Faculty Bibliography

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: 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

The recent development of endovascular catheters that are placed via the femoral artery and vein has enabled patients to be placed on cardiopulmonary bypass without the need for direct visualization of the heart or great vessels via sternotomy. This has allowed cardiac surgery to be performed through smaller, thoracotomy incisions. Placement of these catheters initially was performed under fluoroscopic guidance, which has major imaging limitations. Now, transesophageal echocardiography (TEE) has replaced fluoroscopy as the primary imaging technique to assist in the placement of endovascular catheters during minimally invasive, port-access cardiac surgery. In our institution, 449 port-access procedures have been performed from May 1996 through July 1998. We found that TEE is able to adequately visualize the cardiac structures and assist in the placement of the endovascular catheters in all patients. Fluoroscopy is helpful only as an aid to the use of TEE for placement of the coronary sinus catheter

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.

BACKGROUND: Although minimally invasive techniques for valvular surgery have rapidly come into widespread use, whether such an approach can be safely applied to elderly patients remains an open question. To help resolve this issue, we reviewed our experience with minimally invasive port access (MIPA) valve surgery in elderly patients and compared it to the results obtained with the standard sternotomy (STD) approach in the same age group. METHODS: From January 1994 through December 1998, 370 consecutive patients at least 70 years of age underwent isolated aortic or mitral valve surgery at our institution. The standard sternotomy operative approach was used in 259 patients (mean age 77.5 years) and the minimally invasive port access approach was used in 111 patients (mean age 76.0; p=.006). A mitral valve procedure was performed more often in the MIPA patients than in the STD patients (49.5% vs. 35.9%; p < .001). RESULTS: Hospital mortality was comparable in the two groups, 9.7% (25/259) in the STD group and 7.2% (8/111) in the MIPA group (p = .50), as was the incidence of many perioperative complications. The MIPA group, however, had a significantly lower incidence of sepsis or wound complications (1.8% vs 7.7%; p = .027), required less fresh frozen plasma transfusion (median 1.0 unit vs 2.0 units; p =.04), and had a shorter length of hospital stay (11.6 days vs 17.6 days; p = .001). CONCLUSIONS: These results indicate that with appropriate surgical techniques the MIPA approach for isolated valve surgery can be safely applied to the elderly patient population with excellent results. In our initial experience the MIPA approach is associated with significantly less plasma transfusion, fewer postoperative complications, and shorter length of hospital stay

BACKGROUND: In younger patients requiring mitral valve replacement (MVR), mechanical prostheses (MPs) have been reported to give better freedom from all valve-related complications (VRCs) because of the high incidence of late valve degeneration (VD) associated with bioprostheses (BPs). In older patients, however, the risk of VD may be reduced because of the large competing risk of noncardiac death (NCD). Previous studies on VD in the elderly have used actuarial analysis, which overestimates the risk of VD in this population because it assumes that dead patients are still at risk. In contrast, cumulative incidence (actual) analysis acknowledges that patients who die have no risk of VD. This study compares the results of both 'actual' and 'actuarial' analyses of the freedom from VD in elderly patients undergoing MVR. METHODS AND RESULTS: From June 1976 through January 1996, 504 patients > or = 70 years of age underwent MVR at our institution. Isolated mitral operations were performed in 159 patients, and 169 had concomitant CABG. Hospital mortality was 59 of 374 (15.9%) for tissue prosthesis versus 24 of 130 (18.5%) for mechanical prosthesis (P = NS). For tissue versus mechanical prosthesis, 10-year freedom from noncardiac death was 75.0% versus 67.6% (P = NS); 10-year actuarial freedom from valve degeneration was 79.8% versus 93.4% (P = NS); 10-year actual freedom from valve degeneration was 92.6% versus 95.4% (P = NS); and 10-year actual freedom from all VRCs was 84.4% versus 92.3% (P = NS). CONCLUSIONS: In elderly patients undergoing MVR, actuarial analysis overestimates the 10-year risk of VD compared with actual analysis (20.2% versus 7.4% for BP, 6.6% versus 4.6% for MP). In these patients, the actual freedoms from VD and all VRCs do not differ significantly between BP and MP. Thus, in this age group, the necessity for anticoagulation or its avoidance may be the predominant factor in choosing a replacement mitral valve