Biomedical subjects

M Laplace

Publications and source records attributed to M Laplace.

At least 19 recordsLinked to original sources

PubMed2000

Propofol-induced modifications of cardiomyocyte calcium transient and sarcoplasmic reticulum function in rats.

BACKGROUND: Propofol is considered to be an anesthetic agent with few or no negative inotropic effects. This study evaluated a possible direct depressant effect of propofol on sarcoplasmic reticulum Ca2+ accumulation and cardiomyocytes. METHODS: The effects of propofol on intracellular Ca2+ transients were evaluated in isolated rat cardiomyocytes using a microfluorometric technique with Indo-1. Sarcoplasmic reticulum function was also assessed by measuring the oxalate-stimulated Ca2+ uptake from homogenates of rat ventricles. RESULTS: The Ca2+ uptake capacity of the sarcoplasmic reticulum was decreased by propofol (10(-4) M). Large concentrations of propofol decreased the rate of decrease of the intracellular Ca2+ transient, which resulted in an increase of diastolic Ca2+ when the diastolic interval was decreased. The increased diastolic Ca2+ also resulted in a decrease in Ca2+ transient. This effect appeared for lower doses (10(-5) M) after a short diastolic pause rather than after a long (2- to 3-min) rest (appearing at 10(-4) M). CONCLUSIONS: For doses more than 10(-5) M, propofol induces a Ca2+ uptake capacity impairment of the sarcoplasmic reticulum. This is probably responsible for a slowing of the decrease of the Ca2+ transient, which in turn increases the diastolic Ca2+ for high heart rate. These diastolic modifications may participate in the slight negative inotropic effect of the drug.

Anesthetics, Intravenous↗

PubMed1999

Induction of cardiac nitric oxide synthase 2 in rats exposed to chronic hypoxia.

Induction of nitric oxide synthase (NOS2, also designated as iNOS) in the heart is known to occur in response to various stimuli. It is not known, however, whether in vivo hypoxia leads to cardiac NOS2 induction. We thus investigated the effects of normobaric hypoxia (10% O(2)for 8, 15 and 21 days) on NOS2 protein expression and enzyme activity in rat right ventricle (RV) and left ventricle (LV). Chronic hypoxia induced RV hypertrophy: the RV weight to body weight ratio was increased by 45% upon 15 days of exposure, with no change thereafter and no change in left ventricular (LV) weight. Treatment of hypoxic rats with l -NAME for 1 month decreased pulmonary artery pressure and RV hypertrophy compared to hypoxic non-treated rats. NOS2 activity detected by [(3)H]l -arginine to [(3)H]l -citrulline conversion increased in RV during hypoxia, with a maximum at 15 days (+161% of control rats P<0.05), whereas it increased less (by 60%) in LV. In parallel, after 15 days of hypoxia there was a three-fold increase in NOS2 protein abundance detected by Western blotting using an isoform-specific antibody in the RVs (two-fold increase in the LV). Immunochemistry with the specific antibody demonstrated the expression in cardiomyocytes isolated from both ventricles of normoxic and hypoxic rats. Protein kinase C (PKC) content and activity was unchanged in LV of hypoxic rats, but increased in RV as compared with normoxic rats. These results clearly show that, in the heart, NOS2 is upregulated by hypoxia with an expression in cardiomyocytes of both ventricles. In addition, NOS2 is more inducible in the right hypertrophied ventricle than in the left non-hypertrophied hypoxic ventricle.

Amino Acid Sequence↗

PubMed1999

Cytosolic myocardial calcium modulation by ATP-dependent potassium channel openers and NO donors.

The goal of this study was to evaluate, in rat cardiomyocytes, the effects on cytosolic calcium of a pure K-adenosine triphosphate (ATP) channel opener, aprikalim, and those of nicorandil, a dual-acting agent that increases cyclic guanosine monophosphate (cGMP) levels and opens K-ATP channels. These effects were compared with those of a pure NO donor, 3-morpholino-sydnonimine (Sin-1). Ventricular myocytes were isolated from the hearts of adult rats. Changes in cytosolic calcium concentration ([Ca2+]i) were measured by using a Ca2+ indicator, indo-1/AM. Alterations in indo-1 fluorescence were recorded during regular electrical stimulation. After 10 min of pacing, end-diastolic [Ca2+]i was significantly increased as compared with control without significant changes in calcium transient. For doses of 10(-7) to 10(-4) M, aprikalim and nicorandil did not affect significantly the calcium transient. Sin-1 produced a significant decrease in calcium transient (by approximately 20%), which was already maximal at 10(-7) M. When given with the potassium channel antagonist glibenclamide (10(-5) M), nicorandil induced the same effects as those observed with Sin-1. We conclude that potassium channel openers aprikalim and nicorandil do not not decrease calcium transient. Thus the NO-donor properties of nicorandil are not apparent when given alone but appear when ATP-dependent potassium channels are blocked.

Adenosine Triphosphate↗

PubMed1997

Protein kinase C activity and expression in rabbit left ventricular hypertrophy.

Protein Kinase C (PKC) is implicated in the induction of myocardial hypertrophy. Recent studies showed an increased activity and expression of PKC in rat left ventricular hypertrophy, but we demonstrated a decreased PKC activity and content in rabbit heart failure. The present study was designed to evaluate whether these differences were due to species or model differences. PKC activity and expression were measured in a model of mild ventricular overload, induced by a 40-50% constriction of the abdominal aorta in rabbits. Left ventricular (LV) weight/body weight ratio was increased by 14, 21 and 36% after 4, 18 and 42 days of stenosis, respectively. PKC activity was significantly decreased after 18 and 42 days of stenosis in the particulate fraction of LV, but it was not modified in the cytosolic fraction leading to a significantly decreased translocation index (particulate/total activity ratio): 18.6 +/- 2.2% and 19.4 +/- 1.6% at 18 days and 42 days of aortic stenosis, respectively, compared with 25.7 +/- 2.0% and 25.8 +/- 1.2% in corresponding sham-operated rabbits (both Ps < 0.05). Similarly, PKC content, measured by immunoblotting, was not modified in the cytosolic fractions, but decreased significantly in the particulate fractions after 18 and 42 days of stenosis. These data are, thus, different from those obtained in rat LV hypertrophy showing species differences in PKC expression in hypertrophy. They also show that hypertrophy may take place without induction of PKC.

Animals↗

PubMed1997

[Kidney varices: an unusual location].

The authors report the case of a 40-year-old woman who presented with very large right renal varices. Computed tomography and arteriography showed that these varices were situated on the convex surface of the kidney, in front of its anterior surface, and drained venous blood derived from the renal parenchyma. These varices were probably secondary to undiagnosed renal vein thrombosis.

Adult↗

PubMed1996

Role of protein phosphatase in the regulation of Na+-K+-ATPase by vasopressin in the cortical collecting duct.

In the cortical collecting duct (CCD), arginin vasopressin (AVP) has been shown to increase the number and activity of basolateral Na+-K+-ATPase by recruiting or activating a latent pool of pumps. However, the precise mechanism of this phenomenon is still unknown. The aim of this study was to investigate whether this AVP-induced increase in basolateral Na+-K+-ATPase could depend on a dephosphorylation process. To this purpose, the effect of protein serine/threonine phosphatase (PP) inhibitors was examined on both the specific 3H-ouabain binding (to evaluate the number of pumps in the basolateral membrane) and the ouabain-dependent 86Rb uptake (to evaluate pump functionality) in the presence or absence of AVP. In addition, the activity of two PP, PP1 and PP2A, was measured and the influence of AVP was examined on both enzymes. Experiments have been performed on mouse CCD isolated by microdissection. Results show that inhibition of PP2A prevents the AVP-induced increase in the number and activity of Na+-K+-ATPases, independent of an effect on the apical cell sodium entry. In addition, AVP rapidly increased the activity of PP2A without effect on PP1. These data suggest that PP2A is implied in the regulation of Na+-K+-ATPase activity by AVP in the CCD and that the AVP-dependent increase in the number of Na+-K+-ATPases is mediated by a PP2A-dependent dephosphorylation process.

Animals↗

PubMed1996

Characteristics of a rat cortical collecting duct cell line that maintains high transepithelial resistance.

This study describes the establishment of a rat kidney cortical collecting duct (CCD) clonal cell line (RCCD1 cells) that maintains high transepithelial resistance and specific hormonal sensitivities. Immortalized cells were obtained by infection of primary cultured CCD cells with the wild-type simian virus 40. Grown on Petri dishes, RCCD1 cells are organized as monolayers of cuboid cells separated by tight junctions and form domes. Grown on permeable filters, confluent RCCD1 cells exhibit high transepithelial resistance (Rt: 2390 +/- 140 omega. cm2), transepithelial potential difference (PD) of -10.5 +/- 1.2 mV lumen negative, an associated short-circuit current (Isc) of 4.3 +/- 0.5 microA/cm2, and generated significant Na+, K+, H+ and HCO3- gradients, reflecting Na+ and H+ reabsorption and K+ and HCO3- secretion. RCCD1 cells exhibit features of both principal (PC) and intercalated (IC) cells. Consistent with PC phenotype, about 50% of the cells were positively stained by a PC-specific agglutinin. In situ hybridization studies revealed the presence of alpha, beta and gamma subunit mRNAs of the amiloride-sensitive epithelial Na+ channel and alpha 1 and beta 1 subunits of Na(+)-K(+)-ATPase. Moreover, Na(+)-K(+)-ATPase was immunolocalized at the basolateral side of the cells. Arginine vasopressin (AVP) induced a significant increase in both cellular cAMP content and Isc. Amiloride decreased in a dose-dependent manner Isc from untreated and AVP-treated RCCD1 cells. In addition, a barium-sensitive K+ conductance was evidenced in the apical side of the cells. Consistent with IC phenotype, isoproterenol (ISO) provoked a large increase in cellular cAMP and stimulated Isc. The effect of ISO on Isc was blocked by 5 x 10(-3) M DPC, a chloride channel blocker. Finally, AVP plus ISO had additive effect on Isc. Taken together, these results provide evidence that the RCCD1 cell line has maintained many of the original properties of rat CCD from which they were derived.

Animals↗

PubMed1996

[Emphysematous pyelonephritis. A case medically treated].

Authors report on a case of emphysematous pyelonephritis in a woman affected with diabetes and renal failure. In order to avoid chronic dialysis, no nephrectomy was performed and the patient was treated only with drugs. Full recovery was obtained, without worsening of the renal function.

Aged↗

PubMed1995

Regional alterations of left ventricular contraction and inotropic reserve in conscious dogs with heart failure.

OBJECTIVE: The goal was to examine left ventricular (LV) regional contraction alterations and especially, regional inotropic reserve changes in tachycardia-induced heart failure (HF). METHODS: Eleven dogs were chronically instrumented to measure LV pressure and its first time derivative (LV dP/dt), left atrial and aortic pressures and to measure antero-apical (AS), -basal (BS) and postero-apical (PS) subendocardial segmental contractions by ultrasonic crystals. Dobutamine (5-15 micrograms/kg per min) and left atrial pacing (150-240 beats/min) were performed in the control state (C) and in HF induced by chronic right ventricular pacing (240 beats/min, 3 weeks). RESULTS: In HF, as compared with in C, LV dP/dt max decreased and LV end-diastolic pressure and end-diastolic segmental lengths increased (Ps < 0.005). The percentage of systolic shortening was more depressed in PS (from 21 +/- 1% to 7 +/- 1%, P < 0.001) than in AS and BS (from 24 +/- 1% to 17 +/- 1% and from 20 +/- 2% to 13 +/- 1% respectively, Ps < 0.05). During dobutamine infusion, in HF as compared with C, the increases in LV dP/dt max were smaller (dobutamine 15 micrograms/kg per min: HF: + 36 +/- 6% vs C: + 68 +/- 11%, P < 0.01) and the increases in the systolic shortening of the three segments were also smaller. However, the responses of the three segments were similar in HF and in C. During left atrial pacing, LV dP/dt max increased less in HF than in C and the poststimulation potentiation of LV dP/dt max was impaired in HF. However, the responses of the systolic shortening during regular left atrial pacing and the increase in the percentage of systolic shortening of the first poststimulation beat were similar in all regions. CONCLUSION: In tachycardia-induced HF, although LV regional contraction is heterogeneously altered, the inotropic reserve appears to be similarly modified in all regions.

Analysis of Variance↗

PubMed1991

Loading determinants of isovolumic pressure fall in closed-chest dogs.

The respective roles of load level and loading sequence of the left ventricle (LV) are controversial in the in situ heart. They were analyzed under autonomic blockade and sedation in 17 dogs previously instrumented with a pressure micromanometer and ultrasonic crystals measuring LV diameters and wall thickness for computation of LV volume and stress. The time constant of isovolumic pressure fall (T) and end-systolic pressure (ESP) were calculated during the control state, caval occlusion, aortic constriction obtained by inflation of a hydraulic cuff occluder positioned around the aorta, and during the inflation of an intra-aortic balloon. Caval occlusion significantly decreased both ESP (from 124.0 +/- 6.6 to 88.7 +/- 3.7 mmHg; P less than 0.005) and T (from 29.0 +/- 2.2 to 18.8 +/- 2.4 ms; P less than 0.005), which were linearly correlated (mean r = 0.90 +/- 0.03) and inflation of an intra-aortic balloon increased both ESP (from 107.3 +/- 7.1 to 150.6 +/- 10.4 mmHg; P less than 0.005) and T (from 24.6 +/- 2.1 to 32.7 +/- 2.3 ms; P less than 0.005). Both interventions did not modify the loading sequence (analyzed by the evolution of systolic wall stress vs. time). In contrast, aortic constriction delayed to midsystole the time to which wall stress reached its peak and, for matched ESP with intra-aortic balloon inflation, T was not significantly different from control. We conclude that both the level of afterload and the loading sequence of LV are the determinants of T when contractility is not modified.

Animals↗

PubMed1989

Left ventricular pressure-diameter relations in the conscious rabbit.

A model for the study of left ventricular (LV) contractility in a small species was developed using conscious rabbits previously instrumented with a LV catheter and ultrasonic crystals measuring LV internal diameter. Afterload increase produced by methoxamine infusion was associated with a reduction in heart rate from 272(SEM18) to 214(20) beats.min-1, p less than 0.01; and an increase in LV end systolic pressure from 76.3(4.1) to 101(6.5) mm Hg, p less than 0.001, and in end systolic diameter from 8.7(0.7) to 9.9(0.7) mm, p less than 0.01. For matched end systolic pressure and heart rate, the increase in inotropic state produced by noradrenaline infusion significantly shifted the pressure-diameter relation to the left. Similarly, end systolic pressure and diameter were significantly lowered by sodium nitroprusside infusion, with a reflex increase of heart rate; and a decrease in inotropic state produced by verapamil infusion was demonstrated by a significantly larger end systolic diameter for matched end systolic pressure and heart rate. The pressure-diameter relation was not modified by volume loading, which increased end diastolic diameter by 9.6(1.1)% with no evidence of a Bainbridge reflex. The mild depressant effect of diltiazem was not detected by peak dP/dt changes but was demonstrated by the analysis of end systolic pressure-diameter relations. The instrumented rabbit thus appears to be a sensitive model for studying LV function and the cardiovascular effects of drugs.

Animals↗

PubMed1981

[Cardiomegaly due to iron deficiency in the rat (author's transl)].

The effects of chronic iron deficiency were studied in new born rats. Hemoglobin concentrations were significantly depressed throughout the experimental period when compared with those of control animals. At third postnatal month, there was a 56% increase of absolute heart weight and a 230% increase of relative heart weight. Heart weight increased much more than myocytes dimensions. This finding may be interpreted as characteristic of a double process of hypertrophy and hyperplasia. Both cell hypertrophy and multiplication were responsible for the observed hypertrophy of the heart. Number of capillaries/mm2 was unchanged, but both mean capillary diameter and total surface of capillary wall increased progressively during the period of anemia. The adaptation to myocardial hypoxia may be, in this experiment situation, localized at the capillary level rather than at the mitochondria. At cell level, we did not note any particular modification of the ultrastructure and particularly no degenerative change. No mitochondrial lesions were found even in severe anemics (blood hemoglobin below 3.2 g/100 ml).

Anemia, Hypochromic↗

PubMed1979