Search PubMed⌕ Search

Biomedical subjects

S Renaud

Publications and source records attributed to S Renaud.

At least 55 records · Page 3Linked to original sources
PubMed1993

Accelerated coronary artery disease after heart transplantation: the role of enhanced platelet aggregation and thrombosis.

The present study is a prospective examination of the relationship between platelet aggregation and the occurrence of graft failure in a single cohort of heart transplantation (HT) recipients. One-hundred-and-twenty-four patients underwent platelet function study and were then followed for 1 to 24 months (mean 6.7 months). There were nine re-transplantations and 13 deaths (11 related to ischaemic events, and two others). In 15 patients, pathologic examination confirmed or revealed that recent acute myocardial infarction was the obvious cause of the graft failure. In five patients, myocardial fibrosis related to severe and diffuse coronary disease was the only microscopic finding. In the last two patients, the cause of the heart failure was not clearly identified. In recent myocardial infarction there was a high incidence (14/15) of coronary thrombi. Thrombi were multiple, disseminated in the coronary tree end of different age. Their presence at autopsy or after explantation was associated with an enhanced ex vivo platelet aggregability as compared with patients without coronary thrombi (n = 8): 43.3 +/- 1.7% of maximal aggregation vs. 34.4 +/- 2.4 (P = 0.006) and 48.4 +/- 5.2 vs. 22.6 +/- 4.9 (P = 0.003) for the primary and secondary waves of ADP-induced aggregation. These results suggest that thrombosis and platelets may play a major role in the process of accelerated coronary artery disease after HT.

Adult↗
PubMed1993

Temperature and risk factors for ischaemic heart disease in the Caerphilly prospective study.

OBJECTIVE: To examine the associations between air temperature and risk factors for ischaemic heart disease. METHOD: Data on risk factors are available from up to 2036 men in the Caerphilly Prospective Heart Disease Study. Daily temperatures were obtained from the Meteorological Office. Relations between these were examined by regression. RESULTS: The coldest month of the year has a mean temperature that is 16 degrees C lower than that in the warmest month. A fall in temperature of this magnitude is associated with higher blood pressures (by 3-5 mm Hg) and a lower concentration of high density lipoprotein cholesterol (by 0.08 mmol/l). The most important effects however, seem to be on the haemostatic system. Fibrinogen is 0.34 g/l higher in the coldest month than in the warmest (p < 0.001) and alpha 2 macroglobulin, a protein that inhibits fibrinolysis, is also raised. Platelet count is increased by 30% of a standard deviation and the sensitivity of platelets in whole blood to adenosine diphosphate is increased by cold. CONCLUSIONS: These effects on haemostasis, together with the effect on blood pressure, could explain a large part of the increase in ischaemic heart disease in the winter but are unlikely to explain much of the difference in mortality within different areas of England and Wales.

Adenosine Diphosphate↗
PubMed1992

[Hemostatic anomalies and coronary risk].

The main role of thrombosis in the acute coronary event is now well documented. Numerous hemostatic factors are involved in thrombosis. Among them, fibrinogen, factor VII, leucocytes and platelets have been shown by epidemiology, to be closely related to the acute coronary event. The key role seems to be reserved to platelets since the close relationship of their activity as evaluated by platelet aggregation tests, to both coronary episodes and the main risk factors such as smoking, diabetes and dietary habits, has been recently demonstrated. In addition, the role of platelets has been confirmed by the marked protective effect against coronary events, of drugs such as aspirin, inhibiting platelet aggregation.

Blood Coagulation Disorders↗
PubMed1992

Wine, alcohol, platelets, and the French paradox for coronary heart disease.

In most countries, high intake of saturated fat is positively related to high mortality from coronary heart disease (CHD). However, the situation in France is paradoxical in that there is high intake of saturated fat but low mortality from CHD. This paradox may be attributable in part to high wine consumption. Epidemiological studies indicate that consumption of alcohol at the level of intake in France (20-30 g per day) can reduce risk of CHD by at least 40%. Alcohol is believed to protect from CHD by preventing atherosclerosis through the action of high-density-lipoprotein cholesterol, but serum concentrations of this factor are no higher in France than in other countries. Re-examination of previous results suggests that, in the main, moderate alcohol intake does not prevent CHD through an effect on atherosclerosis, but rather through a haemostatic mechanism. Data from Caerphilly, Wales, show that platelet aggregation, which is related to CHD, is inhibited significantly by alcohol at levels of intake associated with reduced risk of CHD. Inhibition of platelet reactivity by wine (alcohol) may be one explanation for protection from CHD in France, since pilot studies have shown that platelet reactivity is lower in France than in Scotland.

Adult↗
PubMed1992

Pharmacokinetics of cyclosporine in hyperlipidaemic long-term survivors of heart transplantation. Lack of interaction with the lipid-lowering agent, fenofibrate.

Cyclosporine (Cy) binds to lipoproteins in plasma. In order to test if its pharmacokinetics would be modified when efficient lipid-lowering treatment is introduced, a study has been done of Cy pharmacokinetics and any interaction with the lipid-lowering agent fenofibrate in hyperlipidaemic long-term, survivors of heart transplantation. Fenofibrate 200 mg once daily significantly reduced blood lipids (cholesterol 6.5 vs 7.7 mmol/l; apoprotein B 1.2 vs 1.6 g/l) but did not modify mean whole blood Cy trough levels (113 before fenofibrate vs 103 ng.ml-1), Cmax (812 ng.ml-1 by RIA and 757 ng.ml-1 by HPLC before fenofibrate versus 865 and 741 respectively, during fenofibrate); tmax (1.6 and 1.7 h before fenofibrate versus 1.4 and 1.4 h respectively), and t1/2 (13.9 and 11.1 h versus 9.5 and 10.7 h). The only adverse effect was an increase in creatinine (157 vs 145 mmol/l). Further studies are needed to investigate the mechanism of Cy-fenofibrate nephrotoxicity and to evaluate the long-term efficiency and safety of fenofibrate after heart transplantation.

Adult↗
PubMed1992

Effect of D-myo-inositol on platelet function and composition and on cataract development in streptozotocin-induced diabetic rats.

Diabetes is known to be associated with an increase in aldose reductase activity, platelet hyperaggregability, lipid peroxidation, and cataract formation. A molecule, D-myo-inositol 1,2,6-trisphosphate (PP-56), derived from phytic acid, could in principle, by supplying myoinositol to tissues and acting as an antioxidant, counteract some of the manifestations of diabetes. Thus, the effects of PP-56 on platelet aggregation, fatty acids, and polyols were investigated in uncontrolled streptozotocin-induced diabetes in rat in relation to cataract and lipid peroxidation. A decrease in the response of platelet aggregation to thrombin and ADP (P less than 0.05, P less than 0.001) and in the level of sorbitol and the ratio sorbitol/myo-inositol (P less than 0.01) in platelets was observed in the rats treated by PP-56 for 7-8 weeks. These beneficial effects were associated with an incidence of cataract reduced by 26 to 44% (P less than 0.05 to P less than 0.001) depending on the duration of treatment. They were also accompanied by a significant lower plasma level of malondialdehyde (P less than 0.05), and, more markedly, of conjugated dienes (P less than 0.001) as well as an increase in platelet lipids of the 20:4(n-6)/20:3(n-6) ratio, an index of delta 5 desaturase activity. PP-56 appears to modulate fatty acid desaturases and aldose reductase in platelets and delay by a few weeks the development of cataract in this acute model of diabetes.

Animals↗
PubMed1992

Importance of the flow perfusion deficit in the response to captopril in experimental myocardial infarction.

Previous results on the effects of angiotensin-converting enzyme (ACE) inhibition in myocardial ischemia are conflicting. To determine whether acute ACE inhibition may influence myocardial perfusion deficit during ischemia and reduce ischemia-reperfusion injury, anesthetized open-chest dogs underwent 2-h left anterior descending coronary artery (LAD) occlusion followed by 6-h reperfusion. After 1-h coronary occlusion, each dog was randomized to receive either captopril [5 mg/kg intravenous (i.v.) bolus and 0.25/kg/h infusion for 7 h] or saline. Whereas arterial pressure was reduced (p = 0.001), captopril did not influence myocardial perfusion deficit: Blood flow in the central ischemic zone represented 17.1 +/- 2.8% of the flow in the nonischemic zone versus 20.5 +/- 3.8% before treatment (NS). The values of the control group were 17.8 +/- 2.5 and 16.7 +/- 2.4%, respectively. In addition, there was no difference in infarct size: 35.9 +/- 3.3% of the area at risk in captopril-treated dogs versus 40.0 +/- 3.6% in controls. Analysis of subgroups based on the level of the collateral flow indicated, however, that ACE inhibition had an adverse effect on infarct size in dogs with high collateral flow: 31.9 +/- 4.6% in captopril dogs versus 17.6 +/- 4.7 (p = 0.048). This effect was related to a decrease in collateral flow because animals exhibiting the highest increase in perfusion deficit presented the greatest increase in infarct size (r = -0.92, p = 0.003). Although in dogs with low collateral flow, ACE inhibition appeared to exert a slight beneficial effect on infarct size, we conclude that at least in this dog model, acute ACE inhibition could exacerbate myocardial injury.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Platelet function and composition in heart transplant recipients compared with nontransplanted coronary patients.

Accelerated coronary artery disease seems to be the main condition limiting long-term survival after heart transplantation. Ninety-one heart transplant recipients were compared with 94 nontransplanted coronary artery disease patients in an attempt to identify the factors responsible for the accelerated form of coronary artery disease occurring after heart transplantation. Among the parameters examined, heart transplant recipients exhibited a higher plasma level of insulin (8.5 +/- 0.5 versus 6.2 +/- 0.3 mIU/l, p = 0.002), a lower plasma level of vitamin E (14.8 +/- 0.4 versus 16.9 +/- 0.7 mg/l, p = 0.03), a higher platelet cholesterol-to-phospholipid ratio (8.9 +/- 0.3 versus 7.6 +/- 0.3, p = 0.007), and an increased response to ADP-induced platelet aggregation (for the first wave, 29.1 +/- 0.9% of maximal aggregation versus 25.1 +/- 1.0%, p = 0.002; for the second wave, 21.4 +/- 1.4% versus 15.9 +/- 1.1%, p = 0.002, after adjustment for hematocrit), but no untoward changes in the level of fibrinogen, plasminogen activator inhibitor-1, antithrombin III, or lipoprotein(a). In addition, platelet aggregation in patients who required retransplantation as a result of severe coronary artery disease was similar before and after retransplantation. This suggests that severe coronary artery disease is not the cause of platelet hyperaggregability. In multiple-regression analysis, ADP-induced platelet aggregation in heart transplant recipients was significantly positively related to blood glucose (r = 0.50, p less than 0.001) and inversely related to n-3 fatty acids from platelet phospholipids (r = 0.40, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1991

Blood lead and platelet aggregation--evidence for a causal association.

Adenosine diphosphate (ADP) and thrombin are agonists of platelet aggregation in which intracellular calcium plays a significant role as a signal transducer. Lead is a well established toxicological agent affecting intracellular mechanisms controlling free ionized calcium concentration in a number of cell lines. This epidemiological study is the first demonstration of a significant relationship between the extent of primary ADP-induced platelet aggregation measured by optical densitometry in platelet rich plasma (PRP) and blood lead concentration. High blood lead levels are associated with decreased aggregation in this population of 2,150 men aged 49-65 years. This is reflected by a negative regression relationship of -0.19% of maximal extent (PRP vs platelet poor plasma) of aggregation per microgram of Pb/dl (T = -3.82, p less than 0.001). In contrast, no relationship is noted between thrombin-induced aggregation and blood lead concentration. Smoking behaviour represents a potential confounder which may be the explanation for the observed relationship. However, because smoking status is simultaneously related to both ADP- and thrombin-induced aggregation, but is simultaneously related to ADP-induced aggregation and blood lead concentration in a different way, the observed relation is likely to be causal. The mechanisms by which ADP and thrombin effect intracellular calcium transduction signals appear to be distinctively different. The findings in this population-based study are not inconsistent with this difference.

Adenosine Diphosphate↗
PubMed1991

U74006F, a novel 21-aminosteroid, inhibits in vivo lipid peroxidation but fails to limit infarct size in a canine model of myocardial ischemia reperfusion.

Peroxidation of membrane lipids has been suggested to play a role in the pathogenesis of myocardial ischemia/reperfusion injury. We therefore assessed the efficacy of U74006F, a potent in vitro vitamin E-like inhibitor of lipid peroxidation, in limiting infarct size in a canine model of transient coronary artery occlusion. Twenty dogs underwent 2 hours of occlusion of the left anterior descending coronary artery and 6 hours of reperfusion. U74006F or saline solution was administered continuously from 1 hour of occlusion to the end of the experiment. U74006F blunted any increase in production of conjugated dienes (an index of lipid peroxidation) at both 30 minutes (1.73 +/- 0.16 mol/L x 10(-4) vs 2.62 +/- 0.22 in control dogs, p less than 0.05) and 6 hours (1.39 +/- 0.22 vs 2.06 +/- 0.18 in control dogs, p less than 0.05) after reperfusion. Furthermore, 6 hours after reflow vitamin E levels tended to be lower than baseline values in control dogs and higher than baseline values in dogs treated with U74006F. However, analysis of infarct size indicated no statistically significant difference between the two groups when expressed either as a percentage of the left ventricle (10.4 +/- 1.8% in U74006F vs 15.2 +/- 2.4% in control dogs) or as a percentage of the area at risk (33.0 +/- 5.5% in U74006F vs 37.8 +/- 4.5% in control dogs). Although U74006F appeared to be a potent in vivo inhibitor of lipid peroxidation, it failed to limit infarct size after 2 hours of occlusion and 6 hours of reperfusion in this canine model.

Animals↗
PubMed1991

Oxidative status and oral contraceptive. Its relevance to platelet abnormalities and cardiovascular risk.

Oral contraceptive (OC) use is a risk for thrombogenic events. This paper reviews effects of OC on oxidative status, coagulation, and platelet activity. Complicating effects of cardiovascular risk factors such as smoking, diabetes, hyperpidemia, and hypertension, are discussed. From these data we conclude that: 1. OC use modifies slightly but significantly the oxidative status in women and in animals by decreasing in plasma and blood cells the antioxidant defenses (vitamins and enzymes). 2. The changes in the oxidative status are related to an increase in plasma lipid peroxides apparently responsible for the hyperaggregability and possibly the imbalance in clotting factors associated with the OC-induced prethrombotic state. 3. These effects of OC appear to be increased by a high intake of polyunsaturated fat and counteracted by supplements of vitamin E. 4. The risk factors acting synergistically with OC, have all been shown to increase platelet reactivity. In addition, smoking, diabetes, and, to some extent, dyslipidemia are associated with an increased level of lipid peroxides and concomitant changes in the antioxidant defenses that can be additive to those induced by OC. Thus, free radicals and lipid peroxidation could be the underlying mechanism in the predisposition to thrombosis induced by most risk factors in OC users. 5. Results of epidemiologic and experimental studies in this field will be concordant only when diet and natural antioxidants will be systematically taken into consideration.

Animals↗
PubMed1991

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.

Animals↗
PubMed1991

Platelet fatty acids and function in two distinct regions of Belgium: relationship to age and dietary habits.

We compared the dietary habits, fatty acid composition of plasma and platelet phospholipids, and platelet function in two groups of healthy Belgian male subjects, known to differ in their mortality rate from coronary heart disease (CHD). In the Walloon subjects, there was a larger intake of saturated and a lower intake of (n-6) polyunsaturated fats, confirmed by the fatty acid composition of plasma and platelet phospholipids. While plasma HDL and total cholesterol were similar in the present samples of the two communities, platelet aggregation to epinephrine was significantly higher in the Walloon subjects. When the two populations were divided into younger (28-54 years) and older (55-73 years) age groups, the older Walloon subjects exhibited platelet hyper-aggregability to most of the agonists, compared to the other three groups. In addition to dietary fats, alcohol and smoking habits, age was an important determinant of platelet phospholipid fatty acids and platelet reactivity. The present results reinforce those of previous studies, indicating that platelet behaviour is significantly affected by the main risk factors for CHD.

Aging↗
PubMed1991

Long-term diet modification and platelet activity.

Platelet activity was assessed in a sub-sample of 56 participants in the MRC Diet and Reinfarction Trial (DART). Men whose diets contained a high ratio of polyunsaturated to saturated fatty acids (a P:S ratio of greater than 0.5) showed reduced secondary platelet aggregation to adenosine diphosphate (ADP) in platelet-rich plasma (PRP), and diminished platelet aggregation to ADP in whole blood. A trend of reduced secondary platelet aggregation to ADP with increasing dietary eicosapentaenoic acid was noted, but this was not statistically significant. The results of this study and the MRC Diet and Reinfarction Trial suggest a mediatory role for platelet activity in the relationship between diet and ischaemic heart disease.

Adult↗