The TCV Lab | Dr. Irving Kron & Dr. Victor Krupnick

The TCV Lab had its origins over 35 years ago in the early 1980’s here at the University of Virginia. Dr. Irv Kron had come here as a TCV resident and found himself looking for ways to study clinical questions in a laboratory environment. He recruited some of the UVA general surgery residents to help with some of these projects, including Dr. Curt Tribble. The first successful project that this group of intrepid residents took on was one of the first studies of what was to become known as ‘the abdominal compartment syndrome’.   At first, these projects were done in off hours in the lab of one of the established investigators in the Department, Dr. Wallace Ritchie, who graciously allowed his lab space to be used for these studies.  Subsequent projects included looking at renal perfusion during sepsis and the spinal cord ischemia that can result from aortic cross-clamping.  Dr. Kron worked to get early funding for these efforts from the American Heart Association, industry (Gore, Merck, DuPont, etc), and various UVA related faculty development programs (Jeffress Foundation and a UVA based NIH funded R&D development award). Drs. Kron and Nolan helped support Dr. Tribble’s post-doctoral fellowship to study adenosine physiology and pharmacology in Dr. Robert Berne’s lab in the Department of Physiology prior to his return to the TCV lab.

The TCV lab’s first RO1 NIH grant was awarded in1992, with Dr. Kron as the Principal Investigator and Dr. Tribble as the Co-Investigator. The focus of this grant was on living lobar transplantation, which paralleled the development of the UVA lung transplant program. Drs. Chuck Hobson, Lorne Blackbourne, and Scott Langenburg were among the first of many UVA residents supported by various training grants related to the TCV lab. All three of these graduates of our program have been academically productive ever since their days of training in the TCV lab, as have many subsequent trainees, both those from UVA and from other institutions. The TCV lab has been continuously supported by RO1 NIH grants since that time.

In 1998, an NIH T32 Cardiovascular Surgery Research Training Grant was awarded to the lab, again with Dr. Kron as the PI and Dr. Tribble as the Co-PI. This program has been continuously funded since that time. Another RO1 grant obtained in 2000 by the TCV lab was based on the long term focus of the lab on spinal cord protection during aortic surgery. Dr. John Kern, now the Chief of the Division of TCV Surgery, was the Principal Investigator for this grant, while both Dr. Kron and Dr. Tribble were Co-Principal Investigators.  Another area of interest to the lab has been ventricular assist device development, through collaboration with researchers in the UVA School of Engineering. Some of this work was supported by the UVA Children’s Hospital with a grant to Dr. Tribble in 2001.

Victor Laubach, PhD joined the lab in ~1995 and helped provide additional focus on the basic science approaches to the work of the lab group and to the education of the residents training in the lab. In addition to Dr. Laubach, there are a number of outstanding individuals who have helped manage and run the lab over the years, including Mr. Tony Herring, who has been the manager of the lab for many years and Ashish Sharma, who obtained his PhD while working in the lab.  There have also been many productive collaborations with other current and former UVA researchers, such as Kevin Lynch from the Department of Pharmacology and Joel Linden now a Professor at the La Jolla Institute in San Diego and the founder of a company known as Adenosine Therapeutics.

Throughout the existence of the TCV lab, there has been a consistent focus on several principles. First of all, the research efforts of the lab have been related to the clinical challenges faced by the UVA TCV faculty surgeons in their clinical programs, including lung transplantation, heart failure, and aortic surgery. Second, there has been an emphasis on creating an optimal educational environment for the residents, with regular lab meetings and consistent mentoring of the medical students, basic science students, and surgical residents (both from UVA and from other programs) spending time in the lab. Third, the lab has always used some large animal models, in addition to a myriad of isolated perfused organ models and small animal models, and this focus on large animal models has allowed the surgical residents to very significantly improve their surgical skills. Fourth, there has always been an additional emphasis on publishing clinical papers related to the work of the Division. The resident trainees have consistently been very productive, publishing from 15 to 30 articles in refereed journals related to their work in the lab. Furthermore, there has been an emphasis on helping the resident trainees become outstanding surgical educators, with many of these residents being recognized by a large number of teaching awards, including numerous James Kindred Awards, given to the UVA resident considered by the graduating medical school classes to have been their single best teaching resident.

An example of an alumnus of the lab is Dr. Brett Reece, who came from his general surgery training program to spend two years in the TCV lab, funded by the T32 training grant. He was very productive during his time in the lab, publishing numerous articles. Brett went on to train in CT surgery at Colorado where he has remained on the faculty. He has established a very productive lab there, primarily studying spinal cord ischemia.

The TCV lab environment has continued to flourish and be productive up to the present time.  As evidence of this productivity, Dr. Kron has been an author or co-author of more papers published in The Annals of Thoracic Surgery than any other author in that journal’s history. The vast majority of these papers were co-authored by residents who spent time in the TCV lab. There are generally two or three UVA surgery residents working in the lab who are carrying on these traditions, with the current focus being on ‘resuscitation of marginal lungs’ for transplantation.  There will be a renewed focus on pediatric lung transplantation in the coming years. The lab group continues to welcome interest from UVA students and surgery residents, as well as from residents other training programs who can be supported with the T32 training grant.

Funding

NIH Grants:  UM1 HL008925 (Cardiothoracic Network Grant),

R01 HL119218, T32 HL007849 (Cardiothoracic Training Grant)

Selected References

Selected references illustrate the depth and breadth of the academic productivity of the faculty and residents who have been a part of this lab over the years.

Tribble CG, Kern JA, Daniel TM, Kron IL: The first single lung transplant in Virginia. Virginia Medical Quarterly 118(3): 116-167, 1991.

Ross SD, Tribble CG, Linden J, Gangemi JJ, Kron IL. Selective adenosineA2A activation reduces lung reperfusion injury following transplantation. J Heart Lung Transplant 18:994-1002, 1999.

Reece TB, Tribble CG, Maxey TS, Ellman PI, Laubach VE, Linden J, Kern JA, Kron IL. Adenosine A2A receptor agonist improves cardiac dysfunction from pulmonary ischemia-reperfusion injury. Ann Thorac Surg 79(4):1189-1195, 2005.

Gazoni LM, Tribble CG, Ellman PI, Laubach VE, Kron IL. Pulmonary macrophage inhibition, inhaled nitric oxide attenuate lung ischemia reperfusion injury. Ann Thorac Surg84:247-53, 2007.

LaPar DJ, Ailawadi G, Bhamidipati CM, Stukenborg G, Kern JA, Kron IL et al. Small prosthesis size in aortic valve replacement does not affect mortality. The Annals of Thoracic Surgery 92: 880-8, 2011.

Kron IL. Surgical Mentorship. The Journal of Thoracic and Cardiovascular Surgery 142: 489-92, 2011.

Mulloy DP, Stone ML, LaPar DJ, Sharma AK, Kron IL, et al. Ex vivo rehabilitation of non-heart-beating donor lungs in preclinical porcine model: delayed perfusion results in superior lung function. The Journal of Thoracic and Cardiovascular Surgery 144: 1208-15, 2012.

Fernandez LG, Sharma AK, LaPar DJ, Kron IL, Laubach VE. Adenosine A(1) receptor activation attenuates lung ischemia-reperfusion injury. The Journal of Thoracic and Cardiovascular Surgery 145: 1654-9, 2013.

Mulloy DP, Sharma AK, Lau CL, Kron IL, Laubach VE. Adenosine A3 receptor activation attenuates lung ischemia-reperfusion injury. Ann Thorac Surgery. 95: 1762-7, 2013

Gillen JR, Zhao Y, LaPar DJ, Stone ML, Kron IL, Lau CL. Rapamycin blocks fibrocyte migration and attenuates bronchiolitis obliterans in a murine model.  Ann Thorac Surg 95:1768-75, 2013.

Wagner CE & Kron IL. Subvalvular techniques to optimize surgical repair of ischemic mitral regurgitation.   Curr Opin Cardiol 29: 140-4, 2014.

CG Tribble & WH Merrill. The Way We Talk is the Way We Teach. Journal of Thoracic and Cardiovascular Surgery 147:1155-9, 2014.

Stone ML, LaPar DJ, Ailawadi G, Kron IL, Bergin JD, Blank RS, Kern JA. Ventricular assist devices and increased blood product utilization for cardiac transplantation.  See comment in PubMed Commons below J Card Surg 30:194-200, 2015.

LaPar DJ, Isbell JM, Mulloy DP, Stone ML, Kern JA, Ailawadi G,  Kron IL. Planned cardiac re-exploration in the intensive care unit is a safe procedure. Ann Thorac Surg 98, 1645-51, 2014.

Stone ML, LaPar DJ, Ailawadi G, Kron IL, Kern, JA. Ventricular assist devices and increased blood product utilization for cardiac transplantation. J Card Surg 30: 194-200, 2015.1

Charles EJ & Kron IL. One step closer to the elimination of primary graft dysfunction. J Thorac Cardiovasc Surg 149: 602-3, 2015.