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Biomedical subjects

A Castaigne

Publications and source records attributed to A Castaigne.

At least 19 recordsLinked to original sources

[Converting enzyme inhibitors and coronary failure].

Nearly 15 years ago, it has been shown that myocardial infarction is accompanied by left ventricular dilatation. In the following years more details were obtained on morphological changes consecutive to myocardial infarction, now grouped together under the term left ventricular remodelling. These changes enable the patients to survive despite reduction of the contractile ventricular mass, but they expose the ventricles to constraints resulting in excessive work load. It has been shown that these changes can be reduced by early myocardial reperfusion and by administration of angiotensin-converting enzyme (ACE) inhibitors. These findings were established first in animals, then in man. Administering ACE inhibitors to patients with symptomatic heart failure consecutive to advanced ischaemic cardiopathy prolongs the patients' survival. When ACE inhibitors are given to patients with severe asymptomatic left ventricular dysfunction which started soon or long after a myocardial infarction, they reduce the frequency of ischaemic events, passage to symptomatic heart failure and, at least in one study, mortality. ACE inhibitors have also been shown to reduce the size of myocardial necrosis when administered in the acute phase of experimental myocardial infarction. Preliminary data have demonstrated that ACE inhibitors given in the acute phase of myocardial infarction reduce the left ventricular dilatation which follows infarction. However, a study of ACE inhibitors administered to a large number of patients in the acute phase of myocardial infarction had to be interrupted because of the over-mortality in the treated group. These facts are reviewed in this article, and attempts have been made at deducing from them the current indications of ACE inhibitors in patients with coronary heart disease.

Angiotensin-Converting Enzyme Inhibitors

Effects of infusion of L-arginine into the left anterior descending coronary artery on acetylcholine-induced vasoconstriction of human atheromatous coronary arteries.

Hypercholesterolemia and atherosclerosis are conditions associated with impaired endothelium-dependent relaxation. In hypercholesterolemic animals, intravenous administration of L-arginine, the precursor of nitric oxide, normalizes endothelium-dependent vasodilator activity. In the present study, we questioned whether intracoronary administration of L-arginine in patients with coronary artery disease could improve coronary vascular reactivity to acetylcholine. Thirteen hypercholesterolemic patients with diffuse coronary atherosclerosis but nonstenotic lesions of the left anterior descending (LAD) coronary artery were investigated. Quantitative coronary angiography and subselective intracoronary Doppler flow velocity measurements were performed to determine LAD diameters and coronary blood flow. Intracoronary infusion of acetylcholine was performed during 3 consecutive 3-minute periods at incremental rates adjusted to achieve estimated final concentrations of 5 x 10(-7), 10(-6) and 5 x 10(-6) M. After evaluation of the response to acetylcholine, L-arginine was infused into the LAD at the rate of 25 mg/min (10(-3) M) and the same stepwise 3-minute infusions of acetylcholine were repeated during infusion of L-arginine. Infusion of acetylcholine induced a dose-dependent reduction of distal epicardial LAD diameter reaching -48.5 +/- 17% at 5 x 10(-6) M (p < 0.01 vs control values). L-arginine alone had no effect on the distal LAD diameter but attenuated acetylcholine-induced vasoconstriction to -21 +/- 9% at 5 x 10(-6) M acetylcholine (p < 0.01). Coronary blood flow showed a biphasic response to acetylcholine, increasing by 41 +/- 12% at 5 x 10(-7) M (p < 0.01) and decreasing by 21 +/- 13% at 5 x 10(-6) M (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

[Which medical treatment after myocardial infarction?].

Patients leaving the hospital after a myocardial infarction are given a prescription containing several drugs. The purpose of this paper is to determine which of these drugs have a proven value and for which types of patients. Antithrombotic agents (be it acetyl-salicylic acid or antivitamin K drugs) have been shown to be efficient after a myocardial infarction. Beta-blockers are certainly useful, notably in cases with severe necrosis. Conversely, the usefulness of calcium antagonists for secondary prevention has not been demonstrated and indeed, it seems probable that the drugs of this class might be harmful in patients who had severe infarction. There is little divergence concerning the necessity to control the risk factors for coronary atherosclerosis after a myocardial infarction. The evidence is strong concerning giving up smoking; it is intuitive as regards controlling arterial hypertension and more controversial as regards the need for lowering blood cholesterol levels. The systematic prescription of antiarrhythmic agents after myocardial is certainly noxious. Finally, prospects are now opened by the prevention of left ventricular remodelling under treatment with angiotensin-converting enzyme inhibitors.

Adrenergic beta-Antagonists

Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.

This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Improvement in exercise performance by inhalation of methoxamine in patients with impaired left ventricular function.

BACKGROUND: Bronchial hyperresponsiveness to cholinergic stimuli such as the inhalation of methacholine is common in patients with impaired left ventricular function. Such hyperresponsiveness is best explained by cholinergic vasodilation of blood vessels in the small airways, with extravasation of plasma due to high left ventricular filling pressure. Because this vasodilation may be prevented by the inhalation of the vasoconstrictor agent methoxamine, we studied the effect of methoxamine on exercise performance in patients with chronic left ventricular dysfunction. METHODS: We studied 19 patients with a mean left ventricular ejection fraction of 22 +/- 4 percent and moderate exertional dyspnea. In the first part of the study, we performed treadmill exercise tests in 10 patients (group 1) at a constant maximal workload to assess the effects of 10 mg of inhaled methoxamine on the duration of exercise (a measure of endurance). In the second part of the study, we used a graded exercise protocol in nine additional patients (group 2) to assess the effects of inhaled methoxamine on maximal exercise capacity and oxygen consumption. Both studies were carried out after the patients inhaled methoxamine or placebo given according to a randomized, double-blind, crossover design. RESULTS: In group 1, the mean (+/- SD) duration of exercise increased from 293 +/- 136 seconds after the inhalation of placebo to 612 +/- 257 seconds after the inhalation of methoxamine (P = 0.001). In group 2, exercise time (a measure of maximal exercise capacity) increased from 526 +/- 236 seconds after placebo administration to 578 +/- 255 seconds after methoxamine (P = 0.006), and peak oxygen consumption increased from 18.5 +/- 6.0 to 20.0 +/- 6.0 ml per minute per kilogram of body weight (P = 0.03). CONCLUSIONS: The inhalation of methoxamine enhanced exercise performance in patients with chronic left ventricular dysfunction. However, the improvement in the duration of exercise at a constant workload (endurance) was much more than the improvement in maximal exercise capacity assessed with a progressive workload. These data suggest that exercise-induced vasodilation of airway vessels may contribute to exertional dyspnea in such patients. Whether or not inhaled methoxamine can provide long-term benefit in patients with heart failure will require further study.

Administration, Inhalation

Beta-adrenergic contractile reserve as a predictor of clinical outcome in patients with idiopathic dilated cardiomyopathy.

To examine the ability of beta-adrenergic contractile reserve assessment to predict the outcome of patients with heart failure, a prospective study was undertaken in 35 patients with idiopathic dilated cardiomyopathy and radionuclide ejection fraction below 40%. During right- and left-sided catheterization, right atrial and left ventricular (LV) pressures, peak positive LV dp/dt, cardiac index, and plasma norepinephrine and epinephrine concentrations were measured at baseline. After a left main intracoronary infusion of dobutamine (25 to 200 micrograms.min-1), beta-adrenergic contractile responsiveness was assessed as the net increase in peak positive LV dp/dt (delta LV dp/dt). After the initial examination, patients were treated with diuretics, digitalis, and angiotensin converting enzyme inhibitors and then followed-up. After a mean follow-up period of 13 +/- 7 months, two groups of patients were distinguished: those who responded to medical therapy (group A, n = 26) and those with clinical deterioration (group B, n = 9) leading to death (n = 4) or heart transplantation (n = 5). Initial peak positive LV dp/dt, LV end-diastolic pressure, cardiac index, and LV ejection fraction were better in group A than in group B (p less than 0.001). Initial plasma norepinephrine and epinephrine concentrations were significantly higher and delta LV dp/dt was lower in group B than in group A (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Relationship among neuropeptide Y, catecholamines and haemodynamics in congestive heart failure.

The relationship among neuropeptide Y (NPY), catecholamines and haemodynamics was assessed both at baseline and during inotropic intervention in patients with congestive heart failure. Eighteen patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction (LVEF) = 26 +/- 10%) underwent both right and left catheterization. Haemodynamic parameters were recorded at baseline and during dobutamine infusion. To measure norepinephrine (NE), epinephrine (E) (nmol.l-1: radioenzymatic assay) and NPY (pmol.l-1: immunoradiometric assay) plasma concentrations, blood samples were drawn from the femoral artery and from the coronary sinus, both at baseline and during dobutamine infusion. At baseline, NPY concentration were 2.15 +/- 0.97 pmol.l-1 in the femoral artery and 1.97 +/- 0.63 pmol.l-1 in the coronary sinus. Peripheral concentrations of NPY were, however, no different from those of patients without congestive heart failure: 2.4 +/- 2.7 pmol.l-1. Peripheral NE concentration was correlated to haemodynamic parameters: LVEF (r = -0.65; P less than 0.01), cardiac index (r = -0.54; P less than 0.05), LV end-diastolic pressure (r = +0.59; P less than 0.05), while peripheral NPY and E concentrations were not. Dobutamine improved haemodynamics, since cardiac index increased by 30% and LV end-diastolic pressure decreased by 40% (P less than 0.01). Peripheral NE concentration decreased from 6.48 +/- 4.5 to 4.82 +/- 2.69 nmol.l-1 (P less than 0.05) but there was no change in E (0.99 +/- 0.61 vs 1.04 +/- 0.74 nmol.l-1) or NPY concentrations (2.41 +/- 0.99 pmol.l-1). In the coronary sinus, neither NE nor NPY concentrations changed during dobutamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Myocardial beta-adrenergic desensitization and neuronal norepinephrine uptake function in idiopathic dilated cardiomyopathy.

Desensitization of myocardial beta-adrenergic receptors may result both from an impairment of the norepinephrine (NE) neuronal uptake function and from an increase in circulating NE concentrations. The respective role of these two mechanisms of desensitization was examined in 18 patients with congestive heart failure related to an idiopathic dilated cardiomyopathy. The neuronal NE uptake system was evaluated by [123I]metaiodobenzylguanidine (MIBG) scintigraphy. The desensitization level of beta-adrenoceptors was assessed as the net increase in peak positive left ventricular (LV) dP/dt during intracoronary dobutamine infusion. Arterial NE concentrations were determined at baseline. To obtain control values, we performed MIBG scintigraphy and determined baseline NE concentration in 12 normal subjects. Cardiac MIBG uptake was significantly decreased in patients as compared with controls. This decrease was related to the severity of the disease based on hemodynamic indexes. The inotropic response to intracoronary dobutamine infusion of heart failure patients correlated with both increased baseline NE concentration and diminished cardiac MIBG uptake (r = -0.63, p less than 0.01 and r = 0.73, p less than 0.001, respectively). These findings indicate that the desensitization process is related both to impaired neuronal NE uptake function and increased circulating NE concentrations. Moreover, a subset of 11 patients with moderate heart failure was identified who had diminished cardiac MIBG uptake but normal circulating NE concentrations. This suggests that impairment of the NE uptake function is an early mechanism of desensitization in idiopathic cardiomyopathy. Cardiac MIBG imaging may be a noninvasive means to assess severity of heart failure patients and may also be used to evaluate therapy effects on myocardial alterations of the adrenergic pathway.

3-Iodobenzylguanidine

L-arginine improves endothelium-dependent relaxation of conductance and resistance coronary arteries in coronary artery disease.

To assess the ability of L-arginine to improve endothelium-dependent vasodilation in atheromatous coronary arteries, we determined whether intracoronary infusion of L-arginine could improve coronary vascular reactivity to acetylcholine (ACh) examining both conductance and resistance vessels. Coronary blood flow velocity was assessed by positioning a 3 Fr Doppler catheter into the proximal coronary artery segment (six left anterior descending and one circumflex coronary artery). Computed quantitative angiography allowed the measurement of distal diameters. After baseline measurements, ACh was infused at incremental infusion rates through the Doppler lumen catheter (3 min period each) to obtain the estimated concentrations of 5 x 10(-7), 10(-6), and 5 x 10(-6) M. After returning to baseline, L-arginine was infused at the rate of 25 mg/min (10(-3) M) through the Doppler lumen catheter. Infusion of ACh was then repeated according to the same protocol than in the absence of L-arginine. The heart rate and mean arterial blood pressure did not change at any step of the protocol. Infusion of ACh induced dose-dependent vasoconstriction of coronary distal segments with a reduction in coronary distal segments by 39 +/- 15% at 5 x 10(-6) M (p < 0.01). During infusion of L-arginine, the coronary diameter was reduced by only 16 +/- 10% (p < 0.05) at the highest ACh dose. The coronary blood flow velocity increased by 100 +/- 15% at 5 x 10(-7) M ACh (p < 0.05) but only to 16 +/- 15% at 5 x 10(-6) M ACh (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

[Hemodynamic study of intravenous milrinone in 26 patients with NYHA class III or IV cardiac failure].

The hemodynamic effects of milrinone (WIN 47203) were studied in 26 NYHA Class III or IV patients. The compound was administered intravenously using a protocol including an initial push dose of 50 micrograms/kg in 10 min, followed by a 24 hour infusion at the dose of 0.5 microgram/kg/min. Maximal response was obtained after 15 min and persisted during the infusion: cardiac index increased from 2.08 +/- 0.36 l/min/m2 to 3.09 +/- 0.68 l/min/m2, while capillary pressure fell from 25 mmHg to 16-17 mmHg. These variations were significant (p = 0.01). Heart rate was stable. Mean peripheral blood pressure fell modestly (6%). Systemic vascular resistance fell by 30% and pulmonary vascular resistance by 20%. All these results confirmed the beneficial effect of this inotropic agent administered intravenously. The increase in ventricular premature contractions noted by many justifies the careful surveillance of these patients by monitoring.

Adult

[Role of antithrombotic agents after myocardial infarction].

Thrombosis is the causal mechanism of myocardial infarction: severe atherosclerotic narrowing, ulceration of the atherosclerotic plaque and disequilibrium between pro and antithrombotic factors, predispose to this complication. Recurrent myocardial infarction is a common complication in the year following an initial event: the risk is higher when the diseased artery has been recanalized in the acute phase. Reocclusion of the recanalized artery without signs of infarction is also a common occurrence. It was therefore logical to have striven over the years to prevent reinfarction and/or rethrombosis after reperfusion. Mechanical methods have not been crowned with resounding success and antithrombotic drugs are the only products associated with real benefits in this prevention. In this article, the authors review the efficacy of aspirin and vitamin K antagonists in the prevention of recurrent myocardial infarction; the data in favour of an efficacy of aspirin in preventing early reinfarction is also analysed; finally, results suggesting a benefit of platelet antiaggregant therapy (Flurbiprofen or aspirin) on the risk of reocclusion after therapeutic recanalisation are also assessed.

Anticoagulants

[Artificial hearts. The experience of Henri Mondor University Hospital].

Results obtained with 52 patients referred for urgent heart transplantation or when transplantation was impossible because no graft, mechanical assistance or circulatory support were available, are reported. These suggest that the protocol used to select the indications of assistance and transplantation, based on the response to the introduction of enoximone into the medical treatment, allows reconciling the patients' interest-their survival-with the community's interest-i.e. the control of the costs of implemented treatments.

Adult

[Prehospital thrombolytic therapy].

The objective of pre-hospital thrombolytic therapy is to reduce the delay between the time of initial contact with a patient with acute myocardial infarction and the administration of thrombolytic therapy. To validate feasibility and utility. Its feasibility has been demonstrated in many pilot studies throughout the world. The utility of the technique is the gain of nearly 60 minutes compared with patients treated on hospital admission; another advantage is the fact that emergency medical teams are alerted to their new medical responsibility. On the other hand, there are no published reports showing a decreased infarct size or mortality when compared with in-hospital thrombolysis. The results of studies currently under way are expected in the near future and should throw new light on the value of this technique. Nevertheless, pre-hospital thrombolysis is only one facet in the improved management of acute myocardial infarction.

Emergency Medical Services

[Coronary vascular reserve in heart transplantation. Normalization after therapy for rejection].

Acute rejection is associated with severe impairment of coronary reserve in heart transplants. To evaluate the effects of rejection therapy, coronary reserve was assessed in 6 patients before and after treatment of an acute episode of rejection. Coronary reserve was significantly enhanced after rejection therapy (4.7 +/- 0.8, vs 2.3 +/- 0.5, P less than 0.001) and was not significantly different from that of transplanted patients without rejection (5.4 +/- 0.8). This study provides evidence that alterations of coronary reserve due to acute rejection are reversible after treatment of the rejection episode.

Acute Disease

[Neuroendocrine adaptations in chronic congestive heart failure].

Chronic congestive heart failure is typically accompanied by an abnormal production of vasoconstrictor antinatriuretic hormones and vasodilator natriuretic hormones. Decompensation occurs when the former prevail over the latter. These neuroendocrine abnormalities are increasingly taken into account to determine the prognosis and to decide on the best therapeutic approach in individual patients with chronic heart failure.

Adaptation, Physiological

Hemodynamic response to intracoronary infusion of atrial natriuretic factor in patients with normal or altered left ventricular function.

To assess the effects of atrial natriuretic factor (ANF) on cardiac function, synthetic human ANF was infused directly into the left main coronary artery of eight patients with congestive heart failure (CHF) and six subjects with normal left ventricular (LV) function (controls) who underwent cardiac catheterization. ANF infusion at the incremental rates of 60, 125, 400, and 800 ng/min induced a dose-related increase in plasma ANF concentrations in the coronary sinus, from 1,223 +/- 590 to 3,923 +/- 1,123 pg/ml in patients with CHF (p less than 0.01) and from 1,041 +/- 605 to 2,710 +/- 1,741 pg/ml in controls (p less than 0.01). Peripheral plasma ANF concentrations (femoral artery) increased from 538 +/- 278 to 752 +/- 262 pg/ml (p less than 0.01) in patients with CHF and from 193 +/- 63 to 401 +/- 147 pg/ml (p less than 0.01) in controls. The increase in peripheral or coronary sinus plasma ANF concentrations did not differ between patients with CHF and controls. At the three lowest ANF infusion rates, cardiac index (CI), systemic vascular resistance (SVR), and LV contractility assessed by peak positive dP/dt remained unchanged both in patients with CHF and in controls. At the highest ANF infusion rate, CI increased from 2.18 +/- 0.53 to 2.54 +/- 0.49 L/min/m2 (p less than 0.01) and SVR decreased from 14.6 +/- 3.6 to 12.8 +/- 4.5 mm Hg.min/L (p less than 0.01) in patients with CHF. There was no associated change in heart rate (HR), mean arterial blood pressure (MAP), cardiac filling pressures, or peak positive dP/dt.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult