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Previous Volume 333:1111-1116 October 26, 1995 Number 17 Next

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ABSTRACT

Background An aggressive and potentially fatal form of coronary artery disease may develop after cardiac transplantation. We studied the role of vascular tissue plasminogen activator (t-PA), the primary mediator of fibrinolysis, in the development of this problem.

Methods We studied 78 consecutive recipients of cardiac allografts over a five-year period, and we collected follow-up data over a mean (±SE) of 32.5±2.0 months. The patients were studied with ventricular function tests, serial endomyocardial biopsies (16.6±0.5 per patient), and annual coronary angiography. Measurements of t-PA and its inhibitor were performed immunocytochemically on unfixed cryostat sections of endomyocardial-biopsy specimens with the use of monoclonal antibodies to t-PA and its inhibitor.

Results In biopsy specimens obtained during the first three months of follow-up, 38 allografts had a normal distribution of t-PA in arteriolar smooth-muscle cells, whereas in 40 allografts there was depletion of t-PA that persisted in subsequent follow-up. Coronary artery disease developed during follow-up in 31 of 40 allografts (78 percent) with depletion of t-PA, but the disease developed in only 9 of the 38 allografts (24 percent) with normal t-PA levels (P<0.001). Allografts with depletion of t-PA also had the t-PA inhibitor and were at greater risk for earlier and more severe disease than were allografts with normal arteriolar t-PA levels. Twelve patients whose allografts were depleted of t-PA either received a second transplant or died, whereas only one of the patients whose allografts had persistently normal t-PA levels died (P<0.001).

Conclusions These findings reveal an association between the depletion of t-PA from arteriolar smooth-muscle cells and the subsequent development of coronary artery disease and decreased graft survival. Although we cannot be certain about a cause-and-effect relation, our data suggest a possible role for deficient fibrinolysis in the development of coronary artery disease in transplanted human hearts.

Source Information

From the Center for Reproduction and Transplantation Immunology (C.A.L., W.P.F.), the Department of Transplantation (D.P.), and the Center for Health Services Research (D.R.N.), Methodist Hospital of Indiana, Indianapolis.

Address reprint requests to Dr. Faulk at the Center for Reproduction and Transplantation Immunology, Methodist Hospital, 1701 N. Senate Blvd., Indianapolis, IN 46202.

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