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Biomedical subjects

M Yacoub

Publications and source records attributed to M Yacoub.

At least 217 records · Page 12Linked to original sources
PubMed1991

Effect of heart-lung transplantation on airway potential difference in patients with and without cystic fibrosis.

Measurement of the potential difference (PD) across the airways provides an indication of the viability and integrity of the lining epithelium. PD was recorded from the lower airways in "diseased controls" and in patients following heart-lung transplantation. Diseased controls showed a high PD centrally which fell (became less negative) peripherally (trachea -15.8 mV (SEM 1.0), lobar bronchi -12.6 mV (1.2), segmental bronchi -9.8 mV (1.2]. Following heart-lung transplantation (HLT) the profile of PD with airway size was altered in comparison to non-transplanted patients with reduced values in the large airways. Host tracheal values above the anastomosis were similarly reduced. Two episodes of rejection were associated with a lower mean airway PD; no significant changes were found with infection. In patients with cystic fibrosis (CF), values in the donor lung did not differ from those in non-CF transplanted patients up to one year following transplantation, although nasal PD in the host remained elevated. HLT selectively alters the PD profile only of larger airways, which may relate to the interruption of the bronchial arterial supply to these sites.

Biological Transport, Active↗
PubMed1990

The ultrastructure of plexogenic pulmonary arteriopathy.

The lungs from 16 cases of plexogenic pulmonary arteriopathy obtained at heart-lung transplantation, half of which had primary pulmonary hypertension, were examined by electron microscopy. From these the probable pathogenesis of pulmonary arterial intimal fibrosis in plexogenic pulmonary arteriopathy was deduced. The earliest detectable change was migration of smooth muscle cells from the media, through the internal elastic lamina into the intima. These cells collected beneath the endothelium and lost many of their myofilaments to become myofibroblasts. They were associated with ground substance but scanty collagen fibrils. As the quantity of interstitial collagen increased, the myofibroblasts reverted to a muscular structure, became elongated, and assumed a regular, circumferential orientation. This later stage coincided with the development of plexiform lesions. At both early and later stages, the muscular pulmonary arteries were contracted but not markedly so, and muscular evaginations were not seen. On the other hand, the cellular intimal proliferations developed early and were occlusive. This suggests that occlusion of small pulmonary arterial vessels by myofibroblasts may be at least as important as vasoconstriction in the early elevation of the pulmonary vascular resistance in primary pulmonary hypertension.

Adolescent↗
PubMed1990

Effect of histamine on human bronchial arteries in vitro.

Histamine caused a concentration-dependent relaxation at lower concentrations (1 pmol/l-1 mumol/l) and contraction at higher concentrations (0.01-1 mmol/l) of isolated precontracted human bronchial arteries. In the vessels at resting tension only concentration-dependent contraction was evoked by histamine (0.01-1 mmol/l). Both the contractile and relaxant responses were significantly antagonised by mepyramine (1 mumol/l), with an estimated pKB value of 8.4, but not by cimetidine (100 mumol/l). Our results indicate that histamine induces biphasic effects on human bronchial arteries via H1-receptors.

Adult↗
PubMed1990

Enhanced deposition of predominantly type I collagen in myocardial disease.

The myocardium consists of a muscle fibre array surrounded and interspersed by a network of connective tissue, principally collagen, which maintains the functional integrity of the heart. Changes in collagen composition may therefore contribute to altered ventricular function. Collagen composition was examined in cardiac tissue from 15 patients undergoing orthotopic cardiac transplantation. Of these, 10 had severely impaired left ventricular function due to coronary artery disease. The remaining five had dilated cardiomyopathy. Normal heart tissue was taken at autopsy from 25 patients who died of causes unrelated to cardiovascular disease. Left ventricular collagen concentration, estimated from hydroxyproline levels, increased from 48.6 +/- 4.1 mg/g dry weight of tissue in the control group to 95.3 +/- 9.7 mg/g (P less than 0.01) in patients with dilated cardiomyopathy and to 63.5 +/- 9.8 mg/g in the coronary artery disease group. This increase was attributable to an increase in absolute concentrations of both type I and III collagen, determined by separation of cyanogen bromide peptides by sodium dodecyl sulphate polyacrylamide gel electrophoresis. However, there was a significant decrease in the proportion of type III collagen (compared with type I plus III) from 41.8 +/- 1.1% in controls, to 34.6 +/- 1.5% (P less than 0.01) in the coronary artery disease group and 35.8 +/- 2.8% (P less than 0.05) in the dilated cardiomyopathy group. These results suggest that excessive collagen production, with a preponderance of type I, occurs in these forms of myocardial disease, indicative of a remodelling of the collagen matrix, which, by increasing passive myocardial stiffness may contribute to impaired heart function seen in these groups of patients.

Adult↗
PubMed1990

Beneficial effect of adenosine during reperfusion following prolonged cardioplegic arrest.

STUDY OBJECTIVE: The aim of the study was to investigate the effect of reperfusion with adenosine after prolonged cardioplegic arrest in the isolated working rat heart. DESIGN: After 3 h or hypothermic (20 degrees C) ischaemic arrest with multidose (every 30 min) infusions of St Thomas's Hospital cardioplegic solution No 1, rat hearts were reperfused with either ordinary perfusion fluid (Krebs-Henseleit bicarbonate buffer) or with additional adenosine (1 mg x litre-1) for 15 min prior to assessing recovery of function. EXPERIMENTAL MATERIAL: Hearts (n = 10) in each group) were obtained from male rats weighing 250-300 g. MEASUREMENTS AND MAIN RESULTS: Mean coronary flow during the period of reperfusion was increased from 11.8(SEM 0.8) ml x min-1 with ordinary perfusate to 17(0.7) ml x min-1 with adenosine reperfusate (p less than 0.001). Mean recoveries of functional indices (as percent of preischaemic control values) in hearts receiving ordinary reperfusates v adenosine reperfusates were: peak aortic pressure 76.2(2.8)% upsilon 86.9(2.2)%, dP/dt 35.6(6.0)% upsilon 66.2(4.3)%, aortic flow 26.1(7.4)% upsilon 60.9(4.2)%, coronary flow 50.1(3.4% upsilon 75.6(3.6)%, and cardiac output 31.4(6.4)% upsilon 64.5(3.2)%. Recovery of all indices was significantly superior with adenosine than without (peak aortic pressure p less than 0.01, other indices p less than 0.001). A parallel series of experiments showed that the nucleotide content of both groups was similar at the end of the 15 min reperfusion period. CONCLUSIONS: Improvement in functional recovery occurs with low dose adenosine during reperfusion. This is likely to be due to an increase in coronary flow to the microvasculature rather than to an increase in intramyocardial ATP.

Adenosine↗
PubMed1990

Immunohistology of Epstein-Barr virus-associated antigens in B cell disorders from immunocompromised individuals.

Proliferating B cell lesions developing in a series of immunosuppressed organ transplant recipients and patients with X-linked lymphoproliferative syndrome were examined for Epstein-Barr virus and cellular gene expression using immunocytochemistry and immunoblotting techniques. Results indicate that all the lesions examined from the patients in this series expressed Epstein-Barr virus gene products that were consistent with a latent, nonproductive type of infection. No lytic cycle antigens associated with productive viral infection were detected. This pattern is similar to the viral gene expression in normal B cells immortalized by Epstein-Barr virus in vitro. The demonstration in this study of Epstein-Barr virus viral gene expression in posttransplant and X-linked proliferative syndrome B cell disorders provides important new evidence for the primary role of Epstein-Barr virus in the development of these lesions. This is in contrast to the subsidiary role that the Epstein-Barr virus has in the etiology of Burkitt's lymphoma.

Antibodies, Monoclonal↗
PubMed1990

The histopathology of 36 cases of plexogenic pulmonary arteriopathy.

A detailed histopathological study was made of the lungs of 36 cases of plexogenic pulmonary arteriopathy coming to combined heart-lung transplantation. It revealed two dissimilar processes involved in the pathogenesis of this disease. One comprised histological appearances consistent with constriction of muscular pulmonary arteries, a condition that would be likely to be reversed by pulmonary vasodilators. The other was the proliferation of myofibroblasts in the intima and lumen of pulmonary arteries, a disorder of growth unlikely to be influenced by this type of therapy. In previous ultrastructural studies we have shown that the source of these cells of muscular pedigree is muscle cells from the inner half of the media which migrate into the intima through gaps in the inner elastic lamina. In the present study we found a similar proliferation of myofibroblasts in the intima, not only of pulmonary arteries, but also of pulmonary veins, in plexogenic pulmonary arteriopathy. Arterial thrombi found were considered to be a complication rather than a cause of plexogenic pulmonary arteriopathy. Siderophages, cholesterol granulomas and focal fibrosis in the lung were considered to be a consequence of intrapulmonary haemorrhage early in the course of the disease. It is concluded that, while plexogenic pulmonary arteriopathy has an important vasoconstrictive element, it is also based on a disorder of growth of cells of muscular pedigree. This view has clear implications for the therapy of primary plexogenic pulmonary arteriopathy.

Adolescent↗
PubMed1990

Pulmonary endocrine cells in hypertensive pulmonary vascular disease.

A study was made of the number of pulmonary endocrine cells, immunoreactive for gastrin-releasing peptide (bombesin) or calcitonin, in the terminal bronchioles of 39 cases of pulmonary vascular disease. In 25 of these, the form of vascular disease was plexogenic pulmonary arteriopathy, primary in 12 and secondary in 13, while the remaining 14 subjects had a wide range of other varieties of hypertensive pulmonary vascular disease. We found that pulmonary endocrine cells, especially those containing bombesin, were increased in number in both the primary and secondary forms of plexogenic pulmonary arteriopathy but not in other varieties of pulmonary hypertension. The prominent bombesin-containing cells were found in cases with cellular plexiform lesions but occurred even more prominently at an earlier stage when vascular smooth muscle cells were migrating from the inner media into the intima.

Adult↗
PubMed1990

Mitral valve prolapse and occult aortic coarctation.

A 22 year old man developed symptoms of left ventricular failure secondary to atrial fibrillation and congenital mitral regurgitation. After operation for mitral valve repair he was unable to be successfully weaned from cardiopulmonary bypass and this was ascribed to poor left ventricular function. He therefore underwent emergency cardiac transplantation but again was unable to be weaned from bypass. At post-mortem examination a previously undiagnosed aortic coarctation was revealed. The presentation of occult aortic coarctation is discussed, and its association with congenital mitral valve abnormalities reviewed.

Adult↗
PubMed1990

Autoradiographic mapping of calcitonin gene-related peptide receptors in human and guinea pig hearts.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide that is a potent coronary vasodilator. Although CGRP is found in high concentrations around coronary arteries, its precise function in the control of coronary vasomotor tone remains unclear. We studied the distribution of specific receptors for CGRP in guinea pig and human hearts and found that the highest concentration of specific receptors for CGRP was in the major coronary arteries, which is consistent with the hypothesis that CGRP is implicated in control of coronary vasomotor tone. Areas of coronary artery with atheroma contained significantly decreased (158 +/- 35 grains/1,000 microns 2 tissue, n = 3) binding sites compared with binding sites in normal arteries (266 +/- 10 grains/1,000 microns 2 tissue, n = 11; p less than 0.001, t test). The decrease in receptors for CGRP around atheroma may predispose these vessels to coronary spasm.

Animals↗
PubMed1990

Pulmonary endocrine cells in different varieties of pulmonary vascular disease.

The rôle of the endocrine cells which populate the airways of the lung is uncertain, although it has been suggested that one of their functions might be to regulate the pulmonary vasculature. We have studied the number, content and distribution of these cells in 26 pairs of lungs removed during heart-lung transplantation for the treatment of pulmonary hypertension of various causes, none of which were characterized by plexogenic arteriopathy. In comparison with the controls, there were no differences in the number, content or distribution of these cells, although in two cases of recurrent pulmonary thromboembolism they were aggregated into abnormal disorderly clusters.

Adult↗
PubMed1990

Pulmonary endocrine cells in plexogenic pulmonary arteriopathy.

A study of the numbers of pulmonary endocrine cells per cm2 of section of lung obtained at combined heart-lung transplantation in 25 cases of plexogenic pulmonary arteriopathy demonstrated that the peptide which may become unduly prominent in pulmonary arterial disease is bombesin. The type of vascular disease in which bombesin becomes prominent is plexogenic pulmonary arteriopathy, be this primary or secondary to congenital heart disease. The increased prominence of bombesin appears to be related to the stage reached in the arteriopathy. Increased numbers of pulmonary endocrine cells are found in association with classic cellular plexiform lesions with narrow vascular channels. Their numbers are within normal limits when the plexiform lesions are mature with wide vascular channels and narrow intervening septa. The pulmonary endocrine cells are most prominent in the pre-plexiform stage when smooth muscle cells in the inner half of the media of the pulmonary artery show increased electron density, and migrate through gaps in the inner elastic lamina to reach the intima. Here they are transformed into myofibroblasts and proliferate. The migration of muscle cells may be related in some way to long-acting trophic factors released from the pulmonary endocrine cells into the surrounding tissues from which they reach the blood and hence the pulmonary arteries.

Adolescent↗
PubMed1990

Prolonged cardiac preservation. Evaluation of the University of Wisconsin preservation solution by comparison with the St. Thomas' Hospital cardioplegic solutions in the rat.

The University of Wisconsin solution differs from other types of solutions used for organ preservation because it contains high-energy phosphate precursors (adenosine and phosphate), impermeants (lactobionate and raffinose), an oncotic agent (pentafraction), and antioxidants (allopurinol and glutathione). These components have the potential to enhance the preservation of ATP, reduce intracellular and extracellular edema, and attenuate free-radical-mediated injury. The University of Wisconsin solution has been demonstrated to enhance and extend the preservation of the liver, pancreas, and kidney, but its potential role in the heart remains unproven. We have evaluated the University of Wisconsin solution (Du Pont) by comparing it with the St. Thomas' Hospital cardioplegic solutions No. 1 and No. 2 (Plegisol), which are used in Europe and the United States for routine cardiac surgery and transplantation. For each solution, 10 isolated working rat hearts were arrested by 10 ml of the solution (at 4 degrees C) and then maintained immersed in the same solution for 4 hours at 4 degrees C. Mean recovery of functional indexes (expressed as a percentage of their preischemic control values) after use of the University of Wisconsin solution were as follows: peak aortic pressure, 90.6 +/- 1.0; dP/dt, 71.5 +/- 5.5; aortic flow, 81.6 +/- 4.7; coronary flow, 87.5 +/- 3.5; and cardiac output, 82.6 +/- 3.5. In contrast, the mean recoveries after St. Thomas' Hospital solution No. 1 were as follows: peak aortic pressure, 82.8 +/- 1.3; dP/dt, 49.7 +/- 3.0; aortic flow, 58.4 +/- 5.3; coronary flow, 79.6 +/- 5.9; and cardiac output, 63.0 +/- 4.9. In contrast still, mean recoveries after St. Thomas' Hospital solution No. 2 were as follows: peak aortic pressure, 83.1 +/- 1.2; dP/dt, 40.7 +/- 6.1; aortic flow, 37.0 +/- 5.1; coronary flow, 65.8 +/- 3.6; and cardiac output, 43.1 +/- 5.6. The recovery of all indexes were significantly superior (p less than 0.005) after preservation with University of Wisconsin solution compared with either of the St. Thomas' Hospital solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗