Gigantic biatrial myxoma in a young female with an atrial septal defect: a case report.

Background: Myxomas are uncommon and benign cardiac neoplasms that can present with various cardiac, systemic, embolic, or without symptoms depending on their location and size. Very few cases of large, truly biatrial, or tumours connected via the cardiac atria have been reported throughout the years. Case summary: We present an unusual case of an apparently healthy 25-year-old French woman, who presented with dyspnoea at Munich's Octoberfest. Echocardiography and computed tomography identified gigantic masses in left and right atrium, which were connected through an atrial septal defect. They were successfully removed by emergent cardiac surgery. Discussion: This case describes an uncommon tumour and highlights the importance of a quick diagnosis and prompt surgery. We describe the management and surgery for atrial myxomas as well as demonstrating pre- and intraoperative pictures.

Metastatic Penile Squamous Cell Carcinoma: Unmasked by an Acute Myocardial Infarction and Terminal Heart Failure.

A young patient, recently treated for squamous cell penile carcinoma, presented with acute myocardial infarction and severe heart failure. Despite repeatedly ruling out metastatic disease on imaging, surgery for a mechanical assist device revealed unexpected squamous cell metastasis in the pericardium. Consequently, palliative care was initiated.

Pre-Implant Immune Status is Associated with Infection Risk After Left Ventricular Assist Device Implantation.

Purpose: Infection is the most common complication after left ventricular assist device (LVAD) implantation. The immune status of LVAD patients is relevant for the incidence and severity of infection, but it is unknown if there is a predisposing immune status prior to LVAD implantation that contributes to an increased risk for infection in the post-implant period. We analyzed the pre-LVAD immune status in patients with infection within 3 months after LVAD implantation in comparison to infection-free patients. Patients and Methods: Fifty-four consecutive LVAD patients were included in this study. According to their infectious history in the first 3 months after LVAD implantation, these patients were grouped into an infection (n=23) and an infection-free group (n=31). Pre-LVAD blood samples were obtained for flow cytometric analysis of immunological parameters including B cells, subsets of T, dendritic and natural killer cells. Patient-specific, clinical and laboratory data were recorded. Results: Blood count analysis prior to LVAD implantation showed comparable counts of erythrocytes (p=0.19), platelets (p=0.33) and leukocytes (p=0.50) between patients with infection and infection-free patients in the post-implant period. Patients with infection in the first 3 months after LVAD implantation had lower concentrations of lymphocytes (p=0.02). Forty percent of the patients with infection showed more often pre-LVAD neutrophil-to-lymphocyte ratios (NLR) >7 than patients without infection in the first 3 months after LVAD implantation (14%, p=0.05). Patients with infection already had lower percentages of CD3+ T cells (p=0.03), CD19+ B cells (p<0.01), BDCA2+ pDCs (p=0.03) and BDCA4+ plasmacytoid DCs (pDCs) (p=0.05) prior to LVAD implantation than infection-free patients. Conclusion: Our results demonstrated that patients with infection in the early post-implant period showed lower concentrations of lymphocytes, especially of CD3+ T cells and CD19+ B cells, decreased percentages of BDCA2+ and BDCA4+ pDCs, and had more often NLRs >7 indicating moderate-to-severe inflammation. Thus, we identified specific immunological changes pre-LVAD that could help to identify patients at risk for infection in the early post-implant period.

Bicuspid Morphology and Rapid Deployment Valve Replacement: Is This Still a Contraindication?

When using rapid deployment surgical aortic valve replacement (RD SAVR) in treating bicuspid aortic valve morphology (BAV), several challenges are faced due to annular asymmetry. The Sievers classification has been traditionally used for the description of BAV morphology. In this study, we aimed to conduct a retrospective feasibility analysis of RD SAVR in relation to the Sievers classification. From January 2014 to March 2022, 31 patients with BAV morphology (15 patients with Sievers type 0 BAV and 16 with Sievers type 1 BAV) underwent RD SAVR. Specific surgical techniques were applied depending on the BAV morphology. Comparable clinical outcomes were observed. No paravalvular leaks and no valvular re-interventions occurred in either group. CPB and cross-clamping times, as well as the prosthesis sizes used, were also not significantly different. Postoperative mean gradients were comparable in both groups. No significant distinction was found between the groups in terms of postoperative pacemaker indication, postoperative stroke, or death. Annular symmetry can be adequately restored through precise prosthesis sizing and placement according to an individual's valve morphology regardless of the Sievers classification of BAV by choosing a different landmark for the initial suture. RD SAVR seems to be a safe approach for any bicuspid morphology, with good hemodynamic results and time-saving potential in experienced hands.

Body mass index-dependent immunological profile changes after left ventricular assist device implantation.

Purpose: Infection is a common complication following left ventricular assist device (LVAD) implantation. Patients with obesity are particularly at risk due to their high percentage of adipose tissue and the resulting chronic inflammatory state and resulting immunological changes. This study investigated changes of immunological parameters in relation to body mass index (BMI) during the first year after LVAD implantation. Methods: Blood samples were obtained prior to LVAD implantation and at 3 (1st FU), 6 (2nd FU) and 12 mo (3rd FU) after LVAD implantation. Patients were divided into three groups (normal weight: BMI of 18.5-24.9 kg/m2; n=12; pre-obesity: 25.0-29.9 kg/m2; n=15; obesity: ≥ 30.0 kg/m2; n=17) based on their BMI at the time of LVAD implantation. Flow cytometric analyses for CD4+ and CD8+ T cells, regulatory T cells (Tregs), B cells as well as dendritic cells (DCs) were performed. Results: After LVAD implantation, obese patients (0.51 ± 0.20%) showed a higher proportion of overall DCs than normal-weight (0.28 ± 0.10%) and pre-obese patients (0.32 ± 0.11%, p<0.01) at 3rd FU. The proportion of BDCA3+ myeloid DCs was lower in obese patients (64.3 ± 26.5%) compared to normal-weight patients (82.7 ± 10.0%, pnormal-weight vs. obesity=0.05) at 2nd FU after LVAD implantation. The analysis of BDCA4+ plasmacytoid DCs revealed a reduced proportion in pre-obese (21.1 ± 9.8%, pnormal-weight vs. pre-obesity=0.01) and obese patients (23.7 ± 10.6%, pnormal-weight vs. obesity=0.05) compared to normal-weight patients (33.1 ± 8.2%) in the 1st FU. T cell analysis showed that CD4+ T cells of obese patients (62.4 ± 9.0%) significantly increased in comparison to pre-obese patients (52.7 ± 10.0%, ppre-obesity vs. obesity=0.05) and CD8+ T cells were lower in obese patients (31.8 ± 8.5%) than in normal-weight patients (42.4 ± 14.2%; pnormal-weight vs. obesity=0.04) at the 3rd FU. Furthermore, we observed significantly reduced proportions of Tregs in pre-obese patients compared to normal-weight and obese patients at 2nd FU (p=0.02) and 3rd FU (p=0.01) after LVAD implantation. Conclusion: This study reported changes of the innate and adaptive immune system of pre-obese and obese compared to normal-weight patients one year after LVAD implantation. DCs and their subsets, CD8+ T cells and Tregs were affected immune cell populations that indicate immunological changes which might increase the incidence of postoperative infection.

Coronary Sparing Aneurysmectomy.

Repairing left ventricular aneurysms that form after myocardial infarction may be challenging, especially if located close to the important native coronary arteries. Here, we describe a rare case of anterolateral aneurysm of the basal LV wall and a safe, efficient approach for a patch plasty sparing the native left anterior descending.

Evaluation of a rapid deployment prosthesis strategy for the treatment of aortic valve endocarditis.

OBJECTIVES: The aim of this study was to evaluate the surgical outcome of patients suffering from native aortic valve (NVE) or prosthetic aortic valve endocarditis (PVE) treated with the EDWARDS INTUITY Elite rapid-deployment valve prosthesis. METHODS: Between February 2019 and June 2020, 25 patients suffering from NVE (n = 9; 36%) and PVE (n = 16; 64%) of the aortic valve received an INTUITY valve at our institution. Preoperative, operative and follow-up data were collected. RESULTS: In our cohort, the mean EuroSCORE II was 13.4%. Eleven patients (44%) received concomitant aortic root patch plasty. Four patients (16%) received coronary artery bypass graft surgery, 3 patients (12%) received mitral valve repair and 2 patients (8%) underwent replacement of the ascending aorta. The cardiopulmonary bypass and aortic cross-clamp times were 124 ± 56 and 75 ± 39 min, respectively. The mean intensive care unit stay was 5 days. The mean size of the implanted prostheses was 25 ± 2 mm and the mean prosthesis transvalvular gradient 3 months after surgery was 9 ± 4 mmHg. During follow-up, no case of recurrent endocarditis occurred, 1 patient died of multisystem organ failure which had already been present preoperatively. CONCLUSIONS: Surgery for NVE and PVE of the aortic valve may be safely performed using the EDWARDS INTUITY Elite valve system. This procedure could be well implemented in cases with extensive infection, fragile root tissue and root abscesses requiring root reconstruction. In our institution, the rapid-deployment aortic valve replacement strategy has become an important tool in the armamentarium of the surgical endocarditis treatment.

Interdisciplinary Management of the Emergency Treatment in an Atrioesophageal Fistula.

The atrioesophageal fistula is a fulminant complication of radiofrequency ablation in atrial fibrillation, with a mortality as high as 80%. Surgical approaches have been insufficiently dealt with in literature. Treating a 42-year-old male patient, we developed an interdisciplinary two-step concept: (1) resection of the affected third of the esophagus and closing of the atrial defect using cardiopulmonary bypass and cardioplegic cardiac arrest; and (2) a second surgery to restore gastrointestinal continuity after an adequate term. Our patient has fully recovered.

Impact of Operative Timing in Infective Endocarditis with Cerebral Embolism-The Risk of Intermediate Deterioration.

Cerebral embolism due to infective endocarditis (IE) is associated with significant morbidity and mortality. The optimal time-interval between symptomatic stroke and cardiac surgery remains unclear. This study aimed to analyze the patients' outcomes and define the potential risk factors with regard to surgical timing for IE patients with preoperative symptomatic cerebral embolism (CE). A total of 119 IE patients with CE were identified and analyzed with regard to operative timing: early (1-7 days), intermediate (8-21 days), and late (>22 days). The preoperative patient data, comorbidities and previous cardiac surgical procedures were analyzed to identify potential predictors and independent risk factors for in-hospital mortality using univariate and multivariate regression analysis. Actuarial survival was estimated by the Kaplan-Meier method. In-hospital mortality for the entire study cohort was 15.1% (n = 18), and in comparison, between groups was found to be highest in the intermediate surgical group (25.7%). Univariate analysis identified preoperative mechanical ventilation dependent respiratory insufficiency (p = 0.006), preoperative renal insufficiency (p = 0.019), age (p = 0.002), large vegetations (p = 0.018) as well as intermediate (p = 0.026), and late (p = 0.041) surgery as predictors of in-hospital mortality. The presence of large vegetations (>8 mm) (p = 0.019) and increased age (p = 0.037)-but not operative timing-were identified as independent risk factors for in-hospital mortality. In the presence of large vegetations (>8 mm), cardiac surgery should be performed early and independently from the entity of cerebral embolic stroke. Postponing surgery to achieve clinical stabilization and better postoperative outcomes of IE patients with CE is reasonable, however, worsening of the disease process with deterioration and resulting heart failure during the first 3 weeks after CE results in a significantly higher in-hospital mortality and inferior long-term survival.

Atrio-aortic erosion caused by Amplatzer Atrial Septal Occluder - a case report.

BACKGROUND: In specialized centers, percutaneous closure using specific occluders is the first-choice treatment in atrial septal defects (ASD). Late complications after this intervention, such as erosion of the aorta or the atria, are rare and have not been sufficiently approached and dealt with in literature. In our clinic we have been faced with the problematic situation of diagnosing and treating such cases. That is why, we have decided to share our experience with other colleagues. CASE PRESENTATION: We present two cases of severe late complications after percutaneous closure of atrial septal defects (ASD). In both cases, the atrial septal occluder (Amplatzer™ Atrial Septal Occluder Device, Abbott, Chicago USA) caused the erosion between the left atrium and the aortic root. The atrio-aortic erosion led to acute cardiac tamponade with upper venous congestion and shock. As the bleeding source remained undetectable for any imaging tools, a diagnostical sternotomy remained the only solution. The cause of the acute bleeding was discovered to be the erosion between the left atrium and the aortic root. The treatment consisted in the removal of the occluder, direct suturing of the perforated areas and the surgical closure of the remaining ASD. The patients fully recovered within the nine to fourteen days' hospital stay. Six months after surgery both patients were well and able to recover their daily routine. CONCLUSIONS: The atrio-aortic erosion after percutaneous closure of atrial septal defects is a surgical emergency. The more so, since it can be complicated by the absence of specific symptoms. A key-element in the diagnosis of this rare pathology remains the medical history of the patient, which the surgeon has to consider thoroughly and launch the diagnostic sternotomy without delay.

Bilirubin and lactate: easy to determine and valuable to predict outcome in cardiac surgery.

BACKGROUND: Cardiopulmonary bypass during cardiac surgery is associated with metabolic changes after operation and results inter alia in increased levels of lactate and bilirubin. Since prediction of the course after operation has become very important for the management of an ICU and the patients themselves, we evaluated easily assessable markers (lactate and bilirubin), regarding their potential to predict mortality 90 days after surgery and the length of stay in ICU. METHODS: All patients within a period of five years undergoing cardiac surgery were enrolled in the study. Among others peak levels of lactate and bilirubin within 48 hours after operation were recorded. A Cox proportional hazard model as well as a logistic regression model were used to predict mortality or rather length of stay in ICU. RESULTS: Increased levels of bilirubin and lactate were associated with a significantly increase in mortality and length of stay in ICU (in a concentration-related manner). Interestingly, creatinine serum levels before operation showed a similar performance. CONCLUSIONS: Three easily assessable and cheap laboratory parameters (bilirubin, lactate, and creatinine) are useful to predict 90-day mortality and length of stay in ICU. These findings might be helpful to give patients a reliable prediction about short and mid-term-survival and to improve the management of an ICU.

Incidence and Surgical Outcomes of Patients With Native and Prosthetic Aortic Valve Endocarditis.

BACKGROUND: The aim of this study was to retrospectively evaluate the incidence and surgical outcomes of patients with native infective endocarditis (IE) and prosthetic aortic valve endocarditis (PVE) over the past decade at a single institution. METHODS: Between January 2005 and December 2015, 289 patients (mean age, 63.3 ± 14.2 years) suffering from native IE (n = 186) and PVE (n = 103) of the aortic valve underwent surgical procedures. Perioperative data were acquired retrospectively for statistical analysis. RESULTS: During the study period the mean incidence of endocarditis increased from 22.0 ± 4.2 (2005-2009) to 29.8 ± 10.1 (2010-2015) cases per year. In-hospital mortality was significantly increased in PVE (22.3%) versus IE (9.1%) patients (P < .001). In elective cases in-hospital mortality between the 2 groups was comparable (2.2% vs 4.6%; P = .288). Multivariate analysis identified urgent surgery (odds ratio [OR], 6.461; 95% CI, 1.941-21.509; P = .002), mitral regurgitation II (OR, 4.230; 95% CI, 1.249-14.331; P = .021), previous homograft operation (OR, 66.096; 95% CI, 2.369-1844.272; P = .0.14), and left ventricular ejection fraction < 40% (OR, 8.267; 95% CI, 1.931-35.388; P = .004) as independent risk factors for in-hospital mortality, whereas pathogen identification by preoperative blood cultures (OR, .228; 95% CI, 0.063-0.817; P = .023) was found to be independently protective. CONCLUSIONS: Surgery for native IE and PVE of the aortic valve may be performed with satisfactorily results at experienced cardiac surgical centers. In comparison PVE patients suffer from a more than twice as high in-hospital mortality, more postoperative complications, and inferior long-term survival. However preoperative identification of causative pathogens in IE and PVE allows for improved in-hospital survival.

Preemptive Extracorporeal Life Support for Surgical Treatment of Severe Constrictive Pericarditis.

BACKGROUND: Surgical treatment of constrictive pericarditis (CP) is particularly challenging because of the increased risk of right heart failure. The necessity of postoperative extracorporeal life support (ECLS) can result in mortality rates of 100%. Preemptive implantation of ECLS may improve postoperative outcomes; however, no data are currently available on its use. We conducted a retrospective study to evaluate the feasibility of our strategy. METHODS: Between September 2012 and June 2016, ECLS was established percutaneously through the groin vessels in 12 individually selected patients with high-risk CP immediately before pericardiectomy in the operating theater as part of the surgical strategy. Prolonged weaning was performed in the intensive care unit. Demographic characteristics, perioperative data, and survival were analyzed. RESULTS: The median patient age was 61.5 years (first quartile, third quartile: 51.3, 68.5 years), with a preoperative central venous pressure of 24 mm Hg (first quartile, third quartile: 21, 28 mm Hg). Furthermore, the pulmonary artery pressure was greater than 60 mm Hg in 50% of patients and a dip plateau sign existed in 75% before surgery. The median duration of ECLS therapy was 132 hours (first quartile, third quartile: 96, 168 hours) with a length of stay on the intensive care unit of 10 days (first quartile, third quartile: 7.0, 16.8 days). There was no intraoperative death. The cumulative 30-day, 1-year, and 5-year survival rates were 83% ± 11%, 75% ± 13%, and 75% ± 13%, respectively. CONCLUSIONS: From our real-world data, preemptive use of perioperative ECLS, assigned by individual team decision in selected patients with severe CP, is a feasible and safe strategy.

Author Correction: Consistent success in life-supporting porcine cardiac xenotransplantation.

In this Letter, Mayuko Kurome and Valeri Zakhartchenko have been added to the author list (affiliated with Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany). The author list and 'Author contributions' section have been corrected online; see accompanying Amendment.

Hypoxia-inducible factor controls immunoregulatory properties of myeloid cells in mouse cardiac allografts - an experimental study.

Hypoxia-inducible factors (HIFs) play a critical role in inflammatory properties of myeloid-derived cells. The effect of HIFs on myeloid-derived cell functions in organ transplantation remains unknown, however. We transplanted hearts into transgenic mice with myeloid cell-targeted deletions of HIF-1α or its negative regulator von Hippel-Lindau (VHL) to investigate the effects of HIF-1α inactivation or HIF pathway activation, respectively, on ischemia-reperfusion injury (IRI) and acute rejection. Deletion of VHL in myeloid cells enhanced mRNA expression of anti-inflammatory genes IDO, Arg-1, and HO-1 in vitro. In vivo, VHL-/- myeloid-derived cells of allograft recipients alleviated IRI and acute rejection, evidenced by reduced cardiomyocyte damage, decreased proinflammatory cytokine mRNA levels, and absence of inflammatory infiltrate at 5 days after transplantation. Ultimately, allograft survival was significantly prolonged. In vitro, VHL-/- myeloid-derived cells dose-dependently inhibited T-cell proliferation. Myeloid cells with HIF-1α-deletion retained proinflammatory qualities in vitro and in vivo. Deletion of VHL in myeloid cells of nonimmunosuppressed cardiac allograft recipients reduced myocardial injury and acute rejection. We suggest that HIF transcription factors induce a regulatory phenotype in myeloid-derived cells, which may be harnessed as a novel therapeutic strategy to regulate immune responses after heart transplantation.

Consistent success in life-supporting porcine cardiac xenotransplantation.

Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1-3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.

Management of Retrograde False Lumen Perfusion After Hybrid Arch Repair in Acute Aortic Dissection.

Patients with acute aortic dissections involving the arch and descending aorta can effectively be treated using the frozen elephant trunk technique. We describe here the novel technique of temporary banding of the descending aorta onto the stent of the hybrid graft in 3 patients who developed unmanageable bleeding from the distal suture line due to retrograde false lumen perfusion and disintegration of the adventitia. Retrograde false lumen perfusion was stopped and therefore bleeding controlled in all patients. Temporal aortic banding represents a novel, feasible, and effective bailout technique for otherwise unmanageable bleeding with fatal outcome in hybrid arch surgery.

Vascular Endothelial Growth Factor-B Overexpressing Hearts Are Not Protected From Transplant-Associated Ischemia-Reperfusion Injury.

OBJECTIVES: Cardiac vascular endothelial growth factor-B transgene limits myocardial damage in rat infarction models. We investigated whether heart transplant vascular endothelial growth factor-B overexpression protected against ischemia-reperfusion injury. MATERIALS AND METHODS: We transplanted hearts heterotopically from Dark Agouti to Wistar Furth rats. To characterize the role of vascular endothelial growth factor-B in ischemia-reperfusion injury, we transplanted either long-term human vascular endothelial growth factor-B transgene overexpressing hearts from Wistar Furth rats or short-term adeno-associated virus 9-human vascular endothelial growth factor-B-transduced hearts from Dark Agouti rats into Wistar Furth rats. Heart transplants were subjected to 2 hours of cold and 1 hour of warm ex vivo ischemia. Samples were collected 6 hours after reperfusion. RESULTS: Two hours of cold and 1 hour of warm ischemia increased vascular endothelial growth factor-B mRNA levels 2-fold before transplant and 6 hours after reperfusion. Transgenic vascular endothelial growth factor-B overexpression caused mild cardiac hypertrophy and elevated cardiac troponin T levels 6 hours after reperfusion. Laser Doppler measurements indicated impaired epicardial tissue perfusion in these transgenic transplants. Recombinant human vascular endothelial growth factor-B increased mRNA levels of cytochrome c oxidase and extracellular ATPase CD39, suggesting active oxidative phosphorylation and high ATP production. Adeno-associated virus 9-mediated vascular endothelial growth factor-B overexpression in transplanted hearts increased intragraft macrophages 1.5-fold and proinflammatory cytokine interleukin 12 p35 mRNA 1.6-fold, without affecting recipient serum cardiac troponin T concentration. CONCLUSIONS: Vascular endothelial growth factor-B expression in transplanted hearts is linked to ischemia and ischemia-reperfusion injury. Cardiac transgenic vascular endothelial growth factor-B overexpression failed to protect heart transplants from ischemia-reperfusion injury.

Long-term outcomes after resection of Stage IV cavoatrial tumour extension using deep hypothermic circulatory arrest.

OBJECTIVES: Renal neoplasms frequently expand into renal veins and inferior vena cava from the early stages of the disease. In this study, we set out to define the long-term outcomes of patients with Stage IV tumorous cavoatrial extension, undergoing radical nephrectomy with excision of cavoatrial extension in deep hypothermic circulatory arrest (DHCA). METHODS: Thirty-five patients with Stage IV cavoatrial extension of renal cell carcinoma underwent radical nephrectomy combined with en bloc excision of cavoatrial tumour-thrombus extension, performed in DHCA. The preoperative staging of the tumour and assessment of the intravascular position of the tumour were performed using standard imaging techniques, including computed tomography angiography, magnetic resonance imaging and echocardiography. Patient data were collected in the patient data bank and analysed retrospectively. RESULTS: In this study cohort, we demonstrate acceptable long-term results (the mean overall survival of 4.9 ± 1.0 years and the 5-year survival rate of 40%) and outline several clear predictors for postoperative long-term survival of the patients. Preoperative evidence of remote tumour metastases and tumourous lymph node involvement conversely predicts inferior postoperative survival. However, a high local postoperative tumour recurrence rate does not limit patient survival in this group. CONCLUSIONS: The data provide evidence for perioperative safety and acceptable long-term results of radical nephrectomy with excision of cavoatrial extension in DHCA in patients with Stage IV cavoatrial extension of renal neoplasm. Thus, this radical surgical procedure can provide effective long-term palliation in the absence of evident metastatic disease.

Platelet-derived Growth Factor-B Protects Rat Cardiac Allografts From Ischemia-reperfusion Injury.

BACKGROUND: Microvascular dysfunction and cardiomyocyte injury are hallmarks of ischemia-reperfusion injury (IRI) after heart transplantation. Platelet-derived growth factors (PDGF) have an ambiguous role in this deleterious cascade. On one hand, PDGF may exert vascular stabilizing and antiapoptotic actions through endothelial-pericyte and endothelial-cardiomyocyte crosstalk in the heart; and on the other hand, PDGF signaling mediates neointimal formation and exacerbates chronic rejection in cardiac allografts. The balance between these potentially harmful and beneficial actions determines the final outcome of cardiac allografts. METHODS AND RESULTS: We transplanted cardiac allografts from Dark Agouti rat and Balb mouse donors to fully major histocompatibility complex-mismatched Wistar Furth rat or C57 mouse recipients with a clinically relevant 2-hour cold ischemia and 1-hour warm ischemia. Ex vivo intracoronary delivery of adenovirus-mediated gene transfer of recombinant human PDGF-BB upregulated messenger RNA expression of anti-mesenchymal transition and survival factors BMP-7 and Bcl-2 and preserved capillary density in rat cardiac allografts at day 10. In mouse cardiac allografts PDGF receptor-ß, but not -α intragraft messenger RNA levels were reduced and capillary protein localization was lost during IRI. The PDGF receptor tyrosine kinase inhibitor imatinib mesylate and a monoclonal antibody against PDGF receptor-α enhanced myocardial damage evidenced by serum cardiac troponin T release in the rat and mouse cardiac allografts 6 hours after reperfusion, respectively. Moreover, imatinib mesylate enhanced rat cardiac allograft vasculopathy, cardiac fibrosis, and late allograft loss at day 56. CONCLUSIONS: Our results suggest that PDGF-B signaling may play a role in endothelial and cardiomyocyte recovery from IRI after heart transplantation.