Faculty Bibliography

OBJECTIVE: Polymorphonuclear leukocyte (PMN) infiltration and microvascular injury are hallmarks of the tissue remodeling associated with multiple organ failure. These processes require the concerted action of various proteolytic enzymes, including serine and matrix metalloproteinases (MMPs). Matrix metalloproteinase-2 (MMP-2) plays an important role in the turnover of various ECM components, including type IV collagen, fibronectin, and gelatins. Like all MMPs, MMP-2 is secreted as an inactive zymogen (proMMP-2) and activated extracellularly by limited proteolytic cleavage. The physiologic mechanism(s) of proMMP-2 activation remains unclear. This study was designed to characterize the effect of PMNs on the activation of proMMP-2 produced by endothelial cells. METHODS: PMNs and human umbilical vein endothelial cells (HUVECs) were grown either separately or together for 2-16 h. To evaluate the role of cell-cell contact, cocultures were also established in which the two cell types were separated by a semipermeable polycarbonate membrane. Alternatively, PMN-conditioned medium was added to HUVEC cultures with or without various proteinase inhibitors (aprotinin, 1,10-phenanthroline, Batimastat, E-64, eglin c peptide, or pepstatin A). After incubation, the culture supernatants were analyzed by gelatin zymography to characterize the gelatinases. RESULTS: HUVECs produce MMP-2 in its inactive (72 kDa) form. PMNs produce high levels of MMP-9 (gelatinase B, 92 kDa) but no MMP-2. Coculture of PMNs with or addition of PMN-conditioned medium to HUVECs results in the production of active (62 kDa) MMP-2. ProMMP-2 activation by PMN-conditioned medium is not blocked by inhibitors of plasmin, cysteine-, acid-, or metalloproteinases. CONCLUSION: PMNs release a soluble factor that activates endothelial cell MMP-2 through a novel mechanism independent of cell-cell contact and not attributable to the activities of plasmin, cysteine-, acid-, or metalloproteinases. These findings may provide insight into the tissue remodeling that accompanies PMN-mediated microvascular injury

In this study, we sought to determine the use of transesophageal echocardiography (TEE) as the primary imaging technique to assist in the placement of endovascular catheters during minimally invasive, port-access cardiac surgery. 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 has previously been performed with fluoroscopic guidance, which has major imaging limitations. Thirty-six patients underwent port-access cardiac surgery at our institution during the study period. All patients underwent intraoperative TEE. We used TEE to visualize the coronary sinus os, right atrium and superior vena cava, and thoracic aorta to assist with placement of the coronary sinus catheter, venous cannula, and endoaortic clamp. Twenty patients underwent mitral valve surgery, 14 patients coronary artery bypass grafting, 1 patient aortic valve replacement, and 1 patient repair of an atrial septal defect by the port-access approach. TEE was able to adequately visualize the cardiac structures and assist in the placement of the endovascular catheters in all patients. Fluoroscopy was only helpful as an aid to TEE for placement of the coronary sinus catheter. TEE is an excellent imaging modality for the proper placement of these new endovascular catheters, obviating the need for fluoroscopy, except to be on standby and for placement of the coronary sinus catheter