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Biomedical subjects

J Delaye

Publications and source records attributed to J Delaye.

At least 19 recordsLinked to original sources

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

The long term prognosis of infective endocarditis.

Three problems hamper the prognosis of patients who survive the initial phase of infective endocarditis (IE): the rate of IE recurrence is 0.3-2.5/100 patient years, about 60% of patients will have to be operated on at some time, 20-30% during the initial stay, 30-40% during the following 5-8 years; five-year survival after the hospital phase is about 75% in previous reports and 85% in more recent papers. Death is mainly due to heart failure. We looked at the long-term survival of 330 patients with IE who were hospitalized in our institution in 1970-1982, and at the potential influence of 10 factors: age, gender, previous heart disease, microorganism, location of IE, onset of IE, congestive heart failure (CHF) at onset, CHF during the first year, persistent fever, surgery at the acute phase. Global survival was 75% at 6 months, and 57% at 5 years. The only non-significant factor was IE location. The annual instantaneous risk of death was 0.55 at 6 months, 0.18 at 1 year, then 0.03. After one year, the only prognostic factor was age. The relative risk of dying among patients with IE who survived the first year, as compared to the risk of dying among the general population, was 3.27. The IE prognosis is not uniform. Mortality is high during the initial phase, but after one year the risk of dying is low, although still above that of the general population. Part of the risk is probably the direct consequence of IE, but part is due to the course of the underlying heart disease.

Age Factors

[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

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

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

Effect of experimental non-insulin requiring diabetes on myocardial microcirculation during ischaemia in dogs.

To examine whether chronic high blood glucose may influence myocardial microcirculation during acute myocardial ischaemia in the dog, a noninsulin-requiring diabetes was induced by the streptozotocin-alloxan method. Seventy-five days later, myocardial ischaemia was provoked by occluding the left anterior descending coronary artery for 2 h and microcirculation regulation was assessed in the ischaemic and non-ischaemic myocardium by the radioactive microsphere method. Diabetic dogs were compared with normal dogs. Diabetic dogs had higher blood glycated haemoglobin (2.66 +/- 0.4%) and fructosamine (397 +/- 62 mumol l-1) than control dogs (0.66 +/- 0.2, P < 0.004 and 229 +/- 13, P < 0.03, respectively). Haemodynamic data in the two groups were not different at any time. The size of the ischaemic zone was similar in both groups. During the 2 h ischaemia in the ischaemic zone subendocardial (P = 0.22) and subepicardial (P < 0.05) blood flow slightly increased in control dogs whereas there was a 63% (P < 0.02) and 35% (P = 0.06) reduction respectively in diabetic dogs. In the non-ischaemic zone, blood flow of controls tended to increase (P < 0.006 in the subepicardium and P < 0.06 in the subendocardium) whereas in diabetic dogs blood flow tended to decrease (P = 0.03 in the subendocardium and in the subepicardium). This first investigation on myocardial microcirculation in diabetic dogs during ischaemia suggests that one of the possible causes of increased mortality rate from ischaemic cardiac disease in diabetics might be related to a paradoxical and unfavourable pattern of myocardial blood flow during ischaemia.

Animals

Postoperative and long-term prognosis of myotomy-myomectomy for obstructive hypertrophic cardiomyopathy: influence of associated mitral valve replacement.

Several surgical techniques have been proposed for obstructive hypertrophic cardiomyopathy (OHCM): myotomy, mitral valve replacement (MVR), or myotomy-myomectomy (MM). We reviewed our series of 47 patients who had undergone surgery in order to determine their prognosis and to know whether MVR+MM was better than MM only. Left intraventricular gradient decreased from 86 +/- 34 mmHg to 15 +/- 20 mmHg (P < 0.0001). Postoperatively, three patients died from low cardiac output (6.4%); five died later. Annual mortality (including postoperative deaths) was 3.0%. Follow-up was 5.7 +/- 0.7 years. Survival was 87 +/- 11% at 12 years. After operation, 91% had NYHA class I or II dyspnoea (before surgery this had been 28%); chest pain was CCS class I in 88% (vs 47%); 12% had had syncope since operation (vs 53%). The gradient decrease was larger in the MM+MVR group (P < 0.05). Survival and functional improvement were similar in the two groups. Mitral regurgitation decreased from 2.7 to 0 in the MM+MVR group (P < 0.0001), whereas it decreased from 1.5 to 1.2 in the MM group (ns). MM appears to be the procedure of choice. When mitral regurgitation is important or when an intrinsic disease of the mitral valve exists, the addition of MVR should be considered.

Adult

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

[Coronary accelerated arteriosclerosis and vasospasm in the transplanted heart].

Accelerated atherosclerosis of cardiac grafts is one of the factors limiting long-term survival after cardiac transplantation. The authors report the case of a patient who had a cardiac arrest associated with severe atherosclerosis 18 months after transplantation. The severity of the coronary lesions was underestimated by coronary angiography. An ergometrine test induced coronary spasm, a phenomenon which has only rarely been observed in transplanted hearts. The patient died one month later despite calcium inhibitor therapy. Autopsy revealed very severe triple vessel disease. This case illustrates the possible rapid evolution of coronary artery disease in cardiac transplant recipients, the difficulty in evaluating the severity of the lesions by coronary angiography and the additional possibility of observing coronary spasm in these cases.

Coronary Angiography

[Myocardial infarction beyond the 48 first hours: treatment with calcium channel antagonists].

Calcium channel blocking agents prevent calcium entering cardiac and smooth muscle cells. With reduction of the blood pressure, heart rate and myocardial contractility, they reduce myocardial oxygen demand. By relieving spasm and coronary constriction, and dilating the collateral coronary vessels, they improve perfusion of the ischemic zones. The results in experimental infarction are contradictory: the reduction in the infarct size and ischaemia is not constant. In the Myocardial Infarction Study, a trial of lidoflazine in 1792 subjects followed up for an average of 5 years, there was no significant difference between the mortality rates of the two groups. In the Danish Verapamil Infarction Trial I, which included 436 subjects receiving 360 mg/day of verapamil or placebo, the 6 months mortality was less (NS) in the verapamil group (12.8%) than in the placebo group (13.9%) as was the reinfarction rate (7.8% versus 9.2%; NS). In the DAVIT II trial of 1775 subjects, treatment was introduced 9 +/- 2.7 days after admission. Mortality was lower (NS) in the verapamil group (11.1%) than in the placebo group (13.8%) and the recurrences were less common (p = 0.04) in the treatment group (11.0%) than with placebo (13.2%). The Secondary Prevention Reinfarction Israeli Nifedipine Trial is a comparison of Nifedipine 30 mg/day and placebo introduced 7-21 days after infarction in 2276 subjects. After 10 months, the mortality and reinfarction rate were similar in both groups, as in the SPRINT II trial (60 mg/day of nifedipine or placebo) at 6 months. In the Multicenter Diltiazem Postinfarction Trial of 2466 patients, Diltiazem 240 mg/day or placebo was administered 3 to 15 days after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Which anti-ischemic treatment can be prescribed during and after the acute phase of myocardial infarction?].

After myocardial infarction, calcium channel blockers are the most prescribed anti-ischemic drugs followed by nitrate derivatives and beta blockers. In order to assess whether this attitude is justified by published data on their efficacy, a meta-analysis of trials of anti-ischemic drugs in myocardial infarction was performed. The early mortality was 13.3% in the group treated by IV nitrates in the acute phase of myocardial infarction and 17.2% in control groups, reducing the risk by a quarter (95% confidence interval of the odds ratio (CI): 0.55-0.95). When all nitrate derivative trials were grouped together, the reduction in the risk of death of 21% was significant (from 15% to 11.8%) (CI: 0.59-0.94). Although oral nitrate derivatives introduced during the acute phase and continued for several weeks induced a non-significant reduction in mortality of 16%, when given intravenously, the benefits on early and longer term mortality were unquestionable. The mortality was 9.8% in the groups treated by calcium channel blockers and 9.3% in control groups (NS); the recurrent infarct rate was 4.8% and 5.4% respectively (NS). In this family of drugs, there was no product which distinguished itself from the others with regard to beneficial or adverse effects. The early mortality decreased from 9.2% to 8.2% in the groups treated by oral beta-blockade--a risk reduction of 10% (NS) and from 4.2% to 3.7% with intravenous beta-blockers--a risk reduction of 12% (p = 0.03). Late mortality decreased from 9.4% to 7.6%, a reduction of 20% (p < 0.00001) in long term trials.2+ contraindication of betablockers in patients without cardiac failure.

Adrenergic beta-Antagonists

[Long-term surgical prognosis of aortic valve diseases with pulmonary hypertension. Apropos of 34 cases].

Thirty-four patients underwent isolated aortic valve replacement with mean pulmonary artery pressures greater than 40 mmHg between 1972 and 1988. The aortic valve disease was stenotic in 10 cases, regurgitant in 14 cases and mixed in 10 cases. Thirty patients (88%) had invalidating cardiac failure (NYHA Classes III and IV). The mean preoperative ejection fraction was 44 +/- 15%. The hospital mortality was 17.6%. Ten patients died secondarily, five with terminal cardiac failure. The 5 year actuarial survival was 70 +/- 16%; the 10 year survival was 60 +/- 18% with an average follow-up of 115 +/- 61 months. None of the patients was lost to follow-up. Fifteen of the 18 survivors (83%) are asymptomatic or pauci-symptomatic after a follow-up of 126 +/- 62 months. Doppler echocardiography (n = 12) showed normal prosthetic valve function in 11 cases and aortic regurgitation in 1 case. Eight patients had tricuspid regurgitation with pulmonary artery systolic pressures less than 30 mmHg in 6 cases and between 30 and 40 mmHg in 2 cases. Severe pulmonary hypertension is therefore a poor early postoperative prognostic factor in aortic valve replacement surgery due to the associated left ventricular dysfunction. However, the long-term results are satisfactory: clinical improvement is usually related to a reduction of pulmonary hypertension.

Actuarial Analysis

[Myxoma of the right atrium. Apropos of 10 surgically treated cases].

In a series of 100 patients with intracardiac myxoma, the lesion was in the right atrium in 10 cases. The authors attempt to define the particular features of right atrial myxoma in terms of clinical aspects, outcome and pathology. The diagnostic difficulty raised by complex clinical pictures (including right ventricular failure, pseudopericardial forms and forms with a predominance of systemic problems) has now been resolved by imaging and, above all echocardiography. Consequences for the right side of the heart may involve the pulmonary artery with myxomatous emboli causing multiple fusiform aneurysms and pulmonary hypertension, or, more rarely, the tricuspid (with need for valve replacement), vena cava (Budd-Chiari syndrome) or atrial septum (right/left shunt). Alongside systemic problems due to interleukin 6, erythrocyte abnormalities are a new feature. Frequent etiological inclusion in a Carney complex explains recurrences and multi-cavity forms. The dominant pathological feature is tumor calcifications, no doubt as a result of the long presymptomatic phase of myxoma.

Adult

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

Influence of associated valvular lesions on long-term prognosis of mitral stenosis. A 20-year follow-up of 202 patients.

Other valvular lesions associated with pure MS were studied in 202 consecutive patients whose mean age was 43.4 +/- 12.7 years; 76.7% were females. MS was isolated in 63.4%, associated with aortic regurgitation (AR) in 27.7%, aortic stenosis in 1.0%, tricuspid stenosis (+aortic valve lesion) in 1.0%. In isolated MS, 42.4% were NYHA class III or IV, compared with 49.0% in MS + aortic valve lesion. One hundred and sixty-nine (85.4%) patients were operated on; 23.1% had mitral valve replacement, 76.9% had closed (31.4%) or open (45.6%) mitral commissurotomy; 7.1% had associated aortic valve replacement. There were perioperative complications in 20.4%, and the perioperative death rate was 4.1%. Two patients were reoperated in the postoperative course, and 28 patients after this period. The follow-up was 13.3 +/- 4.5 years. The survival rate was 77.7 +/- 4.6% (SE) for isolated MS, and 71.1 +/- 6.3% for MS associated with an aortic valve lesion (NS). The prognosis of MS is very good: the survival rate at 20 years follow-up is 75%. The association of aortic stenosis or tricuspid stenosis does not appear to alter this survival, but numbers are small. Important aortic regurgitation is a significant predictor of higher mortality in patients with MS.

Adolescent

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