scholarly journals Combined abdominal heterotopic heart and aorta transplant model in mice

2020 ◽  
Author(s):  
Hao Dun ◽  
Li Ye ◽  
Yuehui Zhu ◽  
Brian W. Wong

AbstractBackgroundAllograft vasculopathy (AV) remains a major obstacle to long-term allograft survival. While the mouse aortic transplantation model has been proven as a useful tool for study of the pathogenesis of AV, simultaneous transplantation of the aorta alongside the transplantation of another organ may reveal more clinically relevant mechanisms that contribute to the pathogenesis of chronic allograft rejection. Therefore, we developed a combined abdominal heart and aorta transplantation model in mice which benefits from reducing animal and drug utilization, while providing an improved model to study the progressive nature of AV.MethodsThe middle of the infrarenal aorta of the recipient mouse was ligatured between the renal artery and its bifurcation. Proximal and distal aortotomies were performed at this site above and below the ligature, respectively, for the subsequent anastomoses of the donor aorta and heart grafts to the recipient infrarenal aorta in an end-to-side fashion. The distal anastomotic site of the recipient infrarenal aorta was connected with the outlet of the donor aorta. Uniquely, the proximal anastomotic site on the recipient infrarenal aorta was shared to connect with both the inlet of the donor aorta and the inflow tract to the donor heart. The outflow tract from the donor heart was connected to the recipient inferior vena cava (IVC).ResultsThe median times for harvesting the heart graft, aorta graft, recipient preparation and anastomosis were 11.5, 8.0, 9.0 and 40.5 min, respectively, resulting in a total median ischemic time of 70 min. The surgery survival rate was more than 96% (29/30). Both the syngeneic C57Bl/6 aorta and heart grafts survived more than 90 days in 29 C57Bl/6 recipients. Further, Balb/c to C57Bl/6 allografts treated with anti-CD40L and CTLA4.Ig survived more than 90 days with a 100% (3/3) survival rate. (3/3).ConclusionsThis model is presented as a new tool for researchers to investigate transplant immunology and assess immunosuppressive strategies. It is possible to share a common anastomotic stoma on the recipient abdominal aorta to reconstruct both the aorta graft entrance and heart graft inflow tract. This allows for the study of allogeneic effects on both the aorta and heart from the same animal in a single survival surgery.

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Haoshu Fang ◽  
Hao Jin ◽  
Chuanfeng Hua ◽  
Anding Liu ◽  
Zichen Song ◽  
...  

Differences in LPS responsiveness influence the outcome of patients with sepsis. The intensity of the response is highly variable in patients and strain dependent in rodents. However, the role of the liver for initiating the LPS response remains ill defined. We hypothesize that hepatic LPS uptake is a key event for initiating the LPS response. In the present study, the severity of the LPS-induced inflammatory response and the hepatic LPS uptake was compared in two rat strains (Lewis (LEW) rats and Brown Norway (BN) rats). Using a transplantation model, we demonstrated the decisive role of the liver. The expression of hepatic TNF-α, IL-6, and IL-1β mRNA levels in BN rats was significantly lower than that in LEW rats. LEW rats were sensitized to LPS via G-CSF pretreatment. Sensitization caused by G-CSF pretreatment induced severe liver injury and mortality in LEW rats, but not in BN rats (survival rate: 0% (LEW) versus 100% (BN), p<0.01). LEW rats presented with higher liver enzymes, more alterations in histology, and higher expression of caspase 3 and higher cytokines levels. One of the reasons could be the increased hepatic LPS uptake, which was only observed in LEW but not in BN livers. Using the transplantation model revealed the decisive role of the LPS responsiveness of the liver. Injection of LPS to the high-responding LEW recipient before transplantation of a low-responder BN liver resulted in a 50% survival rate. In contrast, injecting the same dose of LPS into the high-responding LEW recipient after transplanting the low-responding BN liver resulted in a 100% survival rate. The severity of inflammatory response in different strains might be related to the differences in hepatic LPS uptake. This observation suggests that the liver plays a genetically defined decisive role in modulating the inflammatory severity.


2018 ◽  
Vol 17 (4) ◽  
pp. 4-11 ◽  
Author(s):  
A. О. Shevchenko ◽  
E. A. Nikitina ◽  
N. N. Koloskova ◽  
О. P. Shevchenko ◽  
S. V. Gotje

Aim. To evaluate the prevalence of arterial hypertension (AH) in heart transplant recipients, and its influence on the risk of adverse events, as the efficacy and safety of antihypertension medications (AHM).Material and methods. To the study, were consequently included all heart transplant recipients operated in the Shumakov Centre during the years 2013 to 2016 and survived 90 days after orthotopic heart transplantation.Results. Totally, 353 recipients included, with AH or AHM intake in anamnesis in 62 (17,6%). Within 90 days post-surgery, AH that demanded  for medication therapy was found in 151 (42,8%) patients. In posttransplant AH patients there were the following specific parameters in preoperational period: higher body mass index — 25,7±4,1 vs 24,9±4,4 (р=0,026), blood creatinine concentration — 100,6±62,6 vs 68,8±4,8 (р<0,001), donor heart posterior wall thickness — 11,9±0,8 vs 11,3±0,7 (р=0,034), creatinine concentration in 3 month after operation  — 131,7±101,6 vs 94,1±46,5 (p<0,001). There was relation revealed, of AH development risk with anamnesis of AH and renal failure, as a necessity for renal replacement therapy within 30 days post surgery and episodes of acute antibody-mediated reaction on transplant. In the recipients taking angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEi/ARB) before operation, the survival rate free from adverse events was better than in those taking calcium channel blockers (CCB) (plog-rank=0,042).Conclusion. The results of the study point on high prevalence of AH in heart recipients. Presence of AH in anamnesis, renal failure, episodes of humoral, but not cellular, reaction to the transplant, and donor heart hypertrophy do significantly increase the probability of AH development after transplantation. Comparison revealed significant benefit of ACEi/ ARB versus CCB as antihypertension medications in either monotherapy or in combination with diuretics.


Author(s):  
Hee-jin Kwon ◽  
Dong Seop Jeong ◽  
Hye Ree Kim ◽  
Seung-Jung Park ◽  
Kyoung-Min Park ◽  
...  

Introduction: In patients with non-paroxysmal AF, various ablation strategies have been attempted to target non-pulmonary vein (PV) foci or to achieve substrate modification beyond pulmonary vein isolation (PVI). The efficacy of empirical ablation of the SVC, one of the most common non-PV foci, is unclear. The aim of this study was to investigate the efficacy and safety of additional superior vena cava (SVC) isolation in patients with non-paroxysmal atrial fibrillation (AF) undergoing thoracoscopic surgical ablation. Methods and Results: A total of 191 patients with persistent or longstanding persistent AF was enrolled. All patients underwent total thoracoscopic surgical ablation for AF, and half of them also received empirical SVC isolation. We compared the atrial-tachyarrhythmia (ATa)-free survival rate and procedure-related complications in the two groups of patients. The 3-year ATa-free survival rate was 53% in the SVC-isolation group and 52% in the no-SVC-isolation group, (p = 0.644). There were no differences between the two groups with respect to AF type or LA size. Procedure-related complications occurred in 12 patients (6%). Pacemakers were implanted only in 3 patients from the SVC-isolation group. The only factor influencing recurrence of ATa was LA diameter. Conclusions: Empirical SVC isolation during thoracoscopic ablation for persistent AF did not improve patient outcomes.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Guohua Wang ◽  
Yixuan Wang ◽  
Jing Zhang ◽  
Yongfeng Sun ◽  
Jie Cai ◽  
...  

Background. We report a modified transplantation surgical technique for CHD with dextrocardia which is rare and surgically challenging. Methods. From January 2015 to May 2018, 5 patients with end-stage CHD with dextrocardia underwent heart transplantation at our institute. They were 10, 29, 13, 15, and 22 years old, respectively; 3 of them had dextroversion, and the other 2 had mirror-image dextrocardia and post-TCPC. The atrial-atrial anastomosis was performed first between the donor’s upper-left PVO and the recipient’s lower-left PVO. The apex thereby rotated approximately 90° clockwise (to the right). The end-to-end donor and recipient aortas, vena cava, and pulmonary arteries were then anastomosed. Results. The cold ischemic time of the donor heart was 284.6±108.3 min, and the CPB time was 190.2±43.8 min. The postoperative X-ray showed the apex on the right. Four patients were successfully discharged, and the follow-up times were 47 months, 36 months, 12 months, and 12 months. One post-TCPC patient died because of pneumonia and hypoxia at 59 postoperative days. Conclusions. Heart transplantation with dextrocardial CHD is rare. A 90° rotation at the left atrial level, aortic end-to-end anastomosis, and vena cava reconstruction by vascular prosthesis or systemic atrial cuff is a simple and effective surgical strategy.


2022 ◽  
Author(s):  
Taylor Nordan ◽  
Shant H. Mahrokhian ◽  
Caroline J. Liang ◽  
Jamel P. Ortoleva ◽  
Andre C. Critsinelis ◽  
...  

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Lili Wang ◽  
Desiree Wanders ◽  
Gayani Nanayakkara ◽  
Rajesh Amin ◽  
Robert L Judd ◽  
...  

Adiponectin (ADP) has been reported to exert cardiac protective effects during ventricular remodeling following pressure overload and myocardial ischemia. However, the potential role of ADP in the volume overload induced heart failure has not been reported. In this study we examined the effect of ADP in cardiac myocyte contractile dysfunction following sustained volume overload. Rat model of volume overload induced heart failure was created by infrarenal aorta-vena cava (A-V) fistula. Some rats were administered with adenoviral ADP (Ad-ADP) at 2-, 6-, and 9-weeks following fistula surgery. Serum total ADP levels were measured at 3 days before, 5 weeks and 10 weeks after fistula surgery. Myocyte contractility and intracellular Ca2+ transients were evaluated at 10 weeks following fistula. Results indicated a progressive reduction of serum ADP levels. In ventricular myocytes isolated from 10-week fistula rats, protein expression of ADP, AdipoR1/R2 and T-cadherin were decreased, and AMPK phosphorylation was reduced. Consistent with these, myocytes exhibited significant depression in cell shortening and intracellular Ca2+ transient. In vivo overexpression of adenovirus-mediated ADP in fistula rats significantly increased ADP serum levels, and prevented the depression of myocyte contractile performance. Moreover, in vitro treatment with ADP significantly improved myocyte contractility and intracellular Ca2+ transient from 10-week fistula rats, but had no effect on myocyte performance in control and Ad-ADP animals. These results demonstrate a positive correlation of ADP reduction and ventricular remodeling induced by volume overload. Adiponectin plays a protective role in volume overload-induced heart failure.


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