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Biomedical subjects

M Yacoub

Publications and source records attributed to M Yacoub.

At least 181 records · Page 10Linked to original sources
PubMed1992

The effect of orthotopic transplantation on total, beta 1- and beta 2-adrenoceptors in the human heart.

1. [125I]-(-)pindolol binding was used to determine beta-adrenoceptor density in homogenate preparations of right ventricular endomyocardial biopsies from 43 non-rejecting patients over the first 13 months following cardiac transplantation. The selective beta 1 subtype antagonist ligand CGP 20712A was used to determine the subtype density in 32 of the patients. Biopsy specimens from 15 donor hearts were used as controls. 2. beta-adrenoceptor density (expressed in terms of fmol mg-1 protein) was increased in the group of transplanted hearts as a whole compared with the donor hearts with respect to total (35 +/- 2 vs 23 +/- 2) and the beta 1 subtype (25 +/- 2 vs 16 +/- 2) whereas the beta 2 subtype and radioligand dissociation constant did not differ. 3. Non-parametric analysis of variance of total receptor density over time revealed significant heterogeneity which appears to be due to a discrete increase in beta-adrenoceptor density during the 4th post operative month. 4. These results indicate that beta-adrenoceptor density is not constant following transplantation. Furthermore, the increase in receptor density following transplantation is due mainly to an increase in the beta 1 subtype without a significant change in the beta 2 subtype.

Adult↗
PubMed1992

Optimized hemodynamics by implantation of a dual chamber pacemaker after heterotopic cardiac transplantation.

A patient who underwent prior heterotopic cardiac transplantation had persistent complaints of dyspnea, palpitations, and fatigue in spite of normal pump function of the donor heart. Repeated Holter monitoring excluded paroxysmal arrhythmias. It was thought that synchronization of both heart rates might alleviate his symptoms. The intrinsic heart rate of the donor heart was 90 beats/min, the recipient heart was 60 beats/min with acceleration up to 130 beats/min on exercise. A DDD pacemaker was implanted, the atrial lead was positioned in the right ventricule of the donor heart and the ventricular lead in the atrium of the recipient heart. Search for an optimal AV interval was evaluated by echo-Doppler and intraarterial pressure recordings. By increasing the AV interval from 125 to 300 msec, the maximum aortic flow velocity of the recipient heart increased from 1.0 to 1.2 m/sec. Left ventricular end-diastolic diameter remained unchanged, left ventricular end-systolic diameter decreased from 52 to 48 mm. Wall motion of the recipient left ventricle improved. At an AV interval of 125 msec there was alternate systolic contraction of both hearts, resulting in arterial pressure waves at a rate of 180/min. This did not relieve his symptoms and he complained further of headaches. At an AV interval of 300 msec contraction of the recipient heart just preceded that of the donor heart, resulting in arterial pressure waves at a rate of 90/min, normalization of the wave form, relief of symptoms, and improvement of exercise tolerance.

Adult↗
PubMed1992

Bioelectric properties of cystic fibrosis airways obtained at heart-lung transplantation.

BACKGROUND: The basic defect in cystic fibrosis centres on abnormal ion transport in affected tissues such as the respiratory tract. Heart-lung transplantation provides a limited supply of native lower airways from these patients. The feasibility of in vitro studies of bioelectric properties and ion fluxes in lower airways, obtained at heart-lung transplantation from patients with cystic fibrosis, has been assessed. Comparison was made with airways from patients without cystic fibrosis. METHODS AND RESULTS: Tissue segments were mounted in Ussing chambers under open circuit conditions. The basal potential difference in tissues from nine patients with cystic fibrosis was -3.6 mV (SE 0.3 mV), not different from tissues from 12 patients without cystic fibrosis of -3.6 mV (0.5 mV). Amiloride (10 microM) caused a significantly greater fall in potential difference in bronchi from patients with cystic fibrosis (83.5% (SE 2.9%)) than in those from controls (55.1% (7.1%)). Isoprenaline (100 microM) produced no significant change in bioelectric properties in non-cystic fibrosis tissues, but induced a 26.2% (6.3%) increase in potential difference in cystic fibrosis airways. The latter response was reduced by amiloride pretreatment. Mucosal chloride substituted Krebs-Henseleit solution caused no change in bioelectric properties in cystic fibrosis airways. Sodium substituted Krebs solution produced a substantial fall in potential difference similar in magnitude to that seen after amiloride. Isotropic flux measurements showed no significant differences between non-cystic fibrosis and cystic fibrosis airways. No net movement of Na+ or Cl- was detected under open circuit conditions in either group. CONCLUSIONS: Cystic fibrosis bronchi obtained at heart-lung transplantation provide a viable source of tissue for in vitro studies of bioelectric properties. The increased response to amiloride characteristic of the upper airways in cystic fibrosis is retained in these tissues, as is the reduced chloride conductance. Although no differences in isotopic fluxes were seen between non-cystic fibrosis and cystic fibrosis tissues, heavily infected airways from patients with cystic fibrosis may not be suitable for ion flux measurements.

Amiloride↗
PubMed1992

Pulmonary endothelial permeability following lung transplantation.

During lung transplantation, a number of factors may cause endothelial injury to the donor organ, including ischemia, inadequate preservation, cardiopulmonary bypass, high potassium concentrations, and reperfusion. In this study, protein accumulation index (PAI) was used to assess pulmonary endothelial permeability (PEP) in ten patients immediately after lung transplantation. Six were studied sequentially every other day for ten days postoperatively. The PAI was also measured using the same technique in a group of 11 normal volunteers. Mean PAI x 10(-3)/min +/- (SEM) for ten patients measured within 36 h of transplantation was 1.27 (0.56) compared with 0.45 (0.08) for the normal group (p = 0.09). No correlation was found between preservation time and PAI following reperfusion. Three episodes of lung rejection were observed in two patients during the first ten postoperative days, during which PAI rose to 2.26 (0.26) compared with 0.73 (0.11) for all other studies in the group (p less than 0.01). We conclude that no increase in PEP could be demonstrated after graft reperfusion following lung transplantation as assessed by PAI in this small group of patients. However, further studies may show the technique to be useful in the detection of subsequent episodes of graft rejection.

Cell Membrane Permeability↗
PubMed1992

Aprotinin and heparin monitoring during cardiopulmonary bypass.

BACKGROUND: When high-dose aprotinin is used during cardiopulmonary bypass, there is a prolongation of the activated coagulation time (ACT), which is used to monitor heparinization. The aim of this study was to provide guidelines for monitoring heparin levels by the ACT if aprotinin is used during cardiopulmonary bypass. METHODS AND RESULTS: Heparinized blood from six healthy controls and nine patients on cardiopulmonary bypass was aliquoted and mixed with various concentrations of aprotinin. ACTs were performed on these samples. Activated partial thromboplastin times (APTT) were performed on the citrated plasma mixed with varying concentrations of heparin and aprotinin from the same control patients. Prothrombin times (PT) were performed on plasmas mixed with aprotinin. Aprotinin produced a dose-related prolongation of ACT and APTT but had no effect on PT. This effect occurred whatever the activating agent and in the absence of heparin. CONCLUSIONS: Aprotinin prolongs the ACT and APTT independently of heparin. If high-dose aprotinin is used during cardiopulmonary bypass, ACTs should be maintained at times > 750 seconds to allow for appropriate levels of heparin.

Aprotinin↗
PubMed1992

Detrimental effects of temperature on the efficacy of the University of Wisconsin solution when used for cardioplegia at moderate hypothermia. Comparison with the St. Thomas Hospital solution at 4 degrees C and 20 degrees C.

BACKGROUND: We have previously reported the superior protective properties of the University of Wisconsin (UW) solution compared with the St. Thomas solution (ST) in the rat heart subjected to the deep hypothermia (4 degrees C), thus demonstrating its possible use in cardiac transplantation. We thought it was important to evaluate the potential of the UW solution as a cardioplegic solution under the moderately hypothermic (20 degrees C) conditions of routine intraoperative myocardial protection. METHODS AND RESULTS: Isolated rat hearts were subjected to 60 minutes of ischemia at 4 degrees C or 30 (or 60) minutes of ischemia at 20 degrees C with UW, ST, and ST plus 100 mM K (ST + 100) solutions. Coronary flow, mechanical function, endothelial function, and ultrastructure were observed. Mean time (seconds) to infuse 10 ml of cardioplegic solution under constant pressure, a measure of coronary vascular resistance at 4 degrees C and 20 degrees C, respectively, for each solution were ST, 69.2 +/- 6.9 and 64.7 +/- 3.8; UW, 142.2 +/- 8.8 and 187.2 +/- 10.0 (p < 0.01); and ST + 100, 78.2 +/- 8.0 and 176 +/- 8.1 (p < 0.001). Mean recovery values of cardiac output (expressed as percentage of its preischemic value) after 60 minutes of ischemia at 4 degrees C were ST, 95.5 +/- 2.1%; UW, 93.0 +/- 2.4%; and ST + 100, 96.5 +/- 1.5%. After 30 minutes of ischemia at 20 degrees C, values were ST, 88.0 +/- 1.3%; UW, 72.2 +/- 3.6% (p < 0.005 versus ST); and ST + 100, 53.3 +/- 1.8% (p < 0.001 versus ST). CONCLUSIONS: The efficacies of UW and severely hyperkalemic cardioplegic solutions are affected by the degree of hypothermia under which they are used. Under moderate hypothermia (20 degrees C), severe hyperkalemia induces a marked increase in coronary vascular resistance that is associated with impaired myocardial protection. These studies discourage the use of UW for routine intraoperative cardioplegic arrest where the degree of hypothermia cannot be readily controlled. The ST solution does not share this constraint.

Adenosine↗
PubMed1992

The effectiveness of danazol therapy in postmenopausal women affected by endometrial hyperplasia.

Forty eight patients in postmenopause affected by histologically confirmed endometrial hyperplasia (34 with simplex and 14 with complex forms) were administered Danazol therapy, 400 mg/day for 3 consecutive months. At the end of treatment, regression of the endometrial hyperplasia was histologically ascertained in 46 patients (95.9%) with disappearance of the metrorrhagia. Endometrial atrophy was obtained in 75% of the cases, while secretive (14.7%) or proliferative (6.2%) aspects resulted in the others. Only 2 patients (4.1%) showed persistence of the hyperplastic endometrium. On the basis of this experience, treatment with Danazol appears to be effective and safe with only scarce and transient side effects. This therapy is therefore proposed as a valid alternative to progestogen therapy in cases of postmenopausal endometrial hyperplasia.

Aged↗
PubMed1992

Endothelial dysfunction caused by University of Wisconsin preservation solution in the rat heart. The importance of temperature.

The superiority of the University of Wisconsin solution over routinely used crystalloid cardioplegic solutions for myocardial preservation has been demonstrated in animal studies. We have investigated the effect of the University of Wisconsin solution at different temperatures on endothelial function by examining its influence on 5-hydroxytryptamine- and nitroglycerin-induced increase in coronary flow in the isolated rat heart. Thirty-eight rat hearts were perfused on a modified Langendorff preparation. In the control experiments, there was no significant difference in the percentage increase in coronary flow induced by 5-hydroxytryptamine and nitroglycerin after 30 minutes of perfusion with Krebs-Henseleit buffer (n = 6). Continuous infusion of the University of Wisconsin solution for 30 minutes at 4 degrees C or at 10 degrees C did not alter the 5-hydroxytryptamine or nitroglycerin response. However, infusion at 15 degrees C reduced the 5-hydroxytryptamine-induced vasodilation, while at 20 degrees C the 5-hydroxytryptamine response was converted to vasoconstriction without a significant change in nitroglycerin effect (15 degrees C, 5-hydroxytryptamine, before: 30.2% +/- 1.5%, after: 6.0% +/- 1.0%, nitroglycerin, before: 28.8% +/- 1.3%, after: 31.2% +/- 1.8%; 20 degrees C, 5-hydroxytryptamine, before: 32.2% +/- 2.5%, after: -23.8% +/- 3.6%, nitroglycerin, before: 30.3% +/- 1.9%, after: 33.5% +/- 1.7%). Coronary vascular resistance in the control experiments rose from 55.0 +/- 2.5 cm H2O/ml/gm/min to 58.4 +/- 2.3 cm H2O/ml/gm/min (p = not significant). The increase after University of Wisconsin solution infusion at 4 degrees C and at 10 degrees C was similarly not significant. Coronary vascular resistance increased significantly following infusion of University of Wisconsin solution at 15 degrees C (p < 0.001) or at 20 degrees C (p < 0.01). We conclude that University of Wisconsin solution produces temperature-dependent endothelial dysfunction in the isolated rat heart.

Adenosine↗
PubMed1992

Lung allograft transplantation: indications, preoperative assessment and postoperative management.

In spite of a shortage of available donors, an increasing number of heart-lung transplantations have been performed within the last decade. This procedure, first limited to patients with pulmonary vascular disease, has been successfully extended to patients with end stage lung disease, including cystic fibrosis. More recently, single lung, double-lung and bilateral single lung transplantation have become other therapeutic options. Better selection of patients and donors as well as improvements in surgical techniques and immunosuppression regimens have contributed to the reduction in the high perioperative mortality experienced in the early stages. Moreover, the introduction of daily spirometry and transbronchial lung biopsies have permitted early and reliable diagnosis of opportunistic infection and rejection. The most serious late complication of lung transplantation is obliterative bronchiolitis and further research is urgently required to improve diagnosis and management of this condition.

Graft Rejection↗
PubMed1992

Antigenic heterogeneity of vascular endothelium.

The antigenic status of vascular endothelium from different sites of the normal adult and fetal human cardiovascular system was investigated. Tissues included aorta (n = 9), pulmonary artery (n = 8), coronary artery (n = 6), ventricle/atrium (n = greater than 10), lymph node (n = 2), fetal whole heart (n = 3), and umbilical cord (n = 7). Frozen sections were studied using monoclonal antibodies recognizing endothelial markers (EN4, vWf, Pal-E, and 44G4), vascular adhesion molecules (ICAM-1, ELAM, VCAM, and PECAM), the monocyte/endothelial marker (OKM5), and major histocompatibility complex (MHC) molecules (class I and class II). Results demonstrate that capillary endothelium is phenotypically different from endothelial cells (EC) lining large vessels. Capillary EC strongly express MHC classes I and II, ICAM, and OKM5, which are variably weak to undetectable on large vessels. In contrast, the large vessels strongly express vWf and appear to constitutively express ELAM-1. This suggests that the capillary EC may be more efficient at antigen presentation or more susceptible to immune attack in vivo. Interestingly, normal coronary arteries, unlike all other large vessels, express MHC class II and VCAM molecules. Future studies should concentrate on comparative functional studies between capillary, coronary, and large vessel EC.

Antibodies, Monoclonal↗
PubMed1991

Determination of the 5' exon structure of the human cardiac alpha-myosin heavy chain gene.

We have deduced the exon structure of the 5' untranslated region of the human cardiac alpha-myosin heavy chain gene by cloning a cDNA for this region using the polymerase chain reaction. Comparison of the cDNA and genomic DNA sequences demonstrates that the 5' non-coding region of the alpha-myosin heavy chain gene is interrupted by two introns of 645 and 337 nucleotides. Secondly we have identified the transcriptional start-site by primer extension, corroborating the previous putative assignment for the alpha-myosin heavy chain promoter based on comparisons between the rat and human genes.

Amino Acid Sequence↗
PubMed1991

Relationship of immunosuppression and serum lipids to the development of coronary arterial disease in the transplanted heart.

Coronary arterial disease in the cardiac allograft has emerged as the most serious long term complication of cardiac transplantation. The influence of patient-related and other potential risk factors on the development of coronary arterial disease at 1 year subsequent to cardiac transplantation was examined in 207 recipients. The mean age of donors in patients with coronary arterial disease was 28.5 +/- 9.5 years, compared to 22.6 +/- 7.9 years in patients without coronary arterial disease (P less than 0.01). Eight of the 35 patients who received immunosuppression by means of prednisone and azathioprine developed coronary arterial disease compared to 5 of the 172 patients who were treated with cyclosporin and azathioprine without routine oral prednisone (P less than 0.01). The relationship of levels of serum lipids to the subsequent development of coronary arterial disease was investigated in 95 patients with angiographically normal coronary arteries one year after cardiac transplantation. The cumulative probability of coronary arterial disease in those with total cholesterol greater than 5.8 mmol/l was 9.3% at 2 years (n = 40), 24.4% at 4 years (n = 21) and 45% at 4 years (n = 9) compared with 4.3% at 2 years (n = 45), 7.4% at 3 years (n = 32) and 14% at 4 years (n = 14) in those with a total cholesterol less than 5.8 mmol/l (P less than 0.05). Similarly, the incidence of coronary arterial disease was increased in patients with serum triglyceride greater than 1.4 mmol/l (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Biochemical and structural adaptation of autologous skeletal muscle used for counterpulsation.

We have studied in a normal animal model (sheep), the biochemical and morphological adaptation of electrically stimulated skeletal muscle used for extra aortic counterpulsation. Immunocytochemical analysis of latissimus dorsi, using monoclonal antibodies to slow and fast myosin heavy chains, indicated an increase in the population of mixed fibres after stimulation for one week. By one month, up to 70% of fibres expressed both slow and fast myosin heavy chains in addition to the 15% of fibres expressing only slow myosin heavy chains. After 4 months, the population of mixed fibres was further transformed towards purely slow fibres to give values of 40 and 67% of fibres expressing only slow myosin heavy chain at 4 and 6 months, respectively. Increased staining, both in intensity and area, for NADH tetrazolium reductase activity (an enzyme of the oxidative metabolic pathway) was detected by 28 days. An increase in mitochondrial number was observed also by 28 days, further indicating a shift towards an oxidative metabolism. The molecular adaptation of latissimus dorsi was achieved by stimulation every fourth cardiac cycle at 35 Hz, 3 V, initiated 48 hours after the operation; this being a marked reduction in the delay from operation prior to stimulation. Evaluation of other regimes indicated that more frequent modes, or an increase in voltage or frequency, caused damage to the muscle during the early phase of molecular adaptation. A thorough understanding of the time sequence of the different adaptive processes is required to determine the ideal regime of stimulation initiated promptly after mobilisation of the muscle; aimed at harvesting the maximum amount of energy from the autologous muscle.

Adaptation, Physiological↗