Regression of left ventricular hypertrophy by converting enzyme inhibition in 12-15-month-old spontaneously hypertensive rats: effects on coronary resistance and ventricular compliance in normoxia and anoxia.

The effects of trandolapril, a converting enzyme inhibitor (CEI), on left ventricular (LV) diastolic stiffness and coronary vascular resistance (CVR), were studied with an isolated heart preparation in 15-month-old spontaneously hypertensive rats (SHR). The hypertensive animals were treated for 3 months with trandolapril (0.3 mg/kg/day) (SHRT), and compared with untreated age-matched Wistar-Kyoto rats (WKY) and SHR. Trandolapril treatment resulted in 15% diminution in blood pressure (BP). In contrast, it completely normalized left ventricular (LV) weight. Untreated SHR, as compared with WKY, had a dilated LV and increased diastolic tissue stiffness. Trandolapril had no effect on either chamber or tissue stiffness. Five-minute anoxia resulted in the same dramatic increase in chamber stiffness in every experimental group. During anoxia, as during normoxia, tissue stiffness was still greater in SHR than in WKY. A major effect of CEI was to normalize the tissue stiffness of SHR under anoxia. Coronary vascular resistance (CVR) was increased in SHR as compared with WKY. Trandolapril improves CVR and significantly shifts the coronary pressure flow curve to the dilatory side. Both collagen concentration (approximately 2 mg/g) and the content in slow V3 myosin isoform, used as biologic markers of cardiac senescence, were the same in the three experimental groups, but higher than in young hearts. Trandolapril had no effect on these parameters. In semisenescent SHR, despite having rather slight effect on arterial pressure, trandolapril completely normalized LV weight. In addition, collagen content and its physiologic counterpart, tissue stiffness, were unaffected by 3-month treatment with trandolapril. Nevertheless, the anoxia-induced increase in LV tissue stiffness was improved by trandolapril in parallel with reduction in LV hypertrophy (LVH).

Left ventricular compliance in the DOCA-salt model of hypertension in the rat. Effects of propranolol.

The aim of this study was to see if an enhanced myocardial stiffness is an inevitable consequence of the increase in cardiac mass and to analyze the effects of beta-adrenergic blockade on this parameter. The DOCA-salt model of hypertension was used to induce cardiac hypertrophy in the rat. After 6 weeks, the hearts of the DOCA-salt-treated animals were hypertrophied by 67%, and the left ventricular weight, the left ventricular/body weight ratio and the left/right ventricular weight ratio were similarly increased. Isolated hearts were retrogradely perfused at a constant flow of 15 ml/min/g tissue. Contractile parameters were recorded using an intraventricular balloon whose volume was manually adjusted. For each heart, a sequence of three systolic and diastolic pressure-volume curves were constructed: in Krebs alone, after addition of 10(-6) M of propranolol, and after KCl-arrest. In spite of a pronounced degree of hypertrophy, the DOCA-salt hearts had a normal diastolic pressure-volume curve and both the chamber and tissue stiffness constants were not modified. This result indicates that a depressed compliance does not necessarily accompany hypertrophy, especially in a DOCA-salt model in which the collagen content of the heart is unchanged. The systolic pressure-volume curve was greatly modified and shifted to the left indicating an enhanced capacity of the hypertrophied heart to generate force. This increase persisted even when the systolic pressure has been divided by the heart weight. beta-Blockade slightly depressed the contractility of the isolated heart at pharmacological concentrations. At high concentrations, cardiac dilatation was induced. This enhancement in ventricular distensibility had no consequences on diastolic compliance constants. It is thus concluded that, during cardiac hypertrophy, the changes in passive stiffness of the ventricle are more related to collagen content than to the cardiac mass and that beta-adrenergic blockade has no effect on the passive properties of the ventricle.

[Update of a selected technique for uric acid determination in plasma and serum. Experimental study and value of derivative spectrophotometry]. / Mise au point d'une technique sélectionnée de dosage de l'acide urique dans le plasma et le sérum. Etude expérimentale et intérêt de la spectrophotométrie dérivée.

A critical study of the candidate reference method for evaluation of uric acid in plasma proposed by the American Association of Clinical Chemistry is followed by testing in six laboratories. The dispersion of results is wide (CV greater than 5%). The importance of turbidity remaining after the deproteinization by trichloracetic acid is clearly demonstrated. This turbidity is really not reproducible from an operation to another one on the same serum. It is very likely responsible of the great dispersion of the results. After that, other deproteinization methods are tried. Ultrafiltration and ultracentrifugation give both defect errors because uric acid is in part bound to proteins. So it is necessary to find another technic which cancels the effects of turbidity on the absorbance readings in the ultra-violet domain. Experimental studies showed that uric acid may be evaluated with a good accuracy by derivative spectrophotometry, in lipid solutions as well as in cloudy ones. Turbidity was created by intralipid suspension additions. Various parameters hitting the method were examined (linearity, smoothing window...), taking as criterion the measure of overloaded serums at different levels. At last, the method is successfully transferred in several sites. In the case of blood serum, the respective influences of derivation and of repetition of final centrifugations are studied in order to estimate the effect of remaining turbidity. By the use of derivative spectrophotometry the improvement of the method of evaluation of uric acid proposed by A.A.C.C. is very noticeable; it reduces the variation coefficient between sites to less than 2%.

Comparison of HbA1 and fructosamine in diagnosis of glucose-tolerance abnormalities.

Total glycosylated hemoglobin (HbA1) and fructosamine were evaluated as screening tools for detection of glucose-tolerance abnormalities in 144 asymptomatic subjects undergoing a 75-g oral glucose tolerance test. Subjects were classified according to World Health Organization criteria as having normal (n = 78), impaired (n = 40), or diabetic (n = 26) glucose tolerance. We found good specificity for HbA1 and fructosamine (100 and 97%, respectively) but low sensitivity (15 and 19%, respectively). At the intersection of the curves of sensitivity and specificity drawn from various thresholds of normality, both sensitivity and specificity were 75% for HbA1 and 55% for fructosamine. Thus, neither HbA1 nor fructosamine seems to be suitable for the diagnosis of mild abnormalities in glucose tolerance.

Comparison of fructosamine with glycated hemoglobin as an index of glycemic control in diabetic patients.

Fasting and postprandial (or post-glucose load) plasma glucose, total HbA1 and fructosamine (F) were simultaneously assessed in 371 diabetic patients (125 insulin dependent and 246 non-insulin dependent) and in 122 nondiabetic subjects, (98 with normal glucose tolerance and 24 with impaired glucose tolerance). Fructosamine yielded nearly similar information as HbA1 about glycemic control, since similar relationships were observed between plasma glucose values and HbA1 or fructosamine levels in the different groups. A longitudinal study performed during a three-month follow-up in 74 diabetic patients and extended to six months in 19 of them, without any modification of treatment, indicated that reproducibility of HbA1 and fructosamine was nearly the same with a slight advantage for HbA1. The only clinically significant difference results from the longer half-life of hemoglobin when compared to serum proteins. Fructosamine assay should be proposed as a complement of HbA1 in the management of diabetic patients when detection of recent metabolic changes is needed.

Remodelling of the heart in DOCA-salt hypertensive rats by propranolol and by an alpha-2 agonist, rilmenidine.

The effects of rilmenidine [(N-dicyclopropylmethyl) amino-2-oxazoline; S 3341], an alpha 2 agonist, on the hypertensive rat heart have been compared with those of propranolol, using a model of deoxycorticosterone acetate (DOCA)-salt hypertension. One week after nephrectomy and initial treatment with DOCA-salt, which was continued for an additional 7 weeks, the two drugs were added to the rats drinking water at a concentration of 10 mg/kg per day for rilmenidine and 15 mg/kg per day for propranolol. Both drugs had a slight and similarly significant antihypertensive effect at their respective concentrations [systolic blood pressure in controls, 141 +/- 15 mmHg (n = 20); after DOCA-salt, 209 +/- 22 mmHg (n = 24); after propranolol, 182 +/- 19 mmHg (n = 20, P less than 0.01); after rilmenidine, 192 +/- 15 mmHg (n = 19, P less than 0.05)]. They also lowered the systolic blood pressure x frequency product (P less than 0.001). Propranolol, but not rilmenidine, significantly reduced the left ventricular weight: body weight ratio [in controls, 2.00 +/- 0.2 mg/g; after DOCA-salt, 3.04 +/- 0.5 mg/g; after propranolol, 2.67 +/- 0.4 mg/g (P less than 0.05); after rilmenidine, 3.13 +/- 0.6 mg/g (P = NS)]. However, both propranolol and rilmenidine reduced left ventricular weight [in controls, 676 +/- 57 mg; after DOCA-salt, 827 +/- 114 mg; after propranolol, 732 +/- 108 mg (P less than 0.01); after rilmenidine, 760 +/- 100 mg (P less than 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)

[The heart in patients with hypertension: effects of rilmenidine on experimental cardiac hypertrophy of hypertensive origin in rats]. / Le coeur des hypertendus: effet de la rilmenidine sur l'hypertrophie cardiaque expérimentale d'origine hypertensive chez le rat.

The hypertensive heart is an example of myocardial adaptation to a chronic mechanical overload. In this model, the myocardium adapts by quantitative mechanisms such as hypertrophy and by qualitative processes at sarcomere and cell membrane level. Cardiac failure occurs when these mechanisms become inadequate although other phenomena such as collagen, coronary resistances, adverse hormonal effects and associated pathologies also play a role. This report describes an experimental model: uninephrectomised rats were made hypertensive by administering a DOCA-salt diet. The resulting cardiac hypertrophy was reduced and the hypertension corrected by propranolol. Rilmenidine, a new antihypertensive agent, has no effect on cardiac hypertrophy but it does reduce myocardial collagen concentrations significantly which has potentially important beneficial consequences.

Relationship between hair, serum and bone aluminium in hemodialyzed patients.

To establish the predictive value in osteodystrophy of hair aluminium content in patients on hemodialysis, we compared the aluminium levels in serum, cortical and trabecular bone and hair of 40 such patients with the levels in 23 healthy controls. In the patients, mean hair aluminium content was significantly higher than the controls (0.226 mumol/g, range: 0.09-0.500 mumol/g, n = 39 versus 0.126 mumol/g, range: 0.020-0.330 mumol/g, n = 49) but there was a large overlap between the two groups. The patients exhibited a significant correlation between serum and cortical bone aluminium measured by atomic absorption spectrometry (rs = 0.67, n = 37, p less than 0.05), but no correlation between aluminium in hair and in serum or bone, whether cortical or trabecular. Bone histomorphometric studies also indicated that unlike aluminium levels in cortical or trabecular bone, its levels in hair are not predictive of aluminium-induced osteomalacia. Consequently, hair aluminium cannot suitably replace bone and serum aluminium as a criterion of osteodystrophy in hemodialyzed patients.

[A recommended method for determination of uric acid in serum]. / Méthode recommandée pour le dosage de l'acide urique dans le sérum.

SFBC work group on uric acid propose a method for evaluation in blood serum which is modeled on the one defined by American Association for Clinical Chemistry. Serum is deproteinized by trichoracetic acid and the supernatant, buffered to pH 8.5, is submitted to uricase action. The disappearing of the strong band of uric acid in UV is measured by derivative spectrophotometry; this procedure vanished the effect of trouble which remains in the supernatant. This spectrophotometric technic permit to reach, in multiple sites, a variation coefficient near of 1 p. cent.

Analytical problems encountered in determining aluminum status from hair in controls and hemodialyzed patients.

The problems involved in evaluating aluminum concentrations in hair are reviewed, especially those concerning removal of contaminating metals, a critical factor. In the few published studies of Al concentrations in hair, acetone was usually used for its removal. Here, its use in the washing sequence was found to give less precise results and higher Al values than the use of isopropanol. With isopropanol, the whole analysis can be done in a single tube. We compared results with those in the literature. We found that the Al concentration in the hair of control subjects was not related to sex or hair color and that there was a highly significant (P less than 0.001) difference between values for control subjects and hemodialyzed patients: 126 (SD 58) nmol/g, n = 49, vs 226 (SD 104) nmol/g, n = 39, respectively.

Experimental bone marrow alterations following single and multiple high-dose steroids in rabbits.

Nineteen New Zealand white rabbits received one (n = 5), two (n = 5), or three (n = 9) injections of 60 mg methylprednisolone and were sacrificed 10, 20, 30, and 60 days following the last treatment. They were compared to 15 controls for histological examination of femoral and humeral epiphyses and femoral condyles. Treated animals had a significant rise in serum triglycerides (p less than 0.01) 10 days following treatment. 15 treated animals and 6 controls had grade I lesions of bone marrow (p less than 0.05). Lesions of grades II and III were only observed in 5 treated animals. The severity of histological lesions were not correlated with steroid doses. Tetracycline fixation was suppressed in treated rabbits.

[Determination of erythrocyte sorbitol]. / Détermination du sorbitol érythrocytaire.

An increase in the intra-cellular concentrations of sorbitol can be responsible, at least in part, for certain long term complications of diabetes. Since the erythrocyte concentration of this polyol is a good indicator of that of other cells, we propose a simple, rapid enzymatic assay technique for red blood cells. The results already obtained reveal a significant difference between the erythrocyte sorbitol concentration in non-diabetic subjects and that in diabetic patients.

[Assay of cystine aminopeptidase activity on a centrifuge analyser]. / Dosage de l'activité cystine-aminopeptidase sérique sur analyseur centrifuge.

The assay of the serum cystine-aminopeptidase activity, of placental origin, is a useful test for monitoring pregnancy. The authors present an adaptation of Van Oudheusen's method on a centrifuge analyser which allows a rapid kinetic measurement of this activity and they justify their choice of procedure. The values obtained in non-pregnant women and in pregnancies of between 8 and 40 weeks of amenorrhoea are presented.

[Determination of the serum concentration of lipoproptein x (author's transl)]. / Détermination de la concentration sérique de la lipoprotéine X.

Lipoprotein X (LPX) is a cholestase marker. The authors wish to set forth a simple and quick method for the quantity determination of this abnormal--a method which could be combined with other biochemical tests permitting the demonstration and monitoring of a cholestatic syndrome. The phospholipid composition of lipoprotein X is thought to be constant; therefore, the proposed method of quantity determination consists in an enzymatic quantity determination of phospholipids, performed on the lipoprotein, isolated from the normal serum lipoproteins by means of a simple operative protocol: elimination of the LDL and VLDL by means of immuno-precipitation, followed by separation of the HDL by means of the action of phosphotungstate. In addition to its quantitative characteristic, the proposed method has been shown to be more selective than the traditional demonstration which uses electrophoresis on agar. This electrophoretic research can in effect, show itself to be negative if practised on biological samples which are rich in biliary acids or free fatty acids; conversely, the operative protocol described permits the demonstration of the quantification of lipoprotein X.

[Cortisone-induced osteonecrosis: knowledge acquired from observations in man and comparison with the results of animal experimentation]. / Ostéonécroses cortisoniques: acquistions tirées de l'observation chez l'homme et confrontation avec les résultats de l'expérimentation animale.

Aseptic osteonecrosis is observed in 25% of cases after renal transplantation. This etiological variety of osteonecrosis is unusual in that it is frequently bilateral and has multiple localisations. Apart from the classical radiological signs, attention in attracted by isolated images of osteocondensation in the metaphyses and/or the diaphyses suggesting massive bony infarction and the appearances of fatigue fractures observed frequently (14%). In 43% of cases, the obvious necrosis was proceeded by early bone pain, around the 7 th day, during massive administration of corticosteroids in the prevention or cure of graft resection. This finding suggested to us that the best time to observe ischemia of the bone or marrow is very early and led us to undertake an experimental study in the rabbit. Two series of New Zealand White rabbits were treated with massive doses of corticosteroid and sacrificed between the 3rd and the 21st day. The treated animals presented an early peak of hyperlipemia from the 7th day onwards, and diffuse lesions of hepatic and renal steatosis. Fat emboli associated with appearances of parietal thrombosis were observed in most cases. In the same animals, there were also appearances of stage I or stage II necrosis. Referring to the description of bone marrow necrosis in stages by Arlet and Ficat, there was observed in all the series, a frequency of marrow lesions of all stages much higher in treated animals (16 out of 20) than in controls. Only one lesion of stage I was observed in controls; the difference was highly significant. (0,000001 < p < 0,00001). If one only considers necroses of stage II and III (10/20 in the treated group nil in controls) the frequency was still significant p < 0.001. The preliminary results of the fixation of tetracycline are reported.

[A simple method for evaluation of the lecithin/sphingomyelin ratio in amniotic fluid. Variation in normal and abnormal pregnancies (138 cases) (author's transl)]. / Evaluation simple du rapport lécithines/sphingomyélines du liquide amniotique. Variations au cours des grossesses normales et pathologiques (a propos de 138 cas)

The determination of the lecithin/sphingomyelin ratio in amniotic fluid is a useful index for assessing fetal pulmonary maturity. The authors propose a simple and specific method : the amniotic lipids are extracted and thin layer chromatography is carried out in an acetic acid containing medium. The L/S ratio was studied and discussed in 138 normal and pathological cases.