response ◽  
Cyclic Gmp ◽  
Time Course ◽  
Hormone Action ◽  
Acute Response ◽  
Cyclic Amp Accumulation ◽  
Ovulatory Follicles ◽  
Higher Doses

ABSTRACT Cyclic AMP and cyclic GMP accumulation in hamster pre-ovulatory follicles was determined after in vitro stimulation by LH and FSH. Combined time course and dose response experiments determined that the acute response of the follicles (0–30 min) to LH and FSH was similar with respect to cyclic AMP accumulation. The pattern of cyclic GMP accumulation was, however, distinctly different in LH and FSH stimulated follicles. LH increased follicular cyclic GMP only at the lowest dose (0.005 IU/ml), while higher doses of LH had no effect. In contrast, FSH at all doses stimulated cyclic GMP accumulation. The different cyclic AMP to cyclic relationships generated in the follicles by LH and FSH may be determinants in specificity of hormone action in pre-ovulatory follicles.

scholarly journals Comparison of time taken to obtain an arterial blood gas result at the bedside using the ProximaTM point of care machine vs. a standard remote arterial blood gas analyser: A randomized controlled trial

2020 ◽  
pp. 175114372097384
Author(s):  
Kay Mitchell ◽  
Karen E Salmon ◽  
David Egbosimba ◽  
Gavin Troughton ◽  
Mike PW Grocott
Keyword(s):  
Point Of Care ◽  
Controlled Trial ◽  
Blood Gas ◽  
Sampling System ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
The Mean ◽  
Time Away ◽  
Mean Time ◽  
Reduced Time

Introduction The ProximaTM point of care (POC) device enables arterial blood gas (ABG) samples to be analysed without the nurse leaving the patient. The benefits of this for work efficiency have not been evaluated. Methods We compared the time taken to obtain an ABG result using ProximaTM versus a standard ABG sampling system. Twenty patients were randomized to ABG sampling using ProximaTM, or a standard ABG system. Nurses were observed performing all ABG sampling episodes for a minimum of 24 hours and no more than 72 hours. Results The mean time taken to obtain a result using ProximaTM was 4:56 (SD = 1:40) minutes compared to 6:31 (SD = 1:53) minutes for the standard ABG technique (p < 0.001). Mean time away from the patient's bedside was 3.07 (SD = 1:17) minutes using the standard system and 0 minutes using ProximaTM (p < 0.001). Conclusions Reduced time for blood gas sampling and avoidance of time away from patients may have significant patient safety and resource management implications, but the clinical and financial significance were not evaluated.

Unique Pattern of Pulmonary Function after Exercise in Patients with Cystic Fibrosis

1994 ◽  
Vol 6 (3) ◽  
pp. 275-286 ◽  
Author(s):  
Ted. A. Kaplan ◽  
Gina Moccia ◽  
Robert M. McKey
Keyword(s):  
Cystic Fibrosis ◽  
Pulmonary Function ◽  
Time Course ◽  
Forced Expiratory Volume ◽  
Distinct Pattern ◽  
Degree Pattern ◽  
Function Test ◽  
The Mean ◽  
Exercise Induced ◽  
Mean Time

The purpose of this study was to assess the incidence, degree, pattern, and time course of pulmonary function test (PFT) changes measured after a dynamic exercise challenge. Forced expiratory maneuvers were performed before and serially after a 7-min run-walk in 44 patients with cystic fibrosis (CF). Twenty-four patients met at least one PFT criterion for exercise-induced bronchospasm (EIB) within 21 min after exercise, and 38 patients had >5% increase in a PFT parameter at some point after exercise. The mean time of greatest increase in PFTs occurred sooner than the greatest decrease, which was later than for 22 patients with asthma or allergic rhinitis found to have EIB. Age was inversely related to percentage fall in forced expiratory volume in 1 s (FEV,) after exercise. These results demonstrate a distinct pattern of PFTs measured after exercise in most patients with CF, with an early bronchodilation followed by a significant decrease in PFTs.

Prognostic factors in methanol poisoning

2007 ◽  
Vol 26 (7) ◽  
pp. 583-586 ◽  
Author(s):  
H. Hassanian-Moghaddam ◽  
A. Pajoumand ◽  
S.M. Dadgar ◽  
Sh. Shadnia
Keyword(s):  
Mortality Rate ◽  
Cross Sectional Study ◽  
Time Interval ◽  
Poison Center ◽  
Cross Sectional ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
Significant Difference ◽  
The Mean ◽  
Mean Time

The aim of this study was to assess the clinical and laboratory factors in methanol poisoned patients to determine the prognosis of their toxicity. This survey was done as a prospective cross-sectional study in methanol-poisoned patients in Loghman-Hakim hospital poison center during 9 months from October 1999—June 2000. During this time 25 methanol-poisoned patients were admitted. The mortality rate was 12 (48%). Amongst survivors, three (23%) of the patients developed blindness due to their poisoning and the other 10 (77%) fully recovered without any complication. The mortality rate in comatose patients was nine (90%) while in non-comatose patients it was three (20%) ( P < 0.001). There was a significant difference in mean pH in the first arterial blood gas of patients who subsequently died (6.82 ± 0.03) and survivors (7.15 ± 0.06) ( P < 0.001, M-W). The mean time interval between poisoning and ED presentation in deceased patients were (46 ± 15.7) hours, in survived with sequelae were (16.7 ± 6.7) and in survived without sequelae were (10.3 ± 7.2) hours ( P < 0.002, K-W). We found no significant difference between the survivors versus the patients who died regarding methanol. Simultaneous presence of ethanol and opium affected the outcome of the treatment for methanol intoxication favourably and unfavourably, respectively. In our study, poor prognosis was associated with pH < 7, coma on admission and >24 hours delay from intake to admission. Human & Experimental Toxicology (2007) 26: 583—586.

Effective Reversal of Moderate Rocuronium- or Vecuronium-induced Neuromuscular Block with Sugammadex, a Selective Relaxant Binding Agent

2007 ◽  
Vol 106 (2) ◽  
pp. 283-288 ◽  
Author(s):  
Koen Suy ◽  
Karl Morias ◽  
Guy Cammu ◽  
Pol Hans ◽  
Wilbert G. F. van Duijnhoven ◽  
...  
Keyword(s):  
Dose Response ◽  
Neuromuscular Block ◽  
Muscle Relaxation ◽  
Dose Finding ◽  
Reversal Agent ◽  
Muscle Twitch ◽  
Train Of Four ◽  
The Mean ◽  
American Society ◽  
Mean Time

Background Sugammadex rapidly reverses rocuronium-induced neuromuscular block. This study explored the dose-response relation of sugammadex given as a reversal agent at reappearance of the second muscle twitch after rocuronium- and vecuronium-induced block. A secondary objective was to investigate the safety of single doses of sugammadex. Methods In this two-center, phase II, dose-finding study, 80 patients (age &gt;or= 18 yr, American Society of Anesthesiologists physical status I or II, surgery &gt;or= 60 min requiring muscle relaxation for intubation) were randomly assigned to receive rocuronium (0.60 mg/kg) or vecuronium (0.10 mg/kg). Sugammadex or placebo was administered at reappearance of the second muscle twitch. The primary efficacy endpoint was time from starting sugammadex administration until recovery of the train-of-four ratio to 0.9. Results Compared with placebo, sugammadex produced dose-dependent decreases in mean time to recovery for all train-of-four ratios in the rocuronium and vecuronium groups. The mean time for recovery of the train-of-four ratio to 0.9 in the rocuronium group was 31.8 min after placebo compared with 3.7 and 1.1 min after 0.5 and 4.0 mg/kg sugammadex, respectively. The mean time for recovery of the train-of-four ratio to 0.9 in the vecuronium group was 48.8 min after placebo, compared with 2.5 and 1.4 min after 1.0 and 8.0 mg/kg sugammadex, respectively. Sugammadex was well tolerated. Conclusion Sugammadex rapidly reversed rocuronium- or vecuronium-induced neuromuscular block at reappearance of the second muscle twitch and was well tolerated. A dose-response relation was observed with sugammadex for reversal of both rocuronium- and vecuronium-induced neuromuscular block.

scholarly journals PHENOTYPIC EXPRESSION OF A GENETIC PROPERTY INTRODUCED BY DEOXYRIBONUCLEATE

1959 ◽  
Vol 42 (4) ◽  
pp. 737-748 ◽  
Author(s):  
Maurice S. Fox
Keyword(s):  
Standard Deviation ◽  
Time Course ◽  
Distribution Curve ◽  
Phenotypic Expression ◽  
Normal Distribution Curve ◽  
Phenotypic Alteration ◽  
The Mean ◽  
Definition Of ◽  
Two Parameters ◽  
Mean Time

The time course of the appearance of cells showing a new phenotype, following treatment with a specific DNA, has been analyzed. A plot as a function of time of the number of cells showing the new property closely resembles the summation under a normal distribution curve. Describing the appearance of the new phenotype in these terms permits the definition of two parameters, the mean time, and the standard deviation of the distribution curve. This distribution is not affected either by the DNA concentration with which the transformable population has been treated, or by the streptomycin concentration with which the transformed population has been challenged. Interruptions of the expression process, by cooling to 20° or 0°C., serve only to displace the expression curves, without changing their shape, while small reductions in temperature change both the mean time of expression and the standard deviation of the distribution curve. On the basis of these observations a number of hypotheses have been examined concerning the mechanism whereby transforming DNA manifests a phenotypic alteration in the transformed cells. It can be concluded that there exist at least two stages in the process of expression. The completion of the first stage, causing the randomization, occurs with a mean time of about 60 minutes, and a terminal step, that of the transition of phenotype, occurs in less than 3 minutes.

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