Elevated Wall Shear Stress in Aortic Type B Dissection May Relate to Retrograde Aortic Type A Dissection: A Computational Fluid Dynamics Pilot Study.

OBJECTIVE: Retrograde aortic type A dissection (RTAD) is a known complication in patients with aortic type B dissection. The purpose of this computational fluid dynamics (CFD) study was to identify haemodynamic risk factors for the occurrence of RTAD. METHODS: Computed tomographic angiography (CTA) images of 10 patients with type B dissections, who subsequently developed a RTAD, were retrospectively analysed together with patients constituting a control group (n = 10) where no further vascular events after the initial type B dissection occurred. CFD simulations were conducted based on 3D surface models of the aortic lumen derived from CTA datasets. For both groups, pressures, velocity magnitudes and wall shear stress (WSS) were compared at the site of the future RTAD entry tear and the surrounding aortic wall. RESULTS: WSS at the site of the future entry tear was significantly elevated compared with the surrounding wall (15.10 Pa vs. 5.15 Pa, p < .001) and was significantly higher in the RTAD group than in the control group (6.05 Pa, p < .002). Pressures and velocity magnitudes were not significantly elevated at the entry tear (3825.8 Pa, 0.63 m/s) compared with the aortic arch (3549.8 Pa, 0.50 m/s) or control group (3501.7 Pa, 0.62 m/s). CONCLUSIONS: Increased WSS accompanies the occurrence of RTAD. The results merit the design for a prospective study to confirm whether WSS is a risk factor for the occurrence of RTAD.

[Genetics and prevention of genetic aortic syndromes (GAS) and of the Marfan syndrome]. / Genetik und Prävention am Beispiel genetischer Aortensyndrome (GAS) und des Marfan-Syndroms.

BACKGROUND: Genetic aortic syndromes are autosomal-dominantly heritable aneurysms of the thoracic aorta, which carry a high risk of aortic rupture or acute thoracic aortic dissection at young age. OBJECTIVES: We introduce the reader to the principles of genetic diagnostics and the medical and surgical prevention of thoracic aortic dissection in patients with genetic aortic syndromes. METHODS: A cardiologist, a health economist, a patient representative, a heart surgeon, and a molecular geneticist teamed up to elucidate their perspective on major aspects of genetics and prevention of genetic aortic syndromes. RESULTS: Genetic aortic syndromes reflect a broad spectrum of diverse disease entities comprising the Marfan syndrome, the Loeys-Dietz syndrome or the vascular Ehlers-Danlos syndrome. The diagnosis of each respective disease entity requires combined assessment of phenotype and genotype information. A medical prevention of aortic complications such as dissection is mandatory although a curative therapy currently appears unlikely in humans. The single most important measure against acute aortic dissection is the preventive replacement of the aortic root, where valve preserving techniques appear preferable. Comprehensive prophylaxis including molecular diagnostics seem reasonable also from an economic point of view. DISCUSSION: Optimal prevention requires individualization of concepts, which entail a detailed diagnostic characterization of each specific genetic aortic syndrome including characterization of the genotype.

[German Registry for Acute Aortic Dissection Type A (GERAADA): initial results]. / Deutsches Register für akute Aortendissektion Typ A (GERAADA): Erste Ergebnisse.

BACKGROUND: The working group "Aortic Surgery and Interventional Vascular Surgery" of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) set up the German registry for acute aortic dissection type A (GERAADA) in July 2006. This web-based database was developed to record data of patients who had undergone surgery for aortic dissection type A (AADA). The aim of GERAADA is to learn from analyzing the data of AADA patients how to improve the perioperative management and surgical treatment of patients with AADA and to identify possible parameters affecting patient risk and outcome. PATIENTS AND METHODS: Between July 2006 and June 2009 (2010), 1558 (2137) patients with AADA were enrolled in the multi-center, prospective GERAADA database by 50 cardiac surgery centers in German-speaking countries in Europe. Data on patients' preoperative and intraoperative status, postoperative complications, midterm results and circumstances of death were recorded. Data were analyzed to identify risk factors influencing the outcome of these patients. The Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) in Mainz performed the statistical analyses. RESULTS: Analyses from GERAADA reveal a thirty-day mortality of 17% in 2137 AADA patients. Only short interventions in aortic arch surgery are safe during hypothermic circulatory arrest even without selective cerebral perfusion. If circulatory arrest times of over 30 min. are anticipated, antegrade cerebral perfusion is strongly recommended during the entire arch intervention using cardiopulmonary bypass. Surgical strategy in terms of isolated ascending aortic replacement versus ascending aortic replacement combined with aortic arch repair had no statistical relevant influence on 30-day mortality. AADA surgical results in elderly patients are more encouraging than those treated without surgery. Surgery is even feasible in octogenarians with a 35% mortality rate. CONCLUSION: The aim of this registry is to optimize AADA patients' medical care, thereby reducing their morbidity and mortality. AADA treatment should always involve open surgery. Initial analyses from GERAADA provide clinically relevant insights concerning patients with AADA, and may enable therapeutic recommendations for improving perioperative and surgical management. Our latest study detected significant influencing risk factors for the outcome of AADA patients and may contribute to a consensus in setting guidelines for standard medical treatment. PERSPECTIVE: A European Registry of Aortic Diseases ("EuRADa") is being established this year under the leadership of the "Vascular Domain" of the European Association for Cardio-Thoracic Surgery (EACTS). This database will collect parameters on all aortic diseases, dissection types A and B, aneurysms, perforating ulcer (PAU), intramural wall hematoma (IMH), traumatic aortic ruptures, and all potential treatment strategies (medical treatment, open surgical and endovascular).

[Modern aortic surgery in Marfan syndrome--2011]. / Moderne Aortenchirurgie beim Marfan-Syndrom 2011.

Marfan syndrome is a hereditary disease with a prevalence of 2-3 in 10,000 births, leading to a fibrillin connective tissue disorder with manifestations in the skeleton, eye, skin, dura mater and in particular the cardiovascular system. Since other syndromes demonstrate similar vascular manifestations, but therapy may differ significantly, diagnosis should be established using the revised Ghent nosology in combination with genotypic analysis in specialized Marfan centres. The formation of aortic root aneurysms with the subsequent risk of acute aortic dissection type A (AADA) or aortic rupture limits life expectancy in patients with Marfan syndrome. Therefore, prophylactic replacement of the aortic root needs to be performed before the catastrophic event of AADA can occur. The goal of surgery is the complete resection of pathological aortic tissue. This can be achieved with excellent results by using a (mechanically) valved conduit that replaces both the aortic valve and the aortic root (Bentall operation). However, the need for lifelong anticoagulation with Coumadin can be avoided using the aortic valve sparing reimplantation technique according to David. The long-term durability of the reconstructed valve is favourable, and further technical improvements may improve longevity. Although results of prospective randomised long-term studies comparing surgical techniques are lacking, the David operation has become the surgical method of choice for aortic root aneurysms, not only at the Heidelberg Marfan Centre. Replacement of the aneurysmal dilated aortic arch is performed under moderate hypothermic circulatory arrest combined with antegrade cerebral perfusion using a heart-lung machine, which we also use in thoracic or thoracoabdominal aneurysms. Close post-operative follow-up in a Marfan centre is pivotal for the early detection of pathological changes on the diseased aorta.

German Registry for Acute Aortic Dissection Type A (GERAADA)--new software design, parameters and their definitions.

BACKGROUND: The working group for aortic surgery and interventional vascular surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) initiated the web-based German Registry for Acute Aortic Dissection type A (GERAADA). It is the project's aim to collect standardized data from a large pool of patients with acute aortic dissections type A (AADA) to gain a deeper insight and knowledge to improve surgical therapies and perioperative management for these patients in the future. METHODS: In addition to new medical insights, the working group has gained more experience over the last 4 years in how to collect valid and high-quality data. This experience led us to revise the database completely. In this article we describe the new version of GERAADA, providing an overview as well as defining the parameters, and explaining the new features. This overview fulfills a request by the users of GERAADA in the participating centers. RESULTS: Since its inception, 50 cardiac centers in Germany, Austria and Switzerland have provided over 2000 records and the first statistical results have been published. CONCLUSION: GERAADA's new design allows it to stay abreast of changes in medicine and to focus on the essentials necessary for statistically relevant results, while keeping the work load low for the data providers at each cardiac center.

German registry for acute aortic dissection type A (GERAADA)--lessons learned from the registry.

A German registry for acute aortic dissection type A (GERAADA) was initiated by the Working Group for Aortic Surgery and Interventional Vascular Surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) in July 2006. This web-based database was developed to record the data of patients who had undergone surgery for aortic dissection type A. From analyzing the data, we aim to learn how to improve surgical treatment and to identify parameters affecting patient outcome. In the beginning, 33 cardiac centers participated via online access to the registry on the GSTCVS' homepage. Since then, 43 centers in Germany, Switzerland and Austria have begun entering data on the pre- and intraoperative status of their patients, postoperative complications, mid-term results and circumstances of death. We have succeeded in interpreting the initial results and trends from the registry now available to all of the participating centers, which benefit from this shared pool of analyzed data by optimizing their therapy regimes and comparing their success with that in the other centers.

Intraoperative bypass graft angiography: cooperation between cardiologist and surgeons in the operation room for optimal postoperative results -- is this the way for the future?

OBJECTIVE: To confirm the quality of total arterial CABG carried out using the left internal thoracic artery (LITA) and a radial artery (RA) T-graft and distal anastomoses immediately in the OR, we developed a new technique using intraoperative graft angiography. METHODS: A 5-Fr sheath is inserted in the proximal radial artery stump, through which a catheter for LITA angiography is later introduced. From July 2004 to March 2005, 23 patients underwent total arterial CABG with the T-graft and intraoperative graft angiography. RESULTS: On-pump CABG was performed in 22 patients and off-pump CABG in 1 patient. Mean procedure time for the angiography was 13.7 +/- 7.3 minutes, and mean fluoroscopy time was 6.2 +/- 4.6 minutes. In two patients, the RA-marginal artery side-to-side anastomosis was stenosed and had to be revised as demonstrated by graft angiography. In one patient, the RA was kinked and in another, there was a kinking of the LITA. In both cases, kinking was corrected. The remaining anastomoses were seen to have unobstructed flow with no evidence of stenosis. CONCLUSIONS: Intraoperative graft angiography can be performed in patients undergoing total arterial CABG. This concept of intraoperative cooperation between an interventional cardiologist and surgeons could significantly improve the operative outcome in CABG surgery.

Acute aortic dissection versus aortic root aneurysm: comparison of indications for valve sparing aortic root reconstruction.

OBJECTIVES: To prove whether different indications for valve sparing aortic root reconstruction may have an impact on the outcome and longevity of the repair. METHODS: From July 1993 to March 2003, the reimplantation technique for valve sparing aortic root reconstruction was applied to 232 patients. In 44 patients, indication for operation was acute aortic dissection type A (AADA). These patients were compared with 44 randomised patients operated for aortic root aneurysm (root) by matched pair analysis with respect to age, gender, time point of operation and presence of Marfan's syndrome. Peri- and post-operative courses with focus on survival and valvular stability were analysed. RESULTS: Pre-operative grade of aortic insufficiency was 2.4+/-1 in root vs. 1.5+/-1.7 in AADA (P = 0.004) Mean CPB-time (214+/-60 vs. 171+/-42 min;P < 0.001), aortic cross clamp time (158+/-40 vs. 129+/-39 min; P = 0.001) and stay on ICU (5.2+/-9 vs. 1.7+/-1 days; P = 0.034) were longer for AADA, while hospitalisation was comparable (14+/-10 vs. 14+/-7 days; P = 0.88). Five patients (11.4%) from AADA died peri-operatively compared to no patient from root (P = 0.055). None of the early deaths were valve-related. Re-thoracotomy rate was 6.8% for both groups. Mean follow-up was 19+/-21 months for AADA vs. 28+/-21 months for root (P = 0.038) Survival at 3 years was 88+/-5% for AADA and 100% for root (P = 0.028). Freedom from valvular reoperation was 97+/-2.7% for root and 97+/-3% for AADA at 3 years (P = 0.44). At last investigation, mean grade of aortic insufficiency for AADA was 0.2+/-0.3 compared to 0.3+/-0.3 for root (P = 0.34) CONCLUSIONS: Regardless of the underlying indication, the aortic valve preserving reimplantation technique can be performed with favourable functional results.

Acellularized porcine heart valve scaffolds for heart valve tissue engineering and the risk of cross-species transmission of porcine endogenous retrovirus.

OBJECTIVE: Acellularized porcine heart valve scaffolds have been successfully used for heart valve tissue engineering, creating living functioning heart valve tissue. However, there is concern about the possibility of porcine endogenous retrovirus transmission. In this study we investigated whether acellularized porcine heart valve scaffold causes cross-species transmission of porcine endogenous retrovirus in a sheep model. METHODS: Acellularized porcine pulmonary valve conduits (n = 3) and in vitro autologous repopulated porcine pulmonary valve conduits (n = 5) were implanted into sheep in the pulmonary valve position. Surgery was carried out with cardiopulmonary bypass support. The animals were killed 6 months after the operation. Blood samples were collected regularly up to 6 months after the operation and tested for porcine endogenous retrovirus by means of polymerase chain reaction and reverse transcriptase-polymerase chain reaction. In addition, explanted tissue-engineered heart valves were tested for porcine endogenous retrovirus after 6 month in vivo. RESULTS: Porcine endogenous retrovirus DNA was detectable in acellularized porcine heart valve tissue. However, 6 months after implantation of in vitro and in vivo repopulated acellularized porcine heart valve scaffolds, no porcine endogenous retrovirus sequences were detectable in heart valve tissue and peripheral blood. CONCLUSION: Acellularized porcine matrix scaffolds used for creation of tissue-engineered heart valves do not transmit porcine endogenous retrovirus.

Impact of preoperative aortic root diameter on long-term aortic valve function after valve sparing aortic root reimplantation.

BACKGROUND: Valve sparing aortic root reimplantation technique in patients with aortic root aneurysm have shown excellent mid-term results. In conjunction with the diameter of the aortic root the mechanical leaflet stress increase, which might have an impact on long-term aortic valve function after valve sparing aortic root reimplantation. METHODS AND RESULTS: From July 1993 to October 2001, 168 patients with aortic root aneurysm underwent valve sparing aortic root reimplantation. Patients with type A aortic dissection were excluded. Thus, 123 patients were analyzed. We identified 47 patients with an preoperative aortic root diameter exceeding 60 mm (group A), 58 patients with an diameter between 50 and 60 mm (group B), and 18 patients with a diameter less than 50 mm (group C). The groups were compared regarding mortality, long-term survival, freedom from reoperation, freedom from severe and moderate aortic valve insufficiency (AI), and postoperative morbidity. Mean follow-up (group A 43+/-26 months, group B 40+/-25 months, group C 23+/-19 months; group C versus group A, P=0.005; group C versus group B, P=0.011) was shorter in group C. Perioperative mortality (group A 2.2%, group B 1.9%, group C 5.2%; P=ns) was comparable between the groups with each one patient. The 3-year survival for group A was 98+/-2%, for group B 96+/-3%, and for group C 100+/-0% (P=ns). Freedom from reoperation for group A was 98+/-2%, for group B 96+/-3%, and for group C 88+/-8% (P=ns). Four patients developed severe or moderate AI, thus freedom from severe and moderate AI for group A was 100+/-0%, for group B 88+/-8%, and for group C 94+/-5% (P=ns). During follow-up no thromboembolic or bleeding events were noticed. CONCLUSIONS: Our data show that the preoperative diameter of the aortic root has no impact on the longevity of the repair. Thus, the reimplantation technique can be recommended for all patients presenting with an aortic root aneurysm and normal leaflets regardless of the aortic root diameter.

Acute dissection of the ascending aorta: first results of emergency valve sparing aortic root reconstruction.

OBJECTIVE: Acute dissection of the ascending aorta requires immediate surgical intervention. In this study, we report our first results with valve sparing aortic root reconstruction removing all the diseased tissues. METHODS: From August 1995 to December 2000, 22 patients with acute aortic dissection of the ascending aorta (Stanford type A) underwent valve sparing aortic root reconstruction. Their ages ranged from 20 to 76 years (52+/-15, 68% males). Dissection was found in the ascending aorta (3 patients) or both in the ascending aorta and aortic arch (19 patients; 86%). Course and length of hospitalization, echocardiographic and clinical follow-up, complications and mortality were analysed. RESULTS: Mean cardiopulmonary bypass time was 212+/-56 min (134-352 min), mean aortic cross clamp time was 157+/-24 min (114-205 min). In patients undergoing additional arch replacement (n=19), circulatory arrest was 35+/-18 min (11-75 min). After reconstruction, intraoperative echocardiography showed aortic insufficiency (AI) grade 0 in 16 patients (84%) and grade 1 in three patients (16%). Stay in intensive care unit was 2.1+/-0.7 days, and postoperative hospitalization was 21+/-14.4 days. There were three perioperative deaths (14%). Mean post-operative follow-up was 18.4+/-18 months (0.4-65.4 month). One patient died 10 months postoperatively. At follow-up, no patient suffered AI grade 2 or higher, and no reoperation for aortic valve failure was necessary. All patients presented with a favorable exercise tolerance being in New York Heart Association functional class I or II. CONCLUSION: Valve sparing aortic root reconstruction in patients with type A dissection can be performed with acceptable intraoperative mortality and morbidity and excellent results during follow-up. The complete resection of the diseased aorta is particularly appealing.

Valve sparing aortic root reconstruction versus composite replacement -- perioperative course and early complications.

OBJECTIVE: In patients with aneurysm of the ascending aorta, dilatation of the sinotubular junction is the major cause of aortic valve regurgitation. Valve sparing aortic root replacement in patients without valvular structural defects offers a new form of treatment. The aim of this study was the assessment of the perioperative course and early complications of this method compared to composite replacement in a large single center cohort. METHODS: From 1992 to 1999, valve sparing replacement of the ascending aorta (recon) has been performed in 78 patients, while 269 patients underwent replacement by a composite graft (comp). A comparison of matched pairs (n=52) with respect to age, gender, presence of Marfan's syndrome, aortic dissection as well as date of surgery, was chosen. Aortic insufficiency was 2.8+/-0.7 for recon vs. 2.2+/-1.1 for comp preoperatively. Course and length of hospitalization, echocardiographic follow-up, complications, and mortality were compared at 1-year follow-up. RESULTS: There were no operative deaths. During follow-up, one patient (2%) died 5 months postoperatively (recon) vs. two patients (3.9%) in the comp group. Bypass-time (123+/-31 vs. 153+/-31 min, P<0.0001) and cross-clamp-time (82+/-22 vs. 120+/-23 min, P<0.0001) were significantly shorter in comp. Stay in ICU (1.9+/-1.6 for recon vs. 2.3+/-2.1 days for comp) and post-op hospitalization (18.3+/-5.7 vs. 21.2+/-11.1 days) were comparable. Improvement of NYHA-class was significant after both operations (recon 2.6+/-0.8 vs. 1.3+/-0.5 and for comp 2.4+/-0.6 vs. 1.5+/-0.7, both P<0.0001). One patient (1.9%) in the recon group had to be reoperated for valve failure. Thrombembolic or bleeding complications were observed in 6 patients (12%) in comp, zero in recon (P=0.027). CONCLUSION: Valve sparing aortic root reconstruction is feasible with low perioperative morbidity and mortality and good early results. Major advantages of recon are significant reduction of thrombembolic and anticoagulation related complications as opposed to longer cross-clamp and bypass times as well as a valve failure in one patient. Further follow-up is needed to confirm our data in a long-term perspective.

[Replacement of the ascending aorta with aortic valve reimplantation: indications, technique and results]. / Aortenklappenrekonstruktion mit Aorta-ascendens-Ersatz. Indikation, Technik und Ergebnisse.

The main cause of aortic valve insufficiency is a dilatation of the sinotubular junction in patients with an ascending aortic aneurysm. Morphologically preserved aortic valve cusps represent an ideal condition for preservation and reconstruction of the aortic valve with an simultaneous replacement of the ascending aorta with a Dacron graft. This report presents the results of 140 patients, who underwent such surgery since 1993 in our institution. Indications for surgery, operative technique and different outcome parameters are discussed. Intra- and perioperative morbidity and mortality are low and quality of life excellent. Reoperation due to progressive aortic valve insufficiency was necessary in 2.1% of patients during follow-up. When compared with the standard operation (composite replacement utilizing a mechanical valve), patients with aortic valve reconstruction demonstrate similar results with regard to hospital stay and functional improvement. However, bleeding complications and thromboembolic events are significantly reduced in patients undergoing valve reconstruction. Due to these long-term results combined with excellent stress hemodynamics and improvement in LV function, aortic valve reconstruction currently represents our standard operative strategy in this patient group.

[Modified endothelial cells in graft vasculopathy]. / Modifizierte Endothelzellen bei Graftvaskulopathie.

Occlusion of venous bypass grafts after coronary revascularization grafting represents the main reason for re-do operations. Arterial pressure as well as mechanical injury of the venous wall lead to endothelial dysfunction, causing intimal hyperplasia with luminal stenosis and eventually occlusion. In the transplanted heart, coronary artery disease limits the long-term success of cardiac transplantation. The disease is characterized by the interaction of activated immunologic cells and donor epicardical and microvascular endothelium. The ex vivo modification of endothelial cells may offer a therapeutic option to overcome both kinds of graft vasculopathy. Seeding of human endothelial cells on artificial and bioartificial acellularized vessel matrices has proven possible. The use of xenogenic matrices initially acellularized and recellularized with autologic endothelial cells and myofibroblasts may help to overcome the lack of vascular and valvular grafts with long durability. In addition, gene therapeutic methods to modify the function of such endothelial cells may offer a new therapeutic strategy, such as over-expression of nitric monoxide or inhibition of matrix metalloprotinases. First results of large animal studies show promising results and may lead to the first clinical trials in the near future.

[Replacement of the ascending aorta with aortic valve reimplantation - indication, technique, and results]. / Aortenklappenrekonstruktion mit Aorta-ascendens-Ersatz Indikation, Technik und Ergebnisse.

The main cause of aortic valve insufficiency is a dilatation of the sinotubular junction in patients with an ascending aortic aneurysm. Morphologically preserved aortic valve cusps represent an ideal condition for preservation and reconstruction of the aortic valve with an simultaneous replacement of the ascending aorta with a Dacron graft. This report presents the results of 140 patients, who underwent such surgery since 1993 in our institution. Indications for surgery, operative technique and different outcome parameters are discussed. Intra- and perioperative morbidity and mortality are low and quality of life excellent. Reoperation due to progressive aortic valve insufficiency was necessary in 2.1% of patients during follow-up. When compared with the standard operation (composite replacement utilizing a mechanical valve), patients with aortic valve reconstruction demonstrate similar results with regard to hospital stay and functional improvement. However, bleeding complications and thromboembolic events are significantly reduced in patients undergoing valve reconstruction. Due to these long-term results combined with excellent stress hemodynamics and improvement in LV function, aortic valve reconstruction currently represents our standard operative strategy in this patient group.

Impact of heparin bonding on pediatric cardiopulmonary bypass: a prospective randomized study.

BACKGROUND: Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass in adult patients; however, little is known about its effects in the pediatric population. Two studies were performed to assess this technology's impact on inflammation and clinical outcomes. METHODS: In a pilot study, complement and interleukins were measured in 19 patients who had either uncoated cardiopulmonary bypass circuits or heparin-bonded circuits. Subsequently, 23 additional patients were studied in a randomized fashion. Respiratory function and blood product utilization were recorded. RESULTS: In the pilot study, heparin-bonded circuit patients had less complement 3a (p < 0.001) and interleukin-8 (p < 0.05) compared with uncoated cardiopulmonary bypass circuit patients. The randomized study revealed that the heparin-bonded circuit was associated with reduced complement 3a (p = 0.02). Multiple variable analysis revealed that the following postoperative variables were increased with bypass time (p = 0.01) and diminished with heparin-bonded circuits: interleukins (p = 0.01), peak airway pressures (p = 0.05), and prothrombin time (p = 0.03). CONCLUSIONS: Heparin-bonded circuits significantly reduce cytokines and complement during cardiopulmonary bypass and lower interleukin levels postbypass; they were also associated with improved pulmonary and coagulation function. Heparin-bonded circuits ameliorate the systemic inflammatory response in pediatric patients from cardiopulmonary bypass.

Comparison of post-operative pain, stress response, and quality of life in port access vs. standard sternotomy coronary bypass patients.

OBJECTIVE: Although it has been postulated that minimally invasive cardiac surgery using the port access method would reduce operative stress and postoperative pain and accelerate postoperative recovery to a good quality of life, few data are currently available to document this intuitively appealing claim. Therefore, this study was designed to examine differences in stress response, postoperative pain, rapidity of recovery, and quality of life after port access (PA) isolated coronary artery bypass surgery compared with standard sternotomy (STD) isolated coronary bypass surgery. METHODS: Fourteen PA and 15 STD coronary bypass patients were studied postoperatively for pain score, FEV, catecholamine and cortisol levels, resumption of activity, and Duke Activity Scale ratings. The surgical approach was based on the surgeon's preference. Although the PA patients were younger, there were no other differences between the groups in gender or preoperative risk factors. RESULTS: There were no operative deaths and no differences between the groups in perioperative complications. Repeated measures analysis of variance showed lower pain scale ratings over the first 4 postoperative weeks in the PA group (P < 0.001). The PA patients also had less muscle soreness, shortness of breath, fatigue, and poor appetite at 1, 2, 4, and 8 weeks (P < 0.05), better FEV at 1 day (1.59 vs. 0.97 l/s; P < 0.02) and 3 days (2.20 vs. 1.49 l/s; P < 0.03), and lower norepinephrine levels at days 1, 2, and 3 (P = 0.005). The Duke Activity Scale questionnaire results demonstrated that more PA patients were able to walk 1-2 blocks at 1 week, climb stairs at 1 and 2 weeks, perform light or moderate housework at 1 and 2 weeks, and engage in moderate recreational activities and perform heavy housework at 4 and 8 weeks (P < 0.05). CONCLUSIONS: These results show that compared with STD coronary bypass patients PA patients enjoyed significant postoperative physiologic and quality of life advantages with less pain, less early stress response, better pulmonary function, and superior Duke Activity scores during the first 2 postoperative months.

Inhibition of endothelial cell migration by gene transfer of tissue inhibitor of metalloproteinases-1.

BACKGROUND: Angiogenesis requires degradation of the vessel's basal lamina and endothelial cell migration into the tissue stroma. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play important roles in this process. MMP activity is tightly regulated during vessel growth. This work was designed to characterize the effect of TIMP-1 upregulation on endothelial cell invasion of the extracellular matrix. METHODS: We constructed replication-deficient recombinant adenoviruses that encode either TIMP-1 (Ad.TIMP-1) or Escherichia coli lac Z (Ad.beta gal) cDNA. Bovine aortic endothelial (BAE) cells were infected with 100 infectious particles/cell. Gene expression was assessed by Northern and Western blotting. TIMP-1 activity in cell-conditioned media was measured by a resorufin-labeled casein protease assay. BAE cell migration was measured by Boyden chamber assays with 0.2% gelatin-coated, 8. 0-mcm polycarbonate membranes. RESULTS: TIMP-1 was overexpressed by Ad.TIMP-1-infected BAE cells relative to control, Ad. beta gal-infected or uninfected cells. TIMP-1 activity in Ad.TIMP-1 cell-conditioned medium was 2.8-fold higher than in control cells. By Boyden chamber assays with gelatin-coated membranes, Ad. TIMP-1-infected BAE cells showed 89.97 +/-1.64% (mean +/- SEM) reduction in migration relative to Ad.beta gal-infected cells (P < 0. 02) and 90.53 +/- 1.12% relative to uninfected cells (P < 0.02). Without gelatin coating, migration was equivalent in all groups. CONCLUSION: The replication-deficient recombinant adenovirus we constructed affords rapid and efficient upregulation of functional TIMP-1 in endothelial cells. Infection results in a dramatic decrease in cell migration and invasion of extracellular matrix. Thus, such a recombinant vector may provide a useful tool for the gene therapy of vascular remodeling and inhibition of angiogenesis.