The biggest cardiovascular center in The Netherlands

I worked temporarily at The Catharina hospital in Eindhoven last month . In the first day I had problems finding the main entrance . I parked the bicycle quickly near an entrance with a large building site . After I finished working in that day I asked at the information desk which one is the main entrance . I found out that I entered through it . While unlocking the bicycle , I looked up and read on a panel that I was standing not in front of an ordinary building site , but in front of the one for the biggest cardiovascular center in The Netherlands . I could not resist the temptation to write a post about it .

The Catharina hospital is a modern clinical training hospital , located in Eindhoven , The Netherlands . Although there are many options to find treatment at any hour , in any part of the city , people come at this hospital . I did not encounter any person living in this city that would not check in here , at some point . I found out on their website that it holds the quality mark in healthcare , awarded by The Netherlands Institute for Accreditation in Healthcare ( The NIAZ ) in 2000 . I found out on their LinkedIn group that the hospital has awarded the certificate of " top employers cure and care 2015" .

Figure 1 . The Catherina hospital , in Eindhoven , The Netherlands

The cardiovascular center is the biggest one in The Netherlands . The center already provides diagnosis and treatment for coronary artery disease and stenosis , heart failure , ablation , arrhythmia , valvulopathy , aortic and mitral valve , heart and valve surgery ; high quality research in blood testing , cardiogenetics , cardio - memo , computerised tomography ( CT ) scanning , echocardiogram , fractional flow reserve ( FFR ) measurement , and cardiac catheterisation .

The location of the cardiovascular center is , at the moment , in the main building of the hospital . When the new building section is ready , the centre will move in the new location , giving space to additional rooms for patients in the main hospital building .

Figure 2 . The biggest heart centre from The Netherlands , at The Catharina hospital in Eindhoven

The program Measurable better connects top clinicians and scientists from fourteen cardiovascular centers , and five intervention centers . The cardiovascular centers that joined the program are : The Catharina hospital , The academic medical center Amsterdam , The Amphia hospital , The Erasmus MC , The Hague hospital , Isala , Maastricht UMC + , The medical center Leeuwarden , The medical spectrum Twente , The " Our dear lady " hospital , Radboudumc , The saint Anthonius hospital , The universitary medical center Groningen , and The universitary medical center Utrecht . The five intervention centers that joined the program are : The " Elizabeth two cities " hospital , The Jeroen Bosch hospital , The Maasstad hospital , The medical center Alkmaar , and The Tergooi .

The Catharina hospital provides complex top clinical assistance in the diagnosis and the treatment of cardiac rhythm , in interventional cardiology , and in the cardiothoracic surgery . It is one of the centers that aims to have high quality patient care , with improved transparency . It was an honour working in the hospital .

The microRNA in tissue regeneration

I found a very interesting article that provides a concise literature review with 80 papers about original research in translational medicine .

The polymeric molecules that are the subject of discussion today are the microRNAs ( miRNA ). They are perfect complements to the target messengerRNA ( mRNA ) in plant cells , but they slightly mismatch in base pairing inside animal cells . The gene regulation using the complex micro RNA - m RNA triggers a wide variety of cellular mechanisms .

The cellular mechanisms that achieve organ regeneration , in a spatiotemporally controlled manner , are the differentiation , the dedifferentiation , the transdifferentiation , and the cellular proliferation . They alter the cellular plasticity .

The researchers learn from the invertebrates , the lower vertebrates , and the mammals how to activate the pluripotent stem cells in order to regrow parts or the entire organism . The trigger for the chain of events in the regeneration process is either the under - or the over - expression for the specific microRNA . The article provides a list for the microRNAs that regulate the human mesenchymal , and the human pluripotent ( the human embryonic , the human induced pluripotent ) stem cells .

The modulation of the regeneration process using microRNAs may be done by varying the modulators , the delivery method , or the cellular strategy ( figure 1 ) . The target cells are either the implanted or the endogeneous cells . The scientist may apply a modulation strategy on the endogenous ( stem ) cells , on the implanted cells prior to implantation , or on both the endogenous cells and the implanted cells . The modulators are either the cells themselves , the synthetic oligonucleotides , or the level of expression . The paper presents four delivery methods for the microRNAs : through direct injection , with viruses , with synthetic nanoparticles , and with cells as delivery vehicles .

Figure 1 . The technique variations for the micro - RNA signaling in the process of tissue regeneration .
Copyright ( 2014 ) AlphaMed Press

The heart has a limited potential for endogenous regeneration . The neonatal heart has a different response to myocardial infarction than the adult heart . The underexpressed microRNAs that trigger the proliferation of the cardiomyocytes are the miR - 15 family , the miR - 17 - 92 cluster , the miR - 199a and the miR - 590 families . They may help in the differentiation for the stem cells , for the cellular lineage commitment , and in the direct reprogramming process of the fibroblasts to generate cardiomyocytes . They are critical components in the signalling network for the adult cellular proliferation .

The microRNAs have a complex behaviour that is still not yet fully understood . The modulation strategy varies with the target organ that requires regeneration , and the research application .

References :

Frith J . E . , Porrello E . R . , Cooper - White J . J . ( 2014 )" Concise review : new frontiers in MicroRNA - based tissue regeneration " , Stem Cells Translational Medicine , 3 ( 8 ) , 969 - 976 .

The production of the spider silk

The structure of the silk fibre has two components , a crystalline one incorporated in the semi - amorphous region . The crystalline section contains poly – ( Gly – Ala ) , and poly – Ala nano – domains , filling in 50 % of the volume . The weak Hydrogen bonds have the functionality to link the nano – domains , in 10 – 15 % of the volume . The overall fibre is a natural block copolymer , with the elastic capacity from 500 % to 1000 % , and with the tensile strength in the GPa magnitude .

The Araneidae , a garden spider , weaves the two - dimensional web to capture insects . The web silk for this spider does not break when the insect attaches . The retraction time of the extended web spiral is small , so that the silk does not attach to unwanted elements . The silk coated naturally with a hydroscopic glue , has increased elasticity . The researchers analyse the natural phenomenon , both in the absence , and in the presence of fluid . Figure 1 summarises two experiments , a and b , conducted with the same setup , in the laboratory . The stretching curve is red , and the retraction curve is blue .

Figure 1 . The force spectra of the silk web molecules for The Araneidae ( the orb – weaving spider ) .
Copyright ( 2003 ) Nature Publishing Group

The natural method to produce silk has yet many unknowns for the researchers . The spider silk produced naturally is in limited volume . A method to produce hand - made silk , similar to the spider silk , with lower tensile strength , is from the transgenic silk worms, and from the milk of the transgenic goats .

A suitable match between the material properties of biomaterials and the ones of the cardiac tissue may be improved . A scaffold may be electrospun with the silk solution , with or without the addition of extra cellular matrix solution .

References :

Becker N . , Oroudjev E . , Mutz S . , Cleveland J . P . , Hansma P . K . , Hayashi C . Y . , Makarov D . E . , Hansma H . G . ( 2003 ) “ Molecular nanosprings in spider capture – silk threads ” , Nature Materials , 2 , 278 - 283 .

The robotic surgery procedure for the mitral valve

The leaflet of the mitral valve may prolapse , and lead to an increased fibrous ring . The surgeon may correct each part of the valve in a procedure that is minimally invasive . The robotic arm aids the surgeon to operate more precisely on the region of interest , from the console . The benefits for the patient from a procedure that does not split the breastbone are : less pain after surgery , short hospitalisation time , low risk of infection , quick recovery , and , of course , less marks on the body .

Waiting for the heart transplant

The first cardiac transplant from America took place at The Stanford Health Care . The experts in the same institute nowadays push the boundaries of science to save lives . They suggest that the total artificial heart is an intermediate option for the patients with right or bi - ventricular failure .

The longitudinal monitoring for the myocardium

The imaging techniques , in suitable parameters , provide the connection between the cell therapies and the clinical procedure . The longitudinal monitoring provides information about the functioning mechanism of the reprogrammed cells in the in vivo environment . The review presents the imaging techniques that are able to explain the cause for the limited restoration process of the cell therapies in the cardiac tissue .

The human body contains approximately 3 , 7 × 10¹³ cells . The heart contains 6 × 10⁹ cells , in 300 grams ( figure 1 ) . The damage of the heart does not lead automatically to the regeneration of the full functional capacity . The scar formation and the inflammatory signals may not be enough to have a full regeneration of the cardiac tissue . The regenerative medicine enhances the healing mechanisms of the body with the cell therapy .

Figure 1 . The number of cells in the parts of the human body .
Copyright ( 2014 ) Katie Vicari / Nature Publishing Group

The minimum number of injected cells that is detectable by the imaging techniques is in the range of 10⁴ - 10⁶ cells . The heart contains 2 × 10⁷ cells in one gram of tissue , in the left ventricle . The fused positron emission tomography ( PET ) - computed tomography ( CT ) image of the porcine heart is an example for the technique ( figure 2 ) . The long arrows point to the trajectory of the thoracotomy . T is the inserted tube . The short arrows point to the 10⁸ human mesenchymal stem cells , injected in the left ventricle ( LV ) . The %ID / g is the percentage of the uptake by the injected human cells in one gram of porcine cardiac tissue .

Figure 2 . The PET - CT imaging of the expression for the reporter gene in the porcine myocardium .
Copyright ( 2009 ) RSNA

The results of a porcine model for the myocardial infarction identifies as the time for the maximum proliferation at an interval of 33 - 35 days after the injection of the mesenchymal stem cells in the myocardium .

The injected cells are not tracked in vivo if they are not labelled in vitro . The nanoparticles , as the exogeneous label , provide a strong contrast in a short acquisition time , but it is unreliable in the long - term monitoring . The incorporation process of reporter genes labels indirectly the target cell . The reporter gene in the nucleus creates reporter proteins secreted in the cytoplasm . The imaging technique detects the reporter proteins . The ideal cell label stays inside the target cells for a long time , is non - toxic , is in a concentration that is stoichiometric related to the number of target cells , and clears the system rapidly after the apoptosis of the target cells .

The challenges of the imaging techniques are the label dilution , and the cell tracking . The label dilution should remain inside the tracked cells until the apoptosis , but sometimes the dilution transfers to the host cells . The long - term tracking of the implanted cells through the imaging techniques has the challenge to quantify the number of cells from the initial implantation procedure that are alive , and the number of cells that proliferate , in the spatial and the temporal dimension .

The infarcted myocardium is trully regenerated with the aid from the cell therapies when the viable cardiac tissue in the infarct area has the volume increased , the fiber architecture is integer in structure , and the regenerated myocardium has synchronous contraction with the host .

References :

Naumova A . V . , Modo M . , Moore A . , Murry C . E . , Frank J . A . ( 2014 ) “ Clinical imaging in regenerative medicine ” , Nature Biotechnology , 32 ( 8 ) , 804 - 818 .

Willmann J . K . , Paulmurugan R . , Rodriguez - Porcel M . , Stein W . , Brinton T . J . , Connolly A . J . , Nielsen C . H . , Lutz A . M . , Lyons J . , Ikeno F . , Suzuki Y . , Rosenberg J . , Chen I . Y . , Wu J . C . , Yeung A . C . , Yock P . , Robbins R . C . , Gambhir S . S . ( 2009 ) “ Imaging gene expression in human mesenchymal stem cells : from small to large animals ” , Radiology - Radiological Society of North America , 252 ( 1 ) , 117 - 127 .

The effects on the heart after the replacement for the mitral valve

The echocardiographic investigation of the mitral valve shows which leaflet is degenerated , if the leaflet , and the ring , maintained the integrity , the state of the attachment for the chorda tendinae , the structure of the papillary muscles . Two follow - up studies present the outcome of the mitral valvuloplasty for the elderly patients .

A study presents the clinical findings for a man of 74 years old . He did not have regurgitation of the tricuspid valve before he had a prosthetic replacement for the mitral valve . The left side of the heart stabilised with the surgery . The aortic valve had an unaffected functioning mechanism . The postoperative atrial fibrillation progressed. The postoperative regurgitation of the tricuspid valve made an impact on the right side of the heart .

The rheumatic heart disease ( RHD ) , and the dilated cardiomyopathy ( DCM ) are the causes for the stenosis ( MS ) , and for the regurgitation ( MR ) of the mitral valve ( figure 1 ) . The effects of the increased pressure in the left atrium are the increased size of the left atrium , the atrial fibrillation , and the pulmonary hypertension . The atrial fibrillation produces the dilation for the ring of the tricuspid valve . The pulmonary hypertension generates the dilation of the right ventricle ( RV ) . The regurgitation of the tricuspid valve ( TV ) worsens the tethering of the tricuspid valve , and the dilation of the right ventricle .

Figure 1 . The regurgitation of the tricuspid valve after the mitral valvuloplasty . Copyright ( 2009 ) Journal of The American College of Cardiology .

Another follow - up study analyses the clinical outcome for 242 patients who had valvuloplasty for the repair of the mitral valve . The patients are free from the non - trivial regurgitation of the mitral valve in 94 . 3 ± 1 . 6 % after one month , 58 . 6 ± 4 . 9 % after five years , and 27 . 2 ± 8 . 6 % after seven years ( figure 2 ) . The freedom from the severe regurgitation of the mitral valve is 98 . 3 ± 0 . 9 % after one month , 82 . 8 ± 3 . 8 % after five years , and 71 . 1 ± 7 . 4 % after seven years .

Figure 2 . The non - trivial regurgitation of the mitral valve . Copyright ( 2003 ) Circulation .

The dysfunction of the mitral valve is generated by the rheumatic heart disease , by the ischemic heart disease , and by the bacterial endocarditis . The succes of the replacement for the mitral valve is assessed both in the short term , and in the long term effects on the quality of life for the patient .

References :

Flameng W . , Herijgers P . , Bogaers K . ( 2003 ) “ The clinical anatomy and pathology of the human arterial valves : implications for repair or replacement ” , Circulation , 107 , 1609 - 1613 .

Shiran A . , Sagie A . ( 2009 ) “ Tricuspid regurgitation in mitral valve disease : incidence , prognostic implications , mechanism , and management ” , Journal of The American College of Cardiology , 53 ( 5 ) , 401 - 408 .