History of surgery at the University of Vienna : The three surgical schools.

There are several publications on the history of surgery at the University of Vienna. None of these publications, however, sought to group the rich history of surgery in Vienna into distinct "surgical schools" of which, upon closer inspection, only 3 have emerged over the last 250 years. The oldest school dates back to Ferdinand Joseph von Leber and Vinzenz von Kern in the eighteenth and nineteenth centuries, the second school was founded by Theodor Billroth in 1867 and his student Anton Eiselsberg in 1900. The third school dates back to Jan Navratil, who was called to Vienna from Brno in 1967. Each of these schools is unique in that it maintained a degree of coherence, as knowledge, methodology and scientific focus were passed down in a chain of succession. These three schools also significantly influenced the rest of surgery in Vienna because most of the department chairs at the Vienna city hospitals or private hospitals were trained in one of these three schools.

One year follow-up of the multi-centre European PARTNER transcatheter heart valve study.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option in high-risk patients with severe aortic stenosis. AIMS: PARTNER EU is the first study to evaluate prospectively the procedural and mid-term outcomes of transfemoral (TF) or transapical (TA) implantation of the Edwards SAPIEN® valve involving a multi-disciplinary approach. METHODS AND RESULTS: Primary safety endpoints were 30 days and 6 months mortality. Primary efficacy endpoints were haemodynamic and functional improvement at 12 months. One hundred and thirty patients (61 TF, 69 TA), aged 82.1 ± 5.5 years were included. TA patients had higher logistic EuroSCORE (33.8 vs. 25.7%, P = 0.0005) and more peripheral disease (49.3 vs. 16.4%, P< 0.0001). Procedures were aborted in four TA (5.8%) and six TF cases (9.8%). Valve implantation was successful in the remaining patients in 95.4 and 96.4%, respectively. Thirty days and 6 months survival were 81.2 and 58.0% (TA) and 91.8 and 90.2% (TF). In both groups, mean aortic gradient decreased from 46.9 ± 18.1 to 10.9 ± 5.4 mmHg 6 months post-TAVI. In total, 78.1 and 84.8% of patients experienced significant improvement in New York Heart Association (NYHA) class, whereas 73.9 and 72.7% had improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores in TA and TF cohorts, respectively. CONCLUSION: This first team-based multi-centre European TAVI registry shows promising results in high-risk patients treated by TF or TA delivery. Survival rates differ significantly between TF and TA groups and probably reflect the higher risk profile of the TA cohort. Optimal patient screening, approach selection, and device refinement may improve outcomes.

Transapical minimally invasive aortic valve implantation: multicenter experience.

BACKGROUND: To evaluate initial multicenter results with minimally invasive transapical aortic valve implantation (TAP-AVI) for high risk patients with aortic stenosis. METHODS AND RESULTS: TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoro-femoral extracorporeal circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Edwards SAPIEN THV, Edwards Lifesciences) was used. Fifty-nine consecutive patients (81+/-6 years, 44 female) were operated on from 02/06 until 10/06 at 4 centers using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27+/-14%. TAP valve positioning was performed successfully in 53 patients, 4 required early conversion to sternotomy. Implantation (23-mm valves in 19 and 26-mm valves in 40 patients) was performed on the beating heart during brief periods of rapid ventricular pacing. Thirty-one patients were operated on without cardiopulmonary bypass. Neither coronary artery obstruction nor migration of the prosthesis was observed, and all valves had good hemodynamic function. Echocardiography revealed minor paravalvular leakage in 26 patients (trace in 11, mild in 12, and severe in 3). Eight patients died in-hospital (13.6%) without any valve dysfunction. Actuarial survival was 75.7+/-5.9% at a follow-up interval of 110+/-77 days (range 1 to 255 days). CONCLUSIONS: TAP-AVI can be performed safely with good early results in high risk patients. Long-term valve performance as well as broader based applications of this promising approach will need to be studied.

Mid-term results after endovascular stent-graft placement due to penetrating atherosclerotic ulcers of the thoracic aorta.

BACKGROUND: To determine mid-term durability of endovascular stent-graft placement in patients with penetrating atherosclerotic ulcers (PAU) involving the thoracic aorta and to identify risk factors for death as well as early and late cardiovascular events. METHODS: From 1997 to 2006, 27 patients (mean age 66 yrs) presented with PAU (rupture n=7). Mean numeric EuroScore was 11 and mean logistic EuroScore was 35. Median follow-up was 42 (10-86) months, being complete in all patients. Outcome variables included death and occurrence of early and late cardiovascular events. RESULTS: In-hospital mortality was 11%. Primary success rate was 100%. Actuarial survival rates at 1, 3 and 5 years were 93%, 78% and 70%, respectively. Hemodynamic instability (HR 2.5, 2.1-3.9; p=0.034) as well as logistic EuroScore (HR 2.8, 2.4-4.3; p=0.019) was identified as independent predictor of early and late cardiovascular events. CONCLUSIONS: Endovascular stent-graft placement in patients with PAU is an effective palliation for a life-threatening sign of a severe systemic process. Hemodynamic instability at referral and a high preoperative risk score predict adverse outcome. During mid-term follow-up, patients are mainly limited by sequelae of their underlying disease.

Low molecular weight heparin as an alternative to unfractionated heparin in the immediate postoperative period after left ventricular assist device implantation.

We present a regimen for anticoagulation in the immediate postoperative period after left ventricular assist device (LVAD) implantation using low molecular weight heparin (LMWH) as an alternative to unfractionated heparin. Between May and September 2007, eight consecutive patients undergoing LVAD implantation for advanced heart failure received the LMWH nadroparin. Nadroparin was given twice daily to achieve anti-Factor Xa activity target peak levels of 0.4 +/- 0.1 U/mL. The antiplatelet therapy consisted of aspirin (100 mg/day) and dipyridamole (3 x 75 mg/day). One patient underwent heart transplantation, three patients died, and four patients continued to receive device support. The median duration of support was 78 days (range, 46 to 174). No major bleeding was observed; minor bleeding occurred in three patients. In two patients, pump thrombosis was suspected. There were two ischemic and no hemorrhagic strokes. The use of LMWH may provide a new anticoagulation treatment option in the immediate postoperative period after LVAD implantation.

Post-transplant survival after lowering fixed pulmonary hypertension using left ventricular assist devices.

OBJECTIVE: We have previously shown that fixed pulmonary hypertension in cardiac transplant candidates can be lowered using left ventricular assist devices (LVADs). The post-transplant survival of these patients is uncertain as pulmonary hypertension may reappear, possibly affecting post-transplant survival. MATERIALS AND METHODS: Between 01/2000 and 01/2005 a total of 26 cardiac transplant candidates (92% male; mean age 56.2 years) in whom fixed pulmonary hypertension was lowered by LVAD implantation (pulmonary vascular resistance (PVR) before implantation: 5.1+/-2.8wood units (WU); PVR before cardiac transplantation: 2.0+/-.9WU) underwent cardiac transplantation at our institution. These patients were age and sex matched with 52 cardiac transplant candidates without pulmonary hypertension undergoing cardiac transplantation during the same time period. Study endpoints were peri-transplant complications and long-term survival. Mean follow-up was 36+/-14 months. RESULTS: Peri-transplant mortality was 5% in patients after LVAD therapy and 7% in patients without prior LVAD therapy (p=.089). We observed 2 cases (4%) of acute right heart failure requiring mechanical support in patients without prior LVAD therapy. None of the patients with LVAD therapy developed peri-transplant right heart failure requiring mechanical support. Incidence of other peri-transplant complications was comparable between the two groups. Log-rank (p=.124) revealed comparable long-term survival between patients with (1 year: 85%, 2 year: 85%, 3 year: 85%) and without (1 year: 90%, 2 year 82%, 3 year prior 79%) prior LVAD therapy. CONCLUSION: LVAD therapy lowers fixed pulmonary hypertension in cardiac transplant candidates with fixed pulmonary hypertension. Thereafter, long-term post-transplant survival is comparable to cardiac transplant recipients without pulmonary hypertension.

Mid-term results of supraaortic transpositions for extended endovascular repair of aortic arch pathologies.

OBJECTIVE: To evaluate mid-term results of supraaortic transpositions for extended endovascular repair of aortic arch pathologies. METHODS: From October 2002 to July 2006, 27 patients (mean age 72 years) with aortic arch diseases were treated (arch aneurysms n=18, type B dissections n=5, perforating ulcers n=4). Strategy for distal arch disease was autologous sequential transposition of the left carotid artery and of the left subclavian artery in 17 patients. Strategy for entire arch disease was total supraaortic rerouting using a reversed bifurcated prosthesis in 10 patients. Endovascular stent-graft placement was performed metachronously thereafter. RESULTS: Two in-hospital deaths occurred (myocardial infarction on the day prior to discharge n=1, rupture while waiting for stent-graft placement n=1). At completion angiography, all reconstructions were fully patent. Four patients had small type Ia endoleaks, two of them resolving spontaneously. Mean follow-up is 15 months (1-43 months). Three late deaths occurred (myocardial infarction n=2, sudden unknown death n=1). One-year survival was 83% and 3-year survival was 72%, respectively. Redo stent-graft placement was performed in one patient after 25 months (type III endoleak). The remaining patients had normal CT scans with regular perfusion of the supraaortic branches without any signs of endoleaks. CONCLUSIONS: Mid-term results of alternative treatment approaches in elderly patients with aortic arch pathologies are satisfying. Extended applications provide safe and effective treatment in patients at high risk for conventional repair.

Matrix metalloproteases and their tissue inhibitor in cardiac transplantation.

OBJECTIVE: Multiple studies have shown that matrix metalloproteases (MMPs) are involved in the pathologic reactions occurring as a consequence of cardiac transplantation, including ischemia-reperfusion injury and allograft rejection. This study sought to determine the temporal profile of MMP serum levels following cardiac transplantation. METHODS: Endomyocardial biopsies and serum samples were obtained from 66 recipients at 1, 2, 3, 4, 7, 12, 24, and 52 weeks post-transplant during the routine follow-up protocol, and MMP-1, MMP-8, MMP-9, and tissue inhibitor of metalloproteases (TIMP)-1 serum concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Immunosuppression comprised cyclosporine A (CyA; n=46) or tacrolimus (TAC; n=20) with mycophenolate mofetil and steroids. RESULTS: Increased MMP-8, MMP-9, and TIMP-1 serum levels were observed during the first 2 weeks following transplantation compared to the later time points. MMP-1 was increased at 2 and 3 weeks post-transplant compared to all later time points. No correlation of MMP or TIMP serum concentrations with infection episodes was observed. CONCLUSIONS: Early increase in MMP and TIMP serum levels following cardiac transplantation indicates involvement of these molecules in the reaction of the transplant to ischemia-reperfusion or early immunologic adaptation processes of the host. Further investigation of the relationship between MMP and TIMP serum levels and clinical conditions following transplantation including allograft rejection and hemodynamic graft function is necessary.

Inflammation and postinfarct remodeling: overexpression of IkappaB prevents ventricular dilation via increasing TIMP levels.

OBJECTIVE: Nuclear factor-kappa B (NF-kappaB) orchestrates genes involved in inflammation and extracellular matrix (ECM) remodeling following myocardial infarction (MI). The objective of the present study was to investigate the effect of overexpression and mode of function of IkappaB, the natural inhibitor of NF-kappaB, on ECM remodeling in a rat model of MI. METHODS: MI was induced in male Sprague-Dawley rats by ligation of the left anterior descending coronary artery (LAD) and was followed by adenovirus-mediated intramyocardial transfection of IkappaB (n = 26) or LacZ reporter genes (n = 26). Sham-operated animals (n = 14) served as controls. RESULTS: In transthoracic echocardiography 49 days after MI, systolic and diastolic left ventricular dimensions were reduced while fractional shortening was preserved in the treatment group. Additionally, evaluation on the isolated heart showed an attenuated downward shift of pressure-volume relationships in the IkappaB group compared to LacZ. NF-kappaB p65 DNA binding activity was diminished both at 5 and 49 days post-MI in the treatment group. Five days post-MI in the treatment group, protein levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were significantly reduced by 72.6% and 73.2%, respectively, compared to LacZ (p<0.05). In parallel, matrix metalloproteinase (MMP)-2 and MMP-9 levels were reduced 5 days post-MI, with MMP-9 still being decreased 49 days post-MI (p<0.01). In contrast, tissue inhibitors of metalloproteinases (TIMP)-1, -2, and -3 were increased compared to LacZ (p<0.01 and p<0.05, respectively) 5 days post-MI. After 49 days, TIMP-2, -3, and -4 expressions were significantly elevated (p<0.05). CONCLUSION: Reducing NF-kappaB activity via IkappaB overexpression after MI positively influences ECM remodeling by reducing MMP-2 and -9 levels while increasing TIMP-1, -2, -3, and -4 levels. Therefore, IkappaB overexpression prevents ventricular dilation and consequently preserves cardiac function.

Tissue engineering of heart valves: decellularized porcine and human valve scaffolds differ importantly in residual potential to attract monocytic cells.

BACKGROUND: Tissue-engineered or decellularized heart valves have already been implanted in humans or are currently approaching the clinical setting. The aim of this study was to examine the migratory response of human monocytic cells toward decellularized porcine and human heart valves, a pivotal step in the early immunologic reaction. METHODS AND RESULTS: Porcine and human pulmonary valve conduits were decellularized, and migration of U-937 monocytic cells toward extracted heart valve proteins was examined in a transmigration chamber in vitro. Homogenized tissue specimens were size fractionated by SDS-PAGE. The decellularization procedure effectively reduced the migration of human monocytes toward all heart valve tissue. However, only the antigen reduction of human pulmonary valves abolished the monocytic response (wall, 0.88+/-0.19% versus 30.20+/-3.93% migrated cells [mean+/-SEM]; cusps, 0.10+/-0.06% versus 10.24+/-1.83%) and was significantly lower (P<0.05) than that of the decellularized porcine equivalent (wall, 5.03+/-0.14% versus 24.31+/-2.38%; cusps, 3.18+/-0.38% versus 10.24+/-1.83%). SDS-PAGE of the pulmonary heart valve tissue revealed that considerable amounts of proteins with different molecular weights that were not detected in the human equivalent remain in the decellularized porcine heart valve. CONCLUSIONS: We describe for the first time that the remaining potential of decellularized pulmonary heart valves to attract monocytic cells depends strongly on whether porcine or human scaffolds were used. These findings will have an important impact on further investigations in the field of heart valve tissue engineering.

Granulocyte-based immune response against decellularized or glutaraldehyde cross-linked vascular tissue.

Supporting structures derived from biological tissue have been used in numerous tissue-engineering applications. This study focuses on the immune response of human leukocytes toward decellularized or glutaraldehyde (GA) cross-linked vascular tissue in vitro. Porcine and human pulmonary roots were sterilized with antibiotics, decellularized or cross-linked with GA. Proteins of the vascular tissue were extracted and the migratory response of human leukocytes toward protein extracts was examined using an in vitro migration chamber. Transmigrated leukocytes were counted and subsets (lymphocytes, monocytes, granulocytes) analyzed by flow cytometry. Decellularization significantly reduced the migration of monocytes compared to native porcine tissue. Although the proportion of transmigrating lymphocytes was much lower, decellularization again reduced the migratory response. Surprisingly, after decellularization granulocyte migration was still significantly higher than the negative control. Results comparable to those obtained with porcine material were found when human tissue was used for the experiments. Interestingly, migratory behavior toward extracts of GA-fixed porcine tissue was similar to that of decellularized specimens. We have shown that decellularization of vascular tissue reduces lymphocyte and monocyte recruitment comparable to cross-linking treatment. However, the migration of granulocytes, which are also known to be strongly involved in early inflammatory reactions, could be abolished neither by decellularization nor by fixation with GA.

Decellularization does not eliminate thrombogenicity and inflammatory stimulation in tissue-engineered porcine heart valves.

BACKGROUND AND AIM OF THE STUDY: In tissue engineering of heart valves using decellularized xenogenic valves, it has been suggested that cell elimination would result in a biologically inert matrix. The aim of this in-vitro investigation was to evaluate different decellularization methods in regard to the completeness of cell removal, inflammatory response, and thrombocyte activation. METHODS: Decellularized porcine Synergraft valves were compared with porcine pulmonary conduits decellularized with Triton X-100, sodium deoxycholate, Igepal CA-630 and ribonuclease. Completeness of decellularization was evaluated with staining for nuclei and alpha-Gal epitope. Decellularized heart valves with and without seeding with endothelial cells (ECs) were incubated with human platelet-rich plasma and stained for CD41 and PAC-1 to evaluate thrombocyte activation. Samples were processed for laser scanning microscopy (LSM) and scanning electron microscopy (SEM). Migration of human monocytic cells towards extracted valve proteins was tested. RESULTS: In contrast to the Synergraft, complete cell removal and elimination of the alpha-gal epitope was achieved with the new decellularization method. Numerous adherent and activated platelets were found on the decellularized matrix. This was inhibited by seeding with ECs. Even in completely cell-free valve tissue extracellular matrix proteins attracted human monocytic cells as in early inflammation, depending on whether porcine or human tissue was used. CONCLUSION: Important differences were found in the decellularization efficacy of treatment methods. However, even complete elimination of cells and their remnants did not result in a biologically inert matrix. The decellularized porcine heart valve matrix has the potential to attract inflammatory cells and to induce platelet activation. These findings suggest that it will be important to control the different inflammation-stimulating factors if porcine tissues are to be used successfully in tissue engineering.

Transposition of the supraaortic branches for extended endovascular arch repair.

BACKGROUND: Supraaortic branches limit extended application of endovascular aortic repair. For this purpose, we applied extensive reconstructions. METHODS: Between October 2002 and March 2005, 11 patients (mean age 72.3 years) presented with acute or chronic aortic diseases originating from the aortic arch (arch aneurysms n=8, type B dissections n=3). Treatment was by autologous sequential transposition of the left carotid artery into the brachiocephalic trunk and of the left subclavian artery into the already transposed left common carotid artery in nine patients and by additional reconstruction of the brachiocephalic trunk in two patients. Endovascular stent-graft placement was successfully performed thereafter. RESULTS: Procedure-related mortality was 0%. At completion angiography, all reconstructions were fully patent. One patient had a small type Ia endoleak that resolved spontaneously within one week. Mean follow-up was 18 months (1-29 months). One patient underwent redo stent-graft placement after 25 months due to a type III endoleak. The remaining patients had normal follow-up CT scans with regular perfusion of the supraaortic branches without any signs of endoleaks. CONCLUSIONS: Extended application of this technique will enable safe and effective treatment of a highly selected group of patients by avoiding conventional repair.

Apoptosis-specific activation markers in on- versus off-pump coronary artery bypass graft (CABG) patients.

BACKGROUND: The relation of epithelial/endothelial apoptosis and secretion of death-inducing receptors (DIR) in comparison to vascular adhesion molecules is not known in patients undergoing the On- versus Off-pump coronary artery bypass graft (CABG) procedure. METHODS: 30 patients were prospectively included in the study (On- vs. Off-pump CABG, each n = 15). Serum samples were obtained prior to, and 30 minutes, 60 minutes and 24 hours after CABG operation. ELISA was utilized to detect caspase-cleaved cytokeratin-18 (CK18) by means of M30 antibody, soluble VCAM-1, soluble ICAM-1, and soluble DIR TNFR-1 and CD95. RESULTS: Soluble caspase-cleaved CK18 was increased and leveled to initial values at 24 hrs. sICAM-1 showed a significant decrease at 30 minutes and 60 minutes in comparison to preoperative values. sTNFR-1/sCD95 showed a rise that was not significant to preoperative values. CONCLUSION: These results indicate for the first time that epithelial/endothelial apoptosis is occurring in patients undergoing bypass operation, irrespective of the CABG procedure selected.

Neurocognitive function in patients with ventricular assist devices: a comparison of pulsatile and continuous blood flow devices.

The effect of successful ventricular assist device (VAD) implantation on neurocognitive function in terminal heart failure is uncertain. Additionally, the different impact of continuous versus pulsatile blood flow devices is unknown. A total of 29 patients (mean age 53 years), surviving implantation of a ventricular assist device as bridge to transplantation were prospectively followed (continuous flow: Micromed DeBakey, n = 11; pulsatile flow: Thoratec and Novacor, n = 18). Normative data were obtained in 40 age- and sex-matched healthy subjects (mean age 54 years). Neurocognitive function was objectively measured by means of cognitive P300 auditory evoked potentials before operation (baseline), at intensive care unit (ICU) discharge, and at the 8-week and 12-week follow-up. Before implantation of the VAD, cognitive P300 evoked potentials were impaired (prolonged) compared with age- and sex-matched healthy subjects (p < 0.001). After successful VAD implantation, P300 evoked potentials markedly improved compared with before operation (ICU discharge, p = 0.007; 8-week follow-up, p = 0.022; 12-week follow-up, p < 0.0001). Importantly, there was no difference between continuous and pulsatile VADs (before operation, p = 0.676; ICU discharge, p = 0.736; 8-week follow-up, p = 0.911 and 12-week follow-up, p = 0.397; respectively). Nevertheless, P300 peak latencies did not fully normalize at 12-week follow-up compared with healthy subjects (p = 0.012). Successful VAD implantation improves neurocognitive impairment in patients with terminal heart failure. Importantly, this effect is independent of the type of VAD (pulsatile vs. continuous blood flow).

The incidence of reoperations in pacemaker recipients.

OBJECTIVE: To evaluate the incidence of reoperation due to complications or battery depletion in patients who underwent endocardial permanent pacemaker implantation during an 8-year period. METHODS: All pacemaker implantation and related procedures from January 1996 to June 2003 were retrospectively collected and entered into a database. During this time period a total number of 3856 operations with 2242 primary implantations and 1614 redo operations were performed at our department. As 809 patients were referred from another hospital, where the primary operation was done, these patients were excluded from further analysis. The mean follow-up time was 48 months, ranging from 6 to 96 months. RESULTS: A total of 547 patients underwent 805 reoperations during this 8-year period. The most common cause for reoperation was lead malfunction, which occurred in 326 patients (8.4%). Atrial leads were affected more commonly (206 patients, 63%) than ventricular leads (120 patients, 37%). Eighty percent of lead failure occurred during the first 3 months after implantation and was due to dislocation of the lead, whereas the remaining 20% occurred more than 3 months after implantation and were caused by lead fracture, insulation failure, and exit block. Elective replacement indication of a pacemaker was necessary in 312 patients (8%), and pacemaker pocket erosion or infection required reoperation in 167 patients (4%). CONCLUSION: Permanent pacemaker implantation is now accepted as a highly effective and safe procedure. However, cost effectiveness and the relatively simple procedure have to be weighed against the need of reoperations due to system malfunction or replacement indication.

Predictors of adverse outcome and transient neurological dysfunction following surgical treatment of acute type A dissections.

Predictors of adverse outcome after replacement of the ascending aorta with resection of the intimal tear and open distal anastomosis were analyzed in 167 patients (109 male, median age 56). Median hypothermic circulatory arrest (HCA) time was 30 minutes (range 12 to 113). Eighty-six patients (pts) had surgery within 24 hours and 81 within 72 hours of symptom onset. Thirty-seven pts had only ascending aortic replacement, 128 had hemiarch repair, and in 2 the entire arch was replaced. The aortic valve was replaced in 37 pts, resuspended in 116, and untouched in 14. Either death or permanent neurological dysfunction was considered an adverse outcome (AO). AO occurred in 30.5% (51/167) of patients overall. Multivariate analysis revealed that the only significant (P<0.05) independent preoperative predictor of AO was hemodynamic instability (OR 6.0). Transient neurological dysfunction (TND) occurred in 19 of 116 patients (16.4%). Significant predictors of TND were increasing age >60 (OR 3.4 and 7.0 in the second and third tertile as compared with the lowest tertile) and coronary heart disease (OR 3.4). Cumulative survival of patients (median follow-up 34 months) was 55% at 1, 49% at 5, and 44% at 8 years, indicating an excessive in-hospital mortality, but excellent long term outcome. Surgical treatment of acute type A dissections is still associated with a high incidence of adverse outcome, but results in excellent long-term survival. Earlier diagnosis, before the development of cardiac tamponade and hemodynamic compromise, is critical to improve the operative salvage rate.

Optimizing ischemia/reperfusion in the failing rat heart--improved myocardial protection with acute ACE inhibition.

BACKGROUND: Whereas the number of patients with reduced left ventricular function after myocardial infarction who need revascularization is increasing, the operative outcome is still inadequate. Consequently, drugs that increase myocardial perfusion and decrease oxygen consumption of the remodeled myocardium are of particular interest to cardiac surgeons. Angiotensin-converting enzyme inhibitors (ACE-I) provide this pharmacologic profile. This study tests the hypothesis whether acute ACE inhibition during cardioplegic arrest improves outcome in failing rat hearts. METHODS AND RESULTS: Male Wistar rats (260+/-15 g) underwent coronary ligation. Ten weeks later the rats had developed heart failure (HF). Hearts were harvested and studied on a red cell-perfused working heart: 60 minutes of ischemia, protected by cold blood cardioplegia (CP) every 20 minutes, and 45 minutes of reperfusion. Rats were randomly assigned to 2 groups, 1 group receiving the ACE-I quinaprilat with CP (QuinaMI, n=11), and 1 group receiving CP only (MI, n=8). Hemodynamic recovery, high-energy phosphates (HEP), and morphometry were analyzed. Groups showed similar degrees of myocardial infarction (44+/-5 versus 39+/-4% of LVmass), LVEDP (5.0+/-1 versus 4+/-1 mm Hg) and no differences in baseline values such as external heart work (EHW) and coronary flow (CF). At the end of reperfusion, EHW and CF were significantly higher in QuinaMI than MI (P<0.05 and 0.01), LVEDP had returned to baseline in QuinaMI (P<0.01). HEP were significantly higher preserved in QuinaMI than MI (P<0.05). CONCLUSIONS: Acute ACE inhibition during CP improves postischemic systolic and diastolic function, coronary perfusion as well as HEP-levels in a rat model of HF. These results may have clinical impact on patients with HF undergoing cardiac surgery.

The decellularized porcine heart valve matrix in tissue engineering: platelet adhesion and activation.

An approach in tissue engineering of heart valves is the use of decellularized xenogeneic matrices to avoid immune response after implantation. The decellularization process must preserve the structural components of the extracellular matrix to provide a biomechanically stable scaffold. However, it is known that in vascular lesions platelet adhesion to extracellular matrix components occurs and platelet activation is induced. In the present study we examined the effects of a decellularized porcine heart valve matrix on thrombocyte activation and the influence of re-endothelialisation in vitro. Porcine pulmonary conduits were decellularized using Triton X-100, Na-deoxycholate and Igepal CA-630 followed by a ribonuclease digestion. Cryostat sections of decellularized heart valves with and without seeding with human umbilical vein endothelial cells (HUVEC) were incubated with platelet rich plasma. Samples were either stained with fluorescent antibodies for CD41 and PAC-I (recognizing the activated fibrinogen receptor) or fixed with glutaraldehyde. Thereafter, the samples were processed for laser scanning microscopy (LSM) or scanning electron microscopy (SEM). Examination by LSM showed numerous platelets with co-localized staining for CD41 and PAC-1 on the nonseeded decellularized heart valve matrix whereas after seeding with endothelial cells no platelet activation was detected. SEM revealed platelet adhesion and aggregate formation only on the surface of the non-seeded or partially denuded matrix specimens. We show in this study that the decellularized porcine matrix acts as a platelet-activating surface. Seeding with endothelial cells effectively abolishes the platelet adhesion and activation and therefore is necessary to eliminate thrombogenicity in tissue engineered heart valves.

Surgical ablation of atrial fibrillation with off-pump, epicardial, high-intensity focused ultrasound: results of a multicenter trial.

BACKGROUND: A simplified alternative to the Cox maze procedure to treat atrial fibrillation with epicardial high-intensity focused ultrasound was evaluated clinically, and the initial clinical results were assessed at the 6-month follow-up visit. METHODS: From September 2002 through February 2004, 103 patients were prospectively enrolled in a multicenter study. Atrial fibrillation duration ranged from 6 to 240 months (mean, 44 months) and was permanent in 76 (74%) patients, paroxysmal in 22 (21%) patients, and persistent in 5 (5%) patients. All patients had concomitant operations, and ablation was performed epicardially on the beating heart before the concomitant procedure. The device automatically created a circumferential left atrial ablation around the pulmonary veins in an average of 10 minutes, and an additional mitral line was created epicardially in 35 (34%) patients with a handheld device by using the same technology. RESULTS: No complications or deaths were device or procedure related. There were 4 (3.8%) early deaths and 2 late extracardiac deaths. The 6-month follow-up was complete in all survivors. At the 6-month visit, freedom from atrial fibrillation was 85% in the entire study group (80% in patients with permanent atrial fibrillation, 88% in the 35 patients who had the additional mitral line, and 100% in patients with paroxysmal atrial fibrillation). A pacemaker was implanted in 8 patients. Only the duration and type of atrial fibrillation significantly increased the risk of recurrence. CONCLUSION: Epicardial, off-pump, beating-heart ablation with acoustic energy is safe and cures 80% of patients with permanent atrial fibrillation associated with long-standing structural heart disease.