No abstract

These results show that elevated pulmonary vascular resistance and pulmonary parenchymal injury are mediated at least in part by antispecies antibody and heat-sensitive pathways. They are consistent with the hypothesis that complement activation contributes significantly to acute lung damage in the pig-to-human species combination.

Prominent components of vascularized xenograft rejection such as platelet activation and microvascular thrombosis may be dependent upon thrombin generation in vivo. To study potential therapeutic benefits of a synthetic low-molecular-weight thrombin inhibitor, SDZ MTH 958, in hyperacute porcine heart rejection by human blood ex vivo, a working model of hyperacute rejection of porcine by fresh, heparinized (6 microM/ml) human blood with or without 1 microM SDZ MTH 958 was used. Thrombin-antithrombin complexes (TAT) and prothrombin fragment F1.2 levels as markers of thrombin activation were determined, and biopsies from rejected hearts were analyzed by immunohistopathology. Control porcine hearts (n=8) underwent a rapid and consistent decline in cardiac output, ceasing function by 60 min. Experimental cardiac output values of 14 ml/g (SEM 1.2) were significantly higher than seen in controls (5 ml/g SEM 0.6) after 5 min of cardiac work, and prolonged survival times up to 120 min were noted (P<0.05). Activity of SDZ MTH 958 was confirmed by functional assays throughout perfusion. Levels of TAT and F1.2 increased consistently in control samples when compared with plasma samples containing SDZ MTH 958. Immunohistopathological examination confirmed diminished fibrin deposition, reduced leukocyte adherence to endothelium, impaired diapedesis and less tissue necrosis in the hearts perfused with SDZ MTH 958. SDZ MTH 958, in this xenoperfusion model, prolonged survival, enhanced function of the explanted organ, and improved histological features at the time of rejection. Effective and specific antagonism of thrombin may be useful as an adjunct therapy to complement inhibition for xenograft rejection

As a potential source of organs for xenotransplantation, pigs that are transgenic for human decay accelerating factor (DAF) have been bred in order to overcome hyperacute rejection. We investigated the protective effect of human DAF in a porcine working heart model perfused by human blood. Hearts of normal landrace pits served as controls. The following parameters were measured: stroke work index, coronary flow and arteriovenous oxygen consumption, 6-keto prostaglandin F1alpha and prostaglandin E2 as markers of endothelial cell activation; creatine phosphokinase and lactate dehydrogenase for evaluation of the extent of myocardial damage; TNFalpha and IL-6 as markers of mononuclear cell activation. Histological and ultrastructural investigations from myocardial tissue sections were done at the end of perfusion. Human (h) DAF appeared to inhibit complement-mediated endothelial cell activation of transgenic pig hearts successfully. This was in contrast to landrace pig hearts, which had a sixfold increase of prostaglandin levels during perfusion with human blood. The cardiac weight increase during perfusion time due to interstitial edema tended to be less in the hDAF group. Myocardial damage was minimal in transgenic hearts, whereas normal pig hearts produced a threefold increase of creatine phosphokinase and lactate dehydrogenase levels. In these hearts, electron microscopy revealed single cell necrosis of myocytes and vacuolization of mitochondria with cristae rupture. According to the results obtained in the working heart model, the breeding of pigs that are transgenic for hDAF represents a promising step to making heart xenotransplantation a clinical reality in the future.

BackgroundThe Medtronic Evolut R (EVR) is a novel transcatheter heart valve designed to allow precise implantation at the intended position and to minimize prosthesis dysfunction as well as procedural complications. Our aim was to compare short-term functional and clinical outcomes of the new EVR with the established Medtronic CoreValve (CV) system.Methods and resultsOf 151 patients undergoing transfemoral transcatheter aortic valve implantation with a self-expanding valve at our institution between January 2013 and January 2016, 86 were treated with EVR and 65 with CV. Patients treated with EVR had a significantly lower rate of more-than-mild aortic regurgitation and a higher rate of device success. Recapture maneuvers to optimize valve deployment were performed in 22.1% of the EVR procedures. Transvalvular post-procedural gradients were slightly higher in the EVR group, while no differences were observed in the incidence of safety endpoints at 30 days, vascular complications, or need for permanent pacemaker implantation following asystole or complete atrioventricular block.ConclusionsThese initial single-center experience data on the short-term outcomes after EVR valve implantation show a substantially reduced rate of more-than-mild paravalvular regurgitation and higher device success, while 30-day safety outcomes were similar to the CV system. Clinical outcome data from long-term follow-up and larger scale multicenter experience are now necessary.

Background and Purpose-Emboli and proinflammatory mediators are suspected of generating cerebral edema after coronary surgery. In contrast to cardiopulmonary bypass (CPB), off-pump coronary artery bypass surgery (OPCAB) reduces microemboli count and proinflammatory mediator release but carries the risk of hemodynamic instability. A microaxial blood pump can augment cardiac output. Methods-Coronary bypasses were constructed in pigs with CPB and cardioplegia (nϭ9), OPCAB (nϭ9), or blood-pump support CAB (nϭ9). Nine animals underwent sham operation. Embolus count was monitored and regional cerebral blood flow was assessed with microspheres in 21 brain specimens per animal (nϭ189 per group). Interleukins 6 and 8 and tumor necrosis factor-␣ concentrations were determined. These variables were studied before, during, and for 4 hours after surgery. Finally, cerebral water content was determined. Results-During CPB and blood-pump CAB, a significant number of emboli were counted in contrast to OPCAB and controls (PϽ0.05). During CPB, regional cerebral blood flow was affected (32 of 189) and showed reactive hyperemia except in 10 specimens after aortic cross-clamp release. This impairment persisted in 20 specimens. During and after OPCAB, regional cerebral blood flow remained nearly unchanged but showed low flow during (58 of 189) and after (35 of 189) the blood-pump run. A significant increase in proinflammatory mediators was observed only in the CPB group. CPB and blood-pump CAB significantly increased cerebral water content (PϽ0.05). A strong correlation between embolic load and cerebral water content was observed in all groups. No correlation between proinflammatory mediator release and cerebral water content was detected. Conclusions-Emboli formation rather than inflammatory mediators are responsible for increased cerebral water content after conventional and assisted beating-heart myocardial revascularization. (Stroke. 2008;39:213-219.)

ECC led to hemodynamic impairment with post-ischemic reactive hyperemia. OPCAB created hemodynamic depression but left RMP unchanged. Hemodynamic depression can be reduced by the Impella pump, however regional myocardial blood flow is decreased.

Background: Median sternotomy is the most frequently used incision for cardiac procedures but carries a substantial risk for deep sternal wound infections and/or sternal dehiscence. In contrast to previous studies that examined risk factors for sternal infections this study evaluates factors that lead to poor outcome after surgical revision of the non healing sternum. Methods: Between 1985 and 1999, 193 adults (mean age 64 ± 9 years, m/f = 3/1) necessitated sternal revisions (incidence 1.93%). Pre-, intra- and post-operative risk factors were evaluated for their influence on the outcome after sternal revision. Results: 65 of the 193 patients had a complicated course: ten (5.2%) died due to sepsis/multi organ failure ( n = 6) or cardiac causes ( n = 4). 32 patients (16.6%) needed several revisions, 17 (9%) were discharged with sternal instability, 5 (3%) with chronic fistula and one with persistent osteomyelitis. Univariate and multivariate analysis identified cardiopulmonary resuscitation (odds ratio ( OR) = 11.188, p = 0.010), corticoid treatment ( OR = 7.043, p = 0.0055), diabetes ( OR = 4.130, p = 0.0128), smoking history ( OR = 2.996, p = 0.0041), renal insufficiency (hazard ratio ( HR) = 1.884), old age ( OR = 1.108, p = 0.0266), high body mass ( HR = 1.06), ECC time ( p = 0.023), cross clamp time ( p = 0.028), systemic hypothermia ( p = 0.016), non-use of IMA ( p = 0.042) or prolonged ventilation as risk factors for mortality or poor outcome. No correlation between sternal closure technique, mediastinal irrigation or antibiotic therapy and outcome after mediastinal revision could be found. Conclusions: To avoid disappointing results after sternal revision one should aim to preoperatively identify high-risk patients and aggressively address risk factors. This rather than modifications of the surgical and medical approach might improve the outcome of patients with mediastinal complications.