Lars Nolke

LUNG TISSUE STORAGE: OPTIMIZING CONDITIONS FOR FUTURE USE IN MOLECULAR RESEARCH

The quality of tissue studied impacts greatly on oligonucleotide microarray results, emphasizing the importance of harvesting techniques. The analyzed RNA extracted from human lung samples preserved via 4 different storage conditions (RNAlater, phosphate-buffered saline, TRIzol, liquid nitrogen). RNA was assessed by denaturing gel electrophoresis, Agilent bioanalysis, real-time polymerase chain reaction (PCR), and Test3 Affymetrix chip hybridization. Results revealed better quality RNA from RNAlater samples on gel electrophoresis and bioanalysis. RNAlater samples also showed greater yield (r18s via PCR P <.05) and resulted in better Test3 chips hybridization (p <.05), suggesting RNAlater was superior at preserving lung tissue nucleic acid.

Pre-operative Determination of an Individual's Neutrophil Response: A Potential Predictor of Early Cardiac Transplant Cellular Rejection

BACKGROUND Success of heart transplantation is affected by allograft rejection, which is known as a lymphocyte-mediated process. Recent studies suggest that neutrophils contribute to this process. We hypothesized that the severity of cardiac rejection can be predicted by evaluating an individuals neutrophil transendothelial migration potential, which can be assessed through artificial stimulation of neutrophils. METHODS Eleven patients were recruited from the active heart transplant list. Pre-operative blood samples were stained with neutrophil adhesion molecule (CD11b, CD62L, and PSGL-1) antibodies before and after in vitro stimulation with phorbol 12-myristate 13-acetate (PMA; 1 ng/ml) and lipopolysaccharide (LPS 1 microg/ml), and assessed using flow cytometry. Stimulated neutrophil responses were correlated with rejection grade of the first endomyocardial biopsy sampled 10 days post-operatively. RESULTS Neutrophil adhesion molecules are upregulated after artificial stimulation. Pre-operative neutrophil surface CD11b expression after in vitro lipopolysaccharide stimulation correlated with rejection grade detected in the first endomyocardial biopsy sample (R = 0.677; p = 0.022). CONCLUSION Pre-operative neutrophil response to in vitro stimuli predicted the rejection grade in the first post-transplant endomyocardial biopsy specimen, suggesting that neutrophils may contribute more to cardiac allograft rejection than previously thought.

Do Statins Have a Role in the Promotion of Postoperative Wound Healing in Cardiac Surgical Patients

Cardiac surgical patients often have associated comorbidities that can impede normal wound healing; however, statin therapy has the potential to improve this process through augmentation of the normal inflammatory response. Outcomes included a 30% earlier rate of wound epithelialization and an 80% greater wound-breaking strength combined with faster wound healing rates (13.0 days vs 18.7 days, p<0.0001). Inhibition of farnesyl pyrophosphate may hold a key role in the mediation of such advantageous effects. This systematic review suggests that there is sufficient evidence to warrant completion of a human trial to assess the effects of statins on wound healing.

The role of 3D printing in preoperative planning for heart transplantation in complex congenital heart disease

BackgroundThe presence of a structural cardiac defect in the setting of dextrocardia is extremely rare. Graspable models allow enhanced appreciation of aberrant structures and vascular relations, particularly in rare and complex cases. This is the first case report of the use of a replica of a patients’ anatomy to plan the surgical strategy in the setting of dextrocardia.AimsWe intend to demonstrate the benefit of three-dimensional printing to enhance preoperative planning in complex congenital heart disease undergoing heart transplantation. The anomalous structures encountered include situs inversus dextrocardia, transposition of the great vessels, a single atrium and a dilated double-outlet single right ventricle.MethodsComputed Tomography acquisition was performed with the use of ECG multiphase gating technology and contrast enhancement. The structures of interest were segmented and the generated 3D mesh was exported as a stereolithographic (STL) file. The model was printed on a Z-Corp 250 binder jetting printer. Post processing techniques were used to enhance model strength.ResultsPre-operative 3D visualisation of the patients’ anatomy allowed for a more comprehensive surgical strategy to be planned, thus reducing the intra-operative duration and cross-clamp time which are recognised to correlate with reduced patient morbidity.ConclusionThe ongoing advances in medical image procurement and 3D processing software and printing technology will continue to enhance preoperative planning and thereby improve patient care. We demonstrate the pivotal role played by such technologies in advancing spatial comprehension of complex aberrant anatomy.

International collaboration: a retrospective study examining the survival of Irish citizens following lung transplantation in both the UK and Ireland.

Objective Prior to 2005, Irish citizens had exclusively availed of lung transplantation services in the UK. Since 2005, lung transplantation has been available to these patients in both the UK and Ireland. We aimed to evaluate the outcomes of Irish patients undergoing lung transplantation in both the UK and Ireland. Design We retrospectively examined the outcome of Irish patients transplanted in the UK and Ireland. Lung allocation score (LAS) was used as a marker of disease severity. Results A total of 134 patients have undergone transplantation. 102 patients underwent transplantation in the UK and 32 patients in Ireland. In total, 52% were patients with cystic fibrosis, 19% had emphysema and 15% had idiopathic pulmonary fibrosis. In Ireland, 44% of the patients suffered from idiopathic pulmonary fibrosis, 31% had emphysema and 16% had cystic fibrosis. A total of 96 double sequential transplants and 38 single transplants have been performed. LAS of all patients undergoing lung transplantation was 37.8 (±1.02). The mean LAS for patients undergoing lung transplantation in Ireland was 44.7 (±3.1), and 35 (±0.4) for patients undergoing lung transplantation in the UK (p<0.05). The 5-year survival of all Irish citizens who had undergone lung transplantation was 73%. The 5-year survival of Irish patients transplanted in the UK was 69% and in Ireland was 91% and 73% at 5.01 years. Conclusions International collaboration can be achieved, as evidenced by the favourable outcomes seen in Irish citizens who undergo lung transplantation in both the UK and Ireland. Irish citizens undergoing lung transplantation in Ireland have a higher LAS score. Despite excellent outcomes, an intention-to-treat analysis of the treatment utility (transplant) indicates the limited effectiveness of lung transplantation in Ireland and emphasises the need for increased rates of lung transplantation.

Successful Palliation of a Child With Left Ventricular Noncompaction Cardiomyopathy and Tricuspid Atresia to Fontan Procedure

A newborn baby girl was diagnosed with tricuspid atresia, ventricular septal defect, normally related great vessels, and hypoplastic right ventricle with no pulmonary stenosis. There was extensive left ventricular noncompaction cardiomyopathy. The left ventricular ejection fraction was 58%. She underwent placement of a pulmonary arterial band at 4 weeks of age, a bilateral bidirectional Glenn at 10 months of age, and fenestrated extracardiac total cavopulmonary connection at 3 years of age. The presence of left ventricular noncompaction in a patient with univentricular circulation does not necessarily circumvent successful cavopulmonary palliation, when left ventricular function is relatively preserved, as in this patient.

Importance of strict patient selection criteria for combined carotid endarterectomy and coronary artery bypass grafting

BACKGROUND Management of patients with severe concomitant carotid and coronary disease remains controversial. We report our experience of combined carotid endarterectomy (CEA) and coronary artery bypass surgery (CABG) over a fifteen year period using strict patient selection criteria. METHODS From 1st January 1995 to December 31st 2009 165 patients underwent combined CABG/CEA procedures at the Mater Hospital. Mean age was 68.2 years (range 43-88) and 127 (77%) were male. Fifty-three (32%) had symptomatic carotid disease. Indications for combined procedures were the presence of symptomatic >70% or asymptomatic >80% internal carotid artery stenosis in a patient requiring urgent CABG because of either unstable angina, recent MI, severe triple vessel disease or severe Left Anterior Descending or Left Main Stem stenosis. RESULTS Thirty-day stroke and death rate was 3%. All neurological events were in the hemisphere contralateral to the carotid surgery and symptoms had completely resolved prior to discharge from hospital. One patient required evacuation of a cervical haematoma and there were two transient XII nerve palsies. CONCLUSION Combined CEA/CABG can be performed safely with acceptable morbidity and mortality in patients selected in accordance with strict criteria in a centre with a large experience of both cardiac and carotid surgery.

A review of the lung transplantation programme in Ireland 2005–2007

OBJECTIVE Lung transplantation is a recognised surgical option for patients with end stage respiratory disease. We present data relating to the initiation of the Irish lung transplant programme in 2005. METHODS Seventeen patients: 7 male and 10 female have undergone lung transplantation. The indications for lung transplantation included COPD (n=8), idiopathic pulmonary fibrosis (n=5), bronchiolitis obliterans (n=2), lymphangioleiomyomatosis (n=1), and cystic fibrosis (n=1). Eleven single lungs transplants were completed, while six patients underwent double sequential lung transplantation. The immunosuppression regimen included basiliximab as induction therapy, with steroids, mycophenolate mofetil nd cyclosporine or tacrolimus. RESULTS The operative mortality was zero. One patient died at 10 months post double lung transplantation secondary to bronchiolitis obliterans. Primary graft dysfunction was observed in two patients who required ventilatory support for 3 and 5 days respectively. Acute cellular rejection was observed in four patients (grade A2 n=3, grade A3 n=2). The cumulative 1-year survival was 94.1%, which compares favourably to an international standard of 78%. CONCLUSIONS The initiation of a lung transplant programme in Ireland has been successfully undertaken and initially provided results comparable to established lung transplant programs.

Percutaneous Transthoracic Computed Tomography-Guided AICD Insertion in a Patient with Extracardiac Fontan Conduit

Percutaneous pulmonary venous atrial puncture was performed under computed tomography guidance to successfully place an automated implantable cardiac defibrillator into a 26-year-old patient with extracardiac Fontan conduit who had presented with two out-of-hospital cardiac arrests. The procedure avoided the need for lead placement at thoracotomy.

The management of thoracic inlet syndrome associated with Hurler's syndrome: a novel surgical technique.

A 21-year-old male developed significant swelling of his tongue after a respiratory arrest. The patient had a history of Hurlers syndrome. Magnetic resonance imaging (MRI) angiogram delineated that the swelling was due to compression of his internal jugular veins at the level of the first rib, resulting in thoracic inlet obstruction. The standard surgical treatment of thoracic inlet obstruction was not suitable in this patients case due to his short thick neck and his characteristic Hurlers syndrome body habitus. Therefore, a novel surgical strategy was used to decompress his head and neck vessels. The manubrium was widened using an iliac crest bone graft, stabilised using internal fixation plates and reconstructed with a pectoral muscle flap.