Enhanced Cardiac S100A1 Expression Improves Recovery from Global Ischemia-Reperfusion Injury.

Gene-targeted therapy with the inotropic Ca2 + -sensor protein S100A1 rescues contractile function in post-ischemic heart failure and is being developed towards clinical trials. Its proven beneficial effect on cardiac metabolism and mitochondrial function suggests a cardioprotective effect of S100A1 in myocardial ischemia-reperfusion injury (IRI). Fivefold cardiomyocyte-specific S100A1 overexpressing, isolated rat hearts perfused in working mode were subjected to 28 min ischemia (37 °C) followed by 60 min reperfusion. S100A1 overexpressing hearts showed superior hemodynamic recover: Left ventricular pressure recovered to 57 ± 7.3% of baseline compared to 51 ± 4.6% in control (p = 0.025), this effect mirrored in LV work and dP/dt(max). Troponin T and lactate dehydrogenase was decreased in the S100A1 group, as well as FoxO pro-apoptotic transcription factor, indicating less tissue necrosis, whereas phosphocreatine content was higher after reperfusion. This is the first report of a cardioprotective effect of S100A1 overexpression in a global IRI model.

Aorta Related and All-cause Mortality in Patients with Aortic Intramural Haematoma.

OBJECTIVES: The prognosis of patients with intramural haematoma (IMH) of the aorta beyond the first year after diagnosis remains largely unknown. In particular, patients that do not undergo interventions are lost to follow-up. The aim was to assess medium-term outcome in IMH patients. METHODS: Post hoc analysis of 63 consecutive patients presenting with IMH between 1999 and 2013 was performed. Patients meeting imaging criteria at the first presentation were included even if follow-up imaging showed evidence of intimal disruption or false lumen flow. RESULTS: Eighteen patients presented with type A and 45 with type B IMH (29% vs. 71%, p < .001). The mean age was 71 ± 9.2 years, range 42-88 years. Follow-up was completed in 97% of patients by May 2017 and represents a mean follow-up of 6.3 ± 3.6 years. Freedom from intervention in patients with type B IMH was 40%. TEVAR was performed in 47% because of development, unmasking of an entry tear (57%), progression to acute type B dissection (24%), or subsequent dilation of the affected aortic segments (19%). Open repair was performed in 13% of type B IMH patients because of dilation of the descending aorta. In type A IMH, 89% underwent open repair. Aorta related 30 day, 6 month, 1 year, and late mortality were 1.6%, 6.3%, 6.3%, and 9.5%, respectively, for all IMH patients. All-cause 30 day, 6 month, 1 year, and late mortality were 1.6%, 6.3%, 6.3%, and 47.6%, respectively, for all IMH patients. Late mortality in type B IMH did not differ whether patients underwent TEVAR, open repair, or received best medical treatment only (26% vs. 22%, p = 1.0). CONCLUSIONS: Late aorta related mortality in IMH was low whereas all-cause mortality was substantial. Aorta related mortality in IMH patients only occurs during the first year after diagnosis. Interventions after the first year are rarely necessary.

Mechanical versus biological aortic valve replacement strategies.

Aortic valve replacement (AVR) is the most frequently performed procedure in valve surgery. The controversy about the optimal choice of the prosthetic valve is as old as the technique itself. Currently there is no perfect valve substitute available. The main challenge is to choose between mechanical and biological prosthetic valves. Biological valves include pericardial (bovine, porcine or equine) and native porcine bioprostheses designed in stented, stentless and sutureless versions. Homografts and pulmonary autografts are reserved for special indications and will not be discussed in detail in this review. We will focus on the decision making between artificial biological and mechanical prostheses, respectively. The first part of this article reviews guideline recommendations concerning the choice of aortic prostheses in different clinical situations while the second part is focused on novel strategies in the treatment of patients with aortic valve pathology.

Management of aortic aneurysms in patients with connective tissue disease.

Acute dissection and rupture of aortic aneurysms comprise for 1-2% of all deaths in developed countries. Dilation of the aorta is caused by several different mechanisms including inherited disorders of connective tissue. Recent reports estimate that 20% of patients presenting with thoracic aortic disease do have an underlying genetic basis of disease.

Acute aortic dissection type A.

BACKGROUND: Acute aortic dissection type A (AADA) is a life-threatening vascular emergency. Clinical presentation ranges from pain related to the acute event, collapse due to aortic rupture or pericardial tamponade, or manifestations of organ or limb ischaemia. The purpose of this review was to clarify important clinical issues of AADA management, with a focus on diagnostic and therapeutic challenges. METHODS: Based on a MEDLINE search the latest literature on this topic was reviewed. Results from the German Registry for Acute Aortic Dissection Type A (GERAADA) are also described. RESULTS: Currently, the perioperative mortality rate of AADA is below 20 per cent, the rate of definitive postoperative neurological impairment approaches 12 per cent and the long-term prognosis after surviving the acute phase of the disease is good. Many pathology- and therapy-associated factors influence the outcome of AADA, including prompt diagnosis with computed tomography and better cerebral protection strategies during aortic arch reconstruction. Endovascular technologies are emerging that may lead to less invasive treatment options. CONCLUSION: AADA is an emergency that can present with a wide variety of clinical scenarios. Advances in the surgical management of this complex disease are improving outcomes.

Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development.

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 µm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.

Efficacy and safety of sirolimus and everolimus in heart transplant patients: a retrospective analysis.

BACKGROUND: Since its introduction as an immunosuppressant in the late 1990s, sirolimus (SRL) has been used to prevent rejections after heart transplantation (HTx) in the United States. An analogue, everolimus (ERL) has been mainly used in Europe. We performed a retrospective longitudinal single-center study to evaluate efficacy and side effects of SRL and ERL. PATIENTS AND METHODS: We analyzed 71 patients, 39 in the SRL and 32 in the ERL group. The following data were collected: Trough levels of SRL and ERL, biopsy-proven rejections, renal function, blood lipids, hematology, blood pressure, pulse rate, and side effects (via an anonymous questionnaire). Follow-up time was 6 months. No prisoners or organs from prisoners were used in the study. RESULTS: Introduction of SRL or ERL into therapy took place 44 or 42 months (average) after HTx. SRL and ERL were equally effective in preventing rejection (8/39 versus 6/32). Hemoglobin levels decreased slightly in the SRL group (nonsignificant). Leucocytes and thrombocyte levels decreased in both groups (P < .05 only in the ERL group). Creatinine levels remained unchanged. Cholesterol and triglyceride levels increased significantly in the SRL group. High-density lipoprotein levels increased significantly in the ERL group. Vital signs remained stable in both groups. Side effects (mainly edema, gastrointestinal symptoms and infections) were considerable and prompted discontinuation in 39% of all patients in both groups. Infections were more frequent in SRL (18/39 versus 12/32, nonsignificant). Calcineurin therapy could be reduced by 25% in SRL and 45% in ERL. CONCLUSION: The impact of SRL and ERL on laboratory values and rejection rates, as well as on clinical parameters, is similar with a slight advantage to ERL regarding lipids and rate of infections (not significant). Both SRL and ERL allow an important reduction of calcineurin-therapy; however, both drugs have considerable side effects, which often require discontinuation of therapy.

Prevention of rupture of abdominal aortic aneurysm.

BACKGROUND AND AIMS: Two thirds of patients with an abdominal aortic aneurysm (AAA) have relevant coronary artery disease (CAD). AAAs are prevalent in up to 16% of smokers with CAD. General screening of AAA is controversial. Aim was to assess the potential of finding AAA prior to rupture among patients with known CAD. Main endpoint was whether AAA could have been found during follow-up by sonography or at other time of cardiovascular evaluation. MATERIAL AND METHODS: Retrospective study. 213 consecutive, formerly unknown emergently operated AAAs, treated emergently for symptoms (n = 91) or rupture (n = 122) (rAAA) between January 1998 and June 2005. Patient charts were analysed and primary care physicians contacted. RESULTS: At presentation, mean age was 71 (+/-9) years, twenty (9%) were female. AAA had a mean diameter of 7.6 cm. Two thirds (143) were clinically obese (BMI 27 +/-5). 137 (64%) were active smokers, 32 (15%) had diabetes, 151 (71%) were hypertensive, and 80 (38%) received statin treatment. CAD had been diagnosed in 95 (45%) 9 years earlier and followed up. Thirty-five (16%) had had myocardial infarction. Echocardiography had been performed in 52 (24%). Thirty day mortality after open surgery was 25 (21%). CONCLUSION: All patients with rAAA had been seen by a GP or cardiologist within a year prior to presentation. The cost effectiveness of selective AAA screening should be evaluated in a larger study.

Quality of life after acute type B dissection in the era of thoracic endovascular aortic repair.

BACKGROUND: Conservative management of acute type B aortic dissection is currently being challenged by primary thoracic endovascular aortic repair. Aim was to assess outcome and quality of life after these different approaches using an adjusted standard population as benchmark. PATIENTS AND METHODS: Observational study of a prospectively collected (January 2000 to December 2005) consecutive series of 87 patients with acute type B aortic dissection. Patients were 63 +/- 13 years old and 68 were men (78.2 %). Seventy-two were managed conservatively (83 %) and 15 invasively (12 by endovascular aortic repair). Follow-up was 36 +/- 19 months. Endpoints were early and late morbidity and mortality, and long-term quality of life as assessed by the Short Form health survey questionnaire. RESULTS: Patient cohorts were similar regarding age, risk profile and local disease. In the conservative cohort, four patients died during early (5.6 %) and eight during long-term follow-up (cumulative four years survival rate 79 %). Thirty-two patients needed secondary surgical management (44 %), i.e. delayed aortic repair (n = 11), or interventions on adjacent aortic sections or major branches (n = 21). In the surgical cohort no patient died, and no repeated interventions were necessary after the peri-operative period. Long-term quality of life scores were 100 (69-115) in conservatively and 94 (75-124) in invasively managed patients. Normal scores range from 85 to 115. CONCLUSIONS: Primary endovascular management of uncomplicated acute type B dissection is safe and leads to excellent long-term results, whereas secondary interventions were required with high incidence after initial conservative management. Long-term quality of life, however, returned to normal with any successful treatment strategy.

Connexin 43 expression in human hypertrophied heart due to pressure and volume overload.

Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution.

[Ascending aortic and pulmonary trunk aneurysms]. / Aneurysmata der Aorta ascendens und des Truncus pulmonalis.

A case of two non-atherosclerotic aneurysms localised in the ascending aorta and in the pulmonary trunk is presented. Histopathologically, a severe granulomatous inflammation affecting the whole aneurysms wall was documented. To the best of our knowledge it is the second ever documented case of simultaneous occurrence of aneurysms in the aorta and the pulmonary artery.

Acute pulmonary embolectomy three days following a coronary artery bypass graft procedure.

Pulmonary embolism is very rarely reported early after cardiac surgery, most probably due to full heparinisation during cardiopulmonary bypass. We report a 66-year-old man without thromboembolic history who presented three days after a coronary artery bypass grafting procedure with acute dyspnoea and haemodynamic instability. A CT scan confirmed paracentral bilateral pulmonary embolism requiring an urgent and successful embolectomy. Review of the literature confirms that pulmonary embolism may occur in up to 3% of post-cardiopulmonary bypass patients. The possibility of pulmonary embolism must be taken into consideration in post-cardiopulmonary bypass patients with acute onset of chest pain and respiratory insufficiency.

PPS-PEG surface coating to reduce thrombogenicity of small diameter ePTFE vascular grafts.

AIMS: Patency failure of small vascular synthetic grafts is still a major problem for coronary and peripheral revascularization. Thus, three new surface coatings of small synthetic grafts were tested in an acute pig model to evaluate their thrombogenicity (extracorporeal arterio-venous shunt) and in a chronic rat model to evaluate the tissue reaction they induced (subcutaneous implantation). METHODS: In five domestic pigs (25-30 kg) an extracorporeal femoro-femoral arterio-venous shunt model was used. The study protocol included first a non-heparinized perfusion sequence followed by graft perfusion after 10,000 UI iv heparin. Grafts were perfused for 3 and 9 minutes. The following coatings were tested on ePTFE grafts: poly-propylene sulphide (PPS)--poly-ethylene glycol (PEG) (wet and dry applications) as well as carbon. Two sets of control were used, one dry and one wet (vehicle only). After perfusion grafts were examined by scanning electron microscopy for semi-quantitative assessment (score 0-3) of cellular and microthrombi deposition. To assess tissue compatibility, pieces of each material were implanted subcutaneously in 16 Wistar rats. At 2, 4, 8, 12 weeks four animals each were sacrificed for semi-quantitative (score 0-3) histologic evaluation of tissue reaction. RESULTS: In the pig model, cellular deposition and microthrombi formation increased over time. In non- heparinized animals, the coatings did not improve the surface characteristics, since they did not prevent microthrombi formation and cellular deposition. In heparinized animals, thrombogenicity was lowest in coated grafts,especially in PPS -PEG dry (p<0.05), and highest in controls. Cell deposition was lowest in PPS-PEG dry, but this difference was not statistically significant vs.controls. In the rat model,no significant differences of the tissue reaction could be shown between materials. CONCLUSION: While all coatings failed to add any benefit for lowering tissue reaction, surface coating with PPS -PEG (dry application) reduced thrombogenicity significantly (in heparinized animals) and thus appears to be promising for improving graft patency of small synthetic vascular prostheses.

Soluble type A substance in fresh-frozen plasma as a function of ABO and Secretor genotypes and Lewis phenotype.

Soluble ABO blood group substance (SAS) in fresh-frozen plasma (FFP) and its cognate alloantibody titer reduction capacity (TRC) are not considered when prescribing this product for plasma exchange (PEX) therapy of ABO incompatible transplant recipients. SAS was quantified in 250 single FFPs using ELISA. Total and IgG class-specific anti-A TRCs of FFPs were measured using a microhemagglutination inhibition assay. SAS level depended not only on the A subtype (p < 0.0001) and the Secretor status (p < 0.0001), but also on the expression of ALe(b) in A1 secretors (p < 0.0001). The variation was as great as 137.6 arbitrary units (aU) for 14 A1 Le(a-b-) secretors and 1.2 aU for 6 A2 non-secretors. Homozygous expression of the A1, A2 and Secretor alleles did not increase SAS levels. Only total anti-A TRC, but not IgG class-specific TRC depended on the detected SAS level (r = 0.566, p = 0.0003).

Administration of steroids in pediatric cardiac surgery: impact on clinical outcome and systemic inflammatory response.

Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response. Pre-bypass steroid administration may modulate the inflammatory response, resulting in improved postoperative recovery. We performed a prospective study in the departments of cardiovascular surgery and pediatric intensive care medicine of two university hospitals that included 50 infants who underwent heart surgery. Patients received either prednisolone (30 mg/kg) added to the priming solution of the cardiopulmonary bypass circuit (steroid group) or no steroids (nonsteroid group). Clinical outcome parameters include therapy with inotropic drugs, oxygenation, blood lactate, glucose, and creatinine, and laboratory parameters of inflammation include leukocytes, C-reactive protein, and interleukin-8. Postoperative recovery (e.g., the number, dosage, and duration of inotropic drugs as well as oxygenation) was similar in patients treated with or without steroids when corrected for the type of cardiac surgery performed. After CPB, there was an inflammatory reaction, especially in patients with a long CPB time. Postoperative plasma levels of interleukin-8 were correlated with the duration of CPB time (r = 0.62, p < 0.001). Administration of steroids had no significant impact on the laboratory parameters of inflammation. Administration of prednisolone into the priming solution of the CPB circuit had no measurable influence on postoperative recovery and did not suppress the inflammatory response.

Solid organ transplantation across the ABO histo-blood group barrier: a case report.

The ABO blood group system until recently constituted an insuperable barrier for solid organ transplantation, but cases of heart transplantation in infants and kidney transplantation in adults have been reported, wherein ABO-incompatible grafts have been successful. In 1990, the molecular genetic basis of three major alleles at the ABO locus was elucidated; A and B glycosyltransferases are specified by a variety of functional alleles at this locus. The antibody response to ABH antigens, namely, naturally occurring anti-A/B IgM and IgG isotype agglutinins, are controlled preoperatively by recipient conditioning using plasma exchange, immunoadsorption, and immunosuppressive regimens. We report an O-type patient who accidentally received a B-type cardiac allograft in 1997 who survived for 5 years, dying for an unrelated reason. Over a period of 45 months semiquantitatively we monitored the expression of ABO-type antigens in graft heart vessels using monoclonal antibodies on sections of formalin-fixed, paraffin-embedded biopsies. We observed a progressive change in the antigenic profile of graft endothelial cells from B- to O-type, which was first detected at 1 year posttransplant and most prominent 3 years later, the end of the observation period. No temporal relationship was observed between the transition from B to O expression, the anti-B antibody levels or the immunosuppressive regimen.

Spontaneous dissection of common iliac artery. A case report.

Spontaneous dissection of the iliac artery is very rare but known as a complication of high-energy traumatic injuries and has been reported in connection with pregnancy, collagen diseases, and alpha-1-antitrypsin deficiency. The authors report a 42-year-old man with an acute dissection of the common iliac artery during exercise. Groin pain and claudication were the early symptoms. Computerized angiotomography was diagnostic. Operative iliac artery reconstruction was performed. A prerelease control computed tomography examination showed a dissection of the distal aorta and left iliac artery. To their knowledge, the combination of the 2 dissections has not been previously published.