Saphenous vein aorto-coronary graft atherosclerosis in patients with chronic kidney disease: more plaque calcification and necrosis, but less vasoconstrictor potential

Abstract

Atherosclerotic coronary arteries are more calcified in patients with than without chronic kidney disease (CKD). We addressed the potential for coronary microvascular obstruction in patients with and without CKD during stenting for saphenous vein aorto-coronary graft (SVG) stenosis under protection with a distal occlusion/aspiration device. In patients with and without CKD (n = 20/20), SVG plaque composition was analyzed from virtual histology using intravascular ultrasound analysis before stent implantation. There was more dense calcium and more necrotic core in patients with than without CKD (14 ± 3 vs. 3 ± 1 % and 21 ± 3 vs. 12 ± 2 % of plaque volume, respectively). Coronary aspirate was retrieved during stent implantation and divided into particulate debris and plasma. Patients with CKD had more particulate debris and calcium release than patients without CKD. In contrast, the release of serotonin was less in patients with than without CKD (0.4 ± 0.1 vs. 1.2 ± 0.3 μmol/L), whereas that of catecholamines, endothelin, tissue factor, thromboxane, tumor necrosis factor α, and C reactive protein was not significantly different. Confirming the biochemical results, aspirate plasma from patients with CKD induced less vasoconstriction of rat mesenteric arteries than that from patients without CKD (with endothelium (+E), 26 ± 7 %; without endothelium (-E): 28 ± 7 % vs. +E, 68 ± 12 %; -E: 95 ± 16 % of maximum KCl-induced vasoconstriction). Graft atherosclerosis of patients with CKD is more degenerated and releases more particulate debris and calcium, but the aspirate has surprisingly less serotonin and vasoconstrictor potential.

Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

“…IVUS was performed before and after stent implantation with a commercial catheter (20 MHz, Eagle-Eye, Volcano, Rancho Cordova, CA) and pullback device (0.5 mm/s, R-100, Volcano). The site and length of the target lesion were retrospectively identified after stent implantation from landmarks in the vascular profile (2,27). Plaque composition was categorized with virtual histology (VH) using customized software (pcVHTM2.1, Volcano).…”

“…Plaque composition was categorized with virtual histology (VH) using customized software (pcVHTM2.1, Volcano). Plaque components (fibrotic, fibro-fatty, necrotic core, dense calcium) were presented as a fraction of total plaque volume (%) (2).…”

“…The calcium concentration (sum of ionized and bound/complexed calcium) was measured in particulate debris and coronary arterial and aspirate plasma after extraction with HCl by atomic absorption spectrophotometry (2). Endothelin, serotonin, thromboxane (Tx)B 2, tissue factor and TNF␣ concentrations in particulate debris, coronary arterial and aspirate plasma were determined using enzyme immunometric assay kits (Cayman Chemical, Ann Arbor, MI, for endothelin, TNF␣ and TxB 2; Assay Designs for serotonin; American Diagnostica, for tissue factor).…”

“…Segments of 2 mm length were mounted in a Mulvany myograph and equilibrated with Krebs-Henseleit buffer. After verification of functionality in response to acetylcholine, vessels were incubated with coronary arterial and aspirate plasma, which was diluted to a final ratio of 1:10 vol/vol (after correction for dilution by the hematocrit) (2,17). In a subset of experiments, we compared the vasoconstrictor response of the rat mesenteric arteries with intact endothelium to aspirate plasma from nRCA and SVG-RCA after dilution to a final ratio of 1:10 and 1:20 vol/vol (n ϭ 4, each).…”

“…In a subset of experiments, we compared the vasoconstrictor response of the rat mesenteric arteries with intact endothelium to aspirate plasma from nRCA and SVG-RCA after dilution to a final ratio of 1:10 and 1:20 vol/vol (n ϭ 4, each). Constrictor responses were recorded over 8 min and normalized to the maximum vasoconstriction induced by 120 mmol/l KCl (%KCl max ϭ 100%) (2,17). In a subset of experiments, the contribution of endothelin to the vasoconstriction by nRCA coronary aspirate plasma was determined using the nonspecific endothelin receptor antagonist PD-142893 (10 Ϫ6 mol/ l), the specific endothelin receptor type A (ETA) receptor antagonist BQ-123 (10 Ϫ6 mol/l), the specific endothelin receptor type B (ETB) receptor antagonist BQ-788 (10 Ϫ6 mol/l), and the endothelin-converting enzyme inhibitor phosphoramidon (10 Ϫ5 mol/l; 30 min preincubation, respectively) (24,26).…”