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Biomedical subjects

J E de la Coussaye

Publications and source records attributed to J E de la Coussaye.

At least 19 recordsLinked to original sources
PubMed2003

Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings.

BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.

Blotting, Western↗
PubMed2000

Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats.

Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. The purpose of this study was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whether they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnl and cTnT release with histological examinations, using isoprenaline-induced cardiac muscle damage as an experimental model in the rat. Eighteen Wistar rats per group were treated with a single dose of either isoprenaline (iso) or with normal saline as a control group. The anti-cTnI and cTnT monoclonal antibodies (mAbs) employed in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rat. A highly significant rise of cTnl or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. The highest cTnI (mean+/-S.D., 1.1+/-2.3 ng/ml) and cTnT (mean+/-S.D. 3.6+/-30 ng/ml) were found 4 h after iso. cTnI and cTnT significantly increased in iso-treated rats in comparison with controls whether the differences between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnl and cTnT curves (AUC) (0-6 h) and the maximal cTnI and cTnT (0-6 h) after iso were significantly different from the controls. For CK and LD, no elevation in comparison with controls could be detected (except a trend for LD whether or not the difference between 6-h levels and basal levels were considered (P=0.08) and for LD AUC (0-6 h) (P=0. 059)). Correlations between maximal cTnI and cTnT and AUC were 0.69 (P=0.0001) and 0.60 (P=0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the myocardial tissue in ten out of 14 rats and showed the earliest alterations 4 h after iso in one treated rat. Only four of the controls exhibited evidence of mild changes and slight mononuclear cell infiltration. cTnl and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary to detect histological myocardial cell injury after iso. cTnI and cTnT were found to be early markers for diagnosing iso-induced myocardial damage in comparison with CK and LD. Elevations of cTnI and cTnT appeared to relate to the severity of histologic changes after myocardial injury. Although there was a difference in the absolute concentration of results between cTnI and cTnT assays, due to a lack of standardization and heterogeneity in the cross-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT can be used as easily measurable target parameters for detection of cardiotoxic and/or cardiodegenerative effects in rats.

Animals↗
PubMed2000

Caruncle single injection episcleral (Sub-tenon) anesthesia for cataract surgery: mepivacaine versus a lidocaine-bupivacaine mixture.

UNLABELLED: We compared the quality of anesthesia provided by mepivacaine 2% or a mixture of lidocaine 2%-bupivacaine 0.5%, both with hyaluronidase, in caruncle single-injection episcleral (sub-Tenon) anesthesia. Sixty patients undergoing cataract surgery were included in this randomized, double-blinded study. The time to the onset of blockade, maximal akinesia, need for supplemental injection, and time to recovery were recorded. With mepivacaine, the time to onset was slightly shorter, and the akinesia score higher, than with the mixture. Although statistically significant, these differences are small. With mepivacaine, the time to recovery was shorter. We conclude that the reproducible short duration of the block may be an advantage in outpatient surgery. IMPLICATIONS: We compared the classic mixture of lidocaine 2% plus bupivacaine 0.5% to mepivacaine 2% for caruncle episcleral (sub-Tenon) anesthesia for cataract surgery. Mepivacaine provided a more efficient block with a quicker onset and a quicker recovery. However, these differences were very small and were of little clinical interest.

Aged↗
PubMed2000

Evaluation of incidence, clinical significance, and prognostic value of circulating cardiac troponin I and T elevation in hemodynamically stable patients with suspected myocardial contusion after blunt chest trauma.

BACKGROUND: The frequency and prognostic influence of myocardial injury in patients with blunt chest trauma is controversial. We investigated the value of cardiac troponin I (cTn-I) and cardiac troponin T (cTn-T), highly specific markers of myocardial injury, to determine whether their measurement would improve the ability to detect myocardial contusion in stable patients with blunt chest trauma in comparison with conventional markers and whether they were associated with significantly worse late clinical outcome. METHODS AND RESULTS: Over an 18-month period, myocardial contusion was diagnosed in 26 of 94 patients (27.6%) with acute blunt chest trauma (motor vehicle crash; 81%), because of echocardiographic abnormalities (n = 12), electrocardiographic abnormalities (n = 29), or both. Patients with myocardial contusion had a significantly higher Injury Severity Score at the time of admission (p = 0.001) and a significantly longer hospital stay (p = 0.0008). All patients survived admission to hospital and were hemodynamically stable. None of the patients died or had severe in-hospital cardiac complications. The percentage of patients with elevated CK, (CK-MB/total CK) ratio, or CK-MB mass concentration was not significantly different between patients with or without myocardial contusion. However, there were significant differences between the two groups when we applied the commonly used threshold levels of CK-MB activity and myoglobin. The percentage of patients with elevated circulating cTn-I and cTn-T (> or = 0.1 microg/L) was significantly higher in patients with myocardial contusion (23% vs. 3%; p = 0.01 and 12% vs. 0%; p = 0.03, respectively). Complete changes in cTn-I and cTn-T correlated well (r = 0.91, p = 0.0001). Sensitivity, specificity, and negative and positive predictive values of cTn-I and cTn-T in predicting a myocardial contusion in blunt trauma patients were 23%, 97%, and 77%, 75%, and 12%, 100%, and 74%, 100%, respectively. Clinical follow-up was available in 83 patients (88%) (mean, 16 +/- 7.5 months). There were no deaths in either group directly attributed to cardiac complications. None of the patients had any long-term cardiac complications or myocardial failure related to blunt chest trauma. CONCLUSION: Although improved specificity of cTn-I and cTn-T compared with conventional markers, it should be emphasized that the main problem with cTn-I and cTn-T is low sensitivity as well as low predictive values in diagnosing myocardial contusion. cTn-I and cTn-T measurement is currently not an improved method in diagnosing blunt cardiac injury in hemodynamically stable patients. Moreover, there was no association of postmyocardial contusion cell injury and late outcome in these patients when cTn-I and cTn-T and other conventional markers were considered.

Abbreviated Injury Scale↗
PubMed1999

Time-course of cardiac troponin I release from isolated perfused rat hearts during hypoxia/reoxygenation and ischemia/reperfusion.

The study was designed to determine the time-course of cardiac troponin I (cTn-I) release in isolated and Langendorff-perfused rat hearts during hypoxia and reoxygenation (H/Reox), and after various durations of total ischemia and subsequent reperfusion (I/R). For this purpose, in H/Reox, cTn-I was measured with the conventional Access immunoassay (ng/ml) and a new immunoassay which operates at pg/ml, and compared with creatine kinase (CK), lactate dehydrogenase (LD) and cardiac troponin T (cTn-T). In I/R, cTn-I was compared with CK and LD. The anti-Tn-I mAbs used in cTn-I assays cross-react with cTn-I of the rat. A clear difference between time-courses and concentration levels of cTn-I in I/R and H/Reox models was found. In I/R, maximum release of cTn-I, CK and LD similarly occurred within minutes following reperfusion; however cTn-I did not return to baseline values. cTn-I levels were not linked to the duration of ischemia. In I/R, we were only able to detect small cTn-I concentrations. In H/Reox experiments, cTn-I, CK and LD increased time-dependently. We found higher cTn-I maximal peak levels detected with the Access immunoassay than with the new assay (median, 0.346 ng/ml per min/g dry wt vs 132 pg/ml per min/g dry wt). cTn-T maximal concentrations were lower than maximal cTn-I levels (median, 0.117 ng/ml per min/g dry wt). Time-courses of cTn-I release were roughly similar with both assays in the H/Reox model (r = 0.90). These data indicate that the cTn-I time-course is related to experimental model (I/R or H/Reox), but also likely depends on the sensitivity of cTn-I assays in such experimental conditions.

Animals↗
PubMed1999

Release kinetics of cardiac troponin I and cardiac troponin T in effluents from isolated perfused rabbit hearts after graded experimental myocardial contusion.

BACKGROUND: Few experimental studies report effects of direct contusion on cardiac enzyme release. Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. This investigation was designed to determine and compare the acute effects of quantified magnitudes of blunt cardiac trauma upon release of cTnI and cTnT in comparison with creatine kinase (CK) and lactate dehydrogenase (LD). METHODS: In 24 rabbit hearts prepared on a standard Langendorff apparatus, myocardial contusion (MC) was produced by a single blow with a ball falling from a predefined height, delivered directly to the surface of the heart. Hearts were divided into control (n = 6) and various quantified impacts: 75 mJoules (mJ) (n = 6), 100 mJ (n = 6), 200 mJ (n = 6). Coronary effluent samples for cTnI, cTnT, CK, and LD were collected at baseline, immediately after MC and 5, 15, 30, 45, and 60 minutes after MC. At the end of experiment, histologic condition was evaluated. RESULTS: The anti-cTnI and cTnT MAbs used in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rabbit. The time-courses of cTnI, cTnT, CK, and LD were monophasic in form. After MC, all parameters rose significantly compared with baseline and with control group. The maximal release occurred immediately after MC. The area under the cTnI curve and the maximal cTnI concentration were linked to the contusion energy when increased at 200 mJ. Maximal concentrations and areas under cTnT, CK, LD time activity curve were not linked to the contusion energy level and showed no between-energy group differences. The correlation found between maximal cTnI and maximal cTnT concentrations was 0.70 (p = 0.0001). Histologic examination showed cellular disruption and after the more severe impact, the extent of pathologic changes was more extensive. CONCLUSION: After graded experimental MC, maximal cTnI concentration and area under cTnI curve increase with the power of impact kinetic energy. Levels of cTnI allow a much higher accuracy in detecting the extent of myocardial injury postMC in comparison with cTnT, CK, and LD in this experimental study. These results should be consistent with the more extensive cTnI release with more severe impact in patients with blunt chest trauma. Furthermore, because specificity and time-course of release, both cTnI and cTnT should have a role in the diagnosis and evaluation of such patients.

Animals↗
PubMed1999

Dispersion-based reentry: mechanism of initiation of ventricular tachycardia in isolated rabbit hearts.

The aim of the study was to determine whether facilitation of reentry by potassium-channel openers is related to dispersion of refractoriness and/or modification of anisotropic properties of ventricular myocardium. The dispersion of ventricular effective refractory period (VERP), longitudinal and transverse ventricular conduction velocities (thetaL and thetaT, respectively), and wavelength [lambda = VERP x theta(L or T)] were studied in Langendorff-perfused left ventricular epicardium in 20 rabbits during infusion of incremental doses of levcromakalim or nicorandil. Dispersion of refractoriness was assessed using standard deviation of VERP mean (SD-VERP), dispersion index (DI; SD-VERP/mean VERP), and maximum dispersion (Dmax = VERPmax - VERPmin). Ventricular conduction velocities and anisotropic ratio were not modified, whatever the dose used. VERP and lambda were significantly shortened at high concentrations of levcromakalim and nicorandil. At these doses, SD-VERP, DI, and Dmax were increased significantly. Analysis of ventricular tachycardia induction, performed using a high-resolution ventricular mapping system, confirmed that heterogeneity and shortening of VERP were factors inducing functional conduction block. Our data suggest that, in rabbit left ventricular epicardium, functional conduction block facilitating the occurrence of reentry could be initiated by shortening and, especially, by dispersion of refractoriness during infusion of potassium-channel openers.

Animals↗
PubMed1998

Noninvasive monitoring of cardiac output in critically ill patients using transesophageal Doppler.

Measurement of cardiac output using thermodilution technique in mechanically ventilated patients is associated with significant morbidity. The goal of the present study was to assess the validity of cardiac output measurement using transesophageal Doppler in critically ill patients. Forty-six patients from three different intensive care units underwent 136 paired cardiac output measurements using thermodilution (COTH) and transesophageal Doppler (COTED). In addition, simultaneous suprasternal Doppler and indirect calorimetry (Fick principle) were used to measure cardiac output in 26 patients from one center. A good correlation was found between COTH and COTED (r = 0.95), with a small systematic underestimation (bias = 0.24 L/min) using transesophageal Doppler. The limits of agreement between COTH and COTED were +2 L/min and -1.5 L/min. Variations in cardiac output between two consecutive measures using either transesophageal Doppler or thermodilution techniques were similar in direction and magnitude (bias = 0 L/min; limits of agreement = +/-1.7 L/min). Suprasternal Doppler and indirect calorimetry yielded similar correlations and agreements in the subset of patients in whom they were used. These results confirm that transesophageal Doppler can provide a noninvasive, clinically useful estimate of cardiac output and detect hemodynamic changes in mechanically ventilated, critically ill patients.

Adult↗
PubMed1994

Clinical pharmacokinetics during continuous haemofiltration.

Continuous haemofiltration is an extracorporeal technique that is increasingly used to remove fluid, electrolytes, and other waste products from the blood supply of critically ill patients with acute renal failure. Continuous arteriovenous haemofiltration (CAVH), where the blood exits the body from an artery and re-enters through a vein, is widely used. Continuous venovenous haemofiltration (CVVH), where blood both exits and enters through a vein by way of a mechanical pump, avoids problems that result from the variable ultrafiltration rate found during CAVH. Continuous arteriovenous or venovenous haemodiafiltration (CAVHD or CVVHD) combine continuous haemofiltration and haemodialysis. All methods involve ultrafiltration of the patient's blood through a filter that is highly permeable to water and small molecules. Drug elimination by haemofiltration depends mainly on the rate of ultrafiltration, the drug protein binding and the sieving coefficient of the membrane. Because patients undergoing continuous haemofiltration have impaired renal function, dosage reduction is often recommended so that adverse drug reactions are avoided. In contrast, if drug removal by haemofiltration is significant, dosage supplementation may be required to ensure therapeutic efficacy of the drug. Therefore, knowledge of the impact of continuous haemofiltration on drug elimination and the pharmacokinetic profile of drugs is essential to good clinical management. The currently available information on the clinical pharmacokinetic aspects of drug therapy during continuous haemofiltration are summarised. Drugs commonly associated with haemofiltration therapy are tabulated with updated pharmacokinetics and drug-monitoring information.

Aminoglycosides↗
PubMed1993

Multiple-dose pharmacokinetics of amikacin and ceftazidime in critically ill patients with septic multiple-organ failure during intermittent hemofiltration.

The pharmacokinetic parameters of amikacin and ceftazidime were assessed in four patients undergoing hemofiltration for septic shock. The parameters were assessed during hemofiltration and in the interim period. The concentration-time profiles of these two drugs in plasma, urine, and ultrafiltrate were investigated after intravenous perfusion (30 min). In all cases a 1-g dose of ceftazidime was administered; for amikacin, the dosage regimen was adjusted according to the patient's amikacin levels (250 to 750 mg). Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection for ceftazidime and by enzyme multiplied immunoassay for amikacin. The elimination half-life (t1/2) and the total clearance of amikacin ranged from 31.1 to 138.2 h and from 5.4 to 8.9 ml/min, respectively, during the interhemofiltration period in anuric patients. Hemofiltration substantially decreased the t1/2 (3.5 +/- 0.49 h) and increased the total clearance (89.5 +/- 11.8 ml/min). The hemofiltration clearance of amikacin represented 71% of the total clearance, and the hemofiltration process removed, on average, 60% of the dose. During hemofiltration, the elimination t1/2 of ceftazidime (2.8 +/- 0.69 h) was greatly reduced and the total clearance increased (74.2 +/- 11.2 ml/min) compared with those in the interhemofiltration period (9 to 43.7 h and 7.4 to 16.8 ml/min, respectively). About 55% of the administered dose was recovered in the filtrate, and the hemofiltration clearance of ceftazidime was 46 +/- 14.3 ml/min. A redistribution phenomenon (rebound) in the amikacin and ceftazidime concentrations in plasma (35 and 28%, respectively) was reported after hemofiltration in two patients. The MICs for 90% of the most important pathogens were exceeded by the concentrations of the two drugs in plasma during the whole treatment of these patients.

Adult↗
PubMed1993

Multiple-dose pharmacokinetics of pefloxacin in patients with hepatocellular deficiency.

Multiple-dose pharmacokinetics of pefloxacin were evaluated in 25 patients with hepatocellular insufficiency. The severity of liver disease was graded A, B or C according to the Child-Pugh classification. Pharmacokinetic parameters evaluated in patients on day 1 of treatment were compared with those computed in 11 healthy volunteers (the control group) after a single dose. Blood samples were taken at frequent intervals after drug administration and assayed by high performance liquid chromatography. The mean age of patients with liver impairment was slightly greater (59.5 years, range 33 to 81 years) than that of the control group (46.7 years, range 42 to 51 years). In the patients with liver disease, the mean (+/- SD) half-life of elimination, although highly variable, was significantly longer (46.3 +/- 42.5 hours) than in the control group (11.3 +/- 3.5 hours, p < 0.001). The total clearance was significantly decreased (1.76 +/- 1.31 L/h vs 6.03 +/- 2.99 L/h in the control group). In groups B and C of the Child-Pugh classification, total body clearance was about 30% of normal values. Elimination half-life increased by 200% in group B and 373% in group C compared with values in healthy volunteers. Intergroup differences (group B vs group C of the Child-Pugh classification) were not statistically significant. The minimum concentrations inhibiting 90% of Gram-negative strains (MIC90) were exceeded by plasma pefloxacin concentrations throughout treatment. For most patients, trough plasma concentrations were above 2 mg/L and peak plasma concentrations averaged 8.5 mg/L. Large inter- and intraindividual variations in the elimination half-life, total clearance and volume of distribution were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Endotracheal and aerosol administrations of ceftazidime in patients with nosocomial pneumonia: pharmacokinetics and absolute bioavailability.

Pharmacokinetic studies on ceftazidime, an aminothiazole cephalosporin with a wide spectrum of antibacterial activity, including activity against Pseudomonas aeruginosa, were performed in patients with nosocomial pneumonia. The concentration-time profiles of ceftazidime in plasma, urine, and bronchial secretions of 12 patients were investigated after intravenous (i.v.) (n = 12), endotracheal (n = 10), and aerosol (n = 5) administrations. In all cases a 1-g dose was administered. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection. The elimination of the drug from the blood followed a biexponential (i.v. administration) or a monoexponential (endotracheal and aerosol administrations) decay, with an elimination half-life of 6 h and a total body clearance of 4.2 liters/h. The apparent volume of distribution was 0.36 liter/kg of body weight. Renal clearance of the drug accounted for 58% of the total clearance; 66% +/- 17.7%, 33.5% +/- 17.3%, and 6.59% +/- 3.45% of the administered dose were eliminated in urine as parent drug after i.v., endotracheal, and aerosol administrations, respectively. The absolute bioavailabilities were 0.47 and 0.08 for endotracheal and aerosol administrations, respectively. Very high concentrations were found in bronchial secretions after local administration. The MICs for 90% of the most important pathogens responsible for nosocomial infections were exceeded by concentrations in bronchial secretion for up to 12 h after i.v. infusion and for up to 24 h after endotracheal and aerosol administrations.

Adult↗
PubMed1989

Is epidural anaesthesia using bupivacaine safe in patients with atrio-ventricular conduction defects?

Bupivacaine is known to interact with the conductive system of the heart, also when used in epidural anaesthesia. Ten patients, undergoing bupivacaine epidural anaesthesia for lower limb or pelvic surgery, who presented a history of cardiac conduction disturbances, were studied. The ECG was continuously monitored and a right ventricular bipolar electrode was used to monitor the following parameters: heart rate, QRS duration, QT, Atria-His and His-Ventricle intervals. No significant change was noticed, even in patients with a high grade conduction defect. The mean plasma level of bupivacaine was 0.33 +/- 0.23 micrograms/ml. Based on this experience, it seems that lumbar epidural anaesthesia with bupivacaine can be safely used in patients with asymptomatic AV conduction abnormalities.

Anesthesia, Epidural↗