Mechanisms of Nitrite Mediated Cardioprotection in Coronary Artery Bypass Surgery
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Troponin T
研究概览
简要总结
The purpose of this study is to determine whether sodium nitrite administration 24 hours prior to or during coronary artery bypass surgery protects the heart better from lack of blood flow which occurs as part of this type of operation. The study will also determine what the mechanisms of this cardioprotection are.
详细描述
In recent years, there has been much interest in sodium nitrite as a cytoprotective agent in in vitro and animal models. A recent study undertaken in a canine model of myocardial infarction demonstrated a 50% reduction in myocardial injury following the administration of sodium nitrite prior to the ischemic event. In humans, the setting of coronary artery bypass surgery lends itself well to study potential cytoprotective agents. During cardiac surgery, the heart undergoes a period of ischemia allowing the surgeons to operate on the heart. This is followed by a period of reperfusion which in itself can add to cellular injury. Such injury can hinder post-operative myocardial recovery.
The aim of this pilot study is to determine whether the cardioprotective effects of sodium nitrite demonstrated in animal models are translated in humans and to determine the exact underlying mechanisms of this cytoprotection. Patients undergoing coronary artery bypass grafting surgery who give written, informed consent will receive sodium nitrite 24 hours prior to surgery, during cardiac surgery or placebo. Myocardial injury will be assessed through the measurement of biochemical markers such as troponin T. Cardiac biopsy samples will be obtained to determine underlying molecular mechanisms of this cardioprotection. The other aim of this pilot study is to determine what dose of sodium nitrite (i.e. 0.2mcg/kg/min or 1mcg/kg/min) is optimal for cardioprotection. This study will form pilot data also for a larger clinical trial with clinical endpoints.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients undergoing elective first time multi-vessel coronary artery bypass surgery
- •Older than 18 years of age
排除标准
- •Significant psychiatric /neurological impairment that might prevent adherence to the requirements of the protocol or the ability to give informed consent
- •Inability to read the Information Sheet.
- •Redo operation
- •Age >80 years
- •Pregnancy
- •Renal Impairment requiring pre-operative renal support
- •Diabetes Mellitus
- •Intended heart valve or additional surgery
- •Episodes of angina or ischemia within 48hours prior to the procedure
研究组 & 干预措施
sodium nitrite 24 hours before
干预措施: sodium nitrite (Drug)
sodium nitrite during surgery
干预措施: sodium nitrite (Drug)
0.9% sodium chloride
干预措施: 0.9% sodium chloride (Drug)
结局指标
主要结局
Troponin T
时间窗: 72 hours post release of aortic cross clamp
Biochemical marker of myocardial injury
次要结局
- Troponin T(48 hours post release of aortic cross clamp)
- troponin T(12 hours post release of aortic cross clamp)
- Creatinine Kinase myocardial Fraction (CKMB)(72 hours post release of aortic cross clamp)
- venous methemoglobinaemia(immediately before infusion of study drug)
- plasma 8-isoprostane(before aortic cross clamp administration)
- Nitric oxide metabolites in cardiac tissue(10minutes after release of aortic cross clamp)
- Cardiac output studies(upto 12 hours after release of aortic cross clamp)
- inotrope usage(up to 12 hours after release of aortic cross clamp)
- venous methemoglobinemia(immediately after infusion of study drug.)
- Plasma 8 isoprostane levels(5minutes after discontinuation of cardiopulmonary bypass)