Blood lipids among young children in Europe: results from the European IDEFICS study.

BACKGROUND: Measurement of cholesterol and triglyceride (TG) fractions in blood has become standard practice in the early detection of atherosclerotic disease pathways. Considerable attention is given nowadays to the presence of these risk factors in children and to start preventive campaigns early in life. In this context, it is imperative to have valid comparative frameworks for interpretation of lipid levels. The aim of this study is to present sex- and age-specific reference values on blood lipid levels in European children aged 2.0-10.9 years. METHODS: Fasting blood was obtained via either venipuncture or capillary sampling. In 13,579 European non-obese children (50.3% boys), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), TG and TC/HDL-C ratio levels were measured with a point-of-care analyser (Cholestech). Sex- and age-specific reference values were computed with the GAMLSS method with the statistical software R. RESULTS: Reference curves and 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th and 99th percentile values are presented. HDL-C showed a positive trend with age, from 2 years onwards, but was relatively stable above the age of 7. For LDL-C and TC, linear but small age-related trends were seen. The TC/HDL-C values showed a gradual negative trend from the age of 2 up to 6 and were relatively stable afterwards. For TG, no age trend was found (P=0.285). Boys had higher mean HDL-C values than girls (1.414 vs 1.368 mmol l(-1)), and lower TC, LDL-C, TC/HDL-C and TG values (3.981 vs 4.087 mmol l(-1); 2.297 vs 2.435 mmol l(-1); 2.84 vs 3.01mmol l(-1); and 0.509 vs 0.542 mmol l(-1), respectively). CONCLUSIONS: These new and recent references could serve as a European orientation of blood lipid values in children in the context of standard medical practice and for the purpose of public health screening.

Dietary patterns and fatty acids levels of three European populations. Results from the IMMIDIET study.

BACKGROUND AND AIMS: Differences in blood fatty acids (FAs) profile among populations with different lifestyle have partly been attributed to differences in food intake. A holistic approach in dietary guidance through dietary patterns is essential. This study aimed at evaluating the main plasma and red blood cell (RBC) FAs in three European populations and assessing the role of dietary patterns in explaining variation in their levels. METHODS: In the framework of the IMMIDIET Project, 1604 subjects (802 male-female pairs) aged 26-65 years were enrolled in Italy, Belgium and UK. Plasma and RBC FAs were measured. One year recall food frequency questionnaires were used to evaluate dietary habits of each individual. RESULTS: Italian cohort showed lower plasma and RBC n-3 levels than participants of the other two populations (P<0.001). Both plasma and RBC arachidonic acid were higher in Italian cohort as compared to Belgian and English. Reduced rank regression analysis indicated two dietary patterns explaining 35% and 17% of the total variation of the sum of plasma and RBC n-3, respectively. In a holistic dietary analysis, neither fish nor mollusks intake seemed to contribute to n-3 variation as compared to vegetable oils and polyphenol-rich foods. CONCLUSION: The Italian cohort presented significant lower plasma and RBC n-3 FA levels compared to Belgians and English. A holistic approach in dietary analysis seemed to explain a relatively high proportion of plasma and RBC n-3 FAs variability. Dietary pattern analysis may contribute to the study of the association of human diet with FAs levels.

Gender differences in copper, zinc and selenium status in diabetic-free metabolic syndrome European population - the IMMIDIET study.

BACKGROUND AND AIMS: The European 'IMMIDIET' study was designed to evaluate the effect of genetic and dietary habit interactions on cardiovascular disease risk factors in non-diabetic subjects. Copper, zinc and selenium are involved in redox balance and modifications of their homeostasis could be associated with metabolic syndrome. Because few studies have dealt with trace element status in metabolic syndrome with conflicting results, we aimed at investigating the relationships between plasma copper, zinc and selenium concentrations and metabolic syndrome in the IMMIDIET population. METHODS AND RESULTS: Male-female couples born and living in Abruzzo, Italy (n = 271); Limburg, Belgium (n = 267), southwest part of London, England (n = 263) and 205 Italian-Belgian mixed couples living in Belgium were enrolled. Data on medical history, hypertension and blood lipid profile, medication use, smoking and alcohol habits, physical activity and socioeconomic status were collected using a standardised questionnaire. Anthropometric, blood pressure, glucose, insulin, lipid profile and copper, zinc and selenium measurements were performed. Participants were classified in two groups according to the presence of metabolic syndrome (Yes/No). Comparison between these two groups, performed separately in men and women, indicated no association in men whereas, in women, metabolic syndrome was associated with higher plasma selenium concentrations (odds ratio (OR) = 1.55(1.28-1.89)); this association remained significant after adjustment for age, group, social status, physical activity, energy intake, alcohol consumption, smoking and hormonal status (OR = 1.33 (1.06-1.67)). CONCLUSION: Our results indicate gender differences in the association between plasma selenium concentration and metabolic syndrome without diabetes and may suggest a sub-clinical deleterious effect of high selenium status in women.

Effects of dietary supplementation with alpha-tocopherol on myocardial infarct size and ventricular arrhythmias in a dog model of ischemia-reperfusion.

OBJECTIVES: We investigated whether dietary supplementation with the antioxidant vitamin alpha-tocopherol (500 mg daily) might reduce lethal ventricular arrhythmias and infarct size. BACKGROUND: Previous studies suggested that dietary supplementation with alpha-tocopherol may be associated with a reduced risk of ischemic heart disease. However, the mechanism of this protection remains unknown. METHODS: Beagle dogs were randomized to either a supplemented or a control group. Because of the low mortality rate in the supplemented group, five dogs were added to the control group. After 2 months, dogs were anesthetized and underwent a 2-h coronary artery occlusion and 6-h reperfusion. Plasma vitamin E, retinol and malondialdehyde concentrations were assessed in all dogs. RESULTS: Fourteen dogs (11 of 25 control vs. 3 of 19 supplemented dogs, p < 0.05) developed ventricular fibrillation during either ischemia or reperfusion. Malondialdehyde concentrations were higher in dogs that subsequently developed arrhythmias (2.7 +/- 0.2 mumol/liter, mean +/- SEM) compared with dogs that did not (2.1 +/- 0.2 mumol/liter, p = 0.03). Among survivors with significant ischemia, infarct size was larger in supplemented (n = 12, 58.5 +/- 3.3% of area at risk) than in control (n = 11, 41.9 +/- 6.5%, p < 0.04) dogs. In addition, for a given collateral flow, supplemented dogs (n = 16) developed larger infarct size than control dogs (n = 15, p < 0.001, analysis of covariance). CONCLUSIONS: The data suggest that dietary alpha-tocopherol supplementation prevented lethal ventricular arrhythmias associated with ischemia and reperfusion. However, its influence on infarct size and long-term prognosis warrants further investigation.

Effect of a mediterranean type of diet on the rate of cardiovascular complications in patients with coronary artery disease. Insights into the cardioprotective effect of certain nutriments.

OBJECTIVES: We sought to describe the various cardiovascular complications that occurred in the Lyon Diet Heart Study (a secondary prevention trial testing the protective effects of a Mediterranean type of diet), to analyze their relations with the associated drug treatments and to gain insights into the possible mechanisms underlying the beneficial effects of certain nutriments. BACKGROUND: Dietary habits are implicated in coronary heart disease, and the traditional Mediterranean diet is thought to be cardioprotective. However, the exact mechanisms of this protection are unknown. METHODS: A total of 605 patients (303 control subjects and 302 study patients) were studied over a mean period of 27 months. Major primary end points (cardiovascular death and nonfatal acute myocardial infarction), secondary end points (including unstable angina, stroke, heart failure and embolisms) and minor end points (stable angina, need for myocardial revascularization, postangioplasty restenosis and thrombophlebitis) were analyzed separately and in combination. RESULTS: When major primary and secondary end points were combined, there were 59 events in control subjects and 14 events in the study patients, showing a risk reduction of 76% (p < 0.0001). When these end points were combined with the minor end points, there were 104 events in control subjects and 68 events in the study patients, giving a risk reduction of 37% (p < 0.005). By observational analysis, only aspirin among the medications appeared to be significantly protective (risk ratio after adjustment for prognosis factors 0.45; 95% confidence interval 0.25 to 0.80). CONCLUSIONS: These data show a protective effect of the Mediterranean diet. However, the risk reduction varied depending on the type of end point considered. Our hypothesis is that different pathogenetic mechanisms were responsible for the development of the various complications. It is likely that certain nutriments characteristic of the Mediterranean diet (omega-3 fatty acids, oleic acid antioxidant vitamins) have specific cardioprotective effects.

Mediterranean dietary pattern in a randomized trial: prolonged survival and possible reduced cancer rate.

BACKGROUND: The Mediterranean dietary pattern is thought to reduce the risk of cancer in addition to being cardioprotective. However, no trial has been conducted so far to prove this belief. METHODS: We compared overall survival and newly diagnosed cancer rate among 605 patients with coronary heart disease randomized in the Lyon Diet Heart Study and following either a cardioprotective Mediterranean-type diet or a control diet close to the step 1 American Heart Association prudent diet. RESULTS: During a follow-up of 4 years, there were a total of 38 deaths (24 in controls vs 14 in the experimental group), including 25 cardiac deaths (19 vs 6) and 7 cancer deaths (4 vs 3), and 24 cancers (17 vs 7). Exclusion of early cancer diagnoses (within the first 24 months after entry into the trial) left a total of 14 cancers (12 vs 2). After adjustment for age, sex, smoking, leukocyte count, cholesterol level, and aspirin use, the reduction of risk in experimental subjects compared with control subjects was 56% (P=.03) for total deaths, 61% (P=.05) for cancers, and 56% (P=.01) for the combination of deaths and cancers. The intakes of fruits, vegetables, and cereals were significantly higher in experimental subjects, providing larger amounts of fiber and vitamin C (P<.05). The intakes of cholesterol and saturated and polyunsaturated fats were lower and those of oleic acid and omega-3 fatty acids were higher (P<.001) in experimental subjects. Plasma levels of vitamins C and E (P<.05) and omega-3 fatty acids (P<.001), measured 2 months after randomization, were higher and those of omega-6 fatty acids were lower (P<.001) in experimental subjects. CONCLUSIONS: This randomized trial suggests that patients following a cardioprotective Mediterranean diet have a prolonged survival and may also be protected against cancer. Further studies are warranted to confirm the data and to explore the role of the different lipids and fatty acids in this protection.

Lignocaine in experimental myocardial infarction: failure to prevent neutrophil accumulation and ventricular fibrillation and to reduce infarct size.

Growing evidence supports the concept that neutrophils accumulating in reperfused ischaemic myocardium play a detrimental role in evolving infarction. Lignocaine, an antiarrhythmic drug commonly used clinically, interferes with neutrophil function in vitro and potentially in vivo. To test the hypothesis that lignocaine may influence infarct size by reducing neutrophil accumulation in reperfused ischaemic myocardium, 31 dogs underwent a 2 h occlusion of the left anterior descending coronary artery, followed by 6 h of reperfusion. One group of dogs received saline (controls) the other a perfusion of lignocaine 0.06 mg.kg-1.min-1 starting 30 min before coronary occlusion and lasting for the duration of the experiment. Blood lignocaine concentrations at the onset of reperfusion were 3.3(0.6) micrograms.ml-1. 111Indium labelled autologous neutrophils were injected at the time of occlusion and their accumulation in the myocardium measured by digital scintigraphy of heart slices. The area at risk and infarct size were evaluated by planimetry of the heart slices (7 mm) after perfusion of Evans blue dye and triphenyltetrazolium staining. Ventricular fibrillation occurred in six controls and in five dogs receiving lignocaine. The phenomenon occurred early during the occlusion period in the lignocaine group (five dogs) and at reperfusion in controls (five dogs; p less than 0.05). In the remaining 20 dogs, 10 in each group, a linear correlation was found between myocardial 111In labelled neutrophil and circulating neutrophil counts at the onset of reperfusion (r = 0.076, p less than 0.05) and with infarct size (r = 0.96 and 0.74, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute myocardial infarction in dogs with experimental diabetes.

OBJECTIVE: The aim was to examine whether diabetes interferes with the development of myocardial injury in a canine ischaemia-reperfusion model. METHODS: Non-insulin-requiring diabetes was induced in dogs by the streptozotocin-alloxan method. After 75 d, the dogs were anaesthetised and myocardial infarction was provoked by occluding the left anterior descending coronary artery for 2 h followed by 6 h reperfusion. RESULTS: Diabetic dogs had higher blood glucose [9.4(SEM 1) mmol.litre-1], fructosamine [417(57) mumol.litre-1], and glycated haemoglobin [3.3(0.7)%], than control dogs [5.5(0.6), p = 0.04, 243(15), p = 0.01, and 0.7(0.2), p = 0.003, respectively], and they also had higher serum lipids (p = 0.001) and platelet aggregation (p = 0.03). Area at risk was similar in diabetic and control dogs but in contrast to controls (r = 0.78, p = 0.007), area at risk and infarct size were not correlated in diabetics (r = 0.08). In both groups, collateral flow was the major determinant of infarct size: r = -0.73 in controls (p = 0.02) and -0.97 in diabetics (p = 0.001). In spite of higher subendocardial collateral flow in diabetics [representing 21.6(6)% of the flow in the corresponding non-ischaemic zone] than in controls [11.2(6)%], infarct size was similar in both groups. However, the mean observed infarct size in the diabetic group [7.5(2.8)% of the left ventricle] was significantly (p < 0.03) larger than the mean predicted infarct size [5.2(2)%]. Multivariate analysis confirmed that diabetes, as well as collateral flow, is an independent (p = 0.03) predictor of infarct size. CONCLUSIONS: For a given collateral flow, diabetic dogs develop larger infarcts than controls. Further studies are required to investigate the biochemical mechanism(s) underlying this deleterious effect. However, this may partly explain the poor prognosis of myocardial infarction in diabetic persons.

Influence of reflow ventricular fibrillation and electrical defibrillation on infarct size in a canine preparation of myocardial infarction.

STUDY OBJECTIVE - The aim of the study was to investigate the influence of reflow ventricular fibrillation and electrical defibrillation on infarct size in a model of myocardial ischaemia. DESIGN - Myocardial ischaemia was induced in an open chest canine model by occluding the left coronary artery for 2 h. This was followed by 6 h reperfusion. The influence of reflow fibrillation and internal electric defibrillation on infarct size was investigated and compared to dogs which did not develop fibrillation. Infarct size and its major determinants, rate-pressure product (RPP), area at risk (AR), and collateral flow (MBF), were measured and their relationships studied in the two situations, using uni- and multilinear regression analysis. SUBJECTS - 21 adult mongrel dogs of either sex were used in the studies, which were done under pentobarbitone anaesthesia. Two were excluded because they developed ventricular fibrillation soon after coronary occlusion, and one did not survive reflow ventricular fibrillation. Of the remaining 18 dogs, six developed reflow ventricular fibrillation and were compared to the control group of 12 which did not develop fibrillation. MEASUREMENTS and RESULTS - A mean of 70.8(SEM 18.7) joules was required to revive the six dogs with reflow ventricular fibrillation. Difference in mean infarct size in the two groups did not reach significance [49.1(4.4) in fibrillation group v 38(6.2) in the controls]. The multiple linear regression model in the control group accounted for 91% of the variation in infarct size (IS): IS = -3.4 + 0.49 (AR) -21.8 (MBF) + 0.025 (RPP). The equation was not modified by including the reflow fibrillation dogs: IS = -3.1 + 0.52 (AR) - 19 (MBF) + 0.02 (RPP). Ischaemic determinants of infarct size in the reflow fibrillation dogs were computed in the control group equation to compare the infarct size predicted by the model to the measured infarct size in each individual dog in the reflow fibrillation group. There was no significant difference between the means: 12.9(2.9)% (predicted) v 14.9(2.5)% (measured). CONCLUSIONS - In this model of myocardial infarction, reflow ventricular fibrillation and low energy internal electric shocks do not damage the myocardium at risk significantly.

Cretan Mediterranean diet for prevention of coronary heart disease.

As a result of the Seven Countries Study, the Mediterranean diet has been popularized as a healthy diet. Nevertheless, it has not replaced the prudent diet commonly prescribed to coronary patients. Recently, we completed a secondary, randomized, prospective prevention trial in 605 patients recovering from myocardial infarction in which we compared an adaptation of the Cretan Mediterranean diet with the usual prescribed diet. After a mean follow-up period of 27 mo, recurrent myocardial infarction, all cardiovascular events, and cardiac and total death were significantly decreased by > 70% in the group consuming the Mediterranean diet. These protective effects were not related to serum concentrations of total, low-density-lipoprotein (LDL), or high-density-lipoprotein (HDL) cholesterol. In contrast, protective effects were related to changes observed in plasma fatty acids: an increase in n-3 fatty acids and oleic acid and a decrease in linoleic acid that resulted from higher intakes of linolenic and oleic acids, but lower intakes of saturated fatty acids and linoleic acid. In addition, higher plasma concentrations of antioxidant vitamins C and E were observed. We conclude that a Cretan Mediterranean diet adapted to a Western population protected against coronary heart disease much more efficiently than did the prudent diet. Thus, it appears that the favorable life expectancy of the Cretans could be largely due to their diet.

High prevalence of thromoembolic complications in heart transplant recipients. Which preventive strategy.?

Consecutive patients transplanted between January 1984 and December 1988 were followed until August 1992 to detect fatal and nonfatal thromboembolic complications, including sudden death, acute and chronic myocardial infarction, pulmonary and peripheral embolisms, stroke, and thrombophlebitis. The probability of developing such complications was 9.86 per 100 patients per year. The probability of fatal complications was 3.97% per year; the mean interval between transplant and death was 1247 days versus 29.5 days for nonthromboembolic deaths. Thromboembolic deaths represented 5.1% of total mortality at the first year posttransplant but 57, 30, 67 and 73% at the second, third, fourth, and fifth years, respectively. Among the prognosis factors that were analyzed, none was significant predictor of thromboembolic complication. This high prevalence of thromboembolic complications suggests that effective antithrombotic strategy should be defined in heart transplant recipients.

The beneficial effect of dietary antioxidant supplementation on platelet aggregation and cyclosporine treatment in heart transplant recipients.

To determine whether dietary antioxidant supplementation can reduce platelet reactivity in heart transplant recipients, 20 patients were prospectively randomized to receive either 500 IU vitamin E orally per day in the form of acetate for 2 months or no vitamin E. Blood creatinine (P = 0.01) and lymphocyte count (P = 0.009) significantly decreased only in supplemented patients, whereas the cyclosporine blood level was not modified. Platelet aggregation was stable in control patients but significantly decreased in supplemented patients in response to either thrombin (from 8.3 +/- 0.9% of maximum aggregation to 3.7 +/- 0.7, P = 0.001) or ADP (secondary wave: from 44.7 +/- 5.9% to 33.2 +/- 7.0, P = 0.02). Thus antioxidant supplementation tended to improve immunosuppression (by reducing lymphocyte count), to reduce cyclosporine nephrotoxicity, and to decrease the high thrombotic risk associated with heart transplantation.

Quantitation of reperfused myocardial infarction by Gd-DOTA-enhanced magnetic resonance imaging. An experimental study.

Because there is evidence that myocardial infarct size is modified by coronary artery reperfusion, an ex vivo experimental model of myocardial infarction was developed to determine the influence of the timing of gadolinium-tetraazacyclododecane tetraacetic acid (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) on the accuracy of infarct size quantitation. Eighteen dogs underwent a 2-hour coronary occlusion followed by 1 (n = 6), 6 (n = 6), or 48 (n = 6) hours of reperfusion. Gd-DOTA was injected 10 minutes before the dogs were killed. T1 (SE 250/26) and T2 (SE 1500/78) weighted images were performed on excised hearts. Gd-DOTA concentration was measured in myocardium by atomic emission spectrometry, and correlated with myocardial blood flow evaluated by radioactive microspheres. All dogs presented with myocardial infarction (mean size 20.4% +/- 3.1% of the left ventricle), and a corresponding area of increased signal intensity on T1-weighted MR images. In none of the three groups did the area of high signal intensity correlate with the ischemic area. By contrast, after 6 and 48 hours of reperfusion, the high signal intensity area (17.9% +/- 2.4%) closely matched the area of nonreversible jeopardized tissue (16.4% +/- 2.5%), as determined on tetrazolium-stained heart slices. Although a noreflow phenomenon was observed in the jeopardized tissue, Gd-DOTA concentration was higher in the subendocardial central ischemic zone than in normally perfused myocardium. Gd-DOTA imaging enhancement seems to be the consequence of a delayed clearance of the agent from the injured tissue. Gd-DOTA-enhanced MRI accurately quantitates the size of reperfused myocardial infarction on the ex vivo heart for more than 6 hours after the beginning of reperfusion. It remains to be determined whether the in vitro results obtained here can be applied to assess the myocardial infarct size in vivo.

Dietary and blood antioxidants in patients with chronic heart failure. Insights into the potential importance of selenium in heart failure.

BACKGROUND: Chronic heart failure (CHF) seems to be associated with increased oxidative stress. However, the hypothesis that antioxidant nutrients may contribute to the clinical severity of the disease has never been investigated. AIMS: To examine whether antioxidant nutrients influence the exercise capacity and left ventricular function in patients with CHF. METHODS: Dietary intake and blood levels of major antioxidant nutrients were evaluated in 21 consecutive CHF patients and in healthy age- and sex-matched controls. Two indexes of the severity of CHF, peak exercise oxygen consumption (peak VO2) and left ventricular ejection fraction (LVEF), were measured and their relations with antioxidants were analysed. RESULTS: Whereas plasma alpha-tocopherol and retinol were in the normal range, vitamin C (P=0.005) and beta-carotene (P=0.01) were lower in CHF. However, there was no significant association between vitamins and either peak VO2 or LVEF. Dietary intake (P<0.05) and blood levels of selenium (P<0.0005) were lower in CHF. Peak VO2 (but not LVEF) was strongly correlated with blood selenium: r=0.76 by univariate analysis (polynomial regression) and r=0.87 (P<0.0005) after adjustment for age, sex and LVEF. CONCLUSIONS: Antioxidant defences are altered in patients with CHF. Selenium may play a role in the clinical severity of the disease, rather than in the degree of left ventricular dysfunction. Further studies are warranted to confirm the data in a large sample size and to investigate the mechanisms by which selenium and other antioxidant nutrients are involved in CHF.

Increased platelet aggregation after heart transplantation: influence of aspirin.

Accelerated graft coronary artery disease remains the most dramatic complication in long-term survivors of heart transplantation. The main purpose of this study was to evaluate ex vivo platelet function of heart transplant recipients as compared with that of healthy subjects and nontransplant coronary patients. The influence of aspirin, the chief antiplatelet agent, was also evaluated. The heart transplant recipients exhibited a marked platelet hyperaggregation to adenosine diphosphate as compared with the two control groups. In addition, platelets of the heart transplant recipients appeared to be resistant to the inhibitory effect of aspirin. These results could, at least partly, explain the failure of antiplatelet agents to prevent myocardial infarction in these patients.

Control of bias in dietary trial to prevent coronary recurrences: The Lyon Diet Heart Study.

BACKGROUND AND OBJECTIVES: A major limitation of dietary trials is that double blind design is not feasible. These trials are therefore prone to biases. The Lyon diet heart study is a single-blind secondary prevention trial to test the hypothesis that a Mediterranean-type of diet may prevent recurrences after a first myocardial infarction. A surprising 73% reduction of the risk of new major cardiac events was observed in the experimental group. For this reason, it is important to describe the methods used in the trial. We now report our techniques to randomize the patients, to change their diet and to control for possible bias, in particular any investigator or attending physician bias. DESIGN: In this dietary trial, a specific design was used to recruit and randomize the patients without informing them and their physicians that they were participating in a comparative trial. The attending physician bias was evaluated by studying drug usage and the investigator bias by constructing a questionnaire from which specific scores were used to evaluate (1) how the patients appreciated their participation in the study and (2) whether this participation resulted in significant changes in their way of living. SUBJECTS: 605 survivors of a first myocardial infarction were randomized into either a control or a Mediterranean group. RESULTS: The two randomized groups were similar for all the variables of prognosis. Drug usage was not significantly different between groups, suggesting that there was no major attending physician bias. Analyses of the appreciation scores and of the change score did not detect any significant investigator bias. CONCLUSIONS: Although the study cannot be completely shielded from minor biases, the data presented here provide evidence that the dietary modifications per se were protective, not other (including psychosocial) changes resulting from the participation to the trial.

Increased production of reactive oxygen species in pharmacologically-immunosuppressed patients.

HIV-infected patients and transplanted patients share similar immunosuppressed status. Recent insights gained through the field of heart transplantation may help to clarify the role of reactive oxygen species in HIV-infected patients.

Superparamagnetic iron oxide particles and positive enhancement for myocardial perfusion studies assessed by subsecond T1-weighted MRI.

Superparamagnetic iron oxide particles (SPIOs) are usually referred to as T2 MR contrast agents, reducing signal intensity (SI) on T2-weighted MR images (negative enhancement). This study reports the original use of SPIOs as T1-enhancing contrast agents, primarily assessed in vitro, and then applied to an in vivo investigation of a myocardial perfusion defect. Using a strongly T1-weighted subsecond MR sequence with SPIOs intravenous (IV) bolus injection, MR imaging of myocardial vascularization after reperfusion was performed, on a dog model of coronary occlusion followed by reperfusion. Immediately after the intravenous bolus injection of 20 mumol/kg of SPIOs, a positive signal intensity enhancement was observed respectively, in the right and left ventricular cavity and in the nonischemic left myocardium. Moreover, compared to normal myocardium, the remaining ischemic myocardial region (anterior wall of the left ventricle) appeared as a lower and delayed SI enhancing area (cold spot). Mean peak SIE in the nonischemic myocardium (posterior wall) was significantly higher than in the ischemic myocardium (anterior wall) (110 +/- 23% vs. 74 +/- 22%, Mann-Whitney test alpha < 1%, n1 = 6, n2-n1 = 0, U > 2). In conclusion, the T1 effect of SPIOs at low dose, during their first intravascular distribution, suggests their potential use as positive markers to investigate the regional myocardial blood flow and some perfusion defects such as the "no-reflow phenomenon."

Effect of dietary cholesterol on low density lipoprotein-receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and low density lipoprotein receptor-related protein mRNA expression in healthy humans.

We investigated the possibility that dietary cholesterol downregulates the expression of low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase genes of circulating mononuclear cells in vivo in healthy humans. We also studied the variations of the LDL receptor-related protein (LRP) gene in the same conditions. Dieters (n = 5) were submitted to a 4-d fat restriction (mean cholesterol intake: 6+/-4 mg/d), followed by a 7-d cholesterol (a mean of 791+/-150 mg/d) supplementation. Controls (n = 3) did not change their diet. During fat restriction, serum total and LDL cholesterol decreased significantly (P < 0.05), and LDL receptor and HMG-CoA reductase mRNA copy numbers in mononuclear cells increased by 57 and 147%, respectively (P < 0.05). After reintroducing cholesterol, serum cholesterol was stable whereas LDL receptor and HMG-CoA reductase mRNA decreased by 46 and 72% (P < 0.05) and LRP mRNA increased by 59% (P < 0.005). The changes in LDL receptor and HMG-CoA reductase mRNA abundance were correlated (r = +0.79, P = 0.02) during cholesterol reintroduction as were LDL receptor and LRP mRNA levels, but negatively (r = -0.70, P = 0.05). Also, 70% of the variability in LRP mRNA (P < 0.005) was explained by dietary cholesterol. Thus, the basic mechanisms regulating cellular cholesterol content, the coordinate feedback repression of genes governing the synthesis and uptake of cholesterol, are operating in vivo in humans. However, serum cholesterol did not increase in response to dietary cholesterol, suggesting that these mechanisms may not play as predominant a role as previously believed in the short-term control of serum cholesterol in vivo in humans. A new finding is that LRP gene is also sensitive to dietary cholesterol, suggesting that it may participate in the control of serum cholesterol. Further in vivo studies in humans are warranted to explore the molecular mechanisms of the physiological response to dietary cholesterol in humans.

[Oxidative stress and lipid-protein peroxidation after cardiac transplantation. New hypotheses for explaining pathogenesis of accelerated forms of ischemic heart disease]. / Stress oxydatif et peroxydation lipido-protéique après transplantation cardiaque. Nouvelles hypothèses pour expliquer la pathogenèse des formes accélérées de cardiopathie ischémique.

The ischaemic heart disease developed by cardiac transplant patients is characterised by its rapid onset, which accounts for a number of its special features when compared with the usual form observed in non-immunosuppressed patients. However, the two forms of the disease are basically similar, that of the transplanted patients being practically a caricature of the non-immunosuppressed patients and thereby allowing a quasi-experimental model for the study of the metabolic causes of the disease which remains the leading cause of death in the world, all ages and sexes included, irrespective of the economic wealth of the countries.