Endovascular Repair of Complicated Type B Aortic Intramural Haematoma: A Single Centre Long Term Experience.

OBJECTIVE: To evaluate the efficacy of thoracic endovascular aortic repair (TEVAR) in the treatment of patients with complicated type B aortic intramural haematoma (IMH). METHODS: A retrospective observational study of patients treated between January 2002 and December 2017 was performed. Complicated type B IMH was defined as persistent pain, rapid dilatation, presence of ulcer-like projections (ULPs), haemothorax, and other signs of (impending) rupture. Thirty day results and long term follow up outcomes were reported. RESULTS: Thirty-nine patients were included for analysis (mean age 68 ± 8 years, 36% male). The thirty day mortality rate was 5%, stroke rate 10%, and re-intervention rate 3%. The median follow up duration was 49 months (25th - 75th percentile: 2 - 96 months). At 10 years, estimated freedom from all cause mortality was 66 ± 9%. During follow up, nine re-interventions were performed, leading to a 10 year estimated freedom from re-intervention rate of 72 ± 8%. Estimated freedom from aortic growth at 10 years was 85 ± 9%. CONCLUSION: Complicated type B IMH can be treated effectively by TEVAR, thus preventing death from aortic rupture. However, severe early post-operative complications, most importantly stroke, are of concern. Long term outcomes are excellent, although re-interventions are not uncommon, either for progression of proximal or distal aortic disease or due to stent graft related complications.

Moderate hypothermia during ex vivo machine perfusion promotes recovery of hearts donated after cardiocirculatory death†.

OBJECTIVES: To establish the optimal machine perfusion temperature for recovery of hearts in a rodent model of donation after declaration of cardiocirculatory death (DCD). METHODS: Hearts from male Lewis rats (n = 14/group) were subjected to 25 min of in situ warm (37°C) ischaemia to simulate DCD. They were then explanted and reperfused with diluted autologous blood for 60 min at 20, 25, 30, 33 or 37°C, after which they were stored at 0-4°C in Custodiol preservation solution for 240 min. Fresh-excised and cold-stored ischaemic hearts were used as controls. The viability of the different groups was assessed by comparing heart rate and left ventricular contractility in a Langendorff circuit, as well as perfusate levels of troponin-t and creatine kinase (CK), and myocardial levels of adenosine triphosphate (ATP) and reduced glutathione. RESULTS: During ex vivo reperfusion, hearts in all groups resumed beating within minutes. The mean heart rate was highest in the 37°C group at 154.72 ± 33.01 beats × min(-1) (bpm), and declined in proportion to temperature to 39.72 ± 5.53 bpm at 20°C. Troponin-t levels were highest in the 37°C group (79.49 ± 20.79 µg/l), the values were significantly lower in all other reconditioned groups with a minimum of 12.472 ± 7.08 µg/l in the 20°C group (P < 0.0001). Tissue ATP levels ranged from 4.32 ± 1.71 µmol/g at 33°C to 4.59 ± 1.41 µmol/g at 30°C, all significantly higher than the mean ATP level of 1.41 ± 0.93 µmol/g in untreated ischaemic hearts (P < 0.0001). During Langendorff assessment, the mean heart rate and contractility of all groups were higher than those of cold-stored ischaemic hearts (P < 0.0001), yet not significantly different from those of fresh controls. The perfusate levels of troponin-t and CK, and myocardial levels of reduced-glutathione and ATP were not significantly different between groups. CONCLUSION: Our results suggest that mild hypothermia during ex vivo reperfusion improves recovery of ischaemic hearts in a rodent DCD model.

Median sternotomy.

Sternotomy is considered to be the gold standard incision in cardiac surgery, resulting in low failure rates and excellent proven long-term outcomes. It can also be used in thoracic surgery for mediastinal, bilateral pulmonary or lower trachea and main stem bronchus surgery. Sternotomy has to be performed properly to avoid short- and long-term morbidity and mortality. The surgical technique is well established and certain principles are recognized to be crucial to minimize complications. The identification of the correct landmarks, midline tissue preparation, osteotomy with the avoidance of injury to underlying structures like pleura, pericardium, innominate vein, brachiocephalic artery and ectatic ascending aorta, and targeted bleeding control are important steps of the procedure. As important as the performance of a proper sternotomy is a correct sternal closure. An override or shift of the sternal edges has to be avoided by placing the wires at a proper distance from each other without injuring the thoracic pedicle. The two sternal halves have to be tightly re-approximated to facilitate healing of the bone and to avoid instability, which is a risk factor for wound infection. With a proper performance of sternotomy and sternal closure, instability and wound infections are rare and depend on patient-related risk factors.

Mid-Term Outcomes of Minimally Invasive Direct Coronary Artery Bypass Grafting.

BACKGROUND: Minimally invasive direct coronary artery bypass grafting (MIDCAB) has gained wide acceptance for the treatment of single vessel disease of the left anterior descending artery (LAD). Here, we present our single center experience of 152 consecutive patients. MATERIALS AND METHODS: All patients underwent MIDCAB through a left anterior minithoracotomy between January 1, 2009, and December 31, 2012. Preoperative, intraoperative, postoperative, and follow-up data including major adverse cardiac and cerebrovascular events (MACCE) and need for re-intervention were collected. RESULTS: Mean age was 64.4 ± 11 years, median additive EuroSCORE 3 (0-11), 84% were male. All except one patient were successfully operated without cardiopulmonary bypass. Seven patients with unexpected severely calcified LADs were converted to sternotomy (4.6%); 91.3% were extubated in the operating room or on the day of surgery. Median stay at the intensive care unit and in hospital were 1 (0-97) and 7 (1-49) days, respectively. Thirty-day mortality was 1.9%. There was no stroke. Five patients (3.2%) had to be re-explored for bleeding and 95% received no transfusion. Median follow-up was 24 months (0-97) and complete in 93.3% with overall survival of 92.4 ± 0.2% and MACCE-free survival of 96.1 ± 1.7%. Two patients had a re-intervention of the LAD. CONCLUSION: MIDCAB is a safe procedure with low postoperative morbidity, mortality, and favorable mid-term MACCE-free survival in selected patients that should be discussed in a heart team setting to evaluate the "ideal" individual treatment option.

Recovery of donor hearts after circulatory death with normothermic extracorporeal machine perfusion.

OBJECTIVES: A severe donor organ shortage leads to the death of a substantial number of patients who are listed for transplantation. The use of hearts from donors after circulatory death could significantly expand the donor organ pool, but due to concerns about their viability, these are currently not used for transplantation. We propose short-term ex vivo normothermic machine perfusion (MP) to improve the viability of these ischaemic donor hearts. METHODS: Hearts from male Lewis rats were subjected to 25 min of global in situ warm ischaemia (WI) (37°C), explanted, reconditioned for 60 min with normothermic (37°C) MP with diluted autologous blood and then stored for 4 h at 0-4°C in Custodiol cold preservation solution. Fresh and ischaemic hearts stored for 4 h in Custodiol were used as controls. Graft function was assessed in a blood-perfused Langendorff circuit. RESULTS: During reconditioning, both the electrical activity and contractility of the ischaemic hearts recovered rapidly. Throughout the Langendorff reperfusion, the reconditioned ischaemic hearts had a higher average heart rate and better contractility compared with untreated ischaemic controls. Moreover, the reconditioned ischaemic hearts had higher tissue adenosine triphosphate levels and a trend towards improved tissue redox state. Perfusate levels of troponin T, creatine kinase and lactate dehydrogenase were not significantly lower than those of untreated ischaemic controls. The micro- and macroscopic appearance of the reconditioned ischaemic hearts were improved compared with ischaemic controls, but in both groups myocardial damage and oedema were evident. CONCLUSIONS: Our results indicate that functional recovery from global WI is possible during short-term ex vivo reperfusion, allowing subsequent cold storage without compromising organ viability. We expect that once refined and validated, this approach may enable safe transplantation of hearts obtained from donation after circulatory death.

Resuscitation of ischemic donor livers with normothermic machine perfusion: a metabolic flux analysis of treatment in rats.

Normothermic machine perfusion has previously been demonstrated to restore damaged warm ischemic livers to transplantable condition in animal models. However, the mechanisms of recovery are unclear, preventing rational optimization of perfusion systems and slowing clinical translation of machine perfusion. In this study, organ recovery time and major perfusate shortcomings were evaluated using a comprehensive metabolic analysis of organ function in perfusion prior to successful transplantation. Two groups, Fresh livers and livers subjected to 1 hr of warm ischemia (WI) received perfusion for a total preservation time of 6 hrs, followed by successful transplantation. 24 metabolic fluxes were directly measured and 38 stoichiometrically-related fluxes were estimated via a mass balance model of the major pathways of energy metabolism. This analysis revealed stable metabolism in Fresh livers throughout perfusion while identifying two distinct metabolic states in WI livers, separated at t = 2 hrs, coinciding with recovery of oxygen uptake rates to Fresh liver values. This finding strongly suggests successful organ resuscitation within 2 hrs of perfusion. Overall perfused livers regulated metabolism of perfusate substrates according to their metabolic needs, despite supraphysiological levels of some metabolites. This study establishes the first integrative metabolic basis for the dynamics of recovery during perfusion treatment of marginal livers. Our initial findings support enhanced oxygen delivery for both timely recovery and long-term sustenance. These results are expected to lead the optimization of the treatment protocols and perfusion media from a metabolic perspective, facilitating translation to clinical use.

A fitness index for transplantation of machine-perfused cadaveric rat livers.

BACKGROUND: The 110,000 patients currently on the transplant waiting list reflect the critical shortage of viable donor organs. However, a large pool of unused organs, from donors after cardiac death (DCD) that are disqualified because of extensive ischemic injury, may prove transplantable after machine perfusion treatment, fundamentally impacting the availability of treatment for end-stage organ failure. Machine perfusion is an ex-vivo organ preservation and treatment procedure that has the capacity to quantitatively evaluate and resuscitate cadaveric organs for transplantation. METHODS: To diagnose whether an organ was fresh or ischemic, an initial assessment of liver quality was conducted via dynamic discriminant analysis. Subsequently, to determine whether the organs were sufficiently viable for successful implantation, fitness indices for transplantation were calculated based on squared prediction errors (SPE) for fresh and ischemic livers. RESULTS: With just three perfusate metabolites, glucose, urea and lactate, the developed MPLSDA model distinguished livers as fresh or ischemic with 90% specificity. The SPE analyses revealed that fresh livers with SPE(F) < 10.03 and WI livers with SPE(WI) < 3.92 yield successful transplantation with 95% specificity. CONCLUSIONS: The statistical methods used here can discriminate between fresh and ischemic livers based on simple metabolic indicators measured during perfusion. The result is a predictive fitness index for transplantation of rat livers procured after cardiac death. The translational implications of this study are that any donor organ procured from controlled, but most especially from uncontrolled cardiac death donors, will be objectively assessed and its recovery monitored over time, minimizing the critical loss of otherwise viable organs.

Subnormothermic machine perfusion at both 20°C and 30°C recovers ischemic rat livers for successful transplantation.

BACKGROUND: Utilizing livers from donors after cardiac death could significantly expand the donor pool. We have previously shown that normothermic (37°C) extracorporeal liver perfusion significantly improves transplantation outcomes of ischemic rat livers. Here we investigate whether recovery of ischemic livers is possible using sub-normothermic machine perfusion at 20°C and 30°C. METHODS: Livers from male Lewis rats were divided into five groups after 1 h of warm ischemia (WI): (1) WI only, (2) 5 h of static cold storage (SCS), or 5 h of MP at (3) 20°C, (4) 30°C, and (5) 37°C. Long-term graft performance was evaluated for 28 d post-transplantation. Acute graft performance was evaluated during a 2 h normothermic sanguineous reperfusion ex vivo. Fresh livers with 5 h of SCS were positive transplant controls while fresh livers were positive reperfusion controls. RESULTS: Following machine perfusion (MP) (Groups 3, 4, and 5), ischemically damaged livers could be orthotopically transplanted into syngeneic recipients with 100% survival (N ≥ 4) after 4 wk. On the other hand, animals from WI only, or WI + SCS groups all died within 24 h of transplantation. Fresh livers preserved using SCS had the highest alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the lowest bile production during reperfusion, while at 28 d post-transplantation, livers preserved at 20°C and 30°C had the highest total bilirubin values. CONCLUSIONS: MP at both 20°C and 30°C eliminated temperature control in perfusion systems and recovered ischemically damaged rat livers. Postoperatively, low transaminases suggest a beneficial effect of sub-normothermic perfusion, while rising total bilirubin levels suggest inadequate prevention of ischemia- or hypothermia-induced biliary damage.

A metabolic index of ischemic injury for perfusion-recovery of cadaveric rat livers.

With over 110,000 patients waiting for organ transplantation, the current crisis in organ transplantation is based on a lack of donors after brain-death (DBD). A very large alternative pool of donor organs that remain untapped are the donors after cardiac death (DCD), recovered after cardiac activity has ceased and therefore sustained some ischemic injury. Machine perfusion has been proposed as a novel modality of organ preservation and treatment to render such cadaveric organs, and in particular livers, transplantable. Two key issues that remain unaddressed are how to assess whether a DCD liver is damaged beyond repair, and whether machine perfusion has rendered an injured organ sufficiently viable for transplantation. In this work, we present a metabolic analysis of the transient responses of cadaveric rat livers during normothermic machine perfusion (NMP), and develop an index of ischemia that enables evaluation of the organ ischemic injury level. Further, we perform a discriminant analysis to construct a classification algorithm with >0.98 specificity to identify whether a given perfused liver is ischemic or fresh, in effect a precursor for an index of transplantability and a basis for the use of statistical process control measures for automated feedback control of treatment of ischemic injury in DCD livers. The analyses yield an index based on squared prediction error (SPE) as log(SPE) >1.35 indicating ischemia. The differences between metabolic functions of fresh and ischemic livers during perfusion are outlined and the metabolites that varied significantly for ischemic livers are identified as ornithine, arginine, albumin and tyrosine.

Management of the left atrial appendage.

Surgical and interventional exclusion left atrial appendage (LAA) are becoming important alternatives to oral anticoagulation for stroke prevention in the setting of atrial fibrillation. Herein we present the different approaches (endocardial vs. epicardial) to LAA occlusion. Each approach is depicted in detail and relevant literature is briefly presented.

Recovery of warm ischemic rat liver grafts by normothermic extracorporeal perfusion.

Liver transplantation is currently the only established treatment of end-stage liver disease, but it is limited by a severe shortage of viable donor livers. Donors after cardiac death (DCD) are an untapped source that could significantly increase the pool of available livers. Preservation of these DCD livers by conventional static cold storage (SCS) is associated with an unacceptable risk of primary nonfunction and delayed graft failure. Normothermic extracorporeal liver perfusion (NELP) has been suggested as an improvement over SCS. Livers recovered from male Lewis rats were subjected to 1 hr of warm ischemia and preserved with 5 hr of SCS or NELP, and transplanted into syngeneic recipients. As additional controls, non-ischemic livers preserved with 6 hr of SCS or NELP and unpreserved ischemic livers were transplanted. After NELP, ischemically damaged livers could be orthotopically transplanted into syngeneic recipients with 92% survival (n=13) after 4 weeks, which was comparable with control animals that received healthy livers preserved by SCS (n=9) or NELP (n=11) for 6 hr. On the other hand, animals from ischemia/SCS control group all died within 12 hr postoperatively (n=6). Similarly, animals that received ischemic livers without preservation all died within 24 hr after transplantation (n=6). These results suggest that NELP has the potential to reclaim warm ischemic livers that would not be transplantable otherwise. The rat model in this study is a useful platform to further optimize NELP as a method of recovery and preservation of DCD livers.

A model for normothermic preservation of the rat liver.

Current techniques for the preservation of donor livers typically rely on cold temperatures (approximately 0-4 degrees C) to slow down metabolic processes. Recently, normothermic extracorporeal liver perfusion (NELP) has regained interest as a potentially promising approach for long-term liver preservation. Unlike cold-storage techniques, NELP attempts to maintain the liver in a near physiological environment, thus enabling normal metabolic and tissue repair processes to take place, which may help in the recovery of ischemically damaged and fatty donor livers, both of which represent significant untapped sources of donor livers. However, NELP is technically more complex than cold-storage techniques, and the lack of standardized small animal models limits its development. Here we describe a rat NELP system that is simple and cost-effective to run. We show that rat livers that underwent NELP for 6 h could be routinely transplanted into syngeneic recipient rats with excellent 1-month survival. During perfusion, the release of cytosolic enzymes, bile and urea production, and oxygen uptake rate could be readily monitored, thus providing a comprehensive picture of hepatic function before transplantation. This system will help in the optimization of NELP in several ways, such as for the improvement of perfusion conditions and the development of quantitative metabolic criteria for hepatic viability.

Bone-marrow-derived cells contribute to glomerular endothelial repair in experimental glomerulonephritis.

Glomerular endothelial injury plays an important role in the pathogenesis of renal diseases and is centrally involved in renal disease progression. Glomerular endothelial repair may help maintain renal function. We examined whether bone-marrow (BM)-derived cells contribute to glomerular repair. A rat allogenic BM transplant model was used to allow tracing of BM-derived cells using a donor major histocompatibility complex class-I specific mAb. In glomeruli of chimeric rats we identified a small number of donor-BM-derived endothelial and mesangial cells, which increased in a time-dependent manner. Induction of anti-Thy-1.1-glomerulonephritis (transient mesangial and secondary glomerular endothelial injury) caused a significant, more than fourfold increase in the number of BM-derived glomerular endothelial cells at day 7 after anti-Thy-1.1 injection compared to chimeric rats without glomerular injury. The level of BM-derived endothelial cells remained high at day 28. We also observed a more than sevenfold increase in the number of BM-derived mesangial cells at day 28. BM-derived endothelial and mesangial cells were fully integrated in the glomerular structure. Our data show that BM-derived cells participate in glomerular endothelial and mesangial cell turnover and contribute to microvascular repair. These findings provide novel insights into the pathogenesis of renal disease and suggest a potential role for stem cell therapy.