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Biomedical subjects

M de Lorgeril

Publications and source records attributed to M de Lorgeril.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effect of trimetazidine on postischemic regional myocardial stunning in the halothane-anesthetized dog.

Trimetazidine (TMZ) has been described as a new antiischemic agent. Whereas its precise mechanism of action remains unknown, antioxidant properties and the ability to preserve high-energy phosphate metabolism have been reported. Accordingly, we studied whether TMZ may limit postischemic regional myocardial stunning (known to be caused by reactive oxygen species) and influence recruitment of contractile reserve by inotropic stimulation in a dog model, using halothane to maintain steady anesthesia throughout the experiment. Dogs were submitted to a 15-min coronary artery occlusion followed by reperfusion. The blinded protocol included a 3-day oral pretreatment (1 mg/kg/day), a bolus injection (0.5 mg/kg), followed by intravenous infusion (0.5 mg/h) initiated 15 min before coronary artery occlusion. Despite lower heart rate (HR) and significant reduction of lipid peroxidation in treated dogs, myocardial stunning and recruitment of contractile reserve by dobutamine infusion in the postischemic myocardium were not modified by TMZ. Adenine nucleotide pool in the postischemic myocardium was considerably reduced as compared with the nonischemic myocardium in both groups. Therefore, in halothane-anesthetized dogs, the antioxidant properties of TMZ were not sufficient to protect myocardium in terms of postischemic dysfunction after 15-min ischemia.

Adenine Nucleotides↗
PubMed1995

Importance of initial coronary artery flow after heart procurement to assess heart viability before transplantation.

BACKGROUND: The objective of this study was to evaluate different tests of heart viability in a pig model of warm ischemia. METHODS AND RESULTS: Pig hearts (n = 30) were submitted to 0 (= group I), 10 (group II), 20 (group III), 30 (group IV), and 60 (group V) minutes of in situ warm ischemia (animal exsanguination). Hearts were removed, then flushed with cardioplegic solution for 3 minutes at a fixed pressure of 60 cm H2O, and edema formation, initial coronary flow, and ionic composition (Na+, K+, and Ca++) of coronary sinus effluent were evaluated. Hearts were then stored for 2 hours in a cold (4 degrees C) preservation solution. Myocardial biopsies (and evaluation of energetic index) were performed, then the hearts were reperfused for 30 minutes with whole blood with an in vitro functional testing system. No edema occurred during cardioplegic flush in the hearts in groups I through IV, but a 37 +/- 11% weight increase (P < .001) occurred in hearts in group V. There was a progressive decrease in initial coronary flow with the increase in the duration of warm ischemia (70 +/- 14 mL/min per 100 g of tissue in group I and 52 +/- 9, 41 +/- 16, 25 +/- 11, and 23 +/- 5 mL/min per 100 g, respectively, in groups II through V (P < .01 to P < .001 versus group I). Initial coronary flow was positively correlated with the energetic index (r = .84, P < .001), and the left ventricle developed pressure at reperfusion (r = .90, P < .001). Finally, there were significant differences between hearts in the control group and those in group V for calcium and sodium release (lower in the control group; P < .001 and P < .01, respectively) and for potassium removal (lower in group V, P < .05). CONCLUSIONS: These data suggest that early measurement of coronary flow after removal of the heart may help to assess heart viability before transplantation. This approach may provide a comprehensive clinical evaluation to increase the number of hearts available for transplantation among those that are rejected in the absence of accurate criteria of viability.

Animals↗
PubMed1995

Noninvasive assessment of no-reflow phenomenon in a canine model of reperfused infarction by contrast-enhanced magnetic resonance imaging.

The aim of this study was to test whether contrast-enhanced magnetic resonance (MR) imaging may assess in vivo the severity of the no-reflow phenomenon in a dog model of infarction with 2-hour coronary occlusion followed by reperfusion (6 hours). Subsecond MR imaging combined with intravenous bolus administration of superparamagnetic iron oxide particles (SPIO) was performed at the fifth hour of reperfusion. An MR index was calculated using the difference of signal-intensity enhancement between ischemic and nonischemic zones during the SPIO first pass. Dogs were separated into two groups according to the severity of ischemia: collateral blood flow in the central ischemic zone at 120 minutes of occlusion (radioactive microsphere technique) < 22.5% of the flow in the nonischemic zone (group I) or > 22.5% (group II). Mean collateral blood flow during occlusion was lower in group I (11.3% +/- 2.9%, n = 7) than in group II (66.8% +/- 19.8%, n = 6, p < 0.05). Mean infarct size was significantly larger in group I (58.6% +/- 4.9% of the area-at-risk, n = 7) than in group II (16.5% +/- 6.5%, n = 6, p < 0.05). For the entire population (n = 13), the infarct size was inversely correlated to the collateral blood flow (r = -0.64, p = 0.02, standard error of estimate = 0.24). The relative rate of enhancement in ischemic myocardium (MR index) was significantly lower in group I (38.1% +/- 10.9%) than in group II (142.8% +/- 32%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

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.

Adult↗
PubMed1995

[Value of coronary angiography in the diagnosis of coronary artery disease of the transplanted heart. Coronary angiography and arteriosclerosis of the graft].

The diagnostic value of coronary angiography, a widespread method of detection of transplant coronary artery disease, was studied in 17 cardiac transplant patients with reference to histological examination. In the 6 coronary segments studied, the only significant but weak correlation that was found was for the distal left anterior descending artery: the correlations were not statistically significant in the other 5 segments. Coronary angiography underestimated lesions and false negative results were frequently reported (66 and 27% respectively). The limitations of coronary angiography may be explained by the technical artefacts related to both methods of evaluation and the anatomically diffuse and distal nature of transplant coronary artery atherosclerosis. A more reliable diagnostic method would seem to be required in view of the clinical importance of this pathology.

Coronary Angiography↗
PubMed1994

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.

Animals↗
PubMed1994

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.

Administration, Oral↗
PubMed1994

Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.

In a prospective, randomised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infarct prudent diet. After a first myocardial infarction, patients were randomly assigned to the experimental (n = 302) or control group (n = 303). Patients were seen again 8 weeks after randomisation, and each year for 5 years. The experimental group consumed significantly less lipids, saturated fat, cholesterol, and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma. Serum lipids, blood pressure, and body mass index remained similar in the 2 groups. In the experimental group, plasma levels of albumin, vitamin E, and vitamin C were increased, and granulocyte count decreased. After a mean follow up of 27 months, there were 16 cardiac deaths in the control and 3 in the experimental group; 17 non-fatal myocardial infarction in the control and 5 in the experimental groups: a risk ratio for these two main endpoints combined of 0.27 (95% CI 0.12-0.59, p = 0.001) after adjustment for prognostic variables. Overall mortality was 20 in the control, 8 in the experimental group, an adjusted risk ratio of 0.30 (95% CI 0.11-0.82, p = 0.02). An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death.

Coronary Disease↗
PubMed1994

Nutrition, atherosclerosis and coronary heart disease.

The main health hazard of atherosclerosis is coronary heart disease (CHD). Its relation to nutrition (chiefly saturated fat) was shown through the Seven Countries Study and confirmed by between country comparisons. Nevertheless, cholesterol, the accepted intermediate link in blood, can no longer be used to explain differences between countries. In addition, when previous trials to decrease CHD by diet were efficient, rapid protection was observed (within a year), an effect not attributed to atherosclerosis but to thrombosis, which is responsible for myocardial infarction. Thrombogenesis is directly increased by saturated fat, but decreased only by n-3 fatty acids and alcohol through decreasing platelet reactivity. A Mediterranean diet with more cereals, vegetables, fruit, less saturated fats and more n-3 fatty acids has recently been shown to afford a rapid and exceptional protection from recurrences and death in coronary patients. The relationship between nutrition and CHD is thus as close as suggested, but more complex, because of additional nutrients, such as alcohol and natural antioxidants, and an appropriate balance between fatty acids.

Arteriosclerosis↗
PubMed1994

Platelet aggregation and HDL cholesterol are predictive of acute coronary events in heart transplant recipients.

BACKGROUND: Sudden death (SD) and acute myocardial infarction (AMI) are the main complications limiting long-term survival after heart transplantation (HT). They are unpredictable and, at present, unpreventable. Platelet aggregation (PA) has recently emerged as a significant prognostic indicator in nontransplanted coronary disease patients. The main purpose of the present study was to evaluate to what extent PA could predict SD and AMI in long-term survivors of HT independently of serum lipid levels. METHODS AND RESULTS: We studied 207 patients. All received triple immunosuppressive therapy. During follow-up, the incidence of SD and AMI was determined, and the independent role of PA as predictor was evaluated with other usual risk factors by a Cox multivariate regression model. There were 11 SDs and 14 AMIs after an average follow-up of 642 days, giving an average incidence rate of 7.3 events per year per hundred patients. By univariate analysis, the most potent predictors were ADP-induced platelet aggregation (positive association) and total cholesterol (negative association). Age and length of time since transplant were not predictors. By multivariate analysis, only the secondary wave of ADP-induced platelet aggregation (P = .001) and high-density lipoprotein cholesterol (P = .03) were independent predictors. The relative risk of SD or AMI based on a comparison between patients with high (> 36%) or low (< 36%) ADP-induced platelet aggregation was 4.3 (95% confidence interval, 1.9 to 9.5, P = .0001). CONCLUSIONS: This study provides the first demonstration of an association between increased platelet aggregation and subsequent SD or AMI in HT recipients. It suggests that platelets and thrombosis also are implicated in the pathogenesis of AMI and SD in HT recipients. Identification of a safe and effective antiplatelet therapy should be actively pursued.

Adolescent↗
PubMed1994

[Oxidative stress and lipid-protein peroxidation after cardiac transplantation. New hypotheses for explaining pathogenesis of accelerated forms of ischemic heart disease].

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.

Heart Transplantation↗