Aortic Homograft Research Articles

A20 Haploinsufficiency Aggravates Transplant Arteriosclerosis in Mouse Vascular Allografts: Implications for Clinical Transplantation.

Inflammation is central to the pathogenesis of transplant arteriosclerosis (TA). We questioned whether physiologic levels of anti-inflammatory A20 influence TA severity. We performed major histocompatibility complex mismatched aorta to carotid artery interposition grafts, using wild type (WT) or A20 heterozygote (HET) C57BL/6 (H-2) donors and BALB/c (H-2) recipients, and conversely BALB/c donors and WT/HET recipients. We analyzed aortic allografts by histology, immunohistochemistry, immunofluorescence, and gene profiling (quantitative real-time reverse-transcriptase polymerase chain reaction). We validated select in vivo A20 targets in human and mouse smooth muscle cell (SMC) cultures. We noted significantly greater intimal hyperplasia in HET versus WT allografts, indicating aggravated TA. Inadequate upregulation of A20 in HET allografts after transplantation was associated with excessive NF-кB activation, gauged by higher levels of IkBα, p65, VCAM-1, ICAM-1, CXCL10, CCL2, TNF, and IL-6 (mostly localized to SMC). Correspondingly, cytokine-induced upregulation of TNF and IL-6 in human and mouse SMC cultures inversely correlated with A20 expression. Aggravated TA in HET versus WT allografts correlated with increased intimal SMC proliferation, and a higher number of infiltrating IFNγ and Granzyme B CD4 T cells and natural killer cells, and lower number of FoxP3 regulatory T cells. A20 haploinsufficiency in allograft recipients did not influence TA. A20 haploinsufficiency in vascular allografts aggravates lesions of TA by exacerbating inflammation, SMC proliferation, and infiltration of pathogenic T cells. A20 single nucleotide polymorphisms associating with lower A20 expression or function in donors of vascularized allografts may inform risk and severity of TA, highlighting the clinical implications of our findings.

Repair of large airway defects with bioprosthetic materials

ObjectivePatients with complicated airway defects that exceed the limits of primary repair represent a challenging clinical problem and require alternative techniques for repair. The aim of this study was to evaluate bioprosthetic reconstruction of large tracheal and bronchial defects. MethodsRetrospective chart review of patients treated at a single tertiary center from 2008 to 2015 who underwent repair of tracheal or bronchial defects with a bioprosthetic device, namely aortic homograft or acellular dermal matrix. ResultsEight patients, 3 men and 5 women with a mean age of 54 ± 13 years, underwent closure of complex central airway defects with bioprosthetic material. All but 1 patient underwent prior operative or stenting procedures. Three patients had isolated airway defects, whereas 5 had fistulas between the airway and enteric tract. Defects involved the membranous wall of the trachea (n = 5), the anterior wall of the trachea (n = 1), or the main stem bronchus (n = 2). Five reconstructions were with aortic homograft and 3 with acellular dermal matrix. Bioprosthetic material was buttressed with muscle flap (n = 4), omentum (n = 2), or left unbuttressed (n = 2). The airway defect was successfully closed in all patients. There was no postoperative mortality or recurrence of the airway defect in short-term follow-up. Two patients required debridement of granulation tissue and 1 additional patient required airway balloon dilation. Progression of underlying metastatic disease explained the majority of long-term mortality (75%). ConclusionsBioprosthetic materials represent a viable option for management of large airway defects, including airway-enteric fistulae, that exceed the limits of primary repair.

Reduction of obliterative bronchiolitis (OB) by prolyl-hydroxylase-inhibitors activating hypoxia-inducible transcription factors in an experimental mouse model

BackgroundObliterative bronchiolitis (OB) is the major limiting factor for long-term survival after lung transplantation. As previously shown, donor treatment with a PHD-inhibitor activating hypoxia-inducible transcription factors (HIFs) prevents graft injury both in an allogenic kidney and aortic allograft transplant model. The aim of this study was to investigate the effect of HIF activation with a PHD-inhibitor on the development of OB. MethodsFully MHC-mismatched C57BL/6 (H-2b) donor tracheas were orthotopically transplanted into CBA/J (H-2k) recipients. Donor animals received a single dose of PHD-inhibitor 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate (ICA) (40mg/kg i.p.) or vehicle control 4h before transplantation. Transplanted tracheas were harvested 14 or 30days after transplantation and were analyzed by histology, by immunofluorescence and by rtPCR for mRNA expression. ResultsDonor pre-conditioning with ICA resulted in HIF accumulation and induction of HIF target genes: HO-1, VEGF, MIF, TGFβ, and EpoR, which persisted during different times of ischemia. Grafts of vehicle treated controls showed substantially more luminal obliteration on postoperative day 30 in contrast to groups pre-treated with ICA [luminal obliteration 29.2±5% (ICA) vs. 36.7±8% (control), p<0.01]. We found significantly lower expression of TNFα, PDGFß, MCP-1, E-selectin, and ICAM-1 14days after ICA premedication. In addition ICA pre-treated groups revealed decreased T-cell and macrophage infiltration in tracheal grafts on days 30 after transplantation (p<0.05). ConclusionPre-treatment with ICA effectively reduced obliterative bronchiolitis. Our data suggest that activation of hypoxia-inducible transcription factors (HIFs) and thereby adaptation to low oxygen prevents the development of OB and allograft injury. Pharmaceutical inhibition of PHDs appears to be an attractive strategy for organ preservation that deserves further clinical evaluation.

Allografts in aortic position: Insights from a 27-year, single-center prospective study

ObjectiveOver the past decades, the indication for allograft implantation in aortic position has evolved. The purpose of this study is to report long-term survival, allograft durability, and potential risk factors. MethodsBetween 1987 and 2010, 353 patients underwent aortic valve replacements via allograft (92 subcoronary, 261 root replacement; 98% aortic allografts). Patient characteristics, survival, valve durability, and valve-related events were analyzed. Patients also were followed with standardized echocardiography. A joint modeling approach was used to detect the effect of (echocardiographic) variables on mortality and reoperation hazard. ResultsMean age was 45 years (range, 1 month to 84 years); 71% were males. The etiology was endocarditis in 32% (active 22%), congenital 31%, degenerative 9%, aneurysm/dissection 12%, rheumatic 6%, and prosthetic valve failure 10%. Hospital mortality was 5.9% (n = 21). During follow-up (mean 12 years, range, 0-24; 99% complete), 113 patients died. Twenty-year cumulative survival was 41% (95% confidence interval, 32-50). Valve-related reoperations occurred in 117 patients: 100 structural valve deterioration, 9 nonstructural valve deterioration, and 8 endocarditis. Competing-risk analysis predicted that at 20 years 31% died, and 30% were alive without reoperation. Younger patient age was associated with increased reoperation. During follow-up left ventricular dilatation and severe aortic regurgitation were associated with mortality (P = .006 and .005, respectively), and grade 3 or greater aortic regurgitation during follow-up was associated with risk of reoperation (P = .001). ConclusionsAfter almost 3 decades of experience with allografts in aortic position, the indication for use has become selective, mainly because of progressive structural valve deterioration over time. In case of complex aortic root pathology and active endocarditis allografts may still be useful.

Long-Term Outcomes of Homografts in the Aortic Valve and Root Position: A 20-Year Experience.

BackgroundThe advantages of using a homograft in valve replacement surgery are the excellent hemodynamic profile, low risk of thromboembolism, and low risk of prosthetic valve infection. The aim of this study was to evaluate the long-term outcomes of homograft implantation in the aortic valve position.MethodsThis is a retrospective study of 33 patients (>20 years old) who underwent aortic valve replacement or root replacement with homografts between April 1995 and May 2015. Valves were collected within 24 hours from explanted hearts of heart transplant recipients (<60 years) and organ donors who were not suitable for heart transplantation. The median follow-up duration was 35.6 months (range, 0 to 168 months).ResultsAortic homografts were used in all patients. The 30-day mortality rate was 9.1%. The 1- and 5-year survival rates were 80.0%±7.3% and 60.8%±10.1%, respectively. The 1-, 5-, and 10-year freedom from reoperation rates were 92.3%±5.2%, 68.9%±10.2%, and 50.3%±13.6%, respectively. The 1-, 5-, and 10-year freedom from significant aortic dysfunction rates were 91.7%±8.0%, 41.7%±14.2%, and 25.0%±12.5%, respectively.ConclusionHomografts had the advantages of a good hemodynamic profile and low risk of thromboembolic events, and with good outcomes in cases of aortitis.

Pharmacological Inhibition of Vanin Activity Attenuates Transplant Vasculopathy in Rat Aortic Allografts.

Development of transplant vasculopathy is a major cause of graft loss and mortality in solid organ transplant recipients. Previous studies in mice have indicated that vanin-1, a member of the vanin protein family with pantetheinase activity, is possibly involved in neointima formation. Here, we investigated if RR6, a recently developed vanin inhibitor, could attenuate development of transplant vasculopathy. Abdominal allogeneic aorta transplantation from Dark Agouti to Brown Norway rats was performed. Surface neointima was quantified 2 and 4 weeks after transplantation. Systemic vanin activity was measured, and allograft leukocyte infiltration, glutathione-synthesizing capacity, matrix metalloproteinase 9 expression and neointimal smooth muscle cell (SMC) proliferation were assessed by immunohistochemistry. In vitro, the effects of RR6 on SMC proliferation (water-soluble tetrazolium-1 assay) and cytokine-induced apoptosis (flow cytometry) were investigated. RR6 treatment significantly reduced systemic pantetheinase activity during the 4-week follow-up period. RR6 attenuated neointima formation 4 weeks after transplantation. Neointimal SMC proliferation and medial SMC matrix metalloproteinase 9 expression were not altered by RR6. However, RR6 significantly reduced neointimal macrophage influx that was accompanied by increased GCLC messenger RNA expression. In vitro, RR6 inhibited platelet-derived growth factor-induced SMC proliferation and protected SMCs from TNF-α-induced apoptosis. Pharmacological inhibition of vanin activity attenuates development of transplant vasculopathy. This was accompanied by reduced macrophage infiltration and increased glutathione-synthesizing capacity. In vitro, RR6 reduced SMC proliferation and apoptosis that was not confirmed in vivo. Further in-depth studies are warranted to reveal the underlying mechanism(s) of RR6-induced attenuation of transplant vasculopathy in vivo.

Injectable Aorta Tissue Paste for Vocal Fold Medialization: Residence Time, Biocompatibility, and Comparison to Predicates in a Guinea Pig Subdermal Model.

Aortic homografts integrate well with laryngeal tissue when used in reconstructive surgery. It was hypothesized that a paste of aortic homograft, rich in slow-to-degrade elastin, would compare favorably in residence time and biocompatibility to predicate materials used for vocal fold injection-medialization. An injectable aorta paste (AP) was made by pulverizing aortic homografts at -196°C (cryomilling). To assess residence time and biocompatibility, 0.3 cc was injected subdermally in guinea pigs (n = 3 per 2-, 4-, 8-, 16-, 24-week time points) followed by histological analysis. To test particle size versus residence time, APs made using 80 or 200 seconds of cryomilling were compared. Implant characteristics of AP were then compared to Restylane, Radiesse Voice (Hydroxylapatite), Radiesse Voice Gel, and Cymetra in additional animals (n = 6 per 4-, 8-, 12-week time points). Injected AP formed ovoid masses with minimal inflammation. Cellular infiltration was mild and increased with survival time. There was a gradual reduction of implant volume to ~40% at 24 weeks. Increased residence time for paste with larger particles (80 cryomilling seconds) was noted. Von Kossa staining showed progressive calcification of the AP. Cymetra was difficult to reconstitute reliably but formed subdermal masses similar to AP in shape, size, and reactivity and without calcification. The other predicates showed good biocompatibility but spread more widely and erratically in the tissue. Aortic paste is easy to create, biocompatible, degrades slowly, and forms well-defined implants in guinea pig subdermal tissue. The AP implants calcified over time, and experiments are ongoing to determine the source of calcification and how it might be controlled or exploited clinically.

Severe Aortic Regurgitation in Degenerative Bioprosthetic Aortic Homograft Treated by Valve in Valve

Severe Aortic Regurgitation in Degenerative Bioprosthetic Aortic Homograft Treated by Valve in Valve

57. Aortic valve replacement with sutureless valve and mitral valve repair in patient with infected aortic homograft

The approach of implanting aortic sutureless valve inside the calcific homograft is suitable in redo surgery especially if associated with mitral valve surgery. Aortic valve replacement in patients who have undergone previous aortic root replacement with an aortic homograft remains a technical challenge because of homograft degeneration and the need for a redo Bentall operation. We report a case of redo aortic valve replacement (valve in valve) with a sutureless valve and mitral valve repair by miniband annuloplasty in a female patient aged 64 years old who underwent aortic valve replacement with homograft 14 years ago and presented by sever aortic valve regurge and sever mitral valve regurge because of infective endocarditis. This technique allows rapid aortic valve replacement in a heavily calcified aortic root. It also avoids aortic valve size affection after mitral valve repair by ordinary methods especially in patients with small aortic annulus. This technique is particularly suitable in redo procedures for homograft degeneration, it avoids performing a redo Bentall operation with its known problems as well as to avoid patient prosthesis mismatch.

Endocarditis in patients with ascending aortic prosthetic graft: a case series from a national multicentre registry.

Endocarditis in patients with ascending aortic prosthetic graft (AAPG) is a life-threatening complication. The purpose of this study was to examine the clinical presentation and prognosis of patients with AAPG endocarditis included in a large prospective infectious endocarditis multicentre study. From January 2008 to April 2015, 3200 consecutive patients with infectious endocarditis according to the modified Duke criteria, were prospectively included in the 'Spanish Collaboration on Endocarditis Registry (GAMES)' registry. Twenty-seven definite episodes of endocarditis (0.8%) occurred in patients with AAPG. During the study period, 27 cases of endocarditis were detected in patients with AAPG. The median age of patients was 61 years [interquartile range (IQR) 51-68 years] and 23 (85.2%) patients were male. The median time from AAPG surgery to the episode of AAPG infection was 24 months (IQR 6-108 months). The most frequently isolated micro-organisms were coagulase-negative staphylococci and S. aureus (11 patients, 40.7%). Four patients (14.8%) underwent medical treatment, whereas surgery was performed in 21 (77.7%). Two patients (7.4%) died before surgery could be performed. The median hospital stay prior to surgery was 7 days (IQR 4-21 days). Surgery consisted of replacing previous grafts with a composite aortic graft (10 cases) or aortic homograft (2 patients), and removal of a large vegetation attached to the valve of a composite tube (1 case). Nine patients had an infected aortic valve prosthesis without evidence of involvement of the AAPG. Isolated redo-aortic valve replacement was performed in 8 (88.9%) of these patients. Reinfection occurring during 1 year of follow-up was not detected in any patient. Two patients (7.4%) died while awaiting surgery and 6 did so after surgery (22.2%). A New York Heart Association (NYHA) Class IV was associated with mortality in patients undergoing surgery (P < 0.019). Most cases of endocarditis in patients with AAPG occur late after initial surgery. Mortality rate of patients with AAPG endocarditis who undergo surgery is acceptable. NYHA Class IV before surgery is associated with an increased postoperative mortality.

Over 20 years experience with aortic homograft in aortic valve replacement during acute infective endocarditis.

Despite the controversy, the aortic homograft is supposedly the best option in acute infective endocarditis (AIE), due to its resistance to reinfection. However, the technical complexity and the risk of structural deterioration over time have limited its utilization. The aim of this study was to evaluate the long-term results of aortic homograft for the treatment of infective endocarditis in our institution with particular attention to predictors of survival and homograft reoperation. The cohort includes 112 patients who underwent aortic valve replacement with an aortic homograft for AIE between January 1990 and December 2014. Fifteen patients (13.4%) died during the first 30 days after the operation. Two patients were lost to follow-up after discharge from the hospital; therefore, 95 patients were available for long-term analysis. The median duration of follow-up was 7.8 years (IQR 4.7-17.6). Five patients (5.3%) suffered a recurrence of infective endocarditis (1 relapse and 4 new episodes). Sixteen patients (16.8%) were reoperated for structural valve degeneration (SVD; n = 14, 87.5%) or for infection recurrence (n = 2, 12.5%). Freedom from homograft reoperation for infective endocarditis or structural homograft degeneration at 10 and 15 years postoperatively was 86.3 ± 5.5 and 47.3 ± 11.0%, respectively. For patients requiring homograft reoperation, the median interval to reintervention was 11.6 years (IQR 8.3-14.5). Long-term survival was 63.6% (95% CI 52.4-72.8%) and 53.8% (95% CI 40.6-65.3%) at 10 and 15 years, respectively. The use of aortic homograft in acute aortic valve endocarditis is associated with a remarkably low risk of relapsing infection and very acceptable long-term survival. The risk of reoperation due to SVD is significant after one decade especially in young patients. The aortic homograft seems to be ideally suited for reconstruction of the aortic valve and cardiac structures damaged by the infective process especially in early surgery.

The Effects of Losartan in Preserving the Structural Integrity of Decellularized Small Diameter Vascular Allograft Conduit Implants In Vivo.

Decellularization is a proposed method of preparing nonautologous biological arterial vascular scaffolding; however, the fate of the supporting medial elastic fiber, which is important in preserving the vascular structural integrity, is uncertain. The influence of losartan on preserving the medial elastic fiber integrity in decellularized small diameter vascular conduits (SDVC) was investigated. Decellularized infrarenal abdominal aortic allografts were implanted in Sprague-Dawley rats treated either with (study rats, n = 6) or without oral losartan (control rats, n = 6) and graded 8 weeks later according to a remodeling scoring system (1-mild, 2-moderate, 3-severe) which we devised based on the intimal hyperplasia degree, morphologic changes, and elastic fiber fragmentation of the conduits. DAPI immunohistochemistry analysis was performed in 47 (25 decellularization only and 22 losartan treatment) cross-sectional slide specimens. The losartan versus decellularization only SDVC showed a significantly lower medial elastic fragmentation score (1.32 vs. 2.24, P < 0.001), superior medial layer preservation, and relatively more normal appearing intimal cellular morphology. The results suggested rats receiving decellularized SDVCs treated with losartan may yield superior medial layer elastic fiber preservation.

David Arthur Conn

David Arthur Conn was the son of a general practitioner and a teacher. At the age of 8 he developed exertional chest pain, and his father, Ian (see obituary: http://www.bmj.com/content/336/7646/727.1),...

(470) - Variable Effects of Serotonin Receptor Antagonists on the Development of Transplant Vasculopathy in Murine Aortic Allografts

(470) - Variable Effects of Serotonin Receptor Antagonists on the Development of Transplant Vasculopathy in Murine Aortic Allografts

Invited Commentary

Invited Commentary

Decellularized aortic homografts for aortic valve and aorta ascendens replacement.

OBJECTIVESThe choice of valve prosthesis for aortic valve replacement (AVR) in young patients is challenging. Decellularized pulmonary homografts (DPHs) have shown excellent results in pulmonary position. Here, we report our early clinical results using decellularized aortic valve homografts (DAHs) for AVR in children and mainly young adults.METHODSThis prospective observational study included all 69 patients (44 males) operated from February 2008 to September 2015, with a mean age of 19.7 ± 14.6 years (range 0.2–65.3 years). In 18 patients, a long DAH was used for simultaneous replacement of a dilated ascending aorta as an extended aortic root replacement (EARR). Four patients received simultaneous pulmonary valve replacement with DPH.RESULTSThirty-nine patients (57%) had a total of 62 previous operations. The mean aortic cross-clamp time in isolated cases was 129 ± 41 min. There was 1 conduit-unrelated death. The mean DAH diameter was 22.4 ± 3.7 mm (range, 10–29 mm), the average peak gradient was 14 ± 15 mmHg and the mean aortic regurgitation grade (0.5 = trace, 1 = mild) was 0.6 ± 0.5. The mean effective orifice area (EOA) of 25 mm diameter DAH was 3.07 ± 0.7 cm2. DAH annulus z-values were 1.1 ± 1.1 at implantation and 0.7 ± 1.3 at the last follow-up. The last mean left ventricle ejection fraction and left ventricle end diastolic volume index was 63 ± 7% and 78 ± 16 ml/m2 body surface area, respectively. To date, no dilatation has been observed at any level of the graft during follow-up; however, the observational time is short (140.4 years in total, mean 2.0 ± 1.8 years, maximum 7.6 years). One small DAH (10 mm at implantation) had to be explanted due to subvalvular stenosis and developing regurgitation after 4.5 years and was replaced with a 17 mm DAH without complication. No calcification of the explanted graft was noticed intraoperatively and after histological analysis, which revealed extensive recellularization without inflammation.CONCLUSIONSDAHs withstand systemic circulation, provide outstanding EOA and appear as an alternative to conventional grafts for AVR in young patients. EARR using DAH is a further option in aortic valve disease associated with aorta ascendens dilatation as it avoids the use of any prosthetic material.

NSun2 Deficiency Protects Endothelium From Inflammation via mRNA Methylation of ICAM-1

Vascular endothelial inflammation, including the expression of intercellular adhesion molecule 1 (ICAM-1), is a key event in vascular diseases. However, the mechanisms underlying the regulation of ICAM-1 are largely unknown. To investigate the mechanisms on the regulation of ICAM-1 by NOP2/Sun domain family, member 2 (NSun2)-mediated mRNA methylation and the impact of NSun2-ICAM-1 regulatory process in vascular inflammation and allograft arteriosclerosis. By using in vitro, in cells, and in vivo methylation assays, we showed that the tRNA methyltransferase NSun2 methylated the ICAM-1 mRNA. Methylation by NSun2 promoted the translation of ICAM-1, thereby increasing the adhesion of leukocytes to endothelial cells. Tumor necrosis factor-α or homocysteine activated the methyltransferase activity of NSun2 by repressing the phosphorylation of NSun2 by Aurora-B. The levels of ICAM-1 induction and of leukocyte adhesion to vascular endothelium observed with homocysteine treatment in wild-type rats were markedly decreased in NSun2(-/-) rats. In a rat model of aortic allograft, the lack of donor NSun2 impaired the formation of allograft arteriosclerosis. NSun2 upregulates the expression of ICAM-1 by methylating ICAM-1 mRNA. This regulatory process impacts on vascular inflammation and allograft arteriosclerosis.

Prolyl-hydroxylase inhibitor activating hypoxia-inducible transcription factors reduce levels of transplant arteriosclerosis in a murine aortic allograft model.

The development of transplant arteriosclerosis, the hallmark feature of heart transplant rejection, is associated with a chronic immune response and also influenced by an initial injury to the graft through ischaemia and reperfusion. Hypoxia-inducible transcription factor (HIF)-1 pathway signalling has a protective effect against ischaemia-reperfusion injury and has already been demonstrated to ameliorate allograft nephropathy in previous animal studies. Therefore, the aim of this study was to investigate the effect of stabilization of hypoxia-inducible transcription factors with a prolyl-hydroxylase domain (PHD) inhibitor on transplant arteriosclerosis in an experimental aortic allograft model. MHC-class I mismatched C.B10-H2(b)/LilMcdJ donor thoracic aortas were heterotopically transplanted into the abdominal aorta of BALB/c mice. Donor animals received a single dose of the PHD inhibitor 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate (ICA) (40 mg/kg) or vehicle i.p. 4 h before transplantation. Intragraft HIF accumulation after ICA treatment was detected by immunohistochemistry before and after cold ischaemia (n = 5). Grafts were harvested 30 days after transplantation and analysed by histology (n = 7) and immunofluorescence (n = 7). In addition, intragraft mRNA expression for cytokines, adhesion molecules and growth factors was determined on Day 14 (n = 7). Donor preconditioning with ICA resulted in HIF accumulation in the aorta and induction of the HIF target genes vascular endothelial growth factor and transforming growth factor-beta. Vascular lesions were present in both experimental groups. However, there was significantly reduced intimal proliferation in preconditioned grafts when compared with vehicle controls [intimal proliferation 31.3 ± 8% (ICA) vs 55.3 ± 20% (control), P < 0.01]. In addition, experimental groups revealed a down-regulation of E-selectin (-57%) and MCP1 (-33%) expression after ICA pretreatment compared with controls, going along with decreased T-cell [1.4% CD4+ T-cell infiltration vs 8.4% (control) and 4.9% CD8+ T-cell infiltration vs 10.7% (control)], dendritic cell (0.6% dendritic cells infiltration vs 1.9% infiltration(control)] and macrophage infiltration [4.8% macrophages (ICA) vs 10.9% (control)] within vascular grafts. These data of an animal transplant model show that the pharmaceutical activation of HIF with endogenous up-regulation of protective target genes leads to adaptation of the graft to low oxygen-saturation and hereby attenuates the development of transplant arteriosclerosis and allograft injury. Pharmaceutical inhibition of PHDs appears to be a very attractive strategy for organ preservation that deserves further clinical evaluation.

Variable Effects of Different Serotonin Receptor Subtype Antagonists on the Development of Transplant Vasculopathy in Murine Aortic Allografts

Variable Effects of Different Serotonin Receptor Subtype Antagonists on the Development of Transplant Vasculopathy in Murine Aortic Allografts

Long haul endocarditis and a case of excess baggage

A 50-year-old woman had implantation of an aortic homograft and a mitral valve repair in 2014 for Streptococcus dysgalactiae endocarditis. Nine months later she presented with sepsis and blood cultures again grew Streptococcus dysgalactiae . She had type II diabetes with peripheral vascular disease and investigation showed osteomyelitis of the right great toe and first metatarsal. The transthoracic echocardiogram showed an abscess 5 cm2 in diameter behind the heart in the basal posterolateral …