Faculty Bibliography

BACKGROUND: For minimally invasive cardiac operations to be widely applicable, the risks must be equivalent to those of standard open-chest operations. This study analyzed the outcomes of patients recorded in the multicenter Port Access (PA) International Registry to establish operative risks. METHODS: Data were analyzed for intent to treat in 583 patients who underwent PA coronary artery bypass grafting (CABG), 184 who underwent PA mitral valve replacement, and 137 who underwent PA mitral valve repair at 121 centers. RESULTS: Port Access was attempted in 1,063 patients and completed in 1,004 (94%). The operative mortality rate was 1% for PA CABG, 3.3% for PA mitral valve replacement, and 1.5% for PA mitral valve repair. Perioperative morbidity was low in all categories: stroke = 1.1% to 3.6%, myocardial infarction = 0 to 1%, primary procedure reoperation = 0 to 0.7%, renal failure = 0.2% to 0.7%, multiorgan failure = 0 to 0.5%, and atrial fibrillation = 5% to 7.3%. CONCLUSIONS: Data on 1,063 patients from 121 centers demonstrate that PA CABG and PA mitral valve operations can be performed safely, with morbidity and mortality rates similar to those associated with open-chest operations. Further studies are indicated to establish the long-term efficacy of this method and to analyze its effect on recovery time

Coexisting pectus deformity and congenital heart disease is not uncommon. Traditionally, the approach to this problem has been to repair each one with a separate surgical procedure because of fear of increased complications from bleeding, infections, and anesthesia. More recently, many reports of successful combined repair have been published, particularly in adults with coronary artery or aortic pathology. The authors wished to determine the feasibility of this combined procedure in younger patients, particularly those with a severe pectus deformity. Three patients underwent repair, including a 17 year old with Marfan's syndrome and a severe pectus excavatum deformity. The postoperative course was smooth for these patients, and all had good short- and long-term (over 18 months) results

BACKGROUND: Endothelial damage, such as that associated with balloon angioplasty or preparation of veins for bypass grafts, results in intimal hyperplasia. Growth factors and cytokines that modulate endothelial cell functions through various intracellular signaling pathways mediate rapid endothelial repair, which may prevent or reduce restenosis. Here we investigated the effect of mechanical injury of endothelial cells on the mitogen-activated kinase signaling pathways, extracellular-signal-regulated kinases (ERKs), C-Jun N-terminal kinase (JNK/SAPK), and p38. METHODS: Confluent human umbilical vein endothelial cells or bovine aortic endothelial cells were wounded with a razor blade; mitogen-activated kinase activation was monitored by immunoblotting with antibodies to active ERK, JNK/SAPK, or p38. RESULTS: Wounding of human umbilical vein endothelial cell or bovine aortic endothelial cell monolayers resulted in rapid (5-minute) activation of ERK-1 and -2, which was abolished by monoclonal antibody to basic fibroblast growth factor (FGF-2). This antibody or an inhibitor of ERK activation, PD98059, also blocked endothelial cell migration after the wounding. Thus FGF-2-induced ERK activation mediates the endothelial response to wounding. CONCLUSIONS: ERK-1 and -2 are activated by FGF-2 released from endothelial cells in response to injury. Therapeutic strategies aimed at reducing FGF-2-induced intimal hyperplasia should preserve ERK activation in endothelial cells while abolishing it in smooth muscle cells

Dissection of the ascending aorta is usually associated with severe chest and/or back pain. We describe three young men, with pathologically proven cystic medial necrosis, who presented with atypical clinical symptoms and ascending aortic dissection diagnosed by MR imaging and surgery. Patients with cystic medial necrosis and aortic dissection may not present with a classic acute chest pain syndrome

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

BACKGROUND: We reviewed the initial patient series of three institutions performing large volume port-access (PA) coronary artery bypass grafting (CABG) to evaluate the efficacy of this new procedure. METHODS: From October 1996 until June 1998, 302 consecutive patients underwent isolated CABG using the PA approach. Patients (mean age 60.7 years) were predominantly male (77.5%) and received a mean of 2.3 distal anastomoses; few were New York Heart Association class III or IV (15.9%). The distribution of the number of grafts was: 76 (25.2%) single, 110 (36.4%) double, 73 (24.2%) triple, and 43 (14.2%) four or more bypass grafts. The Society of Thoracic Surgeons (STS) Database data collection form was used prospectively by all three institutions to define patient risk factors and record outcomes. RESULTS: Total 30-day hospital mortality was 0.99% compared to the STS-database-model-predicted risk of 1.2%. Complication rates for the PA CABG patients compared with risk-matched morbidity rates from the STS data for CABG alone were: reoperation for bleeding, 3.3% versus 1.9%; ventilatory support more than 1 day, 1.7% versus 3.8%; stroke, 1.7% versus 1.2%; and perioperative transmural myocardial infarction 0% versus 1.3%. CONCLUSIONS: The STS CABG risk-adjusted model demonstrates that the 30-day mortality for patients undergoing PA CABG is lower than predicted for traditional CABG patients (confidence intervals not available). Likewise, the morbidity was low, with minimal ventilatory support, pulmonary complications, and atrial fibrillation. The port-access technique is an acceptable strategy for multivessel bypass grafting

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.