ABSTRACT
BACKGROUND: Coronary artery bypass grafting (CABG) is the gold standard therapy for unprotected left main coronary artery (ULMCA) stenosis in coronary atherosclerosis. However, the treatment of ULMCA stenosis using drug-eluting stents has recently been reported to lead to a relatively low incidence of cardiovascular events.Thus,drug-eluting stents are a potential surrogate for CABG,and could become the new gold standard treatment for ULMCA stenosis; however, this issue remains controversial. OBJECTIVE: To explore the safety and efficacy of CABG versus rapamycin-eluting stents for ULMCA stenosis in older adult patients with degenerative coronary atherosclerosis. METHODS: The proposed prospective, non-randomized, controlled trial will include 224 older adult patients with degenerative coronary atherosclerosis with ULMCA stenosis being treated at the Department of Cardiology at Taihe Hospital and Renmin Hospital of Shiyan, China. Patients will be divided into two groups in accordance with each patient’s treatment choice and indications (n=112/group): the stent group will receive rapamycin-eluting stents, while the CABG group will undergo CABG.All patients will be followed up at 9, 12, 24, and 36 months postoperatively. The primary outcome measure will be the rate of repeat revascularizations in the target lesion at 36 months postoperatively.The secondary outcome measures will be the rates of repeat revascularizations in the target lesion at 9, 12, and 24 months postoperatively, the rate of restenosis, mortality, causes of death, and survival at 9, 12, 24, and 36 months postoperatively, and the angiographic appearance of the diseased vessels preoperatively and at 9, 12, 24, and 36 months postoperatively. The safety indicator will be the incidence of major adverse cardiac and cerebrovascular events at 9, 12, 24, and 36 months postoperatively. Eighty-six older adult patients with degenerative coronary atherosclerosis who underwent treatment of ULMCA stenosis between January 2016 and December 2017 were included in a pilot study. Pilot study results showed that the stent group (n=48) had a significantly reduced waiting time for surgery, hospitalization time, and rate of complete revascularizations in the target lesion compared with the CABG group (n=38) (P ＜ 0.05). At 6 months postoperatively, there were no significant differences between the two groups in mortality, and incidences of myocardial infarction, repeat revascularizations in the target lesion, and cardiovascular events. The trial was approved by the Ethics Committee of Taihe Hospital (approval No. TH005X) in July 2017 and by the Ethics Committee of Renmin Hospital of Shiyan (approval No. RM011X) in July 2017. All the patients will provide written informed consent with the premise of fully understanding the treatment plan. The study protocol will follow the relevant laws and regulations of the Declaration of Helsinki and relevant hospital’s ethical principles. Design of the trial was completed in January 2018. Recruitment will be initiated in August 2018 and it is expected to be completed in August 2019. Data analysis will be conducted in October 2022 and the trial will be completed in December 2022. The results of the study will be disseminated through presentations at scientific meetings and/or in peer-reviewed publications. The trial has been registered with the Chinese Clinical Trial Registry (registration No. ChiCTR1800016413) and the version number is 1.0 DISCUSSION: The results of this study will indicate the medium-and long-term efficacy and safety of rapamycin-eluting stents versus CABG in older adult patients with ULMCA stenosis, and then identify which of these two treatments has better prognosis, thereby screening out the optimal strategy for treating ULMCA.
ABSTRACT
Injury or inflammation induces release of a range of inflammatory mediators. Bradykinin is one of the most important inflammatory mediators and plays a crucial role in mediating inflammatory pain. It is well known that multiple ion channels located in the nociceptors participate in pain sensation. Recent studies demonstrate an important role of bradykinin in regulating the function and expression of pain-related ion channels. This paper summarizes the recent advances in the understanding of the role of bradykinin in modulation of the channels and discusses future possibilities in the treatment of inflammatory pain.
Subject(s)
Animals , Humans , Acid Sensing Ion Channels , Bradykinin , Pharmacology , Physiology , Inflammation , Inflammation Mediators , Pharmacology , Physiology , Ion Channels , KCNQ Potassium Channels , Metabolism , Physiology , Nerve Tissue Proteins , Metabolism , Pain , Metabolism , Receptors, AMPA , Metabolism , Receptors, N-Methyl-D-Aspartate , Metabolism , Receptors, Purinergic P2X3 , Metabolism , Sodium Channels , Metabolism , TRPA1 Cation Channel , TRPV Cation Channels , Metabolism , Physiology , Transient Receptor Potential Channels , Metabolism , PhysiologyABSTRACT
As an outward, voltage-dependent potassium channel, M type channel is crucial in the regulation of neuronal excitability; it is modulated by a variety of factors in vivo and its dysfunction often results in neuronal system diseases. Great efforts have been made to elucidate the mechanism underlying M channel modulation since its discovery decades ago. It is generally accepted that the Phospholipase C (PLC) signaling pathway plays a significant role in the M channel modulation. This review highlights the relationship between PLC signaling pathway and M channel modulation, as well as some recent progresses in the research of this field.