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Biomedical subjects

M de Lorgeril

Publications and source records attributed to M de Lorgeril.

At least 73 records · Page 4Linked to original sources
PubMed1993

Lipid peroxides and antioxidant defenses in accelerated transplantation-associated coronary arteriosclerosis.

Accelerated coronary artery disease develops in most if not all heart transplant recipients within the first year after transplantation. Increased lipid peroxidation seems to be involved in atherogenesis. In these patients we have investigated whether there is an association between lipid peroxidation, reduced antioxidant defenses, and some conventional coronary risk factors. Lipid peroxides, lipids, uric acid, albumin, antioxidant enzymes and their cofactors (the trace elements selenium, iron, copper, and zinc) have been determined in heart transplant recipients compared with nonrecipients with coronary artery disease. Lipid peroxides (p = 0.002) and uric acid (p = 0.01) were higher and zinc (p = 0.001) was lower in heart transplant recipients. Thirteen of 30 transplant recipients compared with one of 30 nonrecipients (p < 0.001) had very low (less than 10 mumol/L) zinc levels. Antioxidant enzymes and other trace elements were not significantly different. In univariate regression analysis, zinc correlated positively with albumin (p = 0.02) and negatively with lipid peroxides (p < 0.05). Uricemia had a strongly positive correlation with hydroperoxides (r = 0.45; p = 0.0001). In stepwise multivariate regression analysis, lipids, uricemia, creatinine, and zinc were significant (p < or = 0.004) predictors of the lipid peroxide level. Cyclosporine and corticosteroid dosages were significant (p = 0.01) determinants of zinc concentration in the transplant recipients. Although a causal relationship between increased lipid peroxidation and accelerated arteriosclerosis is not definitely demonstrated, the results of this analysis suggest new insights into conventional coronary disease risk factors and possible therapeutic interventions; further controlled trials are needed.

Adult↗
PubMed1993

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."

Animals↗
PubMed1993

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.

Animals↗
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↗
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

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↗
PubMed1992

[Evaluation of non invasive methods for the diagnosis of atherosclerosis of the graft after orthotopic cardiac transplantation].

The frequency and severity of atherosclerosis of the cardiac transplant make it an essential complication of cardiac transplantation. Coronary angiography is the usual diagnostic method but it has severe limitations. In order to evaluate other diagnostic methods coronary angiography and non-invasive techniques: echocardiography, exercise stress ECG, exercise radionuclide ejection fraction, stress Thallium scintigraphy, were performed practically simultaneously in 60 patients after cardiac transplantation. These non-invasive methods were said to be positive in the presence of, respectively, a segmental wall motion abnormality, ischaemic ST segment depression, absence of increased ejection fraction on exercise, reversible or irreversible myocardial hypofixation. Coronary angiography was considered as the reference procedure for distinction between "normal coronary circulation" (no angiographically detectable lesion) and "graft atherosclerosis" (at least one coronary stenosis irrespective of the severity and extension). None of the non-invasive methods had an adequate sensibility when compared with coronary angiography (echocardiography 0.27, exercise stress ECG 0.28, exercise radionuclide ejection fraction 0.64, myocardial scintigraphy 0.62) or negative predictive value (echocardiography 0.56, exercise stress ECG 0.58, exercise radionuclide ejection fraction 0.68, myocardial scintigraphy 0.66). This inadequacy of the non-invasive technique may be explained by the fact that they are more adapted to the diagnosis of myocardial ischaemia than that of coronary studies. In addition, the extent of the coronary lesions may have masked discordance between 2 segments by the global hypovascularisation. The results of this study indicate that the non-invasive methods studied cannot be recommended for diagnosis of atherosclerosis of cardiac transplants.

Adult↗
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

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↗
PubMed1990

Computerized determination of lactate threshold during three modes of exercise.

The lactate threshold (LT) and corresponding exercise levels (rate-pressure product, workload, and exercise duration) have been proposed as objective quantitative parameters of functional capacity and cardiovascular status. The purpose of the present study was to compare three modes of exercise and to evaluate the influence of the body position, using a rapid lactate analyser and computerized determination of the LT. Eight healthy male subjects were studied. No significant difference was found between the LT measured during treadmill (1.55 +/- 0.22 mmol/l), upright bicycle (1.61 +/- 0.17 mmol/l), and supine bicycle (1.41 +/- 0.05 mmol/l) exercises. However, while exercise levels corresponding to the lactate threshold were similar in running and upright bicycling, the supine bicycle was associated with lower exercise duration and workload corresponding to the LT.

Adult↗
PubMed1990

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.

Animals↗
PubMed1990

Inhibition of coronary artery thrombosis by SIN-1, a donor of nitric oxide.

Molsidomine and its metabolite, SIN-1, a donor of nitric oxide, are potent coronary vasodilator and anti-ischemic agents. Recently, SIN-1 and nitric oxide have also been shown to inhibit platelet adhesion and aggregation in vitro. The present study in dogs was designed to evaluate the in vivo antithrombotic properties of SIN-1. Coronary intimal damage and stenosis are known to induce coronary cyclic flow variations that reflect platelet thrombus formation followed by disaggregation and embolization (Folts preparation). This model of coronary artery thrombosis appears to simulate the combination of some of the factors contributing to unstable angina and myocardial infarction in human. SIN-1 infusion (10 micrograms/kg/min) significantly reduced the frequency of cyclic flow variations: 4.9 +/- 6.2/h vs. 14 +/- 4.6/h (before treatment, p less than 0.03, n = 6). Results were similar to those obtained with aspirin (5 mg/kg, bolus i.v.: 1.5 +/- 0.6/h vs. 11.7 +/- 3/h, p less than 0.03, n = 5) whereas saline had no effect (17.8 +/- 2.2/h vs. 19.3 +/- 2.4/h, n = 5). As expected, blood pressure was decreased only in the SIN-1 group: 56.2 +/- 7.8 vs. 87.3 +/- 9.3 mm Hg (p less than 0.02) (mean arterial blood pressure). The present results suggest that the well-documented anti-ischemic properties of SIN-1 could be partly due to its antithrombotic activity, clearly demonstrated with the model of coronary thrombosis used here in the dog.

Animals↗