sirolimus and Coronary-Vasospasm

Renal transplantation is the treatment of choice for patients with end-stage renal disease. While transplantation improves the quality of life and reduces the mortality risk for most patients when compared with maintenance dialysis, it introduces significant morbidity associated with induction and maintenance immune suppression. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is frequently used as a second-line maintenance immunosuppressive agent in solid organ transplant recipients. Sirolimus may, however, have adverse vascular effects and has previously been shown to induce endothelial cell dysfunction and impaired nitric oxide production in vitro. Sirolimus-eluting coronary artery stents have been associated with rare reports of severe coronary artery vasospasm; however, systemic sirolimus therapy has not previously been associated with vasospastic complications.

Topics: Coronary Vasospasm; Coronary Vessels; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Percutaneous Coronary Intervention; Quality of Life; Renal Dialysis; Sirolimus; Spasm; ST Elevation Myocardial Infarction; Treatment Outcome

Topics: Coronary Occlusion; Coronary Vasospasm; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Middle Aged; Recurrence; Sirolimus; ST Elevation Myocardial Infarction

Topics: Angina Pectoris, Variant; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Stenosis; Coronary Vasospasm; Drug-Eluting Stents; Everolimus; Humans; Male; Middle Aged; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome; Vasodilator Agents

The importance of adventitial inflammation has been implicated for the pathogenesis of coronary artery disease. However, the roles of adventitial changes in drug-eluting stent (DES)-induced coronary hyperconstriction remain largely unknown. In the present study, this issue in pigs in vivo with a special reference to adventitial vasa vasorum (VV) formation and Rho-kinase activation, a central mechanism of coronary vasospasm, was examined.. Each animal received a sirolimus-eluting stent (SES) and a biolimus A9-eluting stent (BES), one in the left anterior descending and another in the left circumflex coronary arteries in a randomized manner (n=18). After 1, 3 and 6 months, coronary vasomotion was examined. At 1 month, coronary vasoconstriction to serotonin was significantly enhanced at the SES edges as compared with the BES edges (SES, 52±7% vs. BES, 22±3%, P<0.01), which was equally prevented by a selective Rho-kinase inhibitor, hydroxyfasudil. A significant difference in vasoconstriction between SES and BES was sustained for 6 months. A micro-CT showed VV augmentation at the SES site, extending to the proximal and distal edges. Immunostainings demonstrated that VV formation, macrophage infiltration in the adventitia and Rho-kinase expressions/activation were significantly enhanced at the SES edges as compared with the BES edges.. The DES with durable polymers enhances VV formation and inflammation in the adventitia, associating with the pathogenesis of DES-induced coronary hyperconstriction through Rho-kinase activation in pigs in vivo.

Topics: Animals; Coronary Vasospasm; Drug-Eluting Stents; Enzyme Activation; Gene Expression Regulation, Enzymologic; rho-Associated Kinases; Sirolimus; Swine; Vasa Vasorum

Topics: Animals; Coronary Vasospasm; Drug-Eluting Stents; Gene Expression Regulation, Enzymologic; rho-Associated Kinases; Sirolimus; Vasa Vasorum

We describe a 42-year-old man with very late stent thrombosis (VLST) 35 months after implantation of a sirolimus-eluting stent (SES). Three months after the VLST episode, a follow-up angiography showed a formation of peri-stent coronary artery aneurysm. Sixty-five months after SES implantation, the patient suffered an out-of-hospital cardiac arrest. We performed spasm provocation test using acetylcholine to evaluate coronary vasomotor response and the coronary segments adjacent to the SES showed significant vasoconstriction. Intracoronary pretreatment of Rho-kinase inhibitor, fasudil, markedly attenuated acetylcholine-induced vasoconstriction. This report documents a unique case suffering from multiple fatal complications after SES implantation.

Topics: Adult; Coronary Aneurysm; Coronary Angiography; Coronary Restenosis; Coronary Vasospasm; Drug-Eluting Stents; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Sirolimus; Time Factors; Ultrasonography, Interventional

We describe two cases of severe, multivessel coronary vasospasm that occurred a few months after placement of sirolimus-eluting stents in patients with severe coronary disease, and involved segments not significantly atheromatous and not previously treated. The literature suggests that biocellular interference with the endothelial equilibrium on the part of drugs eluted from a stent poses a serious risk of tardive and widespread postangioplasty coronary spasm in comparison with the use of a bare-metal stent.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Stenosis; Coronary Vasospasm; Drug-Eluting Stents; Humans; Intra-Aortic Balloon Pumping; Male; Middle Aged; Prosthesis Design; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome; Vasodilator Agents

This study sought to determine vasomotor functional responses of conduit coronary artery distal to bare-metal stents (BMS), polymer-only stents (POLY), and sirolimus-eluting stents (SES) in a clinically relevant animal model.. Drug-eluting stents (DES) reduce in-stent restenosis, and also affect neointima formation and vascular remodeling in downstream coronary segments. Whether distal artery vasomotor function is also influenced by DES has not been determined.. Pigs (n = 12) received coronary stent implants, and hearts were harvested at 1 month. Arterial segments >or=15 mm distal to stents were excised and studied in an organ-chamber apparatus. Endothelium-dependent and endothelium-independent relaxation and contraction to classical agonists were measured.. The SES showed increased lumen area and reduced neointima; abnormal vasomotor function of conduit arteries distal to SES also was observed. Contraction to endothelin-1 was significantly enhanced for SES compared with both BMS and POLY. Endothelium-dependent relaxation to a maximal dose of substance P was attenuated for SES compared with both BMS and POLY (46 +/- 6% vs. 71 +/- 3% and 78 +/- 3%, respectively, p < 0.001). Endothelium-independent relaxation to sodium nitroprusside was potentiated for SES, compared with BMS and POLY (100 +/- 5% vs. 69 +/- 7% and 77 +/- 5%, respectively, p = 0.02).. Stent-based local delivery of sirolimus profoundly inhibited neointima formation but caused vasomotor dysfunction in distal conduit vessel segments. These observations suggest that distal coronary vasospasm may be more readily evoked in the presence of DES and contribute to pathophysiological sequela.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Vasospasm; Coronary Vessels; Dose-Response Relationship, Drug; Drug-Eluting Stents; Female; Male; Metals; Models, Animal; Prosthesis Design; Sirolimus; Stents; Sus scrofa; Thrombosis; Time Factors; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Vasospasm; Coronary Vessels; Drug-Eluting Stents; Models, Animal; Myocardium; Sirolimus; Swine

Endothelial dysfunction has been related both to progression of atherosclerotic disease and to future cardiovascular events. We assessed local epicardial endothelial function 6 months after sirolimus-eluting stent (SES) or bare metal stent (BS) implantation.. In 12 patients (seven SES, five BS), endothelium-dependent vasomotion of a coronary segment 15 mm in length, starting 2 mm distal to the stent, was assessed with quantitative coronary angiography immediately after the procedure and at 6 months follow-up, after intracoronary infusion of acetylcholine. Intravascular ultrasound (IVUS) was performed and coronary flow reserve (CFR) assessed in all patients. At follow-up significant vasoconstriction was seen in SES (median 32% diameter reduction from baseline) but not in BS (median 2% reduction) patients after acetylcholine infusion (P=0.03 for SES vs. BS); endothelium-independent vasodilatation to nitrates did not differ significantly between groups (20% SES, 5% BS, P=0.14). IVUS revealed no late unhealed dissections and CFR was comparable between groups (SES 3.1 vs. BS 3.2, n.s.).. SES implantation may have an adverse effect on local endothelium-dependent vasomotor responses compared with BS implantation at 6 months. Long-term clinical consequences of this observation are still unknown.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Coronary Vasospasm; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Nitroglycerin; Prospective Studies; Sirolimus; Stents; Vasodilation; Vasodilator Agents

Topics: Coronary Restenosis; Coronary Vasospasm; Humans; Male; Middle Aged; Sirolimus; Stents

Topics: Acetylcholine; Adult; Coronary Angiography; Coronary Stenosis; Coronary Vasospasm; Coronary Vessels; Drug Implants; Endothelium, Vascular; Humans; Injections, Intra-Arterial; Male; Myocardial Infarction; Nitroglycerin; Sirolimus; Stents; Vasoconstriction; Vasoconstrictor Agents