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EXPERIMENTAL STUDIES

The potent platelet inhibitory effects of S-nitrosated albumin coating of artificial surfaces

Nabil Maalej, PhD^*, Ralph Albrecht, PhD^*, Joseph Loscalzo, MD, PhD, FACC and John D. Folts, PhD, FACC

^* University of Wisconsin Medical School, H6/379 CSC, 600 Highland Avenue, Madison, Wisconsin, USA
Coronary Thrombosis Research Laboratory, H6/379 CSC, 600 Highland Avenue, Madison, Wisconsin, USA
Boston University School of Medicine, 88 E Newton Street, Boston, Massachusetts, USA

Manuscript received January 13, 1998; revised manuscript received November 6, 1998, accepted December 23, 1998.

Reprint requests and correspondence: John D. Folts, Coronary Thrombosis Research Laboratory, University of Wisconsin Medical School, H6/379 CSC, 600 Highland Ave., Madison, Wisconsin 53792
jdf{at}medicine.wisc.edu

OBJECTIVES

We studied the antithrombotic effect of coating glass, collagen and metal stent surfaces with bovine serum albumin (BSA) covalently modified to carry S-NO functional groups denoted (pS-NO-BSA).

METHODS

Video-enhanced light microscopy was used to visualize canine blood platelet adhesion and aggregation in a parallel plate glass chamber. Platelet adhesion was observed for 60 min on glass, glass coated with BSA, glass coated with pS-NO-BSA, collagen I (CO) surface, CO coated with BSA and CO coated with pS-NO-BSA. We also coated Palmaz-Shatz (P-S) stents with pS-NO-BSA. Coated and uncoated stents were then immersed in porcine platelet-rich plasma for two min and the platelet cyclic GMP level was measured. In six anesthetized pigs, coated and uncoated stents were placed in the carotid arteries and [¹¹¹In]-labeled platelets were circulated for 2 h. The stented arteries were then removed and placed in a gamma well counter.

RESULTS

There was significantly less platelet attachment, adhesion and aggregation on the pS-NO-BSA coated surfaces compared with the BSA coated and uncoated surfaces. The pS-NO-BSA coating increased the platelet cGMP levels to 5.9 ± 0.7 pmoles/10⁸ platelets compared with 2.7 ± 0.9 pmoles/10⁸ platelets for control (p < 0.01). The average gamma ray count from [¹¹¹In]-labeled platelets that attached to the coated stents was 90,000 ± 42,000/min and 435,000 ± 290,000/min for the uncoated stents (p < 0.01).

CONCLUSIONS

The pS-NO-BSA coating of thrombogenic surfaces reduces platelet adhesion and aggregation, possibly by increasing the platelet cGMP. This inhibitory effect appears to be a consequence of the direct antiplatelet actions of NO combined with the antiadhesive properties of albumin.

Abbreviations and Acronyms   BSA = bovine serum albumin   pS-NO-BSA = BSA covalently modified to carry multiple S-NO functional groups   EDRF = endothelium-derived relaxing factor   NO = nitric oxide   P-S = Palmaz-Shatz   PRP = platelet rich plasma   TCA = trichloroacetic acid

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