ABSTRACT
Background: The debate on percutaneous coronary intervention (PCI) of the unprotected left main coronary artery (LMCA) has been constant over time. Objective: To investigate the clinical and procedural characteristics and cardiovascular outcomes of PCI of unprotected LMCA. Material and methods: Observational study which included patients with unprotected LMCA disease undergoing PCI; patients with cardiogenic shock prior to the procedure were excluded. We describe the clinical and angiographic characteristics, as well as the major adverse cardiac and cerebrovascular events (MACCE) according to the year of the procedure. Results: We included 73 patients, with a SYNTAX I score of 31.2 ± 9.1, mostly with ST-elevation acute coronary syndrome (35%). There was a higher frequency of triple vessel coronary disease (63%) and distal LMCA lesions (35%). The provisional stent technique was the most used for distal lesions (58%) and the 2-stent technique for bifurcation lesions (78%), supported by intravascular ultrasound (IVUS) in 38%. During follow-up, 19 presented MACCE (26%), out of which cardiac death occurred in 13%, non-cardiovascular death in 5%, non-fatal acute myocardial infarction in 1%, cerebrovascular event in 2%, and revascularization of the treated vessel in 4%. Conclusions: It was observed a similar frequency to the one appearing in other studies of cardiovascular events, mainly in patients with intermediate risk, which supports the increasing use of percutaneous intervention in this population.
Introducción: el debate sobre la intervención coronaria percutánea (ICP) del tronco coronario izquierdo (TCI) no protegido ha sido constante a lo largo del tiempo. Objetivo: investigar las características clínicas, de procedimiento y los desenlaces cardiovasculares de la ICP del TCI no protegido. Material y métodos: estudio observacional que incluyó pacientes con enfermedad del TCI no protegido sometidos a ICP; se excluyeron pacientes con choque cardiogénico previo al procedimiento. Describimos las características clínicas y angiográficas, así como los eventos adversos cardiovasculares y cerebrales mayores (MACCE) según el año del procedimiento. Resultados: incluimos 73 pacientes, con puntuación de SYNTAX I de 31.2 ± 9.1, mayormente con síndrome coronario agudo con elevación del ST (35%). Hubo mayor frecuencia de enfermedad coronaria trivascular (63%) y lesión distal del TCI (35%). La técnica de stent provisional fue la más usada para lesiones distales (58%) y la técnica de 2 stents para las lesiones en bifurcación (78%), con apoyo del ultrasonido intravascular (IVUS) en el 38%. En el seguimiento se presentaron 19 MACCE (26%), de los cuales la muerte de causa cardiaca se presentó en el 13%, muerte no cardiovascular en 5%, infarto agudo al miocardio no fatal en 1%, evento vascular cerebral en 2% y nueva revascularización del vaso tratado en 4%. Conclusiones: se observó una frecuencia similar a la de otros estudios de eventos cardiovasculares, especialmente en pacientes con riesgo intermedio, lo cual apoya el uso creciente de la intervención percutánea en esta población.
Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Humans , Male , Female , Percutaneous Coronary Intervention/methods , Aged , Middle Aged , Coronary Artery Disease/therapy , Coronary Artery Disease/complications , Coronary Artery Disease/surgery , Treatment Outcome , Follow-Up Studies , StentsABSTRACT
Spinal cord injury (SCI) induces a glial response in which astrocytes become activated and produce inflammatory mediators. The molecular basis for regulation of glial-innate immune responses remains poorly understood. Here, we examined the activation of retinoic acid-inducible gene (RIG)-like receptors (RLRs) and their involvement in regulating inflammation after SCI. We show that astrocytes express two intracellular RLRs: RIG-I and melanoma differentiation-associated gene 5. SCI and stretch injury of cultured astrocytes stimulated RLR signaling as determined by phosphorylation of interferon regulatory factor 3 (IRF3) leading to production of type I interferons (IFNs). RLR signaling stimulation with synthetic ribonucleic acid resulted in RLR activation, phosphorylation of IRF3, and increased expression of glial fibrillary acidic protein (GFAP) and vimentin, two hallmarks of reactive astrocytes. Moreover, mitochondrial E3 ubiquitin protein ligase 1, an RLR inhibitor, decreased production of GFAP and vimentin after RIG-I signaling stimulation. Our findings identify a role for RLR signaling and type I IFN in regulating astrocyte innate immune responses after SCI.
Subject(s)
Astrocytes/physiology , Immunity, Innate/physiology , RNA Helicases/metabolism , Signal Transduction/physiology , Spinal Cord Injuries/immunology , Spinal Cord Injuries/metabolism , Analysis of Variance , Animals , Astrocytes/drug effects , Astrocytes/metabolism , Cells, Cultured , DEAD-box RNA Helicases/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Female , Gene Expression Regulation/drug effects , Glial Fibrillary Acidic Protein/metabolism , Immunity, Innate/drug effects , Interferon Regulatory Factor-3/metabolism , Interferon Type I/genetics , Interferon Type I/metabolism , Interferon-Induced Helicase, IFIH1 , Poly I-C/pharmacology , RNA Helicases/pharmacology , RNA, Double-Stranded/pharmacology , Rats , Signal Transduction/drug effects , Stress, Mechanical , Time Factors , Vimentin/metabolismABSTRACT
The activation of oxidative damage, neuroinflammation, and mitochondrial dysfunction has been implicated in secondary pathomechanisms following spinal cord injury (SCI). These pathophysiological processes lead to cell death and are tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. Here, we investigated whether activation of Nrf2/ARE is neuroprotective following SCI. Female Fischer rats were subjected to mild thoracic SCI (T8) using the New York University injury device. As early as 30 min after SCI, levels of Nrf2 transcription factor were increased in both nuclear and cytoplasmic fractions of neurons and astrocytes at the lesion site and remained elevated for 3 days. Treatment of injured rats with sulforaphane, an activator of Nrf2/ARE signaling, significantly increased levels of Nrf2 and glutamate-cysteine ligase (GCL), a rate-limiting enzyme for synthesis of glutathione, and decreased levels of inflammatory cytokines, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) thus leading to a reduction in contusion volume and improvement in coordination. These results show that activation of the Nrf2/ARE pathway following SCI is neuroprotective and that sulforaphane is a viable compound for neurotherapeutic intervention in blocking pathomechanisms following SCI.