Desmin mutations impact the autophagy flux in C2C12 cell in mutation-specific manner.

Desmin is the main intermediate filament of striated and smooth muscle cells and plays a crucial role in maintaining the stability of muscle fiber during contraction and relaxation cycles. Being a component of Z-disk area, desmin integrates autophagic pathways, and the disturbance of Z-disk proteins' structure negatively affects chaperone-assisted selective autophagy (CASA). In the present study, we focused on alteration of autophagy flux in myoblasts expressing various Des mutations. We applied Western blotting, immunocytochemistry, RNA sequencing, and shRNA approach to demonstrate that DesS12F, DesA357P, DesL345P, DesL370P, and DesD399Y mutations. Mutation-specific effect on autophagy flux being most severe in aggregate-prone Des mutations such as DesL345P, DesL370P, and DesD399Y. RNA sequencing data confirmed the most prominent effect of these mutations on expression profile and, in particular, on autophagy-related genes. To verify CASA contribution to desmin aggregate formation, we suppressed CASA by knocking down Bag3 and demonstrated that it promoted aggregate formation and lead to downregulation of Vdac2 and Vps4a and upregulation of Lamp, Pink1, and Prkn. In conclusion, Des mutations showed a mutation-specific effect on autophagy flux in C2C12 cells with either a predominant impact on autophagosome maturation or on degradation and recycling processes. Aggregate-prone desmin mutations lead to the activation of basal autophagy level while suppressing the CASA pathway by knocking down Bag3 can promote desmin aggregate formation.

Molecular effects of cardiac contractility modulation in patients with heart failure of ischemic aetiology uncovered by transcriptome analysis.

Cardiac contractility modulation (CCM) is based on electrical stimulation of the heart without alteration of action potential and mechanical activation, the data on its fundamental molecular mechanisms are limited. Here we demonstrate clinical and physiological effect of 12 months CCM in 29 patients along with transcriptomic molecular data. Based on the CCM effect the patients were divided into two groups: responders (n = 13) and non-responders (n = 16). RNA-seq data were collected for 6 patients before and after CCM including 3 responders and 3 non-responders. The overall effect of CCM on gene expression was mainly provided by samples from the responder group and included the upregulation of the genes involved in the maintenance of proteostasis and mitochondrial structure and function. Using pathway enrichment analysis, we found that baseline myocardial tissue samples from responder group were characterized by upregulation of mitochondrial matrix-related genes, Z disc-protein encoding genes and muscle contraction-related genes. In summary, twelve months of ССM led to changes in signaling pathways associated with cellular respiration, apoptosis, and autophagy. The pattern of myocardial remodeling after CCM is associated with initial expression level of myocardial contractile proteins, adaptation reserves associated with mitochondria and low expression level of inflammatory molecules.

Fluorescent (rhodamine), folate decorated and doxorubicin charged, PEGylated nanoparticles synthesis.

PEGylated silica nanoparticles, giving very stable aqueous sols, were successfully functionalised with rhodamine, one of the more stable fluorophore; they were also decorated with the targeting agent folic acid (FA) and charged with the well known drug doxorubicin. Rhodamine functionalization required a modification of the synthesis route of the nanoparticles (NP). Functionalization with FA required activation with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride. Folate decorated NP were easily charged with doxorubicin. The experimental results proved the successfulness of the functionalization. The bond to the NP does not reduce the therapeutic efficacy of the drug. The calculated encapsulation efficiency (32 %) was only a little lower than the value (47 %) reported for the very popular PEGylated PLGA NP.

Multifunctional mats by antimicrobial nanoparticles decoration for bioinspired smart wound dressing solutions.

Developing advanced materials for wound dressings is a very challenging, yet unaddressed task. These systems are supposed to act as temporary skin substitutes, performing multiple functions, including fluid absorption and antimicrobial action, supporting cell proliferation and migration in order to promote the skin regeneration process. Following a global bioinspired approach, in this study, we developed a multifunctional textile for wound dressing applications. Biodegradable polyhydroxybutyrate/poly-3-caprolactone (PHB/PCL) mats were fabricated by electrospinning to mimic the extracellular matrix (ECM), thus providing structural and biochemical support to tissue regeneration. Furthermore, inspired by nature's strategy which exploits melanin as an effective weapon against pathogens infection, PHB/PCL mats were modified with hybrid Melanin-TiO2 nanostructures. These were combined to PHB/PCL mats following two different strategies: in-situ incorporation during electrospinning process, alternately ex-post coating by electrospraying onto obtained mats. All samples revealed huge water uptake and poor cytotoxicity towards HaCat eukaryotic cells. Melanin-TiO2 coating conferred PHB/PCL mats significant antimicrobial activity towards both Gram(+) and Gram(-) strains, marked hydrophilic properties as well as bioactivity which is expected to promote materials-cells interaction. This study is going to provide a novel paradigm for the design of active wound dressings for regenerative medicine.

Sphingosine 1-phosphate induces differentiation of adipose tissue-derived mesenchymal stem cells towards smooth muscle cells.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid which regulates multiple biological parameters in a number of cell types, including stem cells. Here we report, for the first time, that S1P dose-dependently stimulates differentiation of adipose tissue-derived mesenchymal stem cells (ASMC) towards smooth muscle cells. Indeed, S1P not only induced the expression of smooth muscle cell-specific proteins such as alpha-smooth muscle actin (alpha SMA) and transgelin, but also profoundly affected ASMC morphology by enhancing cytoskeletal F-actin assembly, which incorporated alpha SMA. More importantly, S1P challenge was responsible for the functional appearance of Ca(2+) currents, characteristic of differentiated excitable cells such as smooth muscle cells. By employing various agonists and antagonists to inhibit S1P receptor subtypes, S1P(2) turned out to be critical for the pro-differentiating effect of S1P, while S1P(3) appeared to play a secondary role. This study individuates an important role of S1P in AMSC which can be exploited to favour vascular regeneration.

Syngonanthus nitens (Bong.) Ruhland Derivatives Loaded into a Lipid Nanoemulsion for Enhanced Antifungal Activity Against Candida parapsilosis.

BACKGROUND: Vaginal infections caused by non-albicans species have become common in women of all age groups. The resistance of species such as Candida parapsilosis to the various antifungal agents is a risk factor attributed to these types of infections, which instigates the search for new sources of active compounds in vulvovaginal candidiasis (VCC) therapy. OBJECTIVE: This study evaluated the antifungal activity of Syngonanthus nitens Bong. (Ruhland) derivatives and employed a lipid nanoemulsion as a delivery system.' METHODS: In this study, a lipid nanoemulsion was employed as a delivery system composed of Cholesterol (10%), soybean phosphatidylcholine: Brij 58 (1: 2) and PBS (pH 7.4) with the addition of 0.5% of a chitosan dispersion (80%), and evaluated the antifungal activity of S. nitens Bong. (Ruhland) derivatives against planktonic cells and biofilms of Candida parapsilosis. By a biomonitoring fractionation, the crude extract (EXT) and one fraction (F2) were selected and incorporated into a lipid nanoemulsion (NL) composed of cholesterol (10%), a 1:2 mixture of soybean phosphatidylcholine:polyoxyethylene -20- cetyl ether (10%), and phosphate buffer solution (pH 7.4) with a 0.5% chitosan dispersion (80%). The NL presented a diameter size between 50-200 nm, pseudoplastic behavior, and positive charge. The EXT and five fractions were active against planktonic cells. RESULTS AND DISCUSSION: The incorporation of EXT and F2 into the NL increased antifungal activity and enhanced the anti-biofilm potential. This study classified the use of an NL as an important tool for the administration of S. nitens derivatives in cases of infections caused by this C. parapsisilosis. CONCLUSION: This work concluded that S. nitens derivatives were important sources of active molecules against C. parapsilosis and the use of a lipid nanoemulsion was an important tool to promote more effective F2 release and to improve the antifungal activity aiming the control of C. parapsilosis infections.

A neonate with cyanosis and tortuous great arteries.

This report describes an unusual case with tortuosity of the great vessels in a neonate who presented at birth with cyanosis. The diagnosis was made with magnetic resonance imaging (MRI), then confirmed by genetic analysis.

[Malnutrition in patients on chronic hemodialysis: prevalence, pathogenesis, and treatment]. / La malnutrizione nel paziente in emodialisi cronica: prevalenza, patogenesi, terapia.

Malnutrition is common in patients on hemodialysis and is a strong predicor of morbidity and mortality. Much progress has been made in recent years in identifying the causes and pathogenesis of malnutrition in hemodialysis patients as well as in recognizing the link between malnutrition and morbidity and mortality. Nevertheless, there is no consensus concerning its management. Conventional interventions such as nutritional counseling, oral nutritional supplements and intradialytic parenteral nutrition and novel preventive and therapeutic strategies such as appetite stimulants, growth hormone, androgenic anabolic steroids, and antiinflammatory drugs have been tested with contradictory and inconclusive results. Malnutrition still remains an important challenge for the nephrologist in the third millennium.

Effect of the solution flow rate on the in vitro bioactivity of 2.5CaO x 2SiO(2) glass.

A comparative study of in vitro bioactivity of 2.5CaO x 2SiO(2) glass has been carried out by soaking it in a simulated body fluid, with continuously and periodic exchange of this solution (dynamic and differential protocols). Dynamic assays were carried out at different solution flow rates, 3 mL/h, 6 mL/h, 12 mL/h, to study the influence of flow rate on glass reactivity. Glass surface was studied by Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive spectroscopy so as to compare the behavior in the two procedures, revealing that in both cases an apatite layer is formed on the glass surface, although there are differences on deposition rate and morphology, which are also influenced by the solution flow rate.

Mass-spring models for the simulation of mitral valve function: Looking for a trade-off between reliability and time-efficiency.

Patient-specific finite element (FE) models can assess the impact of mitral valve (MV) repair on the complex MV anatomy and function. However, FE excessive time requirements hamper their use for surgical planning; mass-spring models (MSMs) represent a more approximate approach but can provide almost real-time simulations. On this basis, we implemented MSMs of three healthy MVs from cardiac magnetic resonance (cMR) imaging to simulate the systolic MV closure, including the in vivo papillary muscles and annular kinematics, and the anisotropic and non-linear mechanical response of MV tissues. To test MSM reliability we compared the systolic peak configurations computed by MSMs and FE: mismatches by less than twice the in-plane cMR image resolution were detected over 75% of the leaflets' surface, independently of the MSM mesh refinement and of the specific MV anatomy. Data on MSMs time-efficiency and data from the comparison of MSMs vs. FE models suggest that MSM could represent a suitable trade-off between almost real-time simulations and reliability when computing MV systolic configuration, with the potential to be used in a clinical setting either as a support to the decisional process or as a virtual training tool.

Small bowel intussusception: what is the role of laparoscopy?

Small bowel intussusception in adults is a rare surgical disease which almost always occurs as a complication of either benign or malignant lesion of the bowel that is working as a leading point. In adults, the surgical approach consists of the resection of the bowel involved to ensure the excision of the lesion below. The authors report a case of ileocecal intussusception occurred in a young woman, 35 years old, observed for abdominal pain and signs of small bowel occlusion. She underwent surgical resection of the ileocecal segment with laparoscopic approach. The authors discuss the feasibility of the laparoscopic approach in this rare surgical disease and its benefits in terms of patient's postoperative comfort and outcome.

Modified ultrafiltration reduces morbidity after adult cardiac operations: a prospective, randomized clinical trial.

BACKGROUND: Extracorporeal circulation contributes to morbidity after open-heart surgery by causing a systemic inflammatory reaction. Modified ultrafiltration is a technique able to remove the fluid overload and inflammatory mediators associated with use of cardiopulmonary bypass. It has been shown to reduce morbidity after cardiac operations in children, but the impact on adult cardiac procedures is unknown. METHODS AND RESULTS: Five hundred seventy-three consecutive adult patients were prospectively randomized to either ultrafiltration after cardiopulmonary bypass (treatment) or to no ultrafiltration (control). Parsonnet score was used to assess the severity of the patients' clinical conditions. Analysis was done with Student's t test or Mann-Whitney U test for continuous variables and Fisher's exact test or Pearson's chi(2) for discrete variables. Hospital mortality was 2.5% (7 of 284) in the treatment group versus 3.8% (11 of 289) in the control group (P=0.357). Hospital morbidity was lower in treated patients (66 of 284 [23.2%] versus 117 of 289 [40.5%], P=0.0001). Cardiac morbidity was similar (26 of 284 [9.1%] versus 35 of 289 [12.1%], P=0.251), whereas significantly lower rates of respiratory (20 of 284 [7.0%] versus 36 of 289 [12.5%], P=0.029), neurological (5 of 284 [1.8%] versus 14 of 289 [4.8%], P=0.039), and gastrointestinal (0 of 284 versus 4 of 289 [1.4%], P=0.044) complications were found in treated patients. Transfusion requirements were also lower in treated patients (1.66+/-2.6 versus 2.25+/-3.8 U/patient, P=0.039). Duration of intensive care (39.9+/-49.2 versus 46.3+/-72.8 hours, P=0.218) and hospital stay (7.6+/-3.5 versus 7.9+/-4.4 days, P=0.372) were comparable. CONCLUSIONS: Modified ultrafiltration after cardiopulmonary bypass is associated with a lower prevalence of early morbidity and lower blood transfusion requirements. The impact on length of hospital stay needs further analysis. Routine application of modified ultrafiltration after adult cardiac operations is warranted.

Influence of the aortic valve leaflets on the fluid-dynamics in aorta in presence of a normally functioning bicuspid valve.

In this work, we consider the blood fluid-dynamics in the ascending aorta in presence of a normally functioning bicuspid aortic valve (BAV). In particular, we perform an unsteady finite element study in real geometries with physiological velocity boundary conditions at the inlet to assess the effect of the inclusion of the leaflets on the fluid-dynamic abnormalities characterizing BAV cases. To this aim, we perform a comparison in two geometries (a dilated and a non-dilated ones) among three scenarios which are built up for each geometry: BAV without leaflets, BAV with leaflets, and tricuspid case with leaflets. For each case, we compute four indices quantifying flow asymmetry, reversal flows, helical patterns, and wall shear stresses. Our results show that the inclusion of the leaflets increases the fluid-dynamics abnormalities, especially for the non-dilated configuration, which presents a greater increment of the indices. In particular, we observe that the values of the time-averaged wall shear stress and of the systolic jet asymmetry increase by approximatively 100 and 40%, respectively, when considering the leaflets.

Autoimmunity in ocular and generalised myasthenia gravis.

Restricted ocular myasthenia gravis (OMG) and generalised myasthenia gravis (GMG) have been shown to differ in a number of respects. In OMG, antiacetylcholine receptor, antistriational and antinuclear antibodies were rare relative to their frequency in GMG. In contrast, antithyroid antibodies and a history of thyroid disease were much more prevalent in OMG than in GMG, OMG was not associated with the female predominance seen in GMG and appeared to be relatively common in some races rather than others. It is suggested that different pathogenetic mechanisms are responsible for these two forms of MG.

Predictors of left ventricular outflow obstruction following single-stage repair of interrupted aortic arch and ventricular septal defect.

This study looked at echocardiographic predictors of left ventricular outflow obstruction after primary neonatal repair of interrupted aortic arch and ventricular septal defect. Results of this study indicate that the only significant independent predictor of left ventricular outflow obstruction is aortic valve diameter; all patients with an aortic valve diameter <4.5 mm (Z score <-5) subsequently developed obstruction, whereas patients with annuli >4.5 mm (Z score >-5) remained free from obstruction.

Bicuspid aortic valve disease and pulmonary autograft root dilatation after the Ross procedure: a clinicopathologic study.

OBJECTIVE: Bicuspid aortic valve disease has been associated with histologic abnormalities of the aortic root. Recent reports have suggested similar alterations may exist in the pulmonary artery of patients with bicuspid aortic valve. The present study was undertaken to define the histologic condition of the aortic and pulmonary artery root in bicuspid aortic valve disease and the relationship with pulmonary autograft root dilatation after the Ross procedure. METHODS: In 17 patients undergoing aortic root replacement with the pulmonary autograft, biopsy specimens of the aortic root and pulmonary artery trunk were collected. Clinical and histologic findings of patients with bicuspid aortic valves were compared with those with tricuspid aortic valves. RESULTS: There were 9 patients (8 male, 1 female) with bicuspid aortic valve (group 1) and 8 (all male) with tricuspid aortic valve (group 2). Mean age was comparable (24.4 +/- 9.8 vs 23.6 +/- 10.8 years, P =.9). Aortic insufficiency as an indication for operation was more common in group 1 (9/9 vs 5/8, P =.007), whereas preoperative aortic root dilatation was equally prevalent (4/9 vs 1/8, P =.1). Prior aortic valve repair had been performed in 2 patients (1/9 vs 1/8, P =.9). Prevalence of cystic medionecrosis of the aortic wall was similar in the 2 groups (4/9 vs 3/8, P =.6). Cystic medionecrosis of the pulmonary artery trunk was found only in 1 patient with tricuspid aortic valve (0/9 vs 1/8, P =.3). During a mean follow-up of 26.5 +/- 12.2 months (32.1 +/- 12.7 vs 20.1 +/- 7.4 months, P =.04), prevalence of pulmonary autograft root dilatation (greater than 4.0 cm) was equally represented in patients with native bicuspid or tricuspid aortic valve (3/9 vs 2/8, P =.6). CONCLUSIONS: Histologic abnormalities of the pulmonary artery root are rare and equally prevalent in young patients with bicuspid and tricuspid aortic valves. On the contrary, root dilatation is relatively common late after autograft root replacement but appears unrelated to bicuspid aortic valve disease or to pre-existing degenerative changes of the pulmonary artery root.

Predicting long-term functional results after myocardial revascularization in ischemic cardiomyopathy.

OBJECTIVE: The goal of the present study was to define the early and late functional results after revascularization in ischemic cardiomyopathy and to identify variables predictive of a favorable outcome. METHODS: A retrospective review of all consecutive patients with ischemic cardiomyopathy undergoing myocardial revascularization between January 1991 and June 1998 was undertaken. One hundred sixty-seven patients (140 men) aged 60 +/- 8 years (range, 39-77 years) with angina (n = 107), congestive heart failure (n = 54), or silent ischemia (n = 6) were identified. One hundred six (63%) patients with angina were in Canadian Cardiovascular Society class III or IV, and 40 (24%) patients with congestive failure were in New York Heart Association class III or IV. The preoperative left ventricular ejection fraction averaged 0.28 +/- 0.05 (range, 0.16-0. 30). Thirteen (8%) patients required preoperative mechanical life support. A mean of 2.9 +/- 0.9 grafts per patient were performed, with an average myocardial ischemia time of 53 +/- 23 minutes and bypass time of 104 +/- 31 minutes. RESULTS: There were 3 (1.7%) early deaths and 21 (13%) deaths during follow-up (2.7 +/- 2.1 years; range, 0.3-7.8 years), producing a survival of 94% +/- 2% and 75% +/- 10% at 1 and 5 years, respectively. Despite a significant increase in left ventricular ejection fraction (0.28 +/- 0.05 vs 0. 38 +/- 0.09, P =.0001), only 89 (54%) patients were symptom-free at follow-up. Freedom from recurrent angina was 98% +/- 1% and 81% +/- 8%, whereas freedom from congestive failure was 78% +/- 11% and 47% +/- 20% at 1 and 5 years, respectively. Follow-up New York Heart Association class in patients with congestive failure was improved (40/54 class III-IV vs 11/54 class III-IV, P =.0001). Multivariate analysis showed a lower ejection fraction (P =.01), preoperative congestive failure (P =.03), and a need for preoperative intra-aortic balloon pumping (P =.03) to be associated with a greater prevalence of recurrent congestive failure, whereas male sex (P =.01), preoperative angina (P =.04), use of the internal thoracic artery (P =.03), and higher number of grafts (P =.01) were associated with lower prevalence. Male sex (P =.06), higher number of grafts (P =.04), and shorter duration of myocardial ischemia (P =. 04) were also predictive of improvement in New York Heart Association class at follow-up. CONCLUSIONS: Despite satisfactory early and late survival, late functional outcome after myocardial revascularization in ischemic cardiomyopathy remains suboptimal because of recurrence or persistence of congestive failure. Selection of appropriate surgical candidates and extensive use of complete revascularization with the internal thoracic artery may substantially improve functional results.

The clamshell incision for bilateral pulmonary artery reconstruction in tetralogy of Fallot with pulmonary atresia.

BACKGROUND: Patients with tetralogy of Fallot/pulmonary atresia often have bilateral pulmonary artery lesions, including diminutive central and peripheral vessels, major aortopulmonary collaterals, and distortion from previous operations. Staged procedures through lateral thoracotomies and median sternotomies have traditionally been used for repair. METHODS: Between October 1993 and December 1995, 10 patients 3 months to 15 years old with complex tetralogy of Fallot/pulmonary atresia underwent repair via a clamshell approach. Nine had undergone a mean of 2.8 +/- 0.8 previous operations (range 1 to 4). Indications for operation were repair of pulmonary artery arborization anomalies in 10 (4 unilateral, 6 bilateral), with unifocalization in 6 (2 unilateral, 4 bilateral). RESULTS: Eight of 10 patients had concomitant complete repair. There were no deaths at a mean follow-up of 17.1 +/- 4.0 months (range 12 to 26). Mean ventilation time was 3.7 +/- 2.1 days (range 1 to 14) and hospital stay 8.7 +/- 4.6 days (range 4 to 19). At follow-up, the peak right ventricular/left ventricular pressure ratio in patients who received complete repair was 0.44 +/- 0.13 (0.30 to 0.67). One patient (10%) required reoperation because of pseudoaneurysm of the main pulmonary artery 14 months after repair, and one had successful stent placement because of recurrent left and right pulmonary artery stenosis 8 months after repair. Two infants who underwent complete unifocalization and central pulmonary artery reconstruction are awaiting completion of repair. CONCLUSIONS: The clamshell approach to complex tetralogy of Fallot/ pulmonary atresia provides simultaneous exposure of bilateral central and peripheral pulmonary artery lesions and intracardiac pathologic conditions. This procedure appears safe and may decrease the number of operations required to complete repair of tetralogy of Fallot/pulmonary atresia in selected patients.

Midterm results after aortic valve replacement with freehand stentless xenografts: a comparison of three prostheses.

OBJECTIVE: The ideal substitute for the diseased aortic valve is yet to be found. For the assessment and comparison of the midterm results after aortic valve replacement with three different types of freehand stentless xenografts, all patients who underwent the operation between October 1992 and April 1997 were reviewed. METHODS: Of 231 patients undergoing aortic valve replacement, 106 patients (group 1) were given the Biocor PSB (Biocor Industria e Pesquisa Ltda, Belo Horizonte, MG, Brazil); 76 patients (group 2) were given the Toronto SPV (St. Jude Medical, Inc., St. Paul, Minn.), and 49 patients (group 3) were given the O'Brien-Angell valve (Bravo Cardiovascular model 300, Cryolife, Inc., Marietta, Ga.). The first two xenografts require inflow and outflow suturelines; the third xenograft needs a single-sutureline implantation. Mean age (70 +/- 6 years; 70 +/- 7 years; 72 +/- 9 years; p = 0.6), prevalence of male sex (56 patients, 53%; 37 patients, 49%; 22 patients, 45%; p = 0.7), of aortic stenosis (72 patients, 68%; 54 patients, 71%; 37 patients, 73%; p = 0.6), and need for associated procedures (51 patients, 48%; 30 patients, 40%; 21 patients, 43%; p = 0.1) were comparable among groups. Mean aortic crossclamp time was shorter in group 3 (96 +/- 24 minutes; 100 +/- 23 minutes; 88 +/- 25 minutes;p = 0.01). RESULTS: Early deaths were 3 of 106 (3%) in group 1, 2 of 76 (3%) in group 2, and 2 of 49 (4%) in group 3. Follow-up of survivors ranged from 1 to 54 months (mean 32 +/- 13 months). Survival at 4 years was 90% +/- 3% in group 1, 95% +/- 3% in group 2, 85% +/- 8% in group 3 (p = 0.3). At 4 years, freedom from valve-related events was 95% +/- 6%, 100%, 70% +/- 8% (p = 0.004), while freedom from valve deterioration was 99% +/- 1%, 100%, 73% +/- 8% (p = 0.001), in group 1, 2, and 3, respectively (p = 0.001). At follow-up, reintervention on the xenograft was necessary in one patient (endocarditis) in group 1, none in group 2, and six in group 3 (technical cause, group 3; valve tear, group 2; pannus, group 1). Regression analysis showed O'Brien-Angell type of xenograft to be predictive of valve-related events (p = 0.02), valve deterioration (p = 0.001), and reoperation (p = 0.001) during follow-up. CONCLUSIONS: Midterm survival after stentless aortic valve replacement is good with all three xenografts. Freedom from valve-related events, valve deterioration, and reoperation are excellent with the Biocor PSB or the Toronto SPV stentless valves but less satisfactory with the O'Brien-Angell valve.

Donor shortage in heart transplantation. Is extension of donor age limits justified?

Chronic shortage of donor organs for heart transplantation led us to extend donor age limits. To verify the effectiveness of such a policy we have compared the results of heart transplantation in 45 patients with donors more than 40 years of age (group 1) with those of 72 patients older than 50 years of age who had heart transplantation with younger donors (group 2) between November 1985 and December 1992. The two groups were comparable in terms of mean recipient age, recipient and donor sex, and indication for heart transplantation. Mean donor age was 46 +/- 4 years (range 41 to 59 years) in group 1 and 23 +/- 7 years (range 8 to 39 years) in group 2 (p < 0.001). In group 1 cerebrovascular accidents were more common as the cause of donor death (60% versus 16%, p = 0.001), and no difference was found in ischemic time (144 +/- 47 minutes versus 140 +/- 48 minutes, p = not significant). There were 6 early (< 30 days) deaths in group 1 (13%) and 10 in group 2 (14%; p = not significant). Fatal acute graft failure was more prevalent, but not significantly so, in group 1 (10% versus 5.5%, p = not significant). Mean follow-up was 29 +/- 20 months (range 3 to 78 months) in group 1 and 30 +/- 20 months (range 3 to 80 months) in group 2 (p = not significant). At 5 years actuarial survival was 80% +/- 6% in both groups with comparable graft performance at echocardiographic and hemodynamic control studies. A significant difference was found in freedom from any type of coronary artery abnormality between group 1 (49% +/- 13%) and group 2 (77% +/- 8%) at 5 years (p < 0.05); however, freedom from coronary stenotic lesions only was similar. Major conduction disturbances have occurred more frequently in patients of group 1 (37% versus 12%; p = 0.003) without any difference in the need for permanent pacing. Donors older than 40 years of age can be accepted for heart transplantation with early and long-term results comparable with those obtained with younger donors. The impact of a higher incidence of coronary abnormalities on late performance of older grafts must be assessed at longer follow-up. Our results indicate that, because of the current organ shortage, extension of donor age limits is justified, even up to the sixth decade of life in selected cases.