Publications
2088 results found
Navaratnarajah M, Siedlecka U, Ibrahim M, et al., 2014, Impact of Combined Clenbuterol and Metoprolol Therapy on Reverse Remodelling during Mechanical Unloading, PLOS One, Vol: 9, ISSN: 1932-6203
Background: Clenbuterol (Cl), a b2 agonist, is associated with enhanced myocardial recovery during left ventricular assistdevice (LVAD) support, and exerts beneficial remodelling effects during mechanical unloading (MU) in rodent heart failure(HF). However, the specific effects of combined Cl+b1 blockade during MU are unknown.Methods and Results: We studied the chronic effects (4 weeks) of b2-adrenoceptor (AR) stimulation via Cl (2 mg/kg/day)alone, and in combination with b1-AR blockade using metoprolol ((Met), 250 mg/kg/day), on whole heart/cell structure,function and excitation-contraction (EC) coupling in failing (induced by left coronary artery (LCA) ligation), and unloaded(induced by heterotopic abdominal heart transplantation (HATx)) failing rat hearts. Combined Cl+Met therapy displayedfavourable effects in HF: Met enhanced Cl’s improvement in ejection fraction (EF) whilst preventing Cl-induced hypertrophyand tachycardia. During MU combined therapy was less beneficial than either mono-therapy. Met, not Cl, prevented MUinducedmyocardial atrophy, with increased atrophy occurring during combined therapy. MU-induced recovery of Ca2+transient amplitude, speed of Ca2+ release and sarcoplasmic reticulum Ca2+ content was enhanced equally by Cl or Metmono-therapy, but these benefits, together with Cl’s enhancement of sarcomeric contraction speed, and MU-inducedrecovery of Ca2+ spark frequency, disappeared during combined therapy.Conclusions: Combined Cl+Met therapy shows superior functional effects to mono-therapy in rodent HF, but appearsinferior to either mono-therapy in enhancing MU-induced recovery of EC coupling. These results suggest that combined b2-AR simulation +b1-AR blockade therapy is likely to be a safe and beneficial therapeutic HF strategy, but is not as effective asmono-therapy in enhancing myocardial recovery during LVAD support.
Carr C, Sanoudou D, Dilawar M, et al., 2014, Whole exome sequencing of a family with 3 sibling affected by bicuspid aortic valve disease, Annual Meeting of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 950-951, ISSN: 0195-668X
Kaniewska ED, Sielicka A, Sarathchandra P, et al., 2014, Expression and activity of extracellular ectoenzymes (CD39 and CD73) in aortic valves cells and in endothelial cells under the shear stress conditions, FEBS EMBO 2014 Conference, Publisher: WILEY-BLACKWELL, Pages: 561-562, ISSN: 1742-464X
Yacoub MH, El-Hamamsy I, Sievers H-H, et al., 2014, Under-use of the Ross operation-a lost opportunity, LANCET, Vol: 384, Pages: 559-560, ISSN: 0140-6736
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- Citations: 52
Chester AH, Yacoub MH, 2014, The role of endothelin-1 in pulmonary arterial hypertension., Global Cardiology Science and Practice, Vol: 2014, Pages: 62-78, ISSN: 2305-7823
Pulmonary arterial hypertension (PAH) is a rare but debilitating disease, which if left untreated rapidly progresses to right ventricular failure and eventually death. In the quest to understand the pathogenesis of this disease differences in the profile, expression and action of vasoactive substances released by the endothelium have been identified in patients with PAH. Of these, endothelin-1 (ET-1) is of particular interest since it is known to be an extremely powerful vasoconstrictor and also involved in vascular remodelling. Identification of ET-1 as a target for pharmacological intervention has lead to the discovery of a number of compounds that can block the receptors via which ET-1 mediates its effects. This review sets out the evidence in support of a role for ET-1 in the onset and progression of the disease and reviews the data from the various clinical trials of ET-1 receptor antagonists for the treatment of PAH.
Murphy OH, Borghi A, Bahmanyar MR, et al., 2014, RF communication with implantable wireless device: effects of beating heart on performance of miniature antenna, Healthcare Technology Letters, Vol: 1, Pages: 51-55, ISSN: 2053-3713
The frequency response of an implantable antenna is key to the performance of a wireless implantable sensor. If the antenna detunes significantly, there are substantial power losses resulting in loss of accuracy. One reason for detuning is because of a change in the surrounding environment of an antenna. The pulsating anatomy of the human heart constitutes such a changing environment, so detuning is expected but this has not been quantified dynamically before. Four miniature implantable antennas are presented (two different geometries) along with which are placed within the heart of living swine the dynamic reflection coefficients. These antennas are designed to operate in the short range devices frequency band (863-870 MHz) and are compatible with a deeply implanted cardiovascular pressure sensor. The measurements recorded over 27 seconds capture the effects of the beating heart on the frequency tuning of the implantable antennas. When looked at in the time domain, these effects are clearly physiological and a combination of numerical study and posthumous autopsy proves this to be the case, while retrospective simulation confirms this hypothesis. The impact of pulsating anatomy on antenna design and the need for wideband implantable antennas is highlighted.
Miragoli M, Yacoub MH, El-Hamamsy I, et al., 2014, Side-specific mechanical properties of valve endothelial cells, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol: 307, Pages: H15-H24, ISSN: 0363-6135
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- Citations: 15
Trantidou T, Rao C, Barrett H, et al., 2014, Selective hydrophilic modification of Parylene C films: a new approach to cell micro-patterning for synthetic biology applications, Biofabrication, Vol: 6, ISSN: 1758-5090
We demonstrate a simple, accurate and versatile method to manipulate Parylene C, a material widely known for its high biocompatibility, and transform it to a substrate that can effectively control the cellular microenvironment and consequently affect the morphology and function of the cells in vitro. The Parylene C scaffolds are fabricated by selectively increasing the material's surface water affinity through lithography and oxygen plasma treatment, providing free bonds for attachment of hydrophilic biomolecules. The micro-engineered constructs were tested as culture scaffolds for rat ventricular fibroblasts and neonatal myocytes (NRVM), toward modeling the unique anisotropic architecture of native cardiac tissue. The scaffolds induced the patterning of extracellular matrix compounds and therefore of the cells, which demonstrated substantial alignment compared to typical unstructured cultures. Ca2+ cycling properties of the NRVM measured at rates of stimulation 0.5–2 Hz were significantly modified with a shorter time to peak and time to 90% decay, and a larger fluorescence amplitude (p < 0.001). The proposed technique is compatible with standard cell culturing protocols and exhibits long-term pattern durability. Moreover, it allows the integration of monitoring modalities into the micro-engineered substrates for a comprehensive interrogation of physiological parameters.
Bertazzo S, Steele JAM, Chester AH, et al., 2014, Cardiovascular calcification violet pearl, The Lancet, Vol: 384, Pages: 1294-1294, ISSN: 0140-6736
Chester AH, El-Hamamsy I, Butcher JT, et al., 2014, The living aortic valve: From molecules to function., Global Cardiology Science and Practice, Vol: 2014, Pages: 52-77, ISSN: 2305-7823
The aortic valve lies in a unique hemodynamic environment, one characterized by a range of stresses (shear stress, bending forces, loading forces and strain) that vary in intensity and direction throughout the cardiac cycle. Yet, despite its changing environment, the aortic valve opens and closes over 100,000 times a day and, in the majority of human beings, will function normally over a lifespan of 70-90 years. Until relatively recently heart valves were considered passive structures that play no active role in the functioning of a valve, or in the maintenance of its integrity and durability. However, through clinical experience and basic research the aortic valve can now be characterized as a living, dynamic organ with the capacity to adapt to its complex mechanical and biomechanical environment through active and passive communication between its constituent parts. The clinical relevance of a living valve substitute in patients requiring aortic valve replacement has been confirmed. This highlights the importance of using tissue engineering to develop heart valve substitutes containing living cells which have the ability to assume the complex functioning of the native valve.
Burton PBJ, Yacoub MH, Barton PJR, 2014, Rapamycin (sirolimus) inhibits heart cell growth in vitro, PEDIATRIC CARDIOLOGY, Vol: 19, Pages: 468-470, ISSN: 0172-0643
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- Citations: 8
Pepe G, Nistri S, Giusti B, et al., 2014, Identification of fibrillin 1 gene mutations in patients with bicuspid aortic valve (BAV) without Marfan syndrome., BMC Med Genet, Vol: 15
BACKGROUND: Bicuspid aortic valve (BAV) is the most frequent congenital heart disease with frequent involvement in thoracic aortic dilatation, aneurysm and dissection. Although BAV and Marfan syndrome (MFS) share some clinical features, and some MFS patients with BAV display mutations in FBN1, the gene encoding fibrillin-1, the genetic background of isolated BAV is poorly defined. METHODS: Ten consecutive BAV patients [8 men, age range 24-42 years] without MFS were clinically characterized. BAV phenotype and function, together with evaluation of aortic morphology, were comprehensively assessed by Doppler echocardiography. Direct sequencing of each FBN1 exon with flanking intron sequences was performed on eight patients. RESULTS: We detected three FBN1 mutations in two patients (aged 24 and 25 years) displaying aortic root aneurysm ≥50 mm and moderate aortic regurgitation. In particular, one patient had two mutations (p.Arg2726Trp and p.Arg636Gly) one of which has been previously associated with variable Marfanoid phenotypes. The other patient showed a pArg529Gln substitution reported to be associated with an incomplete MFS phenotype. CONCLUSIONS: The present findings enlarge the clinical spectrum of isolated BAV to include patients with BAV without MFS who have involvement of FBN1 gene. These results underscore the importance of accurate phenotyping of BAV aortopathy and of clinical characterization of BAV patients, including investigation of systemic connective tissue manifestations and genetic testing.
Sohier J, Carubelli I, Sarathchandra P, et al., 2014, The potential of anisotropic matrices as substrate for heart valve engineering, BIOMATERIALS, Vol: 35, Pages: 1833-1844, ISSN: 0142-9612
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- Citations: 32
Alayoubi S, Ricardo CP, Zaman J, et al., 2014, Electrophysiological and Structural Left Ventricle Remodelling in Spontaneously Hypertensive Rat Hearts: A Multicellular Study, 58th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 122A-122A, ISSN: 0006-3495
Gehani A, Al-Suwaidi J, Yacoub M, 2014, NIAMI: Towards the optimization of results in primary PCI, Global Cardiology Science and Practice, Vol: 2014
The NAIMI trial has recently been published (1). It assessed one of the most contemporary and challenging issues in the management of acute myocardial infarction (AMI), namely prevention of reperfusion injury (RPI) after primary PCI for STLelevation myocardial infarction (STEMI). It investigated the effect of the intravenous administration of Na nitrite given immediately prior to primary PCI for STEMI in 229 patients (118 in the treatment group, and 111 in placebo). The myocardial infarction (MI) size did not differ between the two groups as observed by cardiac MRI (CMR) with gadolinium enhancement at 6L8 days or plasma TroponinLI and creatine kinase (CK), or by left ventricular (LV) volume and ejection fraction (EF) as measured by echocardiography at 6L8 days and again at 6 months. They concluded that IV nitrites did not reduce the infarct size. There was, however, a trend towards benefit in diabetic patients in the postLhoc analysis. The small number of these subjects has probably lead to inconclusive outcome in this subset.
Chapron J, Aguib H, Theodoropoulos S, et al., 2014, Quantitative assessment of right ventricular structure and flow dynamics in pulmonary homograft obstruction, Global Cardiology Science and Practice, Vol: 2014
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- Citations: 1
Yacoub M, Radford M, 2014, COMPARE, losartan in marfan, validated in humans at last!, Global Cardiology Science and Practice, Vol: 2014
A landmark study by Habashi et al in 2006, documented for the first time both the prevention and reversal of structural changes in the aorta associated with Marfan syndrome, via pharmacological means. This study, carried out in a rat model, concluded that such results were due to an inhibitor effect by the drug Losartan on TGB-β1. Habashi's paper prompted some physicians, in the absence of human trials, to begin the clinical off-label use of Losartan on Marfan patients, arguing that this was justified due to the drug's excellent safety profile. This has caused some controversy. The COMPARE Trial should be welcomed as the first randomized human trial of Losartan with Marfan patients. In all study patients given the drug, a significantly lower increase in aortic root diameter was observed than in the placebo group after 3 years, although no significant differences were observed in aortic diameter beyond the root itself. The COMPARE trial should impact positively on the clinical use of Losartan with Marfan Syndrome patients, however further trials are required, with longer follow up periods, to better guide the timing and dosage of this promising therapy. Copyright; 2014 Yacoub M, Radford M, licensee Bloomsbury Qatar Foundation Journals.
Beaton A, Sable C, Brown J, et al., 2014, Genetic susceptibility to endomyocardial fibrosis, Global Cardiology Science and Practice, Vol: 2014
Background: Endomyocardial fibrosis (EMF) is the most common form of restrictive cardiomyopathy worldwide. It has been linked to poverty and various environmental factors, but-for unknown reasons-only some people who live in similar conditions develop the disease. EMF cases cluster within both families and ethnic groups, suggesting a role for a genetic factor in host susceptibility. The human leukocyte antigen (HLA) system is associated with predisposition to various diseases. This two-center study was designed to investigate variation in the HLA system between EMF patients and unaffected controls. We provide the first genetic investigation of patients with EMF, as well as a comprehensive review of the literature. Copyright; 2014 Beaton A, Sable C, Brown J, Hoffman J, Mungoma M, Mondo C, Cereb N, Brown C, Summar M, Freers J, Ferreira MB, Yacoub M, Mocumbi AO, licensee Bloomsbury Qatar Foundation Journals.
Sedky Y, Hosny H, Donya M, et al., 2014, Antegrade flow in Anomalous Left Coronary Artery from Pulmonary Artery: Clinical implications, Global Cardiology Science and Practice, Vol: 2014
Anomalous origin of the left main coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly that usually presents in childhood. It results in left ventricular (LV) ischemia with resulting LV dysfunction. This ischemia results from retrograde flow into the pulmonary artery which can act as a coronary steal. We here report antegrade flow detected in ALCAPA caused by severe pulmonary hypertension. Anatomic correction of ALCAPA is the preferred surgical option and should be performed as early as possible.
Ibrahim M, Yacoub MH, 2014, Bridge to Recovery and Weaning Protocols, HEART FAILURE CLINICS, Vol: 10, Pages: S47-+, ISSN: 1551-7136
Hassan M, Yacoub M, 2014, Gauss-2, Rutherford-2, Laplace-2, Descartes, And Tesla part B: PCSK9 inhibitors gain momentum, Global Cardiology Science and Practice, Vol: 2014
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- Citations: 6
Dias P, Navaratnarajah M, Alayoubi S, et al., 2014, IVABRADINE ALTERS FIBROBLAST NUMBER AND TRANSFORMING GROWTH FACTOR BETA 1 EXPRESSION IN HEART FAILURE, HEART, Vol: 100, Pages: A4-A4, ISSN: 1355-6037
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- Citations: 1
Kaniewska E, Sielicka A, Sarathchandra P, et al., 2014, IMMUNOHISTOCHEMICAL AND FUNCTIONAL ANALYSIS OF ECTONUCLEOSIDE TRIPHOSPHATE DIPHOSPHOHYDROLASE 1 (CD39) AND ECTO-5′-NUCLEOTIDASE (CD73) IN PIG AORTIC VALVES, NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, Vol: 33, Pages: 305-312, ISSN: 1525-7770
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- Citations: 14
Raynaud CM, Ahmad FS, Allouba M, et al., 2014, Reprogramming for cardiac regeneration., Glob Cardiol Sci Pract, Vol: 2014, Pages: 309-329, ISSN: 2305-7823
Treatment of cardiovascular diseases remains challenging considering the limited regeneration capacity of the heart muscle. Developments of reprogramming strategies to create in vitro and in vivo cardiomyocytes have been the focus point of a considerable amount of research in the past decades. The choice of cells to employ, the state-of-the-art methods for different reprogramming strategies, and their promises and future challenges before clinical entry, are all discussed here.
Torii R, Ibrahim M, Mittal T, et al., 2014, The wide spectrum of aortic root dilatation after the Ross operation., Pages: 49-50, ISSN: 2305-7823
Dias P, Navaratnarajah M, Alayoubi S, et al., 2014, Ivabradine Reduces α-Smooth Muscle Actin Expression, Proliferation and Collagen Production in Human Cardiac Fibroblasts, Publisher: Elsevier, Pages: 759a-759a
Elguindy A, Yacoub MH, 2013, The discovery of PCSK9 inhibitors: A tale of creativity and multifaceted translational research., Global Cardiology Science and Practice, Vol: 2013, Pages: 343-347, ISSN: 2305-7823
Chapron J, Hosny H, Torii R, et al., 2013, Lessons from patient-specific 3D models of the cardiac chambers after the Mustard operation., Global Cardiology Science and Practice, Vol: 2013, Pages: 409-415, ISSN: 2305-7823
The recent ability to create detailed 3D models of the atrial and ventricular chambers using CT, MRI and rapid prototyping offers unique opportunities to study the size and shape of the different cardiac chambers both before and following operation for complex cardiac anomalies. We here describe the techniques for creating detailed 3D models of the heart and demonstrate the utility of these techniques in a patient studied after the Mustard operation. This can give important insights into the changes in size and shape of the different chambers and the patterns of blood flow from the pulmonary and systemic veins to the 'appropriate' ventricle. This information in turn could be extremely helpful in understanding and optimizing the overall hemodynamic function after the Mustard operation.
El-Sherbiny IM, Yacoub MH, 2013, Hydrogel scaffolds for tissue engineering: Progress and challenges., Global Cardiology Science and Practice, Vol: 2013, Pages: 316-342, ISSN: 2305-7823
Designing of biologically active scaffolds with optimal characteristics is one of the key factors for successful tissue engineering. Recently, hydrogels have received a considerable interest as leading candidates for engineered tissue scaffolds due to their unique compositional and structural similarities to the natural extracellular matrix, in addition to their desirable framework for cellular proliferation and survival. More recently, the ability to control the shape, porosity, surface morphology, and size of hydrogel scaffolds has created new opportunities to overcome various challenges in tissue engineering such as vascularization, tissue architecture and simultaneous seeding of multiple cells. This review provides an overview of the different types of hydrogels, the approaches that can be used to fabricate hydrogel matrices with specific features and the recent applications of hydrogels in tissue engineering. Special attention was given to the various design considerations for an efficient hydrogel scaffold in tissue engineering. Also, the challenges associated with the use of hydrogel scaffolds were described.
Gandhi A, Siedlecka U, Shah AP, et al., 2013, The Effect of SN-6, a Novel Sodium-Calcium Exchange Inhibitor, on Contractility and Calcium Handling in Isolated Failing Rat Ventricular Myocytes, CARDIOVASCULAR THERAPEUTICS, Vol: 31, Pages: E115-E124, ISSN: 1755-5914
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- Citations: 12
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