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Mr Stephen Large

Research Interests

I have been drawn into heart failure which is so often due to ischaemia so these two issues are of particular interest to me. Therefore heart transplantation is of interest and its main clinical barrier is availability of good donor hearts.

We have established a programme of heart transplantation with donation after circulatory determined death (essentially using an ischaemic heart). Areas of special interest include myocardial ischaemia, myocardial protection, measurement of ventricular function and ways to perfuse/store human hearts for later transplantation.

I also have an interest in thoracic aortic disease and am the CI of ETTAA, an HTA-funded observational trial of patients with aneurysmal enlargement of intra-thoracic aortas. This large study finishes recruitment in July 2018 and will report in the following 12 months.

Quality of life is a missed end-point for clinical cardiac surgery. This we are to pursue through at a national level with the intention to demonstrate the impact of heart surgery on quality of life for the patient and to establish a pre-operative calculator that can predict the likelihood of improvement in the quality of life of patients so helping them with informed consent.

Keywords

Myocardial preservation ; aneurysm growth ; myocardial ischaemia ; quality of life after heart surgery ; Aortic aneurysm

Key Publications

 

  1. In Vivo Post-Cardiac Arrest Myocardial Dysfunction Is Supported by Ca2+/Calmodulin-Dependent Protein Kinase II-Mediated Calcium Long-Term Potentiation and Mitigated by Alda-1, an Agonist of Aldehyde Dehydrogenase Type 2. Woods CE, Shang C, Taghavi F, Downey P, Zalewski A, Rubio GR, Liu J, Homburger JR, Grunwald Z, Qi W, Bollensdorff C, Thanaporn P, Ali A, Riemer RK, Kohl P, Mochly-Rosen D, Gerstenfeld E, Large S, Ali ZA, Ashley EA. Circulation. 2016 Sep 27;134(13):961-77. doi: 10.1161/CIRCULATIONAHA.116.021618.

  2. Stenting of the ascending aorta: a stent too far? Mahesh B, Catarino P, Gopalan D, Large S.Interact Cardiovasc Thorac Surg. 2014 May;18(5):685-7. doi: 10.1093/icvts/ivu010.

  3. Rat model of veno-arterial extracorporeal membrane oxygenation. Ali AA, Downey P, Singh G, Qi W, George I, Takayama H, Kirtane A, Krishnan P, Zalewski A, Freed D, Large SR, Ashley EA, Leon MB, Bacchetta M, Ali ZA. J Transl Med. 2014 Feb 7;12:37. doi: 10.1186/1479-5876-12-37.

  4. A cardioprotective preservation strategy employing ex vivo heart perfusion facilitates successful transplant of donor hearts after cardiocirculatory death.White CW, Ali A, Hasanally D, Xiang B, Li Y, Mundt P, Lytwyn M, Colah S, Klein J, Ravandi A, Arora RC, Lee TW, Hryshko L, Large S, Tian G, Freed DH. J Heart Lung Transplant. 2013 Jul;32(7):734-43. doi: 10.1016/j.healun.2013.04.016.

  5. The influence of endoscopic vein harvesting on outcomes after coronary bypass grafting: a meta-analysis of 267,525 patients. Sastry P, Rivinius R, Harvey R, Parker RA, Rahm AK, Thomas D, Nair S, Large SR.Eur J Cardiothorac Surg. 2013 Dec;44(6):980-9. doi: 10.1093/ejcts/ezt121. Review.

  6. Ex vivo perfusion of the swine heart as a method for pre-transplant assessment. Colah S, Freed DH, Mundt P, Germscheid S, White P, Ali A, Tian G, Large S, Falter F. Perfusion. 2012 Sep;27(5):408-13. doi: 10.1177/0267659112449035.

  7. Resuscitating heart transplantation: the donation after circulatory determined death donor. Messer S, Large S. Eur J Cardiothorac Surg. 2016 Jan;49(1):1-4. doi: 10.1093/ejcts/ezv357. Review. No abstract available.eComment. Re: Radiological patterns of primary graft dysfunction after lung transplantation. Parmar J, Dunning J, Large S. Interact Cardiovasc Thorac Surg. 2012 Jun;14(6):791. doi: 10.1093/icvts/ivs147. No abstract available.

  8. Stroke prevention in cardiac surgery. Abah U, Large S. Interact Cardiovasc Thorac Surg. 2012 Jul;15(1):155-7. doi: 10.1093/icvts/ivs012.

  9. The ETTAA study protocol: a UK-wide observational study of 'Effective Treatments for Thoracic Aortic Aneurysm'. Sastry P, Hughes V, Hayes P, Vallabhaneni S, Sharples L, Thompson M, Catarino P, Moorjani N, Vale L, Gray J, Cook A, Elefteriades JA, Large SR; ETTAA Collaborators. BMJ Open. 2015 Jun 2;5(6):e008147. doi: 10.1136/bmjopen-2015-008147.

  10. Hearts from DCD donors display acceptable biventricular function after heart transplantation in pigs. Ali AA, White P, Xiang B, Lin HY, Tsui SS, Ashley E, Lee TW, Klein JR, Kumar K, Arora RC, Large SR, Tian G, Freed DH. Am J Transplant. 2011 Aug;11(8):1621-32. doi: 10.1111/j.1600-6143.2011.03622.x.

 

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