[Post-denervation renal artery stenosis - a matter of concern?]. / Les sténoses artérielles rénales post-dénervation - une problématique préoccupante ?

Renal denervation, an invasive technique indicated in resistant hypertension patients insufficiently controlled by antihypertensive drugs, has a good safety profile. However, an increasing number of post-denervation renal artery stenosis cases has recently been reported. We describe the case of a 49-year-old woman with resistant hypertension who was referred to our university hypertension center for renal sympathetic denervation. Her daily treatment included six antihypertensive drugs. CT angiography prior to denervation showed no renal artery stenosis or vessel wall lesions. A standard renal denervation procedure using the St Jude protocol was performed. After an initial improvement in blood pressure profile, she presented with a blood pressure impairment at 3 months after renal denervation leading to the diagnosis of a severe right renal artery stenosis.

[About an implantable cardioverter-fibrillator]. / Fibrillateur automatique implantable.

A 61-year-old man has been implanted with a Ventritex Profile MD V-186 HV3 ICD for ischemic cardiomyopathy with sustained inducible VT. Three years later, this patient received several inappropriate shocks during the device's interrogation. These shocks provoked ventricular fibrillation. They were caused by a failing soldering between the system random accessory memory (SRAM) module and the hybrid circuit of the device. The device was explanted in emergency.

Modeling of transcellular Ca transport in rat duodenum points to coexistence of two mechanisms of apical entry.

Employing realistic parameters, we have demonstrated that a relatively simple mathematical model can reproduce key features of steady-state Ca2+ transport with the assumption of two mechanisms of Ca2+ entry: a channel-like flux and a carrier-mediated transport. At low luminal [Ca2+] (1-5 mM), facilitated entry dominates and saturates with Km = 0.4 mM. At luminal [Ca2+] of tens of millimolar, apical permeability is dominated by the channel flux that in turn is regulated by cytosolic Ca2+. The model reproduces the linear relationship between maximum Ca2+ transport rate and intestinal calbindin D9K (CaBP) content. At luminal [Ca2+] > 50 mM, local sensitivity analysis shows transcellular transport to be most sensitive to variations in CaBP. At low luminal [Ca2+], transport becomes sensitive to apical entry regulation. The simulations have been run within the Virtual Cell modeling environment, yielding the time course of external Ca2+ and spatiotemporal distributions of both intracellular Ca2+ and CaBP. Coexistence of two apical entry mechanisms accords with the properties of the duodenal Ca2+ transport protein CaT1 and the epithelial Ca2+ channel ECaC.

Extracellular and intracellular regulation of calcium homeostasis.

An organism with an internal skeleton must accumulate calcium while maintaining body fluids at a well-regulated, constant calcium concentration. Neither calcium absorption nor excretion plays a significant regulatory role. Instead, isoionic calcium uptake and release by bone surfaces causes plasma calcium to be well regulated. Very rapid shape changes of osteoblasts and osteoclasts, in response to hormonal signals, modulate the available bone surfaces so that plasma calcium can increase when more low-affinity bone calcium binding sites are made available and can decrease when more high-affinity binding sites are exposed. The intracellular free calcium concentration of body cells is also regulated, but because cells are bathed by fluids with vastly higher calcium concentration, their major regulatory mechanism is severe entry restriction. All cells have a calcium-sensing receptor that modulates cell function via its response to extracellular calcium. In duodenal cells, the apical calcium entry structure functions as both transporter and a vitamin D--responsive channel. The channel upregulates calcium entry, with intracellular transport mediated by the mobile, vitamin D-dependent buffer, calbindin D9K, which binds and transports more than 90% of the transcellular calcium flux. Fixed intracellular calcium binding sites can, like the body's skeleton, take up and release calcium that has entered the cell, but the principal regulatory tool of the cell is restricted entry.

Mannitol enhances intracellular calcium diffusion in the rat ileum--a hypothesis.

The addition of 92 or 136 mM mannitol to a modified saline solution that contained 1.25 mM Ca2+ led to a mannitol concentration-dependent increase in the amount of calcium absorbed in 1 h from 8 cm long ileal loops prepared from fasted male Sprague-Dawley rats, with body weights of 190 +/- 10 g. It is argued that this mannitol-enhanced movement of calcium out of the loop cannot have utilized the paracellular pathway, inasmuch as the luminal calcium concentration of the mannitol instillate decreased during the experiment, with a negative calcium gradient between luminal and body fluids. Instead it is proposed that uncomplexed mannitol and the uncharged calcium complex of mannitol entered the ileal cells. The uncomplexed intracellular mannitol would bind additional calcium that had crossed the brush border down its gradient. The increase in total intracellular calcium will raise the effective intracellular gradient and thereby amplify intracellular calcium diffusion. This in turn increases calcium absorption.

[Value of the analysis of pulmonary venous flow in the evaluation of hemodynamics in dialysed patients]. / De l'intérêt de l'analyse du flux veineux pulmonaire dans l'estimation d'un état hémodynamique. Exemple de la dialyse.

The aim of this study was to assess the value of analysis of pulmonary venous flow in the evaluation of the haemodynamic status of patients with chronic renal failure with normal left ventricular function, treated by haemodialysis. Pulmonary venous flow was recorded immediately before and after haemodialysis in 27 patients with chronic renal failure and a mean age of 44 years. Three groups of patients were defined according to the change in mitral E/A ratio: Group I (E/A < 1 before and after dialysis), Group II (E/A > 1 before and < 1 after dialysis) and Group III (E/A > 1 before and after dialysis). There was a significant difference between these subgroups before dialysis with respect to age, S, D, VTI S, Total VTI, VTI S/Total (p < 0.05). However, because the values overlapped, only a VTI S/Total ratio greater than 59% differentiated patients in Group II from those in group III (p < 0.05). After dialysis, the change in S/D and VTI S/Total ratios increased in Groups I and II and decreased in Group III. The authors concluded that 63% of patients without LV dysfunction on haemodialysis have abnormalities of relaxation which are latent in 47% of cases due to increased filling pressures diagnosed by a VTI S/Total ratio > 59% or simply because the patients are over 50 year old.

[Paradoxal lowering of parasympathetic indices in myasthenic patients]. / Diminution paradoxale des paramètres parasympathiques chez les patients myasthéniques.

Myasthenia gravis is an autoimmune disease presenting antibodies developed against the nicotinic receptors of acetylcholine. The aim of this study was to evaluate heart rate variability in these patients. Heart rate variability was studied with 24 hour Holter recordings. Eighteen myasthenic patients, 7 men and 11 women, under pyridostigmine treatment, with an average age of 40 years (25 to 63 years) were aged and gender matched to a control group of 18 healthy subjects. All patients exhibited normal cardiac status and Doppler echocardiography. The following parameters were collected over 24 hours and the data further differentiated between night and day: for the temporal domain: heart rate, SDNN, pNN50, rMSSD; and for the spectral domain: total power, high frequency (HF) and low frequency (LF) power. The mean heart rate was slightly higher in the myasthenic group (non significant), due to a less marked nocturnal bradycardia. There was a decrease in the observed absolute values of SDNN as well as temporal and spectral parasympathetic indices (pNN50, rMSSD, HF) (p < 0.01) over the 24 hour period. The results were more significant during the night. Cardiac parasympathetic modulation is significantly modified in myasthenic patients. Considering that lack of bradycardia argues against an over active vagal tone, three hypothesis are discussed that favor of a low vagal tone: antibodies effects on the nicotinic receptors of the autonomic nervous system, respiratory impairment and a desensitization of the acetylcholine receptors.

Nutritional aspects of calcium absorption.

The amount of calcium absorbed in the intestine depends on habitual calcium intake. When intake is low, active transcellular calcium transport in the duodenum is upregulated and a larger proportion of calcium is absorbed by the active process than by the passive paracellular process that prevails in the jejunum and ileum. Bioavailability of the calcium source-digestibility and solubilization-plays a role under conditions of low calcium intake but is relatively unimportant when calcium intakes are high (e.g. >800 mg/d in people). Vitamin D intake is a second factor, as active calcium transport is directly and proportionally dependent on the presence in the intestinal cell of calbindin D9k, the biosynthesis of which is totally vitamin D dependent. Passive absorption in jejunum and ileum is the major absorptive process when calcium intake is adequate or high. Passive calcium absorption is a complicated function of solubility in the distal small intestine, the length of sojourn of the chyme in a given intestinal segment, and the rate of paracellular diffusion from lumen to lymph and blood. Calcium that reaches the large intestine undergoes absorption there by both active and passive processes. Probably no more than 10% of total calcium absorption takes place in the large intestine, whether calcium intake is low or high. Calcium absorption by the large bowel can assume nutritional importance under conditions of significant small bowel resection.

Optimizing the hemodynamic performance of the DDD pacemaker: impact of the atrioventricular delay on the pulmonary venous flow pattern.

UNLABELLED: This study evaluated the impact of the atrioventricular delay (AVD) on the pulmonary venous flow pattern (PVFP). METHODS: Transthoracic Doppler PVFP were obtained during atrial and ventricular pacing at a fixed rate of 70 beats/min in 20 patients equipped with a DDD pacemaker, diastolic dysfunction linked to an impaired relaxation, a mean ejection fraction of 49%, and AV block. Two subgroups were analyzed equally: group I: seven patients with a normal ejection fraction and group II: 13 patients with decreased ejection fraction. Three different AVDs were studied: short (50 ms), intermediate (150 ms), and long (250 ms). RESULTS: As the AVD increased, the diastolic filling time and the peak atrial reverse flow wave decreased (P < 0.001). There was a decreasing D wave and no significant change in the peak velocity of the S wave. The S wave became biphasic in all patients at the longest AVD of 250 ms. The systolic (S) velocity time integral (VTI) of the pulmonary wave and the systolic/total PVF-VTI ratio increased significantly (P < 0.001). A similar response was seen in both group of patients. CONCLUSIONS: These data correlated the AVD with PVFP, supplying critical systolic information completing the diastolic data obtained from mitral Doppler patterns. These systolic measurements were especially useful for patients with heart failure and a DDD pacemaker, in order to obtain the longest diastolic filling time at the lowest atrial pressure.

[Variability of heart rate after heart surgery under extracorporeal circulation: aortocoronary bypass or aortic valve replacement]. / Evolution de la variabilité de la fréquence cardiaque après chirurgie cardiaque sous circulation extra-corporelle: pontages aorto-coronariens ou remplacements valvulaires aortiques.

The study of heart rate variability allows analysis of modulations of heart rate by the sympathetic vagal system. The authors studied the course of sinus variability by 24-hour Holter monitoring preoperatively, and on the 6th and 42nd postoperative day, in 25 patients undergoing coronary bypass graft (group I) and 10 patients undergoing aortic valve replacement (group II). Surgery was performed under cardiopulmonary bypass with selective antegrade cold crystalloid cardioplegia. The preoperative ejection fraction of these patients was 62% with a mean age of 59.5 years in group I and 61.5 years in group II. All temporal or spectral parameters were significantly decreased in the two groups on the sixth day (p < 0.05). Parameters which remain altered on D42 compared to baseline values were temporal parameters: pNN50 and rMSSD for group I and ASDNN for group II, with a tendency to return to baseline values, but with a higher mean heart rate in group II on D6 and D42 (p < 0.05). In the spectral domain, TP (total power of the spectrum) and LF (Low frequencies) remained decreased in both groups. A reversible alteration of sinus variability parameters was therefore observed in the two groups of patients. Other studies are necessary to define the mechanisms of these alterations, which are most probably related to catecholaminergic flooding related to CPB or partial vagal denervation by ischaemic or surgical damage to nerve structures.

Development and regulation of calcium metabolism in healthy girls.

The major components of calcium metabolism, as evaluated by a dual-tracer stable isotope method, were determined in 100 studies of 68 healthy girls, aged 5-18 y and analyzed from a developmental and regulatory viewpoint. Bone calcium deposition and removal rates were closely correlated with the size of the exchangeable bone calcium compartment. All three quantities, as well as intestinal calcium absorption, peaked at or near menarche. Both bone calcium deposition and removal rates were positively and linearly correlated with calcium absorption. However, in this correlation, because bone calcium deposition increased 70% faster than calcium absorption, most of the increase in the bone calcium compartment and its turnover must have occurred in response to something other than intestinal calcium input; presumably this occurred in response to developmental signals. Nevertheless, the constancy of the serum calcium in the face of a large intestinal calcium input and the modest way in which excretion overcame the calcium load in this population point to the importance of the exchangeable bone calcium compartment, in dynamic equilibrium with the bone mineral, as the site at which most of the load is taken up. In this population of girls, as in older women, this increase in the skeletal calcium balance resulted from a decrease in the bone calcium removal rate that was greater than the corresponding increase in the bone calcium deposition rate.

Calcium absorption--a paradigm for mineral absorption.

Intestinal calcium absorption proceeds by two mechanisms, an active transcellular process that takes place in the duodenum and a passive paracellular process throughout the small intestine. This article characterizes the three steps of transcellular calcium movement-entry, intracellular diffusion and extrusion-and identifies conditions that must be satisfied for other mineral ions to move transcellularly as part of a transepithelial transport process. Passive calcium movement is down a chemical gradient with the amount absorbed by this pathway determined in large measure by the sojourn time, most of which is spent in the ileum. Because transcellular movement of most mineral ions other than calcium, where measured, is either small or negligible, passive transport is likely to be the major route of intestinal absorption, the nature of which, however, has not been well established experimentally.

1,25-Dihydroxycholecalciferol regulates rat intestinal calbindin D9k posttranscriptionally.

To determine whether calbindin D9k (CaBP) is subject to posttranscriptional control, 6-wk-old Sprague Dawley-derived rats were fed one of three purified diets, 1.5% Ca and 3.0% Ca, mostly as carbonate, and 2.9% Ca, mostly as gluconate. Two weeks later, 5-cm segments of duodenum, jejunum, ileum, cecum and colon were obtained and analyzed for CaBP and CaBP-mRNA. Analysis of the steady-state distribution of CaBP-mRNA and of CaBP revealed a statistically significant (r = 0.95; P < 0.01) linear relationship between CaBP-mRNA and CaBP. When, however, animals that had been fed the 1.5% Ca diet received by intrajugular injection 1.2 nmol 1,25-dihydroxycholecalciferol [1.25-(OH)2-D3] and their CaBP-mRNA and CaBP were analyzed as a function of time after 1,25-(OH)2-D3 administration, the kinetic response of the two molecules differed. The CaBP-mRNA increased linearly by approximately 68% for 4 h after administration and then declined over the next 6 h to a concentration below the preinjection value. Thus, appearance and disappearance of CaBP-mRNA approximated 17% x h(-1). The CaBP, however, increased steeply to 80% above preinjection concentration until 2 h postinjection, i.e., at a rate of 40% x h(-1). Thereafter, CaBP decreased to 35% above the preinjection value between 5 and 10 h postinjection (2.5% x h(-1)). These findings are consistent with a 1,25-(OH)2-D3-mediated posttranscriptional regulation of CaBP concentrations, because the 1,25-(OH)2-D3-mediated increase in CaBP-mRNA is not reflected in an immediately changed CaBP level.

Calcium solubility, intestinal sojourn time and paracellular permeability codetermine passive calcium absorption in rats.

To investigate the nonsaturable, paracellular pathway of intestinal Ca absorption, the luminal contents of 12-cm segments of the intestine of 8-wk-old male Sprague-Dawley rats were analyzed for pH, sojourn time and soluble and insoluble Ca over a 24-h period. The rats had been fed one of two high Ca diets for 2 wk: 1.5% Ca (diet group 3a) and 3.1% (diet group 5a). The pH of the small intestine increased from < 6.6 to > 8.0 from duodenum to ileum; transit time increased from 2.5 min in the duodenum to 58 min in the distal ileum, with the entire ileum accounting on the average for 74% of the transit time of 3 h. The amount of Ca solubilized throughout the intestine was 32 +/- 3.3 mumol in diet group 3a and 53 +/- 5.3 mumol in diet group 5a, i.e., 2.7% and 2.0% of the total luminal Ca. Because absorption by diet group 3a was 1.45 +/- 0.23 mmol/d and that by diet group 5a was 2.50 +/- 0.18 mmol/d, the amounts absorbed were 45.3 and 47.1 times greater than present in the lumen in soluble form at any one time. Thus, over a 24-h period, an average of 3.2% (46.2/1440) of the soluble Ca present in the lumen at any time was absorbed per min. Calculations involving the gradient between luminal and plasma Ca show that the rate of Ca diffusion from lumen to blood is < 2% of what it would be if the paracellular path were unrestricted. Thus, intestinal sojourn time, Ca solubility and mucosal permeability to Ca are factors that determine the rate of passive Ca absorption.

Calcium homeostasis--an old problem revisited.

This article proposes a novel model of calcium homeostasis, based on the concept of a series of bone calcium-binding sites of varying calcium affinities. When an i.v. Ca load is administered to mammals, it is rapidly (t1/2 < 1 min) dispersed into a volume equivalent to the extracellular fluid. Thereafter the calcium concentration drops monoexponentially with a t1/2 of tens of minutes. When a negative Ca load is administered, as by EDTA injection, the return to the preinjection plasma Ca level, [Cas], occurs also mono-exponentially at the same rate as restoration after a positive load. The numerical value of the rate can be arrived at by taking into account the fraction of cardiac output (5%) that is directed to the skeleton. Acute regulation is brought about by controlling access to subpopulations of the Ca binding sites, whose average Km determines [Cas]. Osteoblasts, when active and extended, block low-affinity binding sites; osteoclasts, when active and extended, block high-affinity sites. Exposure of sites is brought about when bone cells respond by rapid shape changes, osteoblasts rounding up in response to parathyroid hormone (PTH) or vitamin D, osteoclasts rounding up in response to calcitonin. These shape changes are the first steps in the cascade of events that lead to bone formation and resorption, but acute regulation need not involve the latter steps of a cascade. The model accounts for the changes in the response times to Ca loads that have been observed in older animals or those deprived of PTH, calcitonin or vitamin D.