Sunday, September 28, 2014

Features of the pulmonary valve

The aortic and the pulmonary valves are anatomical structures of high complexity . The assessment , and the treatment methodology is developed for the disorders of the two semilunar , tricuspid valves . The proper functioning mechanism of the semilunar valve is represented by the closed phase during systole , and the open one during diastole ( figure 1 ) . The valve stenosis is generated by the inability of the valve to open successfully . The regurgitation of the blood is caused by the incapacitation of the valve to close shut .
Figure 1 . The internal videoscopic view of the pulmonary valve in the reanimated human heart , sagittal superior ( a , b ) , sagital inferior ( c , d ) , in systole ( a , c ) , in diastole ( b , d ) . Copyright ( 2013 ) Springer .
The three dimensional arrangement of the pulmonary valve is maintained by the histological structure designed with the fibrosa , the spongiosa , and The Nodulus Arantii ( figure 2 ) . The mean value for the annular diameter of the pulmonary valve is 25 . 4 ± 3 . 2 ( N = 3997 ) , and the mean value for the aortic valve is 22 . 4 ± 2 . 7 ( N = 3370 ) .
Figure 2 . The idealised three - dimensional structure of the semilunar valve . Copyright ( 2013 ) Journal of Cardiovascular Translational Research .
The surgery on the pulmonary valve presents less risk because the pressure gradient across the valve is low , comparing to the one for the aortic valve . Both the pulmonary and the aortic valve have similar dimensions , with slightly different material properties ( figure 3 ) . The pulmonary valve is considered as autograft replacement for the aortic valve in some patients with congenital heart disorders .
Figure 3 . The name of the leaflets for the semilunar valves . Copyright ( 2013 ) Springer .
Four of the 3861 hearts analysed by The European Homograft Bank have the pulmonary valve with two leaflets . Eight of the 109571 autopsies present an aneurysm of the pulmonary artery . A patient with both these conditions may have had an anomaly in the embryonic development .
References :
Batesman M . G . , Hill A . J . , Quill J . L . , Iaizzo P . A . ( 2013 ) “ The clinical anatomy and pathology of the human arterial valves : implications for repair or replacement ” , Journal of Cardiovascular Translational Research , 6 ( 2 ) , 166 - 175 .
Capps S . B . , Elkins R . C . , Fronk D . M . ( 2000 ) “ Body surface area as a predictor of aortic and pulmonary valve diameter ” , The Journal of Thoracic and Cardiovascular Surgery , 119 , 975 - 982 .
Iaizzo P . A . , Bianco R . W . , Hill A . J . , Louis J . D . S . ( 2013 ) “ Heart valves : from design to clinical implantation ” , Springer , part I . 2 , 27 - 45 .

Monday, August 18, 2014

The postoperative atrial fibrillation

The fast and irregular flow of the blood reduces the efficiency of the heart . The incidence of atrial fibrillation after cardiac surgery is 18.8 % of 49 264 patients , from the database between 2001 until 2012 in The Virginia Cardiac Surgery Quality Initiative . It is the cause of one in five strokes , and it reduces the quality of life . When it occurs after heart surgery , the risk of symptomatic hypotension , thromboembolism and heart failure is increased .

The European Society of Cardiology published guidelines for the control of the ventricular rate . There are five types of clinical symptoms for atrial fibrillation ( AF ), based on the time length : newly diagnosed , paroxysmal ( 2 days ) , persistent ( 7 days ) , long - standing persistent and permanent ( 1 year ) . The AF is associated with alterations of the extracellular matrix ( amyloid deposition , inflammatory behaviour , interstitial fibrosis ) , of the myocyte ( apoptosis , hypertrophy , intracellular accumulation of substrate ) , at microvascular level , and with remodelling of the endocardium .

Prolonged hospitalization may be required as the postoperative AF develops in the first three days after heart surgery . The systemic inflammation , triggered by the extracorporeal blood circulation during surgery , and the reactive oxygen species ( ROS ) in the atria are the causes for the postoperative AF .

Monoamine oxidase ( MAO ) is an enzyme on the outer membrane of the mithocondrion in the cardiac cell . It is a major factor in the balance between the reduction and the oxidation reactions in the atrial myocardium . The emission of mitochondrial H2O2 was measured in samples of myocardial tissue from 244 patients for cardiopulmonary bypass . Figure 1 outlines the incidence quartiles of postoperative AF in the cohort based on the enzymatic activity .

Figure 1 . The activity of the MAO and the incidence of the postoperative AF . Copyright ( 2014 ) Journal of The American Heart Association .

There are gaps in the clinical evidence that need to be understood :

  • Diagnosis
    • the increase in the electrocardiogram ( ECG ) screening
    • the benefit of multimodal therapy
  • Epidemiology
    • effective biomarkers for antithrombotic therapy
    • increase the cohort with undiagnosed AF
  • Rhythm control
    • the atrioventricular node ablation

    References :

    Anderson E . J . , Efird J . T . , Davies S . W . , O ‘ Neal W . T . , Darden T . M . , Thayne K . A . , Katunga L . A . , Kindell L . C . , Ferguson B . , Anderson C . A . , Chitwood W . R . , Koutlas T . C . , Williams J . M . , Rodriguez E . , Kypson A . P . ( 2014 ) “ Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation ” , Journal of the American Heart Association , 3 .

    Camm A . J . , Kirchhof P . , Lip G . Y . H . , Schotten U . , Savelieva I . , Ernst S . , Van Gelder I . C. , Al – Attar N . , Hindricks G . , Prendergast B . , Heidbuchel H . , Alfieri O . , Angelini A . , Atar D . , Colonna P . , De Caterina R . , De Sutter J . , Goette A . , Gorenek B . , Heldal M . , Hohloser S . H . , Kolh P . , Le Heuzey J . - Y . , Ponikowski P . , Rutten F . H . ( 2010 ) “ Guidelines for the management of atrial fibrillation ” , European Heart Journal , 31 , 2369 - 2429 .

    LaPar D . J . , Speir A . M . , Crosby I . K . , Fonner E . , Brown M . , Rich J . B . , Quader M . , Kern J . A . , Kron I . L . , Ailawadi G . ( 2014 ) “ Postoperative atrial fibrillation significantly increases mortality , hospital readmission , and hospital costs ” , The Annals of Thoracic Surgery , 98 ( 2 ) , 527 – 533 .

    Wednesday, August 6, 2014

    Key advances in medicine 2014

    Nature Reviews published in february 2014 this electronic book free for download on the website .

    International experts identified key trends in clinical studies from 2013 . They published 45 articles in 8 medical specialities :

  • Cardiology
    • acute coronary syndromes
    • cardiovascular imaging
    • dyslipidaemia
    • heart failure
    • venous thromboembolism

  • Clinical endocrinology
    • adrenal cancer
    • metabolism
    • puberty
    • steroid hormones
    • thyroid cancer
    • type 2 diabetes mellitus

  • Clinical oncology
    • breast cancer
    • cervical cancer
    • colorectal cancer
    • liver cancer
    • lung cancer
    • melanoma

  • Gastroenterology and hepatology
    • acute kidney injury
    • barrett oesophagus
    • cardiovascular disease in chronic kidney disease
    • coeliac disease
    • faecal microbiota transplantation
    • genetics in kidney disease
    • hepatitis c
    • inflammatory bowel disease
    • small bowel endoscopy
    • stem cells
    • transplantation immunology

  • Neurology
    • dementia
    • epilepsy
    • movement disorders
    • multiple sclerosis
    • neuro - oncology
    • stroke

  • Rheumatology
    • epigenetics
    • gout
    • imaging in rheumatology
    • systemic lupus erythematosus
    • rheumatoid arthritis

  • Urology
    • bladder cancer
    • female urology
    • kidney cancer
    • prostate cancer
    • reconstruction
    • testicular cancer

    Each article has the citation information regarding the original publication . Fine reading !

    Thursday, July 24, 2014

    The recovery heart rate time

    It is time for vacation . An idea for doing science , while having a good time , is to study the recovery time of the heart rate . One may have the chance of being an athlete for a day .

    The science project that I have in mind requires little effort from the volunteers . A few minutes are needed to fill in information regarding the physical activity . Then an e - mail is received with the location and time when the science project takes place . On the day of the event the person jogs on a park route for a few minutes . The heart rate is measured immediately after the exercise has finished , and after one and two minutes . The event is finished with refreshments .

    From the technical point of view , the data is processed based on two equations :

    • The maximum heart rate is 220 ( beats per minute ) minus percentage the age of the runner ;
    • The target heart rate zone is 50 - 85 % of the maximum heart rate .
    The variation with age and gender is analysed for both non - athletes and athletes .

    Would you like to participate in this activity , then fill in the form .

    Monday, July 21, 2014

    The anesthetic for valvular regurgitation

    The treatment plans are presented for both the aortic and the mitral valve . The acute and chronic phases are presented . The clinical findings for the functioning mechanism are presented through diagrams .The assessment of the functional capacity , the magnetic resonance images , the electrocardiography , the echo - measurements , and the physical examination are described for the preoperative phase . The presence of infective endocarditis is studied . The anesthetic management is outlined for the clinical environment .

    Sunday, July 13, 2014

    Hydrogels in regenerative medicine

    The muscle tissue of the heart is remodelled following the myocardial infarction . The ventricular wall is thinning and the chamber dilates . The adult cardiomyocytes regenerate at a lower rate than the heart requires to function at the required capacity , without any treatment . The clinical strategies are to either use synthetic implants , or to deliver cells directly into the tissue . A solution to avoid their shortcomings is to use hydrophilic hydrogels as a three dimensional structure to deliver cells into the body . The review in Nature presents the hydrogels that demonstrated the ability to enhance vascularisation , or to promote the differentiation of the delivered stem cells .

    The mechanical properties of the synthetic hydrogels ( Poly – ethylene glycol , Poly – N – isopropylacrylamide , Poly - 2 – hydroxyethyl methacrylate ) have the ability to control the behaviour of the cells in the damaged area of the myocardium . The NIPAAm - co - AAc - co – HEMAPTMC is a thermosensitive hydrogel that reduces the dimensions of the dilated left ventricle , while implanted in the rat with myocardial infarction . Figure 1 presents the rat myocardium eight weeks after the implantation of the hydrogel . Natural hydrogels ( Matrigel , Fibrin , hydrogel from porcine myocardial extracellular matrix ) increase the cell viability .

    Figure 1 . The morphology and the experimental outcomes of the NIPAAm - co - AAc - co – HEMAPTMC thermosensitive hydrogel . ( a ) The composition of the hydrogel . ( b ) The elastic properties of the hydrogel . ( c ) The control experiment with phosphate buffered saline ( PBS ) injection . ( d ) The rat heart after hydrogel injection . ( e ) The histology analysis with hematoxylin / eosin ( H & E ) of the control experiment . ( f ) The H & E histology analysis of the rat cardiac tissue with the injected hydrogel . ( g ) Immunohistochemistry for the tissue grown into the injected hydrogel . Copyright ( 2014 ) Nature Publishing Group .

    The hydrogels that demonstrate elastic behaviour while exposed to mechanical cyclic loading have the potential to repair the cardiac tissue . The hybrid of resilin – like polypeptide and Poly – ethylene glycol promotes cell differentiation after seven days of culture . The properties of Methacrylated tropoelastin ( MeTro ) are summarised in figure 2 . The micropatterned surface promotes the alignment and maturation for the cardiac cells , in the day 8 of the experiment. The frequency of the spontaneous beating rates of the cardiomyocytes was measured during two weeks of culture .

    Figure 2 . The markers expressed by the primary rat cardiomyocytes . ( a ) The troponin I ( green ) and the nuclei ( blue ) on the surface patterned with The Methacrylated Tropoelastin ( MeTro ) hydrogel . ( b ) The sarcomeric &alpha - actinin ( green ) , the connexin - 43 ( red ) , and the nuclei ( blue ) on the patterned surface . ( c ) Thr troponin I ( green ) and the nuclei ( blue ) on the unpatterned surface . ( d ) The sarcomeric &alpha - actinin ( green ) , the connexin - 43 ( red ) , and the nuclei ( blue ) on the unpatterned surface . ( e ) The beating behaviour of the cardiomyocytes on the unpatterned surface . ( f ) The beating behaviour of the cardiomyocytes on the patterned surface . ( g ) Spontaneous beating rates of cardiomyocytes on the unpatterned surface . Copyright ( 2014 ) Nature Publishing Group .

    The conductive hydrogels ( Chitosan , Polypyrrole ) connect areas to propagate the electrical signal into the entire cardiac tissue . The carbon nanotubes in gelatin methacrylate are actuators in the system ( figure 3 ) . The direction of motion varies as a function of the tubular thickness .

    Figure 3 . The actuators were designed by incorporating carbon nanotubes ( CNTs ) in gelatin methacrylate ( GelMA) . ( a ) The tightly and the loosely rolled – up constructs were designed . ( b ) The displacement of the beating constructs are a function of frequency and electrical source . ( c ) The linear displacement of a triangular swimmer as a function of time . Copyright ( 2014 ) Nature Publishing Group .

    The cardiac progenitor cells , the mesenchymal stem cells , and the pluripotent stem cells have increased potential for differentiation . The stem cell differentiation direction into the cardiac lineage is indicated by the hydrogel matrix in figure 4 . The immunostaining in the 2D hydrogels demonstrates that the sarcomere has diminished length in comparison to the one in the 3D structure .

    Figure 4 . The cardiac patch was designed as cardiomyocytes derived from the human embryonic stem cells ( hESCs ) in the hydrogel matrix . ( a ) The result of 2 weeks of in vitro culture . ( b ) The gels microfacricated with elliptical pores . ( c ) The alignment of the hESCs in the hydrogel . The immunostaining on 3D hydrogel of ( d ) troponin T ( red ) , ( e ) myosin heavy chain ( red ) , ( f ) connexin - 43 ( red ) and sarcomeric α – actinin ( green ) . ( g ) The immunostaining on 2D hydrogel of sarcomeric α – actinin ( green ) . Copyright ( 2014 ) Nature Publishing Group .

    The growth factors delivered with cells in the hydrogel may increase the efficiency of the process . Figure 5 presents the effect the basic Fibroblast growth factor ( bFGF ) has in a porcine model . The arteriolar density , the left ventricular ejection fraction , and the myocardial perfusion are increased at 4 weeks in culture , when the bFGF is used .

    Figure 5 . The influence of the released rate of basic Fibroblast growth factor ( bFGF ) on restoring the cardiac function in a porcine model of the myocardial infarction . ( a ) The presence of the sarcomeric α – actin , ( b ) the arteriolar density , ( c ) the myocardial perfusion , and ( d ) the left ventricular ejection fraction ( LVEF ) were measured under control and the bFGF included conditions . Copyright ( 2014 ) Nature Publishing Group .

    Only 10 % of the cells delivered directly in the cardiac tissue survive in vivo . The direct exposure to oxygen , free radicals , and inflammatory cytokines reduces the survival rate of the injected cells . A suitable 3D microenvironment is required . The hydrogel that mimics the cardiac tissue both handles the cyclic loading forces , and maintains the elastic , in addition to conductive , properties . The oxygen – releasing properties of a porous hydrogel , with or without the use of growth factors , increase the control of the system on the cellular environment .

    Sunday, July 6, 2014

    The engineering of complex tissue structures

    The laboratory of transplantation biology for regenerative medicine at The University of Gothenburg in Sweden . The research group lead by Professor Suchitra Sumitran – Holgersson designed the first engineered vein succesfully transplanted in the hepatic portal circulation of a 10 - year old female , in 2012 . A donated nine centimeters long iliac vein was used in the study . The cells of the donor were cleared from the three dimensional structure of the vein . The stem cells from the bone marrow of the patient were cultured in the laboratory . The differentiated endothelial and smooth muscle cells grew and divided onto the vessel . There was no need for using immunisuppressives .

    Professor Holgersson presented her three future research directions in the talk given at Tedx in 2012 . Her research team redesiged blood vessels and the trachea , and would continue with complicated organs as the liver and the larynx . Two human organs were thrown away , and Professor Holgersson considered they should be recycled : the placenta as filling material in face cheeks and thighs , and the amniotic membrane for wrapping around areas requiring skin grafts . The animal organ , for example the pig heart , was recycled and redesigned , with the challenging task to meet the in vivo requirements .

    References :

    Olausson M . , Patil P . B . , Kuna V . K . , Chougule P . , Hernandez N . , Methe K . , Kullberg – Lindh C . , Borg H . , Ejnell H . , Sumitran – Holgersson S . ( 2012 ) “ Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof - of - concept study ” , The Lancet , 380 ( 9838 ) , 230 – 237 .