Collagen‐binding Peptide Attenuates Catheter‐Induced Coronary Vasospasm

Abstract

Catheter-induced coronary vasospasm is a common occurrence in clinical practice and necessites vasodilation via nitroglycerin (NTG). We determined whether a novel peptidoglycan, DS-SILY20, would dilate spastic right coronary arteries (RCA) of Ossabaw miniature swine. DS-SILY20 consists of 20 type I collagen-binding peptides bound to a dermatan sulfate backbone and prevents platelet binding to sub-endothelial collagen. Pre-vasospasm lumen diameter of the RCA was measured via angiography. Subsequently, an intravascular ultrasound catheter was introduced to the RCA, triggering spasm of the artery, visualized via angiography. One minute after initial vasospasm, NTG or DS-SILY (all n=3) was administered via intracoronary bolus over 1 minute. Angiograms were captured at 2 and 10 minutes post-vasospasm. Arteries exposed to DS-SILY20 had significantly greater lumen diameter at 10 minutes post-vasospasm compared to arteries administered saline (p<0.05) and similar lumen diameter as NTG-treated arteries (60±6% saline, 83±3% DS-SILY20, 81±3% NTG). We harvested the distal segments of spastic RCAs and investigated the integrity of the endothelium by pre-constricting with a thromboxane A2 agonist followed by increasing doses of the endothelium-dependent vasodilator bradykinin. We observed a dose-dependent response to bradykinin (n=4), comparable to normal control, indicating that the endothelium is uninjured after catheter introduction. DS-SILY20-mediated dilation after vasospasm may be through an undiscovered endothelium-dependent mechanism. Funding: NIH HL062552, HL106792, T32 GM077229