[Heart transplantation in children].
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Biomedical subjects
Publications and source records attributed to M Bevilacqua.
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Idiopathic orthostatic hypotension (IOH) represents a degenerative disorder of the peripheral nervous system characterized by low values of arterial blood pressure during orthostatism, with reduction in serum catecholamines. Since treatment of symptomatic IOH has been unsatisfactory till now, we studied the hemodynamic response to somatostatin (S) (Octreotide, 100 micrograms sc) at rest (R) and during sympathetic activation (tilting, T) by means of 2D and/or color Doppler echocardiography, in 5 ambulatory IOH patients (4M, 1F; aged 65 +/- 5 years), with simultaneous recording of blood pressure and heart rate. Post-S, an increased blood pressure was evident during T without heart rate modifications (pre- vs post-S, SAP: 92 +/- 9 vs 148 +/- 12; DAP: 61 +/- 4 vs 90 +/- 9 mmHg; p less than 0.05), while systolic echo parameters did not change significantly. Doppler aortic velocity curve showed during T a reduction of Vmax (pre- vs post-S: 0.98 +/- 0.09 vs 0.73 +/- 0.03 m/s; p less than 0.05) and of cardiac output, due to unchanged preload. Pre-S, at rest, Doppler mitral velocity curve presented a normal E/A ratio as in normal subjects, with a reduced E peak and an increased A peak post-S, indirect signs of increased afterload. Pre-S, E and A peak velocities underwent progressive decrease during T, markedly more evident post-S. Total peripheral resistance, at rest and during T, increased post-S too (pre- vs post-S, rest: 2406 +/- 267 vs 3162 +/- 599; T: 1634 +/- 201 vs 2784 +/- 425 dyne*s/cm-5; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelial leukocyte adhesion molecule-1 (ELAM-1) is an endothelial cell adhesion molecule that allows myeloid cells to attach to the walls of blood vessels adjacent to sites of inflammation. ELAM-1 recognizes the sialyl-Lewis X (sialyl-Lex) determinant, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-, a granulocyte carbohydrate also found on the surface of some tumor cell lines. Binding of myeloid cells to soluble ELAM-1 is inhibited by a monoclonal antibody recognizing sialyl-Lex or by proteins bearing sialyl-Lex, some of which may participate in humoral regulation of myeloid cell adhesion. Stimulated granulocytes also release an inhibitor of ELAM-1 binding that can be selectively adsorbed by monoclonal antibody to sialyl-Lex.
Studies were carried out in the rat in order to investigate whether cholinergic mechanisms may be involved in vasopressin (VP) release induced by metoclopramide (MCP). The intravenous injection of MCP induced dose-related increases in plasma VP levels in water-loaded rats. These effects were prevented by atropine sulphate, but not by pirenzepine hydrochloride indicating that activation of cholinergic receptors of M-2 type was possibly required for the biologic response.
A girl affected by a restrictive cardiomyopathy with neuromuscular involvement is described. Morphological examination showed a pattern of multicore myopathy and with electron microscopy a sarcoplasmic accumulation of electron dense granular and filamentous material was demonstrated both in skeletal muscle and heart. This peculiar electron dense material corresponded to increased desmin in muscle and cardiac fibres and was demonstrated immunohistochemically.
The internal mammary artery (IMA) is the graft of choice for CABG but has a limited number and length. For multivessel coronary disease, saphenous vein grafts have to be added but they show poorer long-term patency. Investigation to provide adjunctive reliable grafts has recently focussed on the right gastroepiploic artery (GEA) and encouraging results have been reported employing this vessel as a pedicled graft to bypass distal coronary vessels. From December 1988 to February 1989, to achieve complete myocardial revascularization with only arterial grafts we used a GEA free graft in combination with the two IMAs in 20 consecutive patients under 70 years of age undergoing elective surgery. Before starting, histological studies were carried out and a significant similarity between IMA and GEA was found. In the 20 patients, 76 coronary anastomoses were performed (3.8 bypasses/patient), the GEA graft revascularized the right coronary artery in 9 patients, the circumflex in 8 patients and the anterior descending and/or diagonal in 3 patients; in 7 patients the GEA graft was used for sequential anastomoses. No perioperative deaths, no myocardial infarctions and no gastroenterological complications occurred. Coronary angiographic postoperative control showed 20/20 patent GEA grafts. After follow-up ranging from 7 to 9 months, all patients are free from angina. The GEA free graft is not difficult to harvest, is easier than the pedicled GEA graft to handle in the pericardium and is suitable for sequential anastomoses. The use of GEA graft however increases the complexity of bypass operations.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac surgery in 602 children was not preceded by cardiac catheterization, the diagnosis being based on clinical findings and two-dimensional and Doppler echocardiography. In the 355 operations without cardiopulmonary bypass there were nine major and seven minor diagnostic errors (2.5% and 2%). Among the 247 cases with open-heart surgery there were no major and eight (3.2%) minor errors. The malformations most suitable for nonbypass surgery without catheterization seem to be those with reduced pulmonary blood flow requiring systemic-pulmonary artery shunt, aortic coarctation and patent ductus arteriosus. For open-heart surgery without invasive investigation, atrial septal defect, partial atrioventricular canal, aortic and pulmonary stenosis, cardiac tumor and isolated valve disorder are 'classic' candidates. Recent experience indicated that selected cases of complete atrioventricular canal, tetralogy of Fallot, truncus arteriosus, total anomalous pulmonary venous connection and transposition of the great arteries may safely undergo primary repair without cardiac catheterization. Because of its diagnostic potentialities, pediatric cardiac surgeons must become familiar with echocardiography.
We investigated the effect of respiratory-burst stimulants on beta-2 adrenoceptors in human polymorphonuclear leukocytes (PMNL). Pre-incubation of PMNL with these substances did not affect the number or affinity of the receptors but desensitized them, as shown by the "right-shift" in (-)-isoproterenol competition isotherms. H-7, an established protein kinase C inhibitor, and nimesulide, a new putative inhibitor of this enzyme, blunted both superoxide anion production and beta-2 adrenoceptor desensitization. A positive correlation was found between superoxide anion generation and the "right-shift" in isoproterenol competition isotherm (r = 0.92; p less than 0.01). Desensitization of beta-2 adrenoceptors was not due to superoxide anions per se since incubation of PMNL with superoxide anion scavengers (superoxide dismutase and catalase) did not modify the results.
To determine the effects of beta blockade on hemodynamics during increasing levels of treadmill exercise, 10 healthy volunteers were studied after 1 week of placebo, and then after 1 week of treatment with oral propranolol, 80 mg twice daily, or dilevalol, 400 mg once daily. The study was randomized and double-blind, with a crossover sequence. Hemodynamics were measured by CO2 rebreathing at rest and at 25, 50, 75 and 100% of VO2 max. After placebo, cardiac output increased from 5.8 +/- 2.1 (rest), to 19.4 +/- 6.4 liters/min (100% VO2 max), mainly due to an increase in heart rate from 84 +/- 6 to 169 +/- 15 beats/min. Stroke volume increased from 70 +/- 27 (rest), to 137 +/- 65 ml (25% VO2 max), and then leveled off to 116 +/- 41 at 100% VO2 max. After both beta blockers, exercise cardiac output was maintained at 100% VO2 max: 20.1 +/- 9.3 liters/min with propranolol and 19.1 +/- 8.6 with dilevalol. However, a significant reduction versus placebo values was observed for cardiac output at 25% VO2 max, from 13.7 +/- 5.9 during placebo, to 9.4 +/- 2.5 during propranolol, and to 9.6 +/- 2.3 during dilevalol (both p less than 0.01 vs placebo). Maintenance of cardiac output with both beta blockers at higher levels of exercise came from an increased stroke volume (p less than 0.05 vs placebo), while heart rate (in beats/min) was greatly reduced (propranolol 61.6 +/- 9.4 rest, 90.1 +/- 10.7 at 100% VO2 max; dilevalol 70.8 +/- 6.4 rest, 99.2 +/- 11.8 at 100% VO2 max, p less than 0.01 vs placebo for each).(ABSTRACT TRUNCATED AT 250 WORDS)
beta- And alpha 1-adrenoceptor antagonist properties of bufuralol, carvedilol, celiprolol, dilevalol, labetalol, and pindolol were investigated in human myocardium and mammary artery using binding techniques and functional studies. In myocardial membranes, beta-adrenoceptor antagonists showed monophasic competition isotherms for [125I]pindolol binding with high affinity (Ki from 1-100 nM), except for celiprolol which displayed a biphasic competition isotherm (pKi = 6.4 +/- 0.06 for beta 1- and 4.8 +/- 0.07 for beta 2-adrenoceptors). Drug interactions with alpha 1-adrenoceptors were evaluated in human mammary artery by [3H]prazosin binding and by measuring contractile responses to norepinephrine (NE). Labetalol and carvedilol showed a moderate affinity for alpha 1-adrenoceptors (pKi = 6.2 +/- 0.01 and 6.1 +/- 0.06, respectively), and inhibited NE-induced contractions (pA2 = 6.93 +/- 0.23 and 8.64 +/- 0.24, respectively). Dilevalol, bufuralol, and pindolol displayed weak effect both in binding (Ki in micromolar range) and functional experiments (pA2 = 5.98, 5.54, and 6.23, respectively). Celiprolol did not show antagonist properties up to 100 microM in functional studies, but displayed a slight affinity for alpha 1-adrenoceptors in binding studies. The data indicate that the vasodilating activity of these beta-adrenoceptor antagonists is caused in some instances by an alpha 1-adrenoceptor antagonism (labetalol, carvedilol), whereas for the others alternative mechanisms should be considered.
Discontinuous density sucrose gradient centrifugation was used to isolate membrane vesicles from the left ventricle of three normal subjects (one prospective organ donor and two traffic victims whose hearts were obtained 1 hour after death) and nine patients undergoing cardiac transplantation as a consequence of idiopathic dilated cardiomyopathy. Sarcolemma-enriched subcellular fractions, detected in the interface between 8.55% and 25% sucrose, were identified by the increased activity of Na+,K+-ATPase and by enrichment in beta-adrenergic receptor density. The density of beta-adrenergic receptors was lower in vesicles from diseased hearts (610 +/- 71 fmol/mg protein) than in vesicles from normal hearts (1,410 +/- 226 fmol/mg protein; p less than 0.01). alpha 1-Adrenergic receptors were identified in these membrane vesicles by [3H]prazosin binding. Specific binding of [3H]prazosin was about 50% of the total binding at 1 nM, and alpha 1-adrenergic binding sites were saturable at approximately 3 nM. Scatchard analysis revealed 58 +/- 5 fmol/mg protein (KD = 0.90 +/- 0.08 nM) in pathological hearts and 30 +/- 5 fmol/mg protein (KD = 0.90 +/- 0.03 nM) in normal hearts (p less than 0.01). The displacement curve of (-)-norepinephrine in membrane vesicles from normal hearts delineated one subpopulation of alpha 1-adrenergic receptors; the addition of 0.1 mM GTP did not cause right shift. In membrane vesicles from diseased heart, the displacement curve of (-)-norepinephrine disclosed two subpopulations of alpha 1-adrenergic receptors. A right shift that occurred after addition of GTP showed that in this case alpha 1-adrenergic receptors were functionally coupled with GTP-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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A decreased concentration of vasopressin (AVP) in the plasma of patients with Alzheimer's disease has been shown recently and suggests damage to hypothalamic neurosecretory cells. To verify this, osmolar and hypotension (sodium nitroprusside) stimulations on AVP release were applied. The effect of metoclopramide, a powerful stimulator of AVP, was also assessed. Patients with Alzheimer's disease released AVP normally after hypotension. However, AVP response to osmotic stimulation was altered in eight out of 10 patients, owing to low osmoreceptor sensitivity and/or high threshold. Metoclopramide increased AVP in controls but not in patients. Normal AVP response to hypotension in patients with Alzheimer's disease makes it unlikely that there is a significant anatomical loss or damage of hypothalamic neurosecretory cells. Alterations in osmoreceptor function and AVP unresponsiveness to metoclopramide point to damage in the control of AVP release in Alzheimer's disease.
Adrenergic receptors were identified in healthy human hepatic tissue from thirty-nine subjects undergoing elective abdominal surgery by using the specific alpha 1-antagonist [3H]-prazosin and the beta adrenergic antagonist [3H]-dihydroalprenolol ([3H]-DHA). [3H]-prazosin binding to plasma membranes was rapid, of high affinity, saturable and stereospecific with a maximal binding capacity (Bmax) of 74.1 +/- 5.5 fmol mg-1 of protein. The displacement curve for (-)-norepinephrine was better explained by a one-site binding and after addition of GTP 0.1 mM the curve was not right-shifted, suggesting the majority of alpha receptors in healthy human liver are of the alpha 1 subtype and not linked to a GTP-binding protein. [3H]-DHA binding to liver plasma membranes was also rapid, of high affinity, saturable and stereospecific with a Bmax 96.5 +/- 10.3 fmol mg-1 of protein of receptors. Computer aided analysis of the displacement curve of ICI 118,551, a subtype selective beta 2-antagonist (IC50 = 62 +/- 2 nM), indicated a one-site binding, thus, showing that beta adrenergic receptors are of the beta 2 subtype. The displacement curve of [3H]-DHA for (-)-isoproterenol was right shifted by GTP indicating that beta 2 adrenergic receptors are linked to a GTP-binding protein in human liver. These results indicate that alpha 1- and beta 2-receptors co-exist in human liver but only beta 2-receptors are linked to a GTP-binding protein.
The study was undertaken to define the relationships between the arginine vasopressin (AVP) response to a pressure-volume stimulus (upright posture test), an osmolar challenge, and metoclopramide injection (20 mg, iv) in normal young and elderly subjects. Besides confirming previous findings of increased AVP responsiveness to osmolar challenge and reduced AVP responsiveness to upright posture in the elderly, we found that metoclopramide stimulated AVP release in both young [from 1.09 +/- 0.05 (mean +/- SD) to 1.77 +/- 0.05 pmol/L; P less than 0.05] and elderly subjects (from 1.54 +/- 0.18 to 4.73 +/- 1.82 pmol/L; P less than 0.01). The response was much greater in the elderly (P less than 0.01). The AVP responses to upright posture and metoclopramide were inversely correlated (r = -0.77; P less than 0.01), suggesting that the elderly have increased sensitivity to stimuli, such as metoclopramide, to counteract their reduced sensitivity to baroreceptor stimulation of AVP release.
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To identify the pattern of pulmonary anatomy and pulmonary blood supply, we analyzed the angiocardiograms of 40 patients with pulmonary atresia and complex congenital heart disease. All patients but two (95%) had confluent pulmonary arteries supplied by a patent ductus arteriosus. These two patients (5%) had nonconfluent pulmonary arteries, one with major systemic-pulmonary collateral arteries and absent patent ductus arteriosus and the other with a patent ductus arteriosus supplying the right lung and small collateral arteries supplying the left. The low incidence of pulmonary arterial abnormalities and the uniform pattern of pulmonary blood supply make the patients with pulmonary atresia and complex congenital heart disease potential candidates for palliative operation without cardiac catheterization in the neonatal period.