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P Boissonnat

Publications and source records attributed to P Boissonnat.

16 recordsLinked to original sources

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

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

[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

[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

[Coronary lesions of a cardiac transplant. (Chronic cardiac rejection). Study of 15 retransplantations].

In order to precise the pathologic aspects of coronary lesions observed in the accelerated coronary disease after heart transplantation, 15 cases of explanted hearts have been studied, and compared to the findings of previous coronarography. Histopathological aspects, modes of diffusion involving the three main coronaries and distal branches, thrombotic complications and their ischemic consequences showed that coronary lesions result in a few months or years to diffuse circumferential atheromatous like lesions. Localized lesions are less frequently encountered than in common atheromatous coronary disease, but multifocal thrombosis is frequent, found in 40% of the cases. This feature leads to ischemic cardiopathy expressed by cardiac failure, indolent because of the denervation of the heart. Correlations with coronarographies showed that this method underestimated the importance of coronary lesions, for which retransplantation represents the only hope. Risk factors include vascular immunological inflammation, viral infection enhanced by immunosuppression, increased platelet aggregation but we still ignore the respective importance of these factors at the present time.

Adult

[Causes of failure analysis after cardiac transplantation. From a consecutive series of 91 cases].

Ninety-three cardiac transplantations were carried out in 91 patients (2 retransplantations) between March 1st 1987 and November 1st 1989, in 84 adults and 7 children under 15 years of age. The indications were dilated cardiomyopathy (48%), ischemic cardiomyopathy (35%), decompensated valvular heart disease (11%), congenital heart disease (3%) and two cases of Uhl's anomaly. Twelve patients underwent transplantation after external circulatory assistance (13%), 11 patients after inscription on the list of extreme emergencies, and 68 on an elective basis (74%). The postoperative immunosuppressive protocol was triple therapy: Ciclosporine, Azathioprine and Prednisone. Three of the children died. The early adult mortality was 9 cases (10.7%). It was 8% in patients operated electively. Major infectious complications occurred in 10 patients (11%). Rejection was looked for by systematic endomyocardial biopsy and echocardiography. Three hundred and forty-nine biopsies were made. Thirty-five patients (44%) had no problems of rejection. Seventy-nine patients have now been followed up for an average of 19 months. There were 7 late deaths. Seventy seven per cent of the survivors are asymptomatic. Acute rejection and transplant dysfunction were the two main causes of early mortality after cardiac transplantation. Although the long-term prognosis is uncertain, the medium-term results are very encouraging.

Actuarial Analysis

Use of the Abiomed BVS System 5000 as a bridge to cardiac transplantation.

The Abiomed BVS System 5000 (Abiomed Cardiovascular, Inc., Danvers, Mass.) is a gravity-filled, pneumatically driven external prosthetic ventricle that has been implanted as a circulatory support device in six patients 9 to 58 years of age, presenting with a refractory heart failure nonamenable to any type of corrective operation. Three (including a 9-year-old girl) had an end-stage nonobstructive myocardiopathy, and two (including one patient who had had a massive recent myocardial infarction) had an ischemic heart disease. When first seen, the 58-year-old patient had an acute rejection and graft failure occurring 2 months after a first transplantation. All patients showed evidence of a low-output state (cardiac index less than 1.5 L/min/m2), with renal failure (mean urinary output, less than 27 ml/min) and hypoxia (mean arterial oxygen pressure = 56 torr under 80% forced inspiratory oxygen), despite maximum pharmacologic support (dobutamine, 16 to 18 gamma/kg/min; dopamine, 3 to 18 gamma/kg/min; adrenaline, 0.2 to 0.7 gamma/kg/min; furosemide, 7 to 17 gamma/kg/min). The device was implanted through a midline sternotomy and under peripheral normothermic bypass. Five patients received a biventricular support, and one a single left prosthetic ventricle. The cannulation included a right-angled cannula in both the left and right atrium and a suture of the arterial Dacron tubes onto the ascending aorta and main pulmonary artery. After careful deairing of the tubing and ventricles, the console was activated and the bypass progressively discontinued. Heparin infusion was begun 3 hours after chest closure and was continued for the duration of assist pumping, which was 2 to 11 days (mean duration, 7.43 days). The system could provide a complete support of the circulation with both right and left ventricular index remaining stable at 2.4 to 3 L/min/m2. After a dramatic improvement at the time of the system activation, the urinary output remained adequate, thus allowing for a decreasing need for diuretic therapy. In two cases, including one of isolated left ventricular assist pumping, the circulation could be totally supported during 11 hours and 23 hours, respectively, of refractory ventricular tachycardia. Four of six patients were shortly weaned from inotropic agents. Hematologic studies showed a moderate decrease of the coagulation factors level during the first 6 hours of circulatory support, and this remained stable and within normal limits thereafter. There have been three cases of bleeding complications necessitating surgical revision on the sixth hour, the twelfth hour, and the sixth day, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

[Intracoronary treatments in emergency situations].

Mechanical and medicinal therapies are widely used in coronary disease patients for emergency or semi-emergency situations. Vasodilator drugs injected into arteries that are occluded or narrowed-drugs injected into arteries that are occluded or narrowed by spasm rapidly relieve that spasm; injecting these drugs prior to angioplasty renders the myocardium more tolerant to the ischaemia created by the dilated balloon. In unstable angina coronary angioplasty has a 90 p. 100 primary success rate with immediate complications that are slightly more frequent than in stable angina; compared to historical series with medicinal treatment, angioplasty reduces the risk of myocardial infarction and/or secondary death. In evolving myocardial infarcts the respective values of intracoronary thrombolysis and angioplasty are still under discussion, although the results of recent studies tend to favour intravenous thrombolysis and secondary, elective angioplasty.

Angina, Unstable

Infective endocarditis on stenotic aortic valves.

Charts were reviewed of 42 adult patients (27 men, 15 women, mean age 55 years, with 17 older than 60) hospitalized and/or autopsied between 1970 and 1986 with diagnosis of definite or highly probable infective endocarditis (IE) on pure aortic stenosis (AS). Ring and/or septal abscesses were found in 18/37 patients who were operated upon and/or autopsied. IE was recognized in 32 patients, undiagnosed in 10 (revealed at autopsy in seven, at operation in three). Infecting organisms were identified in 26 patients (Str. viridans, 16; Str. D, three; Staphylo., four; other, three). Twenty-seven patients were treated in our institution, 14 of them more than four weeks after the beginning of the symptoms. Echocardiograms were recorded in 17, with vegetations in only six. Severe cardiac failure was present in 17 cases. One patient was lost to follow-up. Fourteen patients died (mean delay between IE and death 22.4 months): eight of the 13 non-operated patients (cardiac failure, four; myocardial infarction, two; neurological complications, two) and six of the 14 operated patients (peri-operative death, four; late sudden death, two). Twelve patients are alive (mean follow-up 51.6 months), eight of them in NYHA class 1. IE on pure AS is rare, difficult to recognize echocardiographically, and of poor prognosis. It usually requires rapid aortic valve replacement.

Adult

[Are there risk factors for pure systolic hypertension?].

Pure systolic hypertension (PSH) is mainly observed in subjects over 60 years of age, and it is always due to a loss of compliance of the greater arteries. Blood pressure itself is partly responsible for loss of compliance, but other factors have been suggested. We have investigated this matter in a study of 3,388 subjects aged from 20 to 69 years. In a first stage, PSH patients (systolic BP greater than or equal to 160; diastolic BP less than 95 mmHg), aged from 50 to 59 years, were compared with normotensive subjects (systolic BP less than 140; diastolic BP less than 95 mmHg) and with other types of hypertensive patients with regard to cigarette smoking, alcohol consumption, obesity and plasma cholesterol, triglycerides, gamma-GT, glucose and uric acid levels. Several of these variables were significantly higher in all hypertensive patients than in normotensive subjects, but cigarette smoking and gamma-GT levels were predominantly or exclusively higher in PSH patients. In a second stage, correlations between differential BP and the variables listed above were studied in subjects with two levels of diastolic BP: 70-79 and 80-89 mmHg, thus taking into account all degrees between normal BP and PSH proper. Weakly positive correlations were found with alcohol consumption, plasma gamma-GT and glucose levels, and with percentages of smokers or ex-smokers. It is therefore conceivable that in addition to BP itself other factors, such as alcohol consumption, cigarette smoking and hyperglycaemia, contribute to the loss of arterial compliance progressively leading to pure systolic hypertension.

Adult

[Methods of evaluating myocardial revascularization surgery].

The quality of revascularization is evaluated by measurements of blood flow and various imaging methods. The quality of the anastomosis and the graft flow are evaluated per-operatively by ultrasounds and by measurements of intramyocardial pH. After surgery, Doppler velocimetry and radioisotope scanning assess the basal coronary flow and the coronary reserve. Graft patency can be studied by noninvasive methods (Doppler and kinetic CT with contrast injection), but conventional or digital angiography is irreplaceable for visualization. Residual myocardial ischaemia and left ventricular function are evaluated by the usual methods. Angina is not sensitive enough to serve as an indicator of residual or recurrent myocardial ischaemia. ECG at rest detects most peri-operative infarctions; Holter recordings may reveal a silent myocardial ischaemia; exercise stress ECG evaluates (albeit with insufficient sensitivity) post-bypass changes in myocardial ischaemia. Myocardial scintigraphy with thallium-201 is more sensitive, and it locates low perfusion areas. Cardiac wall kinetics and left ventricular function at rest and during exercise are studied by echocardiography and contrast or isotopic ventriculography, pending advances in nuclear magnetic resonance imaging. Surgical results have never been compared with other methods of direct myocardial revascularization, but only with medical treatments. Outstanding among the controlled studies carried out are a European study (E.C.S.S.) and two North American studies (V.A.S. and C.A.S.S.); they have shown what can be expected from coronary bypass, globally and in some subgroups of patients.

Angiography

[Atrial fibrillation: some current practical problems].

We emphasize: the great frequency of atrial fibrillation, present in approximately 10% of men and more than 20 p. cent of women hospitalized in a cardiology department; the advantage of a comprehensive etiological survey, reducing to less than 10 p. cent the percentage of idiopathic permanent atrial fibrillations, in this department; the need to take into account all factors determining the prognosis of atrial fibrillation: ventricular contractility and hemodynamic consequences of the rhythm disorder, volume of the left atrium, condition of the valvular orifices, risk of thrombo-emboly, etc., as well as the difficulty of therapeutic indications, linked on the one hand to the multiplicity of etiologies and prognosis factors, and on the other hand to the diversity of the therapeutic approaches, of which we are here reminded.

Adult

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