The impact of physiological loading on immune cell infiltration and myocardial function evaluated by...
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POSTER PRESENTATION Open Access The impact of physiological loading on immune cell infiltration and myocardial function evaluated by cardiac MRI: a comparison between non- working heart and working heart transplant models Qing Ye 1* , Yi-jen L Wu 1 , Yeh Fang-Cheng 1,2 , Li Liu 1 , Brent Barbe 1 , Lesley M Foley 1 ,T Kevin Hitchens 1 , Chien Ho 1,3 From 15th Annual SCMR Scientific Sessions Orlando, FL, USA. 2-5 February 2012 Summary Rodent models of heterotopic cardiac transplantation are important for gaining a better understanding of heart allograft rejection. This study compared a working heart (WkHt) transplant model, which have developed by our laboratory, with the traditional non-working heart (Non-WkHt) model using cardiac MRI (CMRI) and pathological evaluation. Our results indicate that the physiological hemodynamic loading significantly impacts graft immune cell infiltration and myocardial function. Our WkHt transplant model with intact pul- monary circulation, retains hemodynamic loading close to that of native heart, and is thus more appropriate for both functional and immunological studies, especially for developing the clinically relevant CMRI techniques for comprehensive evaluation of the heart graft. Background The traditional heterotopic heart transplantation rodent model [1,2] lacks blood flow toward left ventricle (LV) and the graft does not pump blood, and therefore is a non-working heart (Non-WkHt). We have developed a new heterotopic working heart (WkHt) transplant model with intact pulmonary circulation to study car- diac allograft rejection.[3] In this study, we used combi- nations of pathology and multi-parameter CMRI, such as cine, Tagging, and T1/T2, to comprehensively evalu- ate the impact of physiological loading on the myocar- dial function, immune cell infiltration and graft pathophysiological condition of these 2 models. Methods WkHt model: En bloc of graft heart and lung was trans- planted into the recipient abdomen. Graft aorta and superior vena cava (SVC) were anastomosed with recipi- ent abdominal aorta and inferior vena cava (IVC), respectively.[3,4] Non-WkHt model: The graft aorta and pulmonary artery were anastomosed with the recipient abdominal aorta and IVC, as previously described.[1,2] CMRI: Cine and tagging MRI were used to assess car- diac function, and cellular MRI was performed using T2*-weighted scans to detect in situ micro-meter sized iron (MPIO) labeled macrophage infiltration at 7 Tesla. At the end point hearts were perfused and fixed for MR microscopy (MRM) at 11Tesla and pathological examination. Results Although isograft hearts from both models had strong heart beats and normal ECG, they exhibited very differ- ent cardiac functions revealed by CMRI (Fig.1). The WkHt displayed filling and ejecting cardiac phases (Fig.1A, B, E) comparable to native hearts. The graft stroke volume (SV, Fig.1F) is near to normal condition, and the ejection fraction (EF) was greater than 90% (Fig. 1 Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, USA Full list of author information is available at the end of the article Ye et al. Journal of Cardiovascular Magnetic Resonance 2012, 14(Suppl 1):P220 http://www.jcmr-online.com/content/14/S1/P220 © 2012 Ye et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transcript of The impact of physiological loading on immune cell infiltration and myocardial function evaluated by...
POSTER PRESENTATION Open Access
The impact of physiological loading on immunecell infiltration and myocardial function evaluatedby cardiac MRI: a comparison between non-working heart and working heart transplantmodelsQing Ye1*, Yi-jen L Wu1, Yeh Fang-Cheng1,2, Li Liu1, Brent Barbe1, Lesley M Foley1, T Kevin Hitchens1,Chien Ho1,3
From 15th Annual SCMR Scientific SessionsOrlando, FL, USA. 2-5 February 2012
SummaryRodent models of heterotopic cardiac transplantationare important for gaining a better understanding ofheart allograft rejection. This study compared a workingheart (WkHt) transplant model, which have developedby our laboratory, with the traditional non-workingheart (Non-WkHt) model using cardiac MRI (CMRI)and pathological evaluation. Our results indicate thatthe physiological hemodynamic loading significantlyimpacts graft immune cell infiltration and myocardialfunction. Our WkHt transplant model with intact pul-monary circulation, retains hemodynamic loading closeto that of native heart, and is thus more appropriate forboth functional and immunological studies, especiallyfor developing the clinically relevant CMRI techniquesfor comprehensive evaluation of the heart graft.
BackgroundThe traditional heterotopic heart transplantation rodentmodel [1,2] lacks blood flow toward left ventricle (LV)and the graft does not pump blood, and therefore is anon-working heart (Non-WkHt). We have developed anew heterotopic working heart (WkHt) transplantmodel with intact pulmonary circulation to study car-diac allograft rejection.[3] In this study, we used combi-nations of pathology and multi-parameter CMRI, such
as cine, Tagging, and T1/T2, to comprehensively evalu-ate the impact of physiological loading on the myocar-dial function, immune cell infiltration and graftpathophysiological condition of these 2 models.
MethodsWkHt model: En bloc of graft heart and lung was trans-planted into the recipient abdomen. Graft aorta andsuperior vena cava (SVC) were anastomosed with recipi-ent abdominal aorta and inferior vena cava (IVC),respectively.[3,4] Non-WkHt model: The graft aorta andpulmonary artery were anastomosed with the recipientabdominal aorta and IVC, as previously described.[1,2]CMRI: Cine and tagging MRI were used to assess car-diac function, and cellular MRI was performed usingT2*-weighted scans to detect in situ micro-meter sizediron (MPIO) labeled macrophage infiltration at 7 Tesla.At the end point hearts were perfused and fixed for MRmicroscopy (MRM) at 11Tesla and pathologicalexamination.
ResultsAlthough isograft hearts from both models had strongheart beats and normal ECG, they exhibited very differ-ent cardiac functions revealed by CMRI (Fig.1). TheWkHt displayed filling and ejecting cardiac phases(Fig.1A, B, E) comparable to native hearts. The graftstroke volume (SV, Fig.1F) is near to normal condition,and the ejection fraction (EF) was greater than 90% (Fig.
1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University,Pittsburgh, PA, USAFull list of author information is available at the end of the article
Ye et al. Journal of Cardiovascular Magnetic Resonance 2012, 14(Suppl 1):P220http://www.jcmr-online.com/content/14/S1/P220
© 2012 Ye et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.
Figure 1 Cardiac functions of isograft hearts from 2 HTx models evaluated by cine MRI. (A, B) cine imaging of an isograft from the WkHt model;(C, D) cine imaging of an isograft from the Non-WkHt model; (A, C) cine images acquired at end-diastole (ED); (B, D) cine images acquired atend-systole (ES); (E) temporal dynamic of normalized left ventricular volume over a cardiac cycle, (F) SV, and (G) EF, of a WkHt (red) and a Non-WkHt (blue).
Figure 2 CMRI of allografts hearts from the WkHt model on POD 47 (top panels, A-E) and the Non-WkHt model on POD 41 (lower panels, F-J).(A, F) in vivo T2* MRI; (B, G) tagging MRI at ED; (C, H) tagging MRI at ES; (D, I) circumferential strain (Ecc) maps derived from tagging MRI; and(E, J) ex vivo T2* MR Microscopy (MRM). The hypointensity regions/sports appeared in A, F, E and J result from MPIO-labeled monocytes/macrophages.
Ye et al. Journal of Cardiovascular Magnetic Resonance 2012, 14(Suppl 1):P220http://www.jcmr-online.com/content/14/S1/P220
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1G). On the contrary, the isograft from Non-WkHtmodel showed very little filling and ejecting (Fig.1C, D,E ), and its SV (Fig. 1F) and EF (Fig. 1G) are signifi-cantly lower than the WkHt. A similar functional discre-pancy can also be seen in allograft hearts (Fig.2) but thedegree is compounded by allograft rejection. TaggingMRI (Fig.2B, C, G, H) and strain analysis (Fig.2D, I )showed that allograft heart from WkHt model preservedmuch more wall motion than Non-WkHt. Interestingly,immune cell infiltration was also affected by the modelchoice. T2*-weighted MRI with MPIO-labeled macro-phages showed different infiltration pattern in two mod-els (Fig. 2A, F, E, J).
ConclusionsOur results indicate that hemodymamic loading signifi-cantly impacts the graft status. The WkHt transplantmodel, with intact pulmonary circulation, retains physio-logical conditions close to that of the native heart, andtherefore is more appropriate for functional and immu-nological studies, especially for developing the clinicallyrelevant CMRI techniques for comprehensive evaluationof the heart graft.
FundingThis study is supported by grants from the NationalInstitutes of Health (P41EB001977 and R01HL-081349).
Author details1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University,Pittsburgh, PA, USA. 2Department of Biomedical Engineering, CarnegieMellon University, Pittsburgh, PA, USA. 3Department of Biological Sciences,Carnegie Mellon University, Pittsburgh, PA, USA.
Published: 1 February 2012
References1. Abbott CP, et al: Arch Surg-Chicago. 1964, 89:645-652.2. Adams DH, et al: Transplantation. 1992, 53:1115-1119.3. Wu YJ, et al: Methods Enzymol. 2004, 386:73-105.4. Ye Q, et al: Circulation. 2008, 118:149-156.
doi:10.1186/1532-429X-14-S1-P220Cite this article as: Ye et al.: The impact of physiological loading onimmune cell infiltration and myocardial function evaluated by cardiacMRI: a comparison between non-working heart and working hearttransplant models. Journal of Cardiovascular Magnetic Resonance 2012 14(Suppl 1):P220.
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