Genotoxic risk of ethyl-paraben could be related to telomere shortening.

The ability of parabens to promote the appearance of multiple cancer hallmarks in breast epithelium cells provides grounds for regulatory review of the implication of the presence of parabens in human breast tissue. It is well documented that telomere dysfunction plays a significant role in the initiation of genomic instability during carcinogenesis in human breast cancer. In the present study, we evaluated the genotoxic effect of ethyl 4-hydroxybenzoate (ethyl-paraben), with and without metabolic activation (S9), in studies following OECD guidelines. We observed a significant increase in genotoxic damage using the Mouse Lymphoma Assay and in vitro micronucleus (MN) tests in the L5178Y cell line in the presence of S9 only after a short exposure. A high frequency of MN was observed in the TK6 cells after a short exposure (3 h) in the presence of S9 and a long exposure (26 h) without S9. We found significant increases in the MN frequency and induced chromosomal aberrations in the lymphocytes of only one donor after ethyl-paraben exposure in the presence of S9 after a short exposure. Cytogenetic characterization of the paraben-treated cells demonstrated telomere shortening associated with telomere loss and telomere deletions in L5178Y and TK6 cells and lymphocytes of the paraben sensitive-donor. In a control cohort of 68 human lymphocytes, telomere length and telomere aberrations were age-dependent and showed high inter-individual variation. This study is the first to link telomere shortening and the genotoxic effect of ethyl paraben in the presence of S9 and raises the possibility that telomere shortening may be a proxy for underlying inter-individual sensitivity to ethyl-paraben. Copyright © 2016 John Wiley & Sons, Ltd.

Cardiovascular risk and lifestyle habits of consumers of a phytosterol-enriched yogurt in a real-life setting.

BACKGROUND: Data on the characteristics of consumers of phytosterol-enriched products and modalities of consumption are rare. An observational study evaluating the lifestyle characteristics and cardiovascular risk (CVR) profile of phytosterol-enriched yogurt consumers was performed in France. METHODS: Subjects were recruited from general practitioners via electronic medical records. Data were obtained from 358 consumers and 422 nonconsumers with 519 subject questionnaires (243 consumers, 276 nonconsumers; 67% response). RESULTS: Consumers had more cardiovascular risk factors than nonconsumers (2.0 ± 1.5 versus 1.6 ± 1.4; P < 0.001) and a higher 10-year SCORE cardiovascular risk (1.8 ± 2.0% versus 1.6 ± 2.2%; P = 0.008); they were older (P = 0.030) and had a higher incidence of hypercholesterolaemia (P < 0.001) and family or personal history of heart disease (P = 0.023/P = 0.026, respectively). Among consumers not on cholesterol-lowering medication, 99% were eligible for lifestyle interventions and 56% were eligible for lipid-lowering drug according to European guidelines. Consumers had a healthier lifestyle, with a higher (fruit/vegetable - saturated fatty acid) score than nonconsumers (P = 0.035), focused more on low-intensity leisure activity (P = 0.023), spent more time travelling by foot or bicycle (P = 0.012) and were more likely to act to reduce CVR. Phytosterol-enriched yogurt intake conformed to recommendations in two-thirds of consumers and was mainly consumed because of concerns over cholesterol levels and CVR. CONCLUSIONS: The higher cardiovascular disease risk profile of phytosterol-enriched yogurt consumers corresponds to a population for whom European guidelines recommend lifestyle changes to manage cholesterol. The coherence of the data in terms of risk factors, adherence to lifestyle recommendations and the consumption of phytosterol-enriched yogurt conforming to recommendations reflects a health-conscious consumer population.

[Use of prolonged-release nicotinic acid in patients treated with statins as a secondary prevention and a persistently low HDL-cholesterol level in France]. / Etude d'utilisation de l'acide nicotinique a libération prolongée en France chez des patients en prévention secondaire sous statine avec persistance d'un taux bas de HDL-c.

UNLABELLED: HDL-c is a potent predictor of cardiovascular risk in all epidemiologic studies, especially as secondary prevention, regardless of LDL-c level obtained on statin treatment. The objective of this longitudinal observational study was to investigate the effects of prolonged-release nicotinic acid in high cardiovascular risk patients on statin treatment and with low HDL-c. METHOD: The selected patients of both genders, aged over 18 years patients showed primary hypercholesterolemia or mixed hyperlipidemia, received statin treatment as secondary prevention and had a HDL-c level

[The behavioral goals of the coronary patient: No longer smoke, eat better, move more and better]. / Les objectifs comportementaux du patient coronarien : ne plus fumer, manger mieux, bouger plus et mieux.

The behavioral goals of the coronary patient require active management by the cardiologist. Every smoker must be clearly informed about the cardiovascular consequences of smoking and the major benefits of smoking cessation. The only advice to "quit smoking" is not enough. Validated "treatments" (cognitive-behavioral therapy, nicotine replacement therapy, varenicline, bupropion) must be used, with a precise strategy and prolonged follow-up. All drugs assistance can be prescribed in coronary patients and nicotine replacement therapy can even be used just after a myocardial infarction. Nutrition plays a significant role in cardiovascular prevention. Counseling today is based on solid evidence, although evidence is harder to obtain than with drugs. It should no longer be advisable only to "suppress cooked fats and starches" because these recommendations are unclear and/or false. Today we need positive food-based benchmarks and complex dietary patterns in which fruits and vegetables, fish, whole grains, pulses, nuts, olive oil and a diet closed to the Mediterranean diet. Dairy products have their place. Sugary foods should be limited especially in case of overweight and metabolic syndrome. Physical activity is part of good nutrition. Indeed, the fight against a very sedentary lifestyle and physical inactivity in coronary and heart failure patients is part of the lifelong treatment of these patients. The cardiologist and the general practitioner must be much more involved in their prescription and education to hope for good compliance.

Evaluation of short food-frequency questionnaires to assess the dietary pattern associated with atherosclerotic cardiovascular diseases.

OBJECTIVES: Cardiovascular diseases are strongly related to dietary habits. Diet can be assessed using dedicated questionnaires that can be self-completed by subjects but with the risk of errors. AIM: To compare the completion error rate of two questionnaires designed to assess dietary pattern linked to cardiovascular diseases and to study the correlation between the two questionnaires. MATERIALS AND METHODS: Two questionnaires were used to assess dietary patterns of students: the 14-item Food-Frequency-Questionnaire (FFQ) that was validated against biomarkers, and the Cardiovascular-Dietary-Questionnaire 2 (CDQ2), which is a 19-item-FFQ derived from the previous 14-item FFQ. Both questionnaires assessed the intake of various food groups associated with either favourable or unfavourable effects on cardiovascular risk. A global dietary score was calculated for each questionnaire. RESULTS: FFQ and CDQ2 were completed by 150 sport degree students. In the case of FFQ, 111 questionnaires out of 150 (74.0%) were incomplete compared to only 1 CDQ2 out of 150 (0.7%) (P<0.001). The correlation coefficient between the overall CDQ2 score and the FFQ dietary score was 0.53 (P<0.01). CONCLUSION: The self-completion of CDQ2 compared to FFQ was associated with far less errors. There was a significant correlation between CDQ2 and FFQ. Preference should be given to CDQ2 in clinical practice and in studies where dietary pattern are evaluated without any interviewer.

[The best of epidemiology and cardiovascular prevention in 2006]. / L'essentiel de 2006 en épidemiologie et prévention cardiovasculaire.

The recent analysis of the French MONICA registries report a reduction in the incidence of fatal MI related to improvement of care whereas the overall incidence of coronary events remain stable, suggesting the need for a better primary prevention. The extensive review of the death certificates and the analysis of the death classification from the same registries indicate an under estimation of MI-related death in the national death registry. It is also confirmed that instead of 50%, approximately 80% of coronary death are explained by the four major risk factors including smoking, hypercholesterolemia, hypertension and diabetes. The international REACH registry has enrolled more than 67 000 individuals including patients with symptomatic atherothrombotic disease and patients with multiple risk factors. The analysis of baseline characteristics and of the one year FU shows a high residual risk and a lack of efficacy of secondary prevention. The existence of a symptomatic disease and the number of symptomatic localization of atherothrombosis are critical factors to predict recurrence of major vascular events Secondary analysis of the INTERHEART study provide the essence of what should any physician know about the relationship between coronary heart disease and smoking, either active or passive. Prevention with respect to this risk factor remains very insufficient. Varenicline, a new nicotinic receptor partial agonist, should help patients involved in smoking cessation program. The established detrimental effects of perioperative smoking represent a unique opportunity to promote smoking cessation in individuals scheduled for surgery. The major cardiovascular impact of second hand smoking has been recently demonstrated by the short-term effects of banning smoking in public places on the incidence of acute coronary events. The SPARCL study has demonstrated the benefit of high dose of atorvastatine to prevent recurrent acute ischemic cerebrovascular event in patients with a prior history of stroke or TIA. In the open ASTEROID study, high doses of rosuvastatine confirm the possibility of reducing the volume of coronary atheroma analyzed by IVUS. The expected benefit of glitazones to reduce the incidence of death, MI and stroke in diabetes patients with a prior history of vascular event has been confirmed in the PROactive study. Pioglitazone provided a clear reduction of recurrent vascular events in diabetes patient with a prior MI at a cost of a significant increase of the risk of heart failure. In the DREAM study, neither ramipril nor rosiglitazone have reduced the incidence of cardiovascular events significantly. The moderate benefit of the fenofibrate to prevent cardiovascular events in the FIELD study, which was carried out in diabetics mostly in primary prevention, needs to be considered after adjustment on statin use in a higher proportion of patients of the placebo group. Postprandial hyperglycaemia, analyzed by the peak of glycaemia after a load in glucose, has been confirmed as a more powerful independent predictive factor of the risk of cardiovascular event than fasting glycaemia. The systematic screening postprandial hyperglycaemia represents an interesting strategy for primary prevention which warrants further investigation. If obesity is a risk factor whose impact on morbi-mortality is well established, a French study shows that body mass index has an unfavourable influence on the cognitive functions in middle-aged men and women.

[The best of epidemiology and cardiovascular prevention in 2005]. / L'essentiel de 2005 en épidémiologie et prévention cardiovasculaire.

It is difficult to summarize in a few pages the wealth of information appeared during the year 2005 in the field of epidemiology and cardiovascular prevention. The general epidemiological data on the evolutionary tendencies of coronary mortality and morbidity make it possible to underline the effectiveness of the control of the great risk factors within the framework of the primary prevention. Although lipids and diabetes have still this year held the front of the scene through many trials, this analysis is also focused on smoking, subject more and more tackled in the cardiologic journals, and to which a larger attention should be paid in our daily practice. The Paris Prospective Study I brought new data concerning the early identification of the subjects at risk of sudden death, starting from the analysis of the evolution of heart rate profile during and after exercise. Is the concept of metabolic syndrome a phenomenon of mode or does it constitute in itself an autonomous prognostic factor beyond the risk related to the plurality of the factors which define it? The cardiologist will have to be interested more and more in the living conditions of his patients and in particular with the environmental factors such as the air pollution, who seems to have a considerable impact on the incidence of the acute coronary events. Lastly, the ADMA (asymmetric dimethylarginine), seems a possible new marker of cardiovascular risk, but its real prognostic interest remains to be defined.

Atrial natriuretic factor during atrial fibrillation and supraventricular tachycardia.

Plasma immunoreactive atrial natriuretic factor was measured in 10 patients with chronic atrial fibrillation before and after cardioversion to sinus rhythm, and in 14 patients during electrophysiologic evaluation of paroxysmal supraventricular tachycardia. The mean plasma concentration of atrial natriuretic factor in atrial fibrillation was 138 +/- 48 pg/ml and decreased to 116 +/- 45 pg/ml 1 hour after cardioversion to sinus rhythm (p less than 0.005). The mean plasma concentration of atrial natriuretic factor increased from 117 +/- 53 pg/ml in sinus rhythm to 251 +/- 137 pg/ml during laboratory-induced supraventricular tachycardia (p less than 0.005). Right atrial pressures were recorded in 12 patients; the baseline atrial pressure was 4.3 +/- 1.9 mm Hg and increased to 7.4 +/- 3.6 mm Hg during supraventricular tachycardia (p less than 0.005). A modest but significant linear relation was noted between the changes in plasma atrial natriuretic factor and right atrial pressure measurements during induced supraventricular tachycardia (r = 0.60, p less than 0.05). In conclusion, changes in atrial rhythm and pressure may be an important factor modulating the release of atrial natriuretic factor in the circulation and raised levels of this hormone may be a contributing factor for the polyuria and the hypotension associated with paroxysmal supraventricular tachyarrhythmias.

Effect of phytosterols/stanols on LDL concentration and other surrogate markers of cardiovascular risk.

Plant sterols and stanols are well-known to reduce LDL-cholesterol (LDL-C) concentrations. It is generally accepted that supplementation with 2g/day of sterols/stanols leads to a 10% reduction in LDL. However, most of the clinical trials supporting this conclusion were of short-term duration, and the results of longer interventions are scanty. In four studies, interventions lasting>6 months were carried out and the LDL-C-lowering effects were maintained over this longer duration, although some results suggest that a reduced effect may be observed with sterols, while stanols maintain their effect. In any case, the data are too limited to be definitive. In a free-living population as well as in multiparametric interventional studies, however, the LDL-C-lowering effect has been confirmed, although to a lesser extent than in clinical studies. In the absence of data on cardiovascular morbidity and mortality, data for surrogate markers of cardiovascular risk could be considered adequate alternatives. Several studies have been conducted on this basis, but their results failed to demonstrate any favourable effects. The present report summarizes the different results obtained in long-term studies, and in those comparing the effects of sterols and stanols on lipids and other surrogate markers of cardiovascular risk.

Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population.

The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets.

LDL sialic acid content in patients with coronary artery disease.

Low density lipoproteins (LDL) are considered to be the most atherogenic of lipoproteins. These LDL can be modified and oxidative modifications are now well known. In addition, other atherogenic modifications of LDL exist, such as desialylation. In the present study sialic acid content was determined in LDL preparations obtained from patients with coronary artery disease (CAD+) and compared with that of healthy subjects and patients without coronary heart disease (CAD-). The sialic acid concentration was found to be statistically lower (P < 0.05) in the LDL of CAD+ patients (11.6 +/- 2.7 micrograms/mg of protein) than in the LDL of controls (16.5 +/- 5.6 micrograms/mg of protein) or in the LDL of CAD- patients (15.3 +/- 3.8 micrograms/mg of protein). In subgroups of CAD+ patients divided according to the severity of the disease, no statistically significant difference was observed in LDL sialic acid content. This work confirms the presence of desialylated LDL in the sera of patients with atheroma.

Use of primary cultures of rat hepatocytes to predict toxicity in the early development of new chemical entities.

The new strategies for development of pharmacologically interesting compounds pose some limitations for standard toxicity assessment approaches due to: (1) increase in the number of compounds to be tested and (2) decrease in the amount of substance available for testing. In vitro methods are thus the only way to overcome such limitations. In this communication we present a cell-based model, using primary rat hepatocyte cultures, which we have validated using 23 compounds of the MEIC list as well as several Synthélabo proprietary products, covering a wide range of therapeutic indications. Our results show that our in vitro model gives a sufficient prediction for general toxicity by the oral route of administration (up to 2-4 weeks of treatment) in the rat to aid in decisions during early development. We also suggest that the comparative evaluation of the different parameters of cell toxicity examined may point to potential organ-related toxicity which could be further studied either with more complex in vitro or in vivo models. In conclusion, our results show that cell-based models for toxicity can be used for general screening purposes to predict in vivo toxicity in the early development of new chemical entities.

[Nutritional counseling for coronary and hypertensive patients]. / Le conseil nutritionnel chez le coronarien et l'hypertendu.

Nutritional recommendations constitute a major aspect of the long term management of coronary and hypertensive patients, for which the established evidence is more and more solid. The benefits are not limited solely to the impact on weight and lipid parameters. In coronary patients, besides the reduction in saturated fatty acids, which is always indicated, an increase in the intake of omega-3 fatty acids is associated with a significant reduction in morbidity and mortality, notably with sudden death. Intake of folates is also beneficial, as well as fruit and vegetable consumption. These elements are constituents of alimentary models such as the mediterranean diet. In hypertensives, weight reduction, limitation of alcohol and sodium intake, and increasing potassium and magnesium intakes have a demonstrable effect. Evaluation of patient compliance to nutritional recommendations is just as important as that of compliance to treatments and control of classic risk factors.

[Results of coronary-angiographic evaluation after endocavitary fulguration of the accessory pathways]. / Résultats d'un bilan angio-coronarographique de principe après fulguration endocavitaire des voies accessoires.

Left ventricular aid coronary angiography was performed systematically in 32 consecutive patients (average age 34 +/- 16 years) to assess the potential risk of coronary and myocardial lesions after high energy catheter ablation of an accessory pathway. The control was performed 2 to 6 months after the procedure in 30 patients and as an emergency immediately after the procedure in 2 patients because of prolonged ST segment elevation in 1 and an echocardiographic abnormality in the other. The catheter ablation was performed by a right heart approach in 19 patients and by retrograde catheterisation of the left heart in the other 13. The average number of shocks delivered was 3.6 +/- 2.4 in 1.8 +/- 1.2 session with an average energy of 632 +/- 220 joules. The global success rate was 88%, 70% complete successes and 18% clinical successes. The left ventricular and coronary angiographies were normal in 31 patients, including the 2 patients investigated as an emergency. On the other hand, one totally asymptomatic patient in whom a left lateral bundle of Kent had been ablated 2 months previously by a retrograde transaortic approach, had a large pseudo-aneurysm of the left ventricular posterior wall and coronary angiography showed a fistula between the first lateral branch of the circumflex artery and the left ventricle. At surgery, a localised rupture of the mitral annulus was confirmed. Two factors may at least partially explain this complication: the quantity of energy delivered (1,000 joules) in a single session to a limited area, and the site of ablation on the ventricular side of the mitral annulus.(ABSTRACT TRUNCATED AT 250 WORDS)

[Influence of exercise on the permeability of accessory pathways and supraventricular arrhythmia in Wolff-Parkinson-White syndrome]. / Influence de l'effort sur la perméabilité des voies accessoires et le comportement des arythmies supraventriculaires dans le syndrome de Wolff-Parkinson-White.

The influence of adrenergic stimulation on the effective anterograde refractory period of the accessory pathways and on supraventricular arrhythmias, was studied in 20 patients (average age 38 +/- 16 years) with an untreated permanent Wolff-Parkinson-White syndrome and a resting anterograde refractory period < or = 400ms. Repeated electrophysiological studies with a single endocavity catheter positioned near the atrial pole of the accessory pathway were performed under basal conditions and during a standardised exercise test on a bicycle ergometer. The effective anterograde refractory period of the accessory pathway, the length of the tachycardia cycle during reciprocating orthodromic tachycardia, the average heart rate, the percentage of preexcited QRS complexes during induced atrial fibrillation, were measured in all patients under basal conditions and at the peak of exercise. Exercise significantly reduced the anterograde refractory period of the accessory pathway (287 +/- 49 ms at rest versus 238 +/- 24 ms on exercise: p < 0.001), the cycle of orthodromic tachycardia (302 +/- 32 vs 260 +/- 22 ms p < 0.001), the minimal R-R interval (270 +/- 65 vs 227 +/- 46 ms: p < 0.05) and % of preexcited QRS complexes (75 +/- 33 vs 51 +/- 39: p < 0.05) in atrial fibrillation whilst increasing the average heart rate (165 +/- 42 vs 202 +/- 39 bpm: p < 0.02). Adrenergic stimulation significantly improves anterograde conduction in the accessory pathway. The reduction in the % of preexcited QRS complexes in atrial fibrillation could indicate a preferential action of catecholamines on the nodo-hisian pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

[Myocardial infarction and massive biventricular thrombosis during thrombocytopenia induced by pentosan polysulfate and heparin]. / Infarctus du myocarde et thrombose biventriculaire massive au cours d'une thrombopénie induite par le pentosane polysulfate et l'héparine.

Many cases of immuno-allergic thrombocytopenia complicated by serious thromboembolism induced by heparin or other heparinoids such as pentosan polysulphate have been reported. This case is of interest for two reasons: first of all, it was induced by pentosan polysulphate and then reactivated by secondary administration of heparin; secondly, it was complicated successively by an infero-apical myocardial infarction with probable spontaneous lysis of a coronary thrombosis because coronary arteriography performed one month later was normal, and then by massive biventricular thrombosis requiring surgical thrombectomy under cardiopulmonary bypass. Tests of platelet aggregation were positive to standard heparin and to several low molecular weight fractions. The outcome was favorable when the responsible substances were withdrawn.

[Benefits and limits of single chamber atrial pacing with adaptive rate]. / Bénéfices et limites de la stimulation monochambre auriculaire à fréquence asservie.

Twelve patients with isolated symptomatic sinus node dysfunction or bradycardia-tachycardia syndrome with atrial chronotropic incompetence during exercise testing were managed by single chamber rate responsive atrial pacing (AAIR) when AV conduction was normal, or by a dual chamber DDDR pacemaker programmed in the AAIR mode when AV conduction was abnormal, and followed up for 12.5 +/- 9.8 months. The patients were assessed clinically, by 3 monthly ECG and Holter recordings and comparative exercise tests in AAI and AAIR modes at the 6th month. One patient with an AAIR system was excluded at M21 because of symptomatic AV block requiring reimplantation of a DDD pacemaker. Ten of the 11 remaining patients are asymptomatic and have an excellent quality of life; one patient had invalidating symptoms on exercise attributed to the "AAIR pacemaker syndrome" which were corrected by reprogramming the pacemaker and modifying the medical therapy. The comparative exercise stress tests showed a significantly higher heart rate in the AAIR mode compared to AAI pacing at the initial and intermediate exercise levels (30 to 70 W); on the other hand, the heart rates were not significantly different at the highest exercise levels although in the AAI mode, the terminal acceleration sometimes occurred in junctional rhythm whereas it was usually an atrial paced rhythm in the AAIR mode. The total duration of exercise was longer in the AAIR mode (+22%; p less than 0.01) when the 8/11 patients with chronotropic incompetence during the baseline study were considered. The spike-R interval adapted normally to exercise in only one case: in the other patients, the interval remained constant or, in the worst of cases (N = 4), it increased paradoxically, to result in the "AAIR pacemaker syndrome": this phenomenon is observed mainly in patients treated by antiarrhythmics and/or betablockers. The AAIR mode would therefore seem to be a simple, effective and reliable method of treating patients with sinus node dysfunction and chronotropic incompetence; however, the failure of adaptation of the PR interval is a real limitation to its use and may constitute an argument in favour of the choice of a DDR pacemaker in these patients.

[Importance of atrioventricular synchrony in hypertrophic obstructive cardiomyopathy treated by cardiac pacing]. / L'importance du synchronisme auriculo-ventriculaire dans la cardiomyopathie hypertrophique obstructive traitée par stimulation cardiaque.

This study was undertaken to evaluate the effect of permanent dual-chamber cardiac pacing in hypertrophic obstructive cardiomyopathy resistant to medication, paying particular attention to atrioventricular synchrony. Sixteen patients, mean age 59 +/- 13 years (range 36 to 80 years) were divided into two groups after in initial catheter study performed under temporary VDD pacing between March 1990 and April 1993. In group I (n = 11), the gradient was decreased by more than 50% whereas in group II (n = 5), the gradient was unchanged or reduced by less than 50%. The reduction of the gradient was immediately significant in group I, the mean value falling from 104 +/- 33 mmHg (range 60 to 170 mmHg) to 25 +/- 13 mmHg (range 10 to 60 mmHg) (p < 0.0001). In group II, the gradient only decreased initially from 132 +/- 13 mmHg (range 120 to 150 mmHg) to 88 +/- 25 mmHg (range 50 to 130 mmHg) (p < 0.003) but improved atrioventricular synchrony, obtained secondarily either by pharmacological prolongation of the PR interval (association of betablocker and verapamil) or by ablation of the atrioventricular junction, improved the haemodynamic benefits. The residual gradient recorded on the 7th day was only 26 +/- 15 mmHg (range 10 to 50 mmHg) (p < 0.0001). The comparison of the two populations showed that the mean PR interval was shorter in group II (p < 0.016) and the mean value of the optimal AV Delay (the longest AV Delay with complete ventricular capture) was also lower (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension induced by repeated exposure to high sustained +Gz (HS + Gz) stress.

The purpose of this study was to determine whether repeated exposure to high sustained +Gz (HS + Gz) stress induced persistent changes in the functional state of the cardiovascular system. Three groups of rabbits--centrifuged, restrained, and control--were studied. After being placed in the restraining system of the centrifuge, the animals were submitted three times in a row to 8-9 +Gz sustained for 40 s. This exposure was repeated three times a week for 3-6 weeks. Restrained animals were not exposed to HS + Gz. Control animals were not restrained. The two types of stress (centrifuge + restraint; restraint alone) determined the appearance of two types of arterial hypertension. Systolic arterial pressure (AP) and left ventricular pressure (LVP) significantly increased in restrained animals. The function of the cardiovascular system was more perturbed in centrifuged rabbits since the significant changes affected not only systolic AP and LVP but alos systemic diastolic AP and the maximum rate of rise of LVP. The myocardium of rabbits repeatedly subjected to HS + Gz exposures, except for those that suffered a fracture of the lumbar spine, was significantly glycogen-depleted.