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C Corot

Publications and source records attributed to C Corot.

51 records · Page 3Linked to original sources

Contrast media for angiography: physicochemical properties, pharmacokinetics and biocompatibility.

Contrast agents are used as diagnostic molecules for the visualization of the vascular system. Despite their rapid pharmacokinetic distribution, and their excretion within a few minutes, their injection is associated with clinical symptoms of relative bioincompatibility. Allergoid reactions and disturbances of the hemostatic system represent the main fields of biological investigations. Due to the extent of clinical and experimental works the ubiquitous interactions between these molecules and cellular and/or protein systems have emerged. The development of a new family of low osmolality ionic or non-ionic contrast molecules had decreased the incidence of minor reactions, but did not modify the frequency of severe accidents and even led to the emergence of new iatrogenic syndromes. Despite extensive laboratory investigations there are still no predictive criteria nor any specific therapeutic prevention of these allergoid reactions. The suggested future line of investigation concerns the physicochemical interaction of CM and targeted biological systems which may allow the analysis and predictivity of these interactions at the molecular level.

Angiography↗

Cefazolin and netilmicin serum levels during and after cardiac surgery with cardiopulmonary bypass.

The kinetics of cefazolin and netilmicin were studied in 10 patients undergoing elective cardiac surgery with hemodilution and cardiopulmonary bypass (CPB). During surgery, but before CPB, cefazolin, 25 mg/kg, and netilmicin, 2 mg/kg, were administered intravenously over 30 minutes. For the 48-hour period following CPB, cefazolin, 25 mg/kg, and netilmicin, 1 mg/kg, were administered intravenously every 8 hours. Initiation of CPB was accompanied by a 28% to 30% decrease in hematocrit and serum antibiotic levels. At the conclusion of surgery, cefazolin and netilmicin serum levels were 41 +/- 12 micrograms/L and 2.5 +/- 0.6 micrograms/mL (mean +/- SD), respectively. During the postoperative period, cefazolin levels were consistently greater than the minimum inhibitory concentration (MIC) for sensitive bacteria (4 micrograms/mL); average netilmicin levels were greater than MIC of sensitive bacteria (2 micrograms/mL) for 2 hours after antibiotic infusion. The netilmicin trough levels were 0.6 +/- 0.5 micrograms/mL. Pharmacokinetic parameters were determined using a model-independent method, and gave the following results during surgery: cefazolin--elimination half-life, 231 minutes, total body clearance, 1.05 mL/kg/min, and steady-state volume of distribution, 243 mL/kg. The values for netilmicin were 249 minutes, 1.18 mL/kg/min, and 353 mL/kg, respectively. Postoperatively there were no significant changes in the disposition of cefazolin, but the elimination half-life of netilmicin was shorter (124 minutes, P less than 0.01) and the total body clearance greater (3.58 mL/kg/min, P less than 0.01) than during surgery.

Adolescent↗

Oxacillin and tobramycin serum levels during cardiopulmonary bypass.

Antibiotic prophylaxis in cardiac surgery is recommended to combat acquired infections caused by staphylococci and gram-negative bacilli. Prophylaxis seems effective provided blood levels are greater than minimal inhibitory concentrations (MIC). In this study, two doses of antibiotics were compared in 45 patients with normal renal function during cardiopulmonary bypass (CPB). All patients received 50 mg/kg of oxacillin. Group 1 (30 patients) also received 1 mg/kg of tobramycin, while group 2 (15 patients) received 2 mg/kg of tobramycin. Blood samples were taken after the administration of antibiotics, as well as at the onset and conclusion of CPB. Additional samples were taken before and after heparin injection before CPB, and from the arterial and venous cannulae of the bubble oxygenator during CPB. In both groups, oxacillin serum levels were constantly greater than MIC for susceptible bacteria. In group 1, tobramycin levels less than 2 micrograms/mL (MIC for most susceptible bacteria) occurred in four patients before CPB, in 14 patients at the onset of CPB, and in 19 patients at the conclusion of CPB. These low levels were not explained by heparin administration or absorption onto the CPB circuit, but were the result of hemodilution. In group 2, in which all the tobramycin levels were higher than 2 micrograms/mL, serum levels decreased from 9.9 +/- 3.4 (mean +/- SD) to 3.7 +/- 0.7 micrograms/mL throughout the procedure. Plasma creatinine did not change significantly in either group. It is concluded that in patients with normal renal function, doses as high as 50 mg/kg of oxacillin and 2 mg/kg of tobramycin may be necessary before CPB to provide adequate serum levels throughout CPB.

Adult↗

Effect of iodinated contrast media on blood clotting.

Recently, blood clot formation in catheters used for the injection of nonionic contrast media (CM) during angiography has been reported as being due to activation of hemostasis in the catheter. However, CM exhibit inhibitory properties regarding coagulation and platelet functions. The effect on blood clotting of iohexol, iopamidol, ioxaglate, diatrizoate, and ioxitalamate at a ratio of 10% v/v with nonanticoagulated human whole blood was evaluated using the kinetics of fibrinopeptide A (FpA) generation. Blood aliquots were taken every 2 minutes until blood clot occurred. Two groups of contrast media were identified: (1) iohexol and iopamidol, which increased the clotting time, and (2) ioxaglate, diatrizoate, and ioxitalamate, for which all clotting times were over 30 minutes and no FpA generation occurred.

Blood Coagulation↗

Evaluation of histamine release following intravenous injection of ionic and nonionic contrast media.

To evaluate histamine release (HR) following injection of radiocontrast media and to test the predictive value of peak-expiratory-flow rate (PEFR) in detecting high-risk patients, the authors performed in two series 90 intravenous pyelograms (IVPs). In the first group, HR was measured by a fluorometric method after injection of Hexabrix (25 patients) and Iopamiron (25 patients). In the second group, HR measured by a radioimmunoassay, and PEFR measured by a peak flowmeter were investigated after injection of Hexabrix (10 patients), Telebrix (10 patients), Omnipaque (10 patients) and Iopamiron (10 patients). Histamine release in groups 1 and 2, and PEFR in group 2, were not significantly modified by the injection of each radiocontrast media. For the four patients (two per group) who experienced minor allergic side effects, the levels of HR and PEFR were always within the normal ranges.

Contrast Media↗

In vitro interactions of gadolinium DOTA meglumine and gadolinium DTPA meglumine on hemostasis.

The interactions of two gadolinium complexes (Gd-DOTA meglumine and Gd-DTPA meglumine) with hemostatic function have been analyzed using: (1) coagulation reactions (extrinsic and intrinsic pathways and fibrinoformation) and (2) platelet function investigations (aggregation, release of Ca++ and ATP after stimulation with collagen 2.5 micrograms/mL). The data obtained with Gd-DTPA meglumine (Mgl) exhibited a significant increase of the intrinsic coagulation pathway and a delay in fibrinoformation, although there is no alteration of the effect of thrombin on fibrinogen (fibrinopeptid A determinations). Platelet aggregation and release are moderately modified. In contrast, Gd-DOTA Mgl exerts no effect on the coagulation system and only minor effects on platelet functions. It is suggested that at least one mechanism involves the complexation of ionized calcium because Gd-DTPA Mgl and Gd-DOTA Mgl complex, respectively, 45% and 23% of ionized calcium in plasma. However, other mechanisms such as an alteration of fibrin polymerization are not unlikely.

Contrast Media↗

[In vitro study of the action of DOTA and DTPA-gadolinium complexes on platelet functions: aggregation and calcium excretion].

Interaction of 2 complexes of Gadolinium (DOTA Gd meglumin and DTPA Gd meglumin) was studied in vitro with regard to platelet function: aggregation and excretion of ATP and of ionised calcium in response to collagen (2.5 Ig/ml). Excretory functions were measured simultaneously with aggregation by bioluminescent techniques using luciferin for the measurements of ATP and aequorin for measurements of ionised calcium. Platelet aggregation and excretion functions, investigated in vitro, were moderately inhibited in the presence of gadolinium complexes. The greatest effects were seen with DTPA Gd meglumin. Complexation of extra-cellular ionised calcium by NMR products in partially responsible for the inhibition of platelet aggregation.

Adenosine Triphosphate↗

Influence of the viscosity of iodixanol on medullary and cortical blood flow in the rat kidney: a potential cause of Nephrotoxicity.

The aim of the present study was to investigate the effects of four iodinated contrast media on cortical, inner medullary and outer medullary blood flow in the rat kidney by using laser-Doppler flowmetry. The high-osmolar contrast medium diatrizoate did not significantly modify medullary perfusion but moderately decreased the cortical blood flow when injected at a dose of 1600 mg iodine kg(-1). Similar effects were obtained with the low-osmolar contrast media ioxaglate and iobitridol. In contrast, the new iso-osmolar contrast medium iodixanol induced a dose-dependent reduction of perfusion in all regions tested. This effect was accompanied by concomitant hypotension. The reduction of inner medullary and cortical blood flow induced by iodixanol was partially alleviated by heating the solution prior to injection and subsequently reducing its viscosity. In the outer medulla, however, this procedure did not improve blood flow. These results suggest that lowering the viscosity may palliate the harmful effects of iodixanol on the inner medulla and cortex, but may not protect the outer medulla from hypoxic injury.

Animals↗

Structure-activity relationship of macrocyclic and linear gadolinium chelates: investigation of transmetallation effect on the zinc-dependent metallopeptidase angiotensin-converting enzyme.

Transmetallation between commercially available solutions of gadolinium (Gd) chelates and the zinc (Zn)-dependent angiotensin-converting enzyme (ACE) was investigated. In vitro, the strongest inhibitions were observed for the linear Gd complexes, Gd diethylenetriamine pentaacetic acid (DTPA) bis-methylamide (BMA) (IC50 = .016 +/- .006 mmol/l) and Gd-DTPA (IC50 = .350 +/- .034 mmol/l). The two macrocycles Gd tetraazacyclododecane tetraacetic acid (DOTA) and Gd-HP-DO3A were similar and 400 times less active than Gd-DTPA-BMA. These effects were mainly due to the presence of free ligand for DTPA and calcium (Ca) chelate in the case of DTPA-BMA because the addition of Zn2+ in the same quantities suppresses their inhibitory effects. In vivo, these two solutions of linear Gd chelates significantly inhibited ACE activity (Gd-DTPA: (67 +/- 9% versus baseline; and Gd-DTPA-BMA: 73 +/- 2% versus baseline at the clinical dose of .1 mmol/kg), whereas no significant effect was observed for the two macrocyclic chelates Gd-DOTA and Gd-HP-DO3A. Formulating the Gd chelate solution with either an excess of free ligand or Ca chelate (to decrease Gd3+ release) in the case of linear Gd chelate may have deleterious biologic consequences.

Chelating Agents↗

Effects of non-ionic monomeric and dimeric iodinated contrast media on renal and systemic haemodynamics in rats.

Non-ionic dimeric contrast media (CM) are a new class of CM which are iso-osmolar with plasma. The aim of this study was to investigate their effects on systemic and renal haemodynamics. The non-ionic dimeric CM iodixanol and the non-ionic monomeric agent iobitridol (both at a dose of 1,600 mgI/kg) were compared in terms of their effects on systemic blood pressure (BP) and renal blood flow (RBF) in two strains of rats (Wistar and Sprague Dawley). Iodixanol significantly lowered BP in Wistar rats (-33 +/- 9% of baseline, 10 min post-injection, P < 0.001 vs. saline and iobitridol). Iobitridol had virtually no effect on BP. Iobitridol and iodixanol significantly decreased RBF. This effect was more marked following injection of the dimer rather than the monomer (iodixanol: -32 +/- 13% iobitridol: -20 +/- 4 of baseline at 16 min, P < 0.05). For both agents, RBF was still decreased 50 min following injection (iodixanol: -30 +/- 11%, and iobitridol: -20 +/- 5% of baseline). Iodixanol also decreased RBF in Sprague Dawley rats, while BP remained unchanged. This suggests that changes in BP/RBF autoregulation do not account for the renal haemodynamic effects of this agent. When measured 2 h following injection, the iodixanol-induced renal hypoperfusion was still detectable (-29% vs. saline-treated rats), although not significant (P = 0.06). This effect was no longer observed 4 h following injection. Increasing the saline infusion rate (18 mL/h vs. 2 mL/h) during the experiment did not significantly decrease the effects of iodixanol on BP and RBF in Wistar rats. In spite of its iso-osmolality, iodixanol, a non-ionic dimeric CM, depressed RBF and BP significantly more than iobitridol, a monomeric non-ionic agent, in Wistar rats. This effect was long-lasting and was not alleviated by increasing the hydration rate.

Animals↗