Combined heart-and-lung transplantation for lymphangioleiomyomatosis.
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Biomedical subjects
Publications and source records attributed to J L Leclerc.
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This morphologic study (X-ray examination of gross specimens, histologic study and histochemical staining) compares two groups of explanted left-sided bioprosthetic valves: group I, 6 valves with normal cusp function and group II, 10 valves with significant dysfunction. Implantation periods ranged from 26 to 79 months. A computerized descriptive statistical method (principal component analysis) is used to analyze the qualitative results. Although qualitatively identical alterations are observed in both groups, the findings in the deep layers of the cusps of severe collagen breakdown, intensive fibrin penetration and various degrees of calcification are restricted to group II. Other findings of interest in both groups include amyloid deposits (four cases) and layering of fusiform host cells on the cusp surface (three cases). The computerized study shows that individuals of one clinical group are morphologically different from those of the other. Mechanical stress may contribute to surface alterations early after implantation, while further collagen breakdown and macrophagic activity result in deep penetration of plasma components and fibrin. Subsequent calcification is likely to be dystrophic rather than metabolic. Colonization of the cuspal surface by endothelial cells after long-term implantation of bioprosthetic valves expresses a new type of relation between host and bioprosthesis.
In a series of 63 surgical patients with a positive history of rheumatic fever and whose aortic valve was removed either singly or in combination with other valves, the histological examination of the aortic valves showed functional lesions in 22 cases (35%). Organic lesions of inflammatory origin, destruction of the architecture with scarring and presence of hypertrophic vessels, were observed in 19 valves (30%). The other cases were doubtful. This ratio was identical in uni- and plurivalvular involvement. Anatomic aspects and significance of microscopic lesions of the aortic valves were discussed. The role of microthrombi and turbulent flow in the pathogenesis of the functional lesions is stressed. The authors conclude that there is no correlation between the anatomic aspects of the aortic valve deformity and the presence of histologically proven organic lesions of inflammatory origin. This provides support to the current opinion that rheumatic carditis is mainly a disease of the mitral valve.
Beta-adrenergic receptors were characterized in a particulate fraction of human auricles obtained from patients operated upon for coronary insufficiency or valvular disease. [125I] Hydroxybenzylpindolol binding was evaluated in terms of kinetics; KD and Bmax values; and inhibition of binding in the presence of 10 microM GTP and of increasing concentrations of four nonselective agonists giving a Hill coefficient of 1 (isoproterenol, salbutamol, fenoterol, and epinephrine), of two nonselective antagonists giving a Hill coefficient of 1 (pindolol and propranolol), and of a series of selective drugs giving a Hill coefficient of 0.60-0.72 that included three beta 1-selective antagonists (practolol, metoprolol, and atenolol) and two beta 2- selective agonists (procaterol and zinterol). KD values for all drugs were compatible with the coexistence in membranes from human auricles of beta 1- and beta 2-adrenergic receptors, the relative proportions of receptors of each subclass being approximately the same.
The beta-adrenergic stimulation of adenylate cyclase in membranes from human auricles, ventricles, and fetal heart was compared with the binding properties of beta-adrenergic receptors in human auricles. In terms of adenylate cyclase activation, three full agonists (isoproterenol, epinephrine, and norepinephrine), four partial agonists (procaterol, salbutamol, fenoterol, and zinterol), and four antagonists (propranolol, metoprolol, atenolol, and practolol) were tested. The beta-adrenergic activation of adenylate cyclase in membranes from rat heart (with a majority of beta 1-adrenergic receptors), rat erythrocytes, and rat reticulocytes (with a homogeneous population of beta 2-adrenergic receptors) served as reference. The reactivity of human heart adenylate cyclase, estimated by the Kact or Ki values of 11 beta-adrenergic agents, indicated that the activation of this enzyme occurred through receptors of the beta 2-subtype only. Receptors of the beta 1-subtype (50% of the total population) were not coupled to the enzyme.
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Considering the recent rediscovery of the use of alpha-blocking agents in the treatment of hypertension and heart failure, we have studied the haemodynamic effects of 10-methyl-1,6-dimethyl-ergoline-8 beta-methanol-(5-bromonicotinate (nicergoline, Sermion), a new alpha-blocking ergot derivative, on the closed-chest anesthetized dog. For comparative reasons, the effects of nitroglycerin and nitroprusside were studied on the same model. The doses were adjusted to give an identical decrease in blood pressure after 30 min infusion (nearly 30%). Nicergoline did not change the heart rate, decreased total and femoral arterial resistance, did not change the cardiac output or the femoral flow, as opposed to nitroglycerin which decreased the cardiac output and systolic volume, causing a reflex tachycardia and femoral constriction, confirming its predominantly venous effect. Nitroprusside did not cause tachycardia, and the femoral resistances were increased, though less so than with nitroglycerin. Both nitroglycerin and nitroprusside apparently had no direct effect on myocardial performance, whilst nicergoline seemed to increase the myocardial compliance (by a decrease of the sympathetic tone). This drug merits further attention in that it is readily soluble and can easily be administered i.v., for treatment of acute heart failure, for example.
The actions of four dopaminergic agonists (apomorphine, bromocriptine, amantadine, piribedil) on a conditioned avoidance response were studied in normoxic or hypobaric hypoxic rats. Low doses of agonists have no effects on normoxia, but induce an antihypoxic protection (improvement of learning both in normoxia and hypobaric hypoxia. The possibility of an antihypoxic property induced by dopaminergic post-synaptic receptors stimulation is discussed and seems to be the main receptors stimulation is discussed and seems to be the main phenomenon while action or other non-specific sites seems to be responsible for the high dose-induced impairment of learning and of resistance to hypoxia.
The learning of a conditioned avoidance response, the catecholamine levels in some cerebral structures, and the evolution of the cortical PO2, were studied under hypobaric hypoxia (300 torr) and under normoxia, in rats treated or not with apomorphine, at the dose of 1 or 10 mg/kg i.p. Apomorphine at 1 mg/kg improves the learning capacity and stabilises the cerebral catecholamine levels under hypoxia; no modification of the evolution of the cortical PO2 during hypoxia was observed between control rats and rats treated with this dose of apomorphine. Apomorphine at 10 mg/kg totally inhibits learning under normoxia or hypoxia. It is therefore possible to suppose that the antihypoxic protective mechanism of low-dose apomorphine is due to a stabilization of the levels of both dopamine and noradrenaline during hypoxia, but not to an increase in the cerebral oxygen availability. These data suggest the clinical possibility of using other dopaminergic stimulating agents for their eventual antihypoxic properties.
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