[A reevaluation of risk factors of coronary disease].
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Blood Platelets↗
Biomedical subjects
M de Lorgeril
Publications and source records attributed to M de Lorgeril.
[The natural history of coronary disease. The role of cholesterol].
The natural history of the complications of coronary heart disease has been defined by anatomicopathological and epidemiological studies, particularly the Framingham study. At the same time, research is being carried out on risk factors which play a role in the progressive development of atheromatous plaque (atherogenic factors: hypertension: hypercholesterolaemia) and those factors which lead to complications in the atheromatous plaque (aggravating or precipitating factors: smoking, thrombosis, etc.). This schematic perspective may lead to the redefinition of the strategy to adopt in fighting atherosclerotic arterial disease; a better aim will thus the taken in the fight against hypercholesterolaemia.
Cholesterol↗
Spacial and temporal profiles of neutrophil accumulation in the reperfused ischemic myocardium.
To elucidate further the pathogenic role of neutrophils in evolving reperfused myocardial infarction, we investigated the dynamics of their accumulation and distribution in the ischemic myocardium. The left anterior descending coronary artery was occluded in dogs for 2 hours followed by reperfusion for 0, 3, 6, or 24 hours. 111In-labeled neutrophils were injected at the time of occlusion or after 16 hours of reperfusion. The area at risk was similar among groups. Infarct size expressed in percent of the area at risk was identical between groups reperfused for 6 (35.2 +/- 4.4%) or 24 (32.3 +/- 3.9%) hours but smaller (22.0 +/- 4.4%; p less than 0.05) after 3 hours of reperfusion. 111In-neutrophils accumulation quantified by scintigraphy correlated positively with infarct size (r = 0.64, p less than 0.005); accumulation rates (cells/h/cm2MI) were high during the first 3 (2288 +/- 754) and 6 hours (1953 +/- 463) but low (490 +/- 192) between 16 and 24 hours of reperfusion. Cells accumulating during reperfusion (12,566 +/- 2307 cells/g at 3 hours) were found within the borders of the necrotic area, and the cell counts (2420 +/- 724 cells/g, p less than 0.05) in the live tissue located within the area at risk after 3 hours of reperfusion were similar to those found in the subepicardium at the onset of reperfusion: (2240 +/- 571 cells/g). Only a few cells were detected in the normally perfused myocardium (67 +/- 33 cells/g). We conclude that reperfusion accumulation in the ischemic myocardium; the reaction takes place within 3-6 hours of reperfusion, a period of time where infarct size is growing by about 40%. These results support the concept that leukocytes may play a pathogenic role on infarct size in models with brief ischemia followed by reperfusion.
Animals↗
Influence of leukopenia on collateral flow, reperfusion flow, reflow ventricular fibrillation, and infarct size in dogs.
Leukocytes contribute to myocardial damage during ischemia and reperfusion. However, the mechanism involved has not been clearly elucidated. The purpose of the present study was to determine whether leukocyte-induced myocardial damage is flow mediated. In open-chest dogs submitted to 2 hours of ischemia, area at risk, infarct size, and regional myocardial blood flow before, during, and after ischemia were measured. Leukopenia was induced by a two-step method (chemotherapy and antineutrophil serum) in a group of 14 dogs as compared to a control group of 18 dogs. The relation of infarct size to the major determinants of infarct size was analyzed by uni- and multilinear regressions. Seven control dogs had ventricular fibrillation at reperfusion compared to one dog with leukopenia. In the group with leukopenia the mean infarct size was smaller (31.1 +/- 5.8% of area at risk) than in the control group (47.7 +/- 2.9, p = 0.02). In addition, the two multiple linear regression equations were significantly different (p = 0.01). Myocardial blood flow to the central ischemic zone did not change significantly between 20 and 120 minutes of ischemia in the control dogs (n = 12; subendocardial = 0.08 +/- 0.03 vs 0.07 +/- 0.03 ml/min/gm; subepicardial = 0.20 +/- 0.07 vs 0.20 +/- 0.05 ml/min/gm) and in the dogs with leukopenia (n = 12; 0.07 +/- 0.02 vs 0.07 +/- 0.02 ml/min/gm and 0.15 +/- 0.004 vs 0.18 +/- 0.04 ml/min/gm). A similar reduction in myocardial blood flow was observed after 6 hours of reperfusion in the control dogs (0.34 +/- 0.07 ml/min/gm vs 1.02 +/- 0.11 at baseline, p less than 0.01) and in the dogs with leukopenia (0.25 +/- 0.04 vs 0.81 +/- 0.08 ml/min/gm, p less than 0.01). It was concluded that the leukocyte-dependent myocardial injury did not appear to be mediated through a flow mechanism during either ischemia or reperfusion.
Animals↗
Dietary lipids and their relation to ischaemic heart disease: from epidemiology to prevention.
From the Seven Countries Study and recent statistics from WHO and the OECD, it is clear that saturated fats, mainly dairy fats, are closely associated with the mortality rate from ischaemic heart disease (IHD). Consumption of alcohol, especially wine, but not polyunsaturated fats, seem to offer protection. Racial and other environmental factors do not seem to be confounding factors for that relationship as evaluated by studies in migrants, Japanese to USA, Southern Europeans to Australia, and in vegetarians in California. By contrast, very few trials using dietary polyunsaturated/saturated (P/S) ratios from 1.5-2.5 vs 0.4-0.7 have really prevented coronary death by diet modification. The only successful trial had a P/S ratio of 0.7. High P/S ratio increases platelet reactivity. Recent studies indicate that thrombosis and platelets play a more prominent role in IHD than expected. To decrease platelet activity and prevent IHD, a P/S ratio of 0.4-0.7 should be preferred.
Coronary Disease↗
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)
Animals↗
Leukocytes, thrombosis, and unstable angina.
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Angina Pectoris↗
Neutrophil accumulation in experimental myocardial infarcts: relation with extent of injury and effect of reperfusion.
The effects of reperfusion on the myocardial accumulation of neutrophils and their role in the extent of injury were investigated in a canine preparation with a 3 hr coronary occlusion followed by 21 hr of reperfusion. The left anterior descending coronary artery (LAD) was permanently occluded in group 1 and reperfused after 3 hr in four others (groups 2 to 5). All but group 5 received lidocaine (1 mg/min over 8 hr). A critical stenosis was produced and left in place at reperfusion only in group 2. In groups 1 and 2, 111In-labeled autologous neutrophils were injected at the time of coronary occlusion. Group 4 animals were rendered leukopenic 2 hr before the coronary ligature and throughout the experiment by injection of an antineutrophil rabbit serum. Quantification of the radioactivity by digitized scintigraphy of the heart slices revealed an 80% (p less than .05) increase in neutrophil accumulation in the infarct region after reperfusion (group 2) as compared with permanent occlusion (group 1). Gamma counting of myocardial tissue samples showed that the neutrophil accumulation ratio in the subendocardial central zone of the infarct was increased five times (p less than .05) by reperfusion, whereas no difference was evident in the subepicardium. Infarct size and myocardial area at risk were not statistically different among the five groups. However LAD flow in the leukopenic group (group 4) was significantly higher (p less than .05) 30 min after reperfusion (40.0 +/- 5 ml/min) when compared with the preocclusion value (21.7 +/- 4 ml/min). In contrast, in a parallel experiment without leukopenia (group 3), LAD flow after reperfusion did not differ from the preocclusion value.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Acute influence of cigarette smoke in platelets, catecholamines and neurophysins in the normal conditions of daily life.
Cigarette smoking is firmly linked to the occurrence of acute coronary events. In twenty-two healthy volunteers in normal conditions of daily life we studied the acute influence of smoking on the following parameters: beta-thromboglobulin, thromboxane B2, epinephrine, norepinephrine, estrogen-stimulated neurophysin, and nicotine-stimulated-neurophysin. Our results show that in our population and following our protocol, smoking did not induce platelet activation, thromboxane formation, catecholamine release or estrogen-stimulated-neurophysin secretion. However, smoking did provoke a significant increase of nicotine-stimulated-neurophysin (p less than 0.05) which reflects vasopressin increase and which might explain the high incidence of ischaemic accidents in cigarette smoking via the vasoactive properties of vasopressin.
Adolescent↗
[Endogenous prostacycline and coronaropathy. Plasma levels of 6-keto-PGF1 alpha].
Prostacycline may play a preventive role in the development of ischaemic complications of coronary atherosclerosis through its vasodilatory and platelet antiaggregant properties. Its biological instability makes it difficult to measure in the plasma; however, it is possible to determine plasma concentrations by radioimmune assay of one of its stable derivatives, 6-Keto-prostaglandin F1 alpha (6KPGF1 alpha). Systemic plasma concentrations at rest of 30 patients with severe atherosclerosis were not significantly different from those of healthy control subjects (7.5 +/- 6.5 vs 10 +/- 5 pg/ml). In addition ischaemia during exercise is not associated with significant variations; at rest 7.1 +/- 6 pg/ml in the "ischaemic" group (n = 20) compared to 7.6 +/- 6.4 pg/ml in the "non-ischaemic" group (n = 10); on effort: 9 +/- 10 pg/ml compared to 13.3 +/- 14 pg/ml. These results show that measuring the plasma 6KPGF1 alpha by peripheral vein blood sampling is of no use in the diagnosis of coronary atherosclerosis or of myocardial ischaemia on effort.
6-Ketoprostaglandin F1 alpha↗
[Late potentials: non-invasive detection in coronary disease and relation to severe ventricular arrhythmia].
Using high-gain amplification and signal averaging techniques, we tried to determine the clinical significance of ventricular late potentials (LP). 85 subjects were included in this study. No LP were detected in normal subjects (n = 25), nor in patients with various non-coronary cardiopathies who had presented ventricular tachycardia and/or fibrillation (VT/VF) (n = 10). LP were recorded only in patients with coronary heart disease (CHD) (n = 50). The prevalence of LP was 50% (9/18) in patients with a history of VT/VF (vs 12.5% = 4/32 in patients without such a history, p less than 0.02). We also found a prevalence of 50% (11/22) in patients with a ventricular aneurysm (vs 7.1% = 2/28 in patients without an aneurysm, p less than 0.01). The prevalence reached 80% (8/10) in patients with VT/VF and a ventricular aneurysm and it was only in this latter group of patients that the interval between the peak of the R wave and the end of ventricular electrical activity exceeded 100 ms (mean 111.2 +/- 12 ms, vs 50 +/- 8 ms in normal subjects, p less than 0.001). In all the cases submitted to surgery, the LP disappeared after resection of the aneurysm. In conclusion, LP, when of long duration, should be considered as a hallmark of malignant ventricular arrhythmias in patients with CHD.
Adolescent↗
Factors affecting left ventricular function after correction of tetralogy of Fallot.
To investigate the possible causes of left ventricular dysfunction after total correction of tetralogy of Fallot, 84 patients, aged 1 1/2 to 16 years, were studied by left ventricular cineangiography both before and a mean of 4.6 months after operation. Left ventricular ejection fraction and mean velocity of circumferential fibre shortening were calculated; using multivariate analysis the results were correlated with age at operation, the degree of hypoxia and polycythaemia before operation, occurrence of hypoxic spells, and the duration of operative procedures (cardiopulmonary bypass and aortic cross clamping). The postoperative left ventricular ejection fraction was decreased slightly or moderately in 46% of patients. The variable most significantly associated with altered left ventricular function was a history of hypoxic spells. Age, the degree of chronic hypoxia, and polycythaemia did not correlate significantly with left ventricular function indices. Although no correlation was found between the duration of cardiopulmonary bypass and left ventricular ejection fraction, bypass times exceeding 120 minutes were associated with decreased ejection fractions; this was statistically significant and independent of the variable "hypoxic spells". Thus repeated episodes of acute hypoxia and long operative procedures appear to have a deleterious effect on left ventricular function in tetralogy of Fallot.
Adolescent↗
[Possible role of vasopressin in ischemic accidents related to tobacco consumption].
Tobacco smoking increases the risk of myocardial infarction and sudden death. When used for diagnostic and therapeutic ends, vasopressin, at low doses, may induce acute ischaemic complications in patients with coronary artery disease. This study showed that in some patients the inhalation of tobacco smoke caused a rise in plasma vasopressin and nicotine-stimulated-neurophysin, a substance easily measured and used as a marker of vasopressin secretion because of the close relationship of the two substances. Twelve out of twenty five subjects presented higher levels of nicotine-stimulated-neurophysin than the normal for the same group before smoking (p less than 0,005): 280 +/- 54 compared to 714 +/- 459 pg/ml. Simultaneous measurement of vasopressin and nicotine-stimulated-neurophysin every 5 minutes in 4 subjects confirmed the parallel changes of these substances during smoking. These results suggest that vasopressin may play a primary role in the acute ischaemic complications of tobacco smoking. The concept of the "vasopressin response" could be used as a biological parameter to identify subjects at "high cardiovascular risk" under the effects of tobacco and so lead to a prophylactic strategy aimed more specifically at these patients.
Coronary Disease↗
[Non-invasive detection of late potentials of ventricular activation: identification and significance in coronary disease].
Using a high-amplification electrocardiograph with signal averaging, an attempt has been made to determine the prevalence of delayed potentials of ventricular activation (DPVA) in coronary heart disease (CHD) and their relation to ventricular tachycardia and/or fibrillation (VT/VF). No DPVA could be recorded in normal subjects (n = 25) or in patients with various cardiopathies with VT/VF but without CHD (n = 10). DPVA have been recorded only in patients with CHD (n = 50) (all patients having undergone ventriculography and coronarography). The prevalence of DPVA is 12.5% without VT/VF, 50% with VT/VF, and 80% when these arrhythmias are associated with the presence of a ventricular aneurysm. The duration of the DPVA is also important, since it is only in the group with VT/VF and with aneurysm that the R-EVEA duration (interval between the peak of the R wave and the end of electrical ventricular activity) exceeds 100 ms. DPVA disappeared in all the cases after aneurysmectomy. The DPVA, when of long duration, can be considered a hallmark of serious ventricular arrhythmias in patients with CHD and a ventricular aneurysm.
Action Potentials↗
[Isotope angiocardiography: amelioration of the measurement of ejection fraction by a new treatment of the image].
Some of the limitations affecting radioisotopic images are their insufficient resolution, structure boundaries and accurate subtraction of background noise. In order to improve the signal-to-noise ratio the images of the recorded heart cycles are treated by the Karhunen-Loeve transformation. Edge detection is based on compression of the image to a bitmap at a chosen level and following of all bits set to one by a pointer. The outlines of the structures as determined by edge tracking are used to define the regions of interest within the enhanced images. Background subtraction applies the principle of interpolative background subtraction by computing an individual background for each point in an irregular region of interest. The resultant images are used to calculate an index of cardiac efficiency which shows high correlation (r = 0.92) with the ejection fraction of contrast biplane left ventricular angiography.
Cardiac Output↗
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.
Adenosine Diphosphate↗
Low-dose aspirin and accelerated coronary disease in heart transplant recipients.
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Aspirin↗