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Biomedical subjects

M Yacoub

Publications and source records attributed to M Yacoub.

At least 235 records · Page 13Linked to original sources

Influence of beta blockade on exercise capacity and heart rate response after human orthotopic and heterotopic cardiac transplantation.

It has been reported that use of beta blockers may not be safe after cardiac transplantation because the denervated hearts may be largely dependent on circulating catecholamines to increase cardiac output. Therefore, the effects of intravenous propranolol were studied during maximal treadmill exercise in 7 patients with heterotopic and 6 with orthotopic cardiac transplantations. An average decrease of about 15% in exercise duration (p less than 0.001), a 34% reduction in systolic blood pressure increase (p less than 0.05) and a 40% attenuation in heart rate increase (p less than 0.001) were observed after beta blockade. In patients with heterotopic transplantation, beta blockade produced similar effects on heart rate in the denervated donor hearts and the innervated recipient hearts during and after mild exercise. During peak exercise, beta blockade attenuated the rate to a greater extent in the donor hearts. Although the denervated donor heart is more sensitive to beta blockade than the innervated recipient heart during exercise, no adverse effects were observed. Beta-blocker therapy should be considered for cardiac transplant patients if longer-term studies confirm their safe use in these patients.

Adrenergic beta-Antagonists↗

Morphological and functional characteristics of myocytes isolated from human left ventricular aneurysms.

Isolated single myocytes were prepared from myocardium of developing ventricular aneurysms and from myocardium within the scar of chronic ventricular aneurysms. The morphology and function of the individual cells were compared. The cells from developing aneurysms were rod-shaped, with a distinct sarcomeric structure, but did not contract even in the presence of high calcium concentrations. The sarcomere length was significantly higher than that of cells from chronic aneurysms and approached the theoretical point at which no contraction can occur. Cells from chronic aneurysms were either rod-shaped and contractile, or rounded due to hypercontracture of the myofilaments. Electron microscopy of cells from developing aneurysms confirmed the presence of elongated sarcomeres, a loss of the actin-myosin interdigitation, and damage to the contractile proteins which was particularly evident in the thin filaments. Cells with similar characteristics have also been isolated from a ruptured, ischaemic papillary muscle. These changes, which are due either to ischaemia or to overstretching of cells, may account for the weakness of the wall of developing aneurysms and be a cause of rupture or enlargement.

Adult↗

Diastolic function after cardiac and heart-lung transplantation.

The mechanical efficiency of left ventricular contraction and relaxation, the asynchrony of the onset of left ventricular relaxation, the time constant of left ventricular isovolumic pressure decay, and left ventricular chamber and myocardial stiffness were analysed in 32 patients after cardiac (24) and heart-lung transplantation (8). After cardiac transplantation left ventricular myocardial stiffness was increased and a mild degree of incoordinate contraction and relaxation was seen. In contrast, after heart-lung transplantation diastolic function was almost normal. Impairment of passive diastolic properties was significantly related to the ischaemic time of the donor heart and the donor's age. The index of left ventricular asynchrony was related to the ischaemic time and the recipient's age. The interval between transplantation and study did not influence the number of rejection episodes. This study confirms the presence of diastolic dysfunction after cardiac transplantation. Impairment of diastolic function seems to be related to the ischaemic time of the donor heart and to a mismatch between the size of the donor heart and the recipient's needs.

Adolescent↗

T10B9.1A-31 anti-T-cell monoclonal antibody: preclinical studies and clinical treatment of solid organ allograft rejection.

T10B9.1A-31 is an immunoglobulin Mk (lgMk), CD3b class, murine monoclonal antibody. It is not itself mitogenic, but it partially blocks mitogenesis produced by concanavilin-A, phytohemagglutinin, and a soluble antigen cocktail and is lytic for human peripheral blood T lymphocytes (PB-T) in the presence of fresh autologous human complement and rabbit complement. It reacts with a monomorphic epitope found on all mature PB-Ts that modulates in vitro and in vivo with the CD3/T-cell antigen receptor (TCR) complex, but unlike OKT3, which reacts with CD3 proteins, T10B9.1A-31 reacts with an epitope of the TCR alpha/beta heterodimer. Immunoprecipitation of HPB-ALL with T10B9.1A-31 or OKT3 revealed that T10B9.1A-31 does not react with the 20-to 26-kd polypeptides that compose CD3, and T10B9.1A-31 failed to bind to the PEER cell, which is CD3 gamma/delta positive, TCR alpha/beta negative. Phase 1 clinical trials demonstrated that T10B9.1A-31 caused a rapid decrease in PB-Ts and no toxic effects other than fever, chills, rigors, and transient hypotension. These side effects were absent in methylprednisolone (MP)-pretreated patients. Phase II studies revealed that T10B9.1A-31 reversed steroid refractory acute rejection in three of five renal allografts treated with cyclosporine (CyA) and prednisone (P) maintenance immunosuppression, reversed steroid and polyclonal antisera refractory rejection in three cardiac allograft recipients receiving CyA/P, and attenuated acute rejection in three of three renal patients receiving baseline azathioprine/prednisone (AZA/P) when used as primary therapy. Rerejection was not seen when patients received CyA baseline immunosuppression but was seen in patients maintained on AZA/P OKT3 was efficacious in treating rejection following T10B9.1A-31 therapy. Side effects of T10B9.1A-31 appears to reverse acute rejection crisis effectively in renal and cardiac transplantation with a low incidence of rerejection in CyA-maintained patients and with fewer, milder side effects. Sequential therapy with OKT3 is possible because OKT3 and T10B9.1A-31 are of different isotypes and idiotypes.

Animals↗

One-stage correction of interrupted aortic arch combined with heart-lung transplantation.

A technique for correction of interrupted aortic arch during heart-lung transplantation is described. This operation was performed in a 14-year-old patient with situs solitus, absent right atrioventricular connection, large atrial septal defect, ventricular septal defect, transposition of the great arteries, type B interrupted aortic arch, and severe pulmonary hypertension. The postoperative course was uneventful. Clinical, radiologic, and nuclear magnetic resonance investigation have shown evidence of good correction of the aortic arch anomaly. We concluded that donor tissue available during heart-lung transplantation is useful in correcting extracardiac anomalies.

Adolescent↗

Pulmonary endocrine cells in pulmonary arterial disease.

Pulmonary endocrine cells containing bombesin or calcitonin have been identified in human lungs by the peroxidase-antiperoxidase method. The numbers of such cells were greatly increased in patients with plexogenic pulmonary arteriopathy whether that condition was associated with primary pulmonary hypertension or with pulmonary hypertension from intracardiac shunts. The numbers of endocrine cells tended to be increased, but to a lesser extent in patients with pulmonary hypertension and medial hypertrophy of the muscular pulmonary arteries in the absence of plexogenic arteriopathy. Increased numbers of endocrine cells comprised both greater numbers of solitary cells and a pronounced clustering, often of a disorganized nature.

Adolescent↗