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Biomedical subjects

Y Edoute

Publications and source records attributed to Y Edoute.

At least 37 records · Page 2Linked to original sources

Cardiac function and responsiveness to beta-adrenoceptor agonists in rats with obstructive jaundice.

The function and role of the heart and the contribution of cardiac beta-adrenoceptors in the pathogenesis of circulatory failure in obstructive jaundice were studied in the 3-day bile duct-ligated (BDL) rat using three different techniques to measure cardiac function and beta-adrenoceptor activity, number, and affinity. The techniques were the pithed rat preparation, the isolated working heart preparation, and a competitive radioligand binding assay for beta-adrenoceptors. The results of these experiments were compared with those obtained in 3-day bile duct-manipulated (sham operated; SO) rats. Impaired indexes of basal cardiac contractility were observed in the BDL pithed rats and isolated working hearts. In these two preparations, responsiveness to norepinephrine and the beta-adrenoceptor agonists, isoproterenol and dobutamine, was unaffected by bile duct ligation. The affinity and number of cardiac beta-adrenoceptors in membranes from the hearts of SO and BDL rats were not significantly different from each other. These experiments have established for the first time that the 3-day BDL rat has a cardiac myopathy associated with intact responsiveness to beta-adrenoceptor agonists, a normal unchanged affinity and number of cardiac beta-adrenoceptors.

Adrenergic beta-Agonists

Ro 5-4864 and PK 11195, but not diazepam, depress cardiac function in an isolated working rat heart model.

The present study was designed to investigate the effects of diazepam, a benzodiazepine (BZ) with high affinity to central BZ receptors and moderate affinity to mitochondrial BZ receptors, and of Ro 5-4864 and PK 11195, ligands specific for mitochondrial BZ receptors, on cardiac function in the isolated working rat heart model. Five concentrations of these drugs (10(-9)-10(-5) mol/l) were used, and the chronotropic (heart rate) and inotropic [maximum elastance of the left ventricle at end systole (Emax), maximal first derivative of left ventricular (LV) pressure (dP/dtmax), LV pressure at dP/dtmax (pressure at dP/dtmax), aortic flow, stroke work, and total pressure-volume area] cardiac parameters were measured. Diazepam, Ro 5-4864, and PK 11195 showed no significant chronotropic activity up to 10(-5) mol/l. Diazepam did not alter the inotropic properties of the heart. Ro 5-4864 at 10(-5) mol/l significantly decreased the indices of contractility, namely, Emax, dP/dtmax, and pressure at dP/dtmax. Aortic flow, stroke work, and total pressure-volume area were significantly depressed at the same concentration. The negative inotropism of PK 11195 appeared to be identical, by most indices, to that of Ro 5-4864, both qualitatively (same pattern) and quantitatively (similar maximal variations); however, for some indices a depressant effect was also found at 10(-7) mol/l. These results show that at high concentrations Ro 5-4864 and PK 11195, but not diazepam, have a depressant effect on mechanical function.

Animals

Beat-to-beat morphologic variability of the electrocardiogram for the evaluation of chest pain in the emergency room.

The value of electrocardiographic, morphologic variability in the early diagnosis of acute myocardial infarction (AMI) and myocardial ischemia was evaluated in 49 nonselected patients presenting to the emergency room with chest pain. High-resolution electrocardiography was used to determine the morphologic variability of consecutive electrocardiographic complexes, and the ratio of the variance of the QRS onset to that of the entire electrocardiogram was calculated. A final diagnosis of AMI was confirmed in 8 patients, acute coronary insufficiency in 8, angina pectoris in 19, and a noncardiac origin for chest pain in 14. Patients with AMI had a significantly higher beat-to-beat electrocardiographic morphologic variability of the QRS onset (1.4 +/- 0.2) than did those with acute coronary insufficiency (1.1 +/- 0.2), angina pectoris (0.9 +/- 0.1) or noncardiac chest pain (0.8 +/- 0.1) (p < 0.05). The sensitivity of the clinical presentation, typical electrocardiographic changes and creatine phosphokinase levels for the diagnosis of an acute ischemic event on admission to the emergency room was 62, 25 and 37.5%, respectively. Relative variance of the QRS onset of > 0.86 had a sensitivity of 75% and a specificity of 61% for diagnosing an acute ischemic event. Logistic regression of these variables showed that the QRS onset relative variability is an independent predictor for an acute ischemic event. It is concluded that an increased beat-to-beat electrocardiographic variability in patients with AMI is present on admission to the emergency room and may assist in establishing the diagnosis in this setting.

Adult

Prediction of immediate ventricular arrhythmias after coronary artery ligation.

OBJECTIVES: Our aim was to test the hypothesis that increased beat to beat morphologic variations in the body surface electrocardiogram (ECG) are associated with fragmented diastolic electrical activity that appears after coronary artery ligation and to correlate the appearance of spontaneous ventricular fibrillation after coronary ligation with the magnitude of the ECG beat to beat variability. BACKGROUND: Unstable and variably delayed electrical activation precedes the development of ventricular fibrillation in dogs with acute ischemia. Detection of these highly variable low amplitude signals from the body surface is currently impossible. We have developed a system designed to measure the degree of beat to beat variability of the ECG. METHODS: With high fidelity electrocardiography, subtle beat to beat ECG morphologic variations were detected in epicardial and body surface electrograms and quantified as the variance of the ECG voltage at specific points of the cardiac cycle. The ratio of the variance at the QRS offset to that of the QRS onset (beat to beat variability index) was then calculated. RESULTS: Ventricular fibrillation developed in 12 of 27 dogs after left anterior descending coronary artery ligation. In 7 of the 12 dogs it occurred immediately (< 15 min) after ligation; in the other 5 it developed late (> 15 min) after ligation. Dogs with subsequently immediate ventricular fibrillation had a significantly higher beat to beat variability index than that of dogs with late or no ventricular fibrillation both before coronary ligation (4.7 +/- 1.4 vs. 1.1 +/- 0.2 and 0.8 +/- 0.1, respectively, p < 0.001) and after ligation (6.4 +/- 2.6, 1.0 +/- 0.6 and 1.2 +/- 0.6, respectively, p < 0.001). In dogs that developed ventricular fibrillation immediately after coronary ligation, the arrhythmia was preceded by fragmented diastolic electrical activity on the epicardial electrogram and a simultaneous increase in the beat to beat morphologic variability of the terminal portion of the body surface ECG QRS complex. CONCLUSIONS: Beat to beat QRS offset morphologic variations appear to be increased before and further increased after coronary artery ligation in dogs that develop ventricular fibrillation immediately after ligation. Increased beat to beat variability index may be associated with the presence of electrophysiologic instability and can predict early ventricular fibrillation.

Analysis of Variance

Fine-needle aspiration and cytologic findings of surgical scar lesions in women with breast cancer.

Benign and/or malignant lesions may occur in surgical scars after mastectomy or lumpectomy (SML) in patients with breast cancer (BC). Early diagnosis of these lesions is essential for both therapeutic and prognostic evaluation. The diagnostic value of fine-needle aspiration (FNA) was determined for these scar lesions. The findings of cytologic and histologic specimens obtained from the same lesion of SML in 83 women with BC were correlated. Twenty-five FNA yielded only acellular specimens. Of the FNA done by the cytopathologist, only 6.2% were not representative. However, 45% of those done by less experienced clinicians were not representative. Representative FNA were obtained from 58 of the women who took part in the study. Based on the histologic diagnosis, 38 patients had malignant scar lesions (MSL), and 20 had benign scar lesions (BSL). In one patient of the 38 with MSL, cytologic examination did not show that the malignant lesion; in four women, the tumor was suspected cytologically; and in the remaining 33, the cytologic findings were consistent with malignancy. In 18 of the 20 patients with BSL, cytologic findings were reported as benign and in the other two, as inconclusive. The sensitivity, specificity, and positive and negative predictive values for the cytologic findings were 97.4%, 100%, 100%, and 94.7%, respectively. The diagnostic accuracy of FNA cytology was 98.2%. No complications followed the procedure. It was concluded that FNA cytologic examination of lesions in SML is a simple, safe, highly accurate, and cost-effective method to distinguish malignant from benign lesions in women with BC. Lesions in SML should be explored routinely by FNA, rather than by the traditional biopsy, provided the FNA is done by an experienced operator.

Adult

Effect of hypertonicity on contractility of isolated working rat left ventricle.

OBJECTIVE: The aim was to evaluate the effect of hypertonic perfusate on isolated left ventricular mechanical and energetic characteristics. METHODS: An isolated working rat heart model was perfused with a hyponatraemic Krebs-Heinseleit bicarbonate buffer (240 mOsmol.litre-1). To this buffer was added increasing amounts of mannitol to achieve 280, 320, and 360 mOsmol.litre-1 perfusates. RESULTS: Left ventricular peak pressure, maximum time derivative of left ventricular pressure (dP/dtmax), and end systolic pressure were all increased to a maximum value at 280 or 320 mOsmol.litre-1 perfusate tonicity. A similar response was evident with cardiac output, which changed from 33.7(SEM 0.6) to 43.5(0.8) ml.min-1 following changing the perfusate tonicity from 240 to 280 mOsmol.litre-1 (p less than or equal to 0.003). However, increasing perfusate tonicity further decreased cardiac output to 36.5(1.3) ml.min-1 at 360 mOsmol.litre-1. Maximal left ventricular elastance remained unchanged during perfusion with increasing perfusate tonicities. CONCLUSIONS: Changing perfusate osmolality using mannitol has a positive inotropic effect at low osmolalities and a negative inotropic effect at perfusate osmolality greater than 320 mOsm.litre-1.

Animals

Effect of phosphamidon and obidoxime on the QT-RR relationship of isolated rat heart.

We studied the effects of phosphamidon (an organophosphate compound), obidoxime (a cholinesterase reactivator), and their combination, phosphamidon/obidoxime (PD/OB) on cardiac cycle length (RR), QT interval, and on QT-RR relationship of isolated rat heart. Cardiac cycle length did not change significantly following perfusion with phosphamidon or obidoxime alone; however, following perfusion with PD/OB, RR significantly increased at high concentrations (10(-3) M) of both drugs. The QT interval lengthened by 5% following perfusion with phosphamidon, did not change following perfusion with obidoxime, and increased by 10% following perfusion with PD/OB. The QT-RR relationship without drugs was positive and linear. Following perfusion with phosphamidon alone, the slope of the relationship decreased significantly, while perfusion with obidoxime alone did not change the QT-RR relationship. Perfusion with PD/OB at low concentrations decreased the slope of the relationship; however, at the highest concentration (10(-3) M) the QT-RR relationship was inverted and became negative. Ventricular arrhythmias as premature ventricular beats, or bigeminies, were noted with increasing frequency following perfusion with increasing doses of phosphamidon. Perfusion with obidoxime did not cause arrhythmias, whereas perfusion with PD/OB caused premature ventricular beats, bigeminies, and ventricular tachycardias at high doses. We suggest that obidoxime modulates the direct effects of phosphamidon on the cardiac repolarization process. PD/OB at high concentrations invert the normal depolarization-repolarization coupling and may therefore potentiate arrhythmias.

Animals

Obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart.

The present study was designed to determine modulation of the direct inotropic effect of an anticholinesterase organophosphorus compound, phosphamidon, by the reactivator obidoxime. We investigated the effects of phosphamidon (n = 9), obidoxime (n = 5), and their combination (n = 5) on the mechanical and energetic indices of left ventricular function, in the isolated working rat heart model. Phosphamidon at a concentration range of 10(-6)-10(-3) M had a positive inotropic effect. Obidoxime at a concentration range of 10(-6)-10(-3) M had no significant effect on heart rate, but did have a statistically significant positive inotropic effect on end-systolic pressure, cardiac output, mean left ventricular pressure, and maximal time derivative of left ventricular pressure (dP/dtmax) (P less than 0.01). Perfusion with 10(-3) M obidoxime caused a 19% increase in left ventricular stroke work and a 31% increase in total pressure-volume area. Perfusion with phosphamidon and obidoxime at concentrations ranging from 10(-6) to 10(-3) M resulted in a more intense inotropic response than the separate drug effects. At the highest combined concentrations tested, cardiac output increased by 60%, left ventricular stroke work increased by 100%, and left ventricular total pressure volume area increased by 111% of their control values (P less than 0.001). We conclude that obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart.

Animals

Sodium modulates inotropic response to hyperosmolarity in isolated working rat heart.

The present study was designed to examine the effects of acute changes in perfusate Na+ concentrations and osmolarities on left ventricular (LV) mechanics in the isolated working rat heart model. Specifically, we separated the effect of isosmotic perfusates with different Na+ concentrations on LV mechanics. After a control period during which the hearts were perfused in a working mode with a control solution of Krebs-Henseleit bicarbonate buffer (Na+ of 136 meq/l, Ca2+ of 2.6 mM, and osmolarity of 300 mosM), the hearts were subjected to different perfusates (Na+ of 96-156 meq/l and osmolarity of 240-380 mosM, using different mannitol concentrations) in a semirandom order. Peak LV pressure (PLVP), maximal time derivative of LV pressure (dP/dtmax), and cardiac output (CO) were recorded. Increasing Na+ concentrations from 96 to 156 meq/l, using isosmotic perfusates, decreased PLVP, dP/dtmax, and CO in a dose-dependent manner. The dose-dependent behavior was evident for tonicities of 240, 280, 320, and 360 but not for 380 mosM. Increasing Na+ concentration from 96 to 136 meq/l at constant perfusate tonicity (320 mosM) decreased dP/dtmax from 6,753 +/- 133 to 5,602 +/- 418 mmHg/s (P < 0.001). Rearranging the same results to examine the effect of perfusate tonicity with iso-Na+ concentration demonstrated that increasing perfusate osmolarity had a dose-dependent effect on PLVP, dP/dtmax, and CO. At a constant Na+ concentration of 116 meq/l, increasing perfusate osmolarity from 240 to 320 mosM increased dP/dtmax from 6,116 +/- 132 to 7,274 +/- 594 mmHg/s (P < 0.01). Further increase in perfusate tonicity to 380 mosM decreased dP/dtmax to 2,338 +/- 398 mmHg/s (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Heart energetic efficiency in O2-exposed rats studied in isolated working heart.

Death in normobaric hyperoxia was related in the past to pulmonary insufficiency of the edematous lung. However, high arterial O2 tension on final collapse led to the suggestion that the heart and not the lung is the first organ that fails. We measured aortic flow, coronary flow, left ventricular pressure, affluent and effluent PO2, PCO2, and pH in the working heart excised from control and normobaric O2-exposed rats (51-63 h). The oxygen consumption (VO2) of experimental hearts was not different from control, but mechanical power output (PVAP) (calculated from pressure-volume area) was reduced as a function of O2 exposure time. Myocardial contractility indexes, maximal elastance and maximal time derivative of pressure, increased as a function of O2 exposure time, being below control values after 50 h and above control values after 60 h. The individual slopes for the regression of VO2 vs. PVAP rose as a function of exposure time from values below control after 50 h exposure to values above control after 60 h. Energetic efficiency (PVAP/VO2) decreased as a function of O2 exposure time and points to possible heart failure in the intact animal. After 50 h O2 exposure the heart was energetically more efficient than the control. Possible changes in the heart are discussed.

Air Pressure

Ultrasonically guided fine-needle aspiration of liver lesions.

The aim of the present study was to determine the diagnostic accuracy of ultrasonically guided fine-needle aspiration for liver lesions detected by ultrasound scan. A total of 142 aspirations were carried out in 129 patients with unifocal or multifocal liver lesions suspected of malignancy. The aspiration was made with a 22-gauge needle, guided by ultrasound. Based on histological, cytological, and clinical findings, final diagnoses were reached in 123 patients, 96 of whom had malignant liver disease and 27 benign liver disease. Among the 96 patients with malignant liver disease, the cytological findings revealed malignancy in 78 patients (81.3%) and suspected malignancy in five patients (5.1%), but failed to demonstrate malignancy in 13 patients (13.3%). Among 27 patients with benign liver disease, all the cytological findings indicated benignancy. The overall sensitivity, specificity, and positive and negative predictive values for cytological findings were 86.5%, 100%, 100%, and 76.9%, respectively. The diagnostic accuracy of ultrasonically guided fine-needle aspiration was 89.4%. In one patient with incipient chronic disseminated intravascular coagulation, a fatal intraperitoneal bleeding complicated the procedure. We conclude that ultrasonically guided FNA for cytologic diagnosis of liver lesions is highly accurate and is only rarely associated with fatal complication.

Adolescent

Fatal hemoperitoneum after fine-needle aspiration of a liver metastasis.

Fine-needle aspiration (FNA) of the liver is a procedure considered virtually risk-free. We report here a patient with carcinoma of the pancreas, who suffered a fatal hemoperitoneum (HP) subsequent to FNA of the liver under the guidance of ultrasound. The patient had presented with migratory deep vein thrombosis (DVT), and recurrent cerebral embolism. The prothrombin time (PT) and partial thromboplastin time (PTT) had been normal, and FNA demonstrated adenocarcinoma cells. Autopsy findings demonstrated carcinoma in the tail of the pancreas with liver and adrenal metastases, massive HP, and findings of chronic disseminated intravascular clotting (DIC). Since chronic DIC with enhanced fibrinolysis might have participated in the fatal bleeding, we recommend that FNA should be contraindicated in patients suspected of having malignancy with migratory DVT and recurrent arterial embolism, despite normal PT and PTT tests, unless the appropriate laboratory tests succeed in excluding DIC.

Adenocarcinoma

Beat-to-beat electrocardiographic morphology variation in healed myocardial infarction.

Using high-fidelity electrocardiographic (ECG) amplifiers, we measured subtle beat-to-beat ECG morphologic variations at different phases of the ECG complex. The electrocardiograms were recorded from 49 men with a documented Q-wave myocardial infarction and from 30 age-matched normal men. Forty consecutive beats were averaged to achieve an average ECG signal from which variance could be calculated. The relative variance, defined as the ratio between the integrated variance of the examined window and the integrated variance of the ECG signal that was close to full cycle length, was calculated at QRS onset and at offset in 2 frequency bands (4 to 40 and 60 to 120 Hz). Patients with healed infarction had a relative variance of 2.1 +/- 0.5 (mean +/- standard deviation [SD]) at QRS offset (a window of 40 ms), which was significantly lower than that of the healthy volunteers: 2.5 +/- 0.33 (mean +/- SD; p less than 0.02) at the low-frequency band. At the high-frequency band, patients with healed infarction had a significantly higher relative variance than the control subjects at QRS onset: 1.95 +/- 0.58 vs 1.55 +/- 0.35 (mean +/- SD; p less than 0.005). A model based on the numerous minor conduction abnormalities that exist in the chronically ischemic myocardium is presented to explain the changes in variance at the onset and offset of the QRS. The variance changes described can eventually serve as quantitative indexes of myocardial injury and electrical stability in patients with ischemic heart disease.

Aged