Remote Ischemic Preconditioning of Human Myocardium
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 134
- 试验地点
- 1
- 主要终点
- Troponin-T
研究概览
简要总结
The investigators aim to definitively show if human myocardium can be remotely preconditioned. In the writings there are no experiments that would prove that the remote preconditioning protocol effects on the higher protection of the human myocardial cells, against the ischemia-reperfusion injury.
120 patients referred for coronary artery bypass grafting (CABG) procedure with use of cardiopulmonary bypass are planned will be included to the research. Patients will be randomized (1:1) to one of two groups: remote preconditioning or "placebo" intervention. On the day of surgery, after induction of anesthesia remote preconditioning will be elicited by 3 cycles of 5min inflation (ischemia) and 5 min deflation (reperfusion) of blood pressure cuff on the right arm. In the control group the blood pressure cuff is going to be placed on the upper limb but the preconditioning protocol will not be carried out. On cannulation for CPB, right atrial appendage and myocardial biopsies of the left ventricular will be harvested. The investigators will study: (1) resistance of myocardium to hypoxia/reperfusion injury in in vitro experiments, assessed in isolated right atrial pectinate muscle trabeculae (2) induction of apoptosis and status of mitochondria in myocardium after the period of ischemia, and reperfusion in vitro (3) amount of myocardial necrosis in-vivo induced by period of ischemia and reperfusion during CABG as assessed by postoperative myocardial necrosis markers release (4) the systolic function of the myocardium at the postoperative and the kidney function in the postoperative period evaluated by the creatinine clearance; (5) induction of apoptosis and status of mitochondria in myocardium after the period of ischemia, and reperfusion during coronary artery bypass grafting, assessed in myocardial.
There is going to be an ability to define does the remote preconditioning influence on the occurrence of apoptosis in the human myocardium in the in vivo conditions and does it influence on the postoperative course in patients undergoing cardiac surgery procedures. The investigators will try to study if remote preconditioning modify induction of apoptosis and its structure in response to injury. In case the effect of remote preconditioning is not measurable in ex-vivo assessment, the future attempt at implementing this phenomenon in clinical practice may be futile and should not be continued until the effect can be confirmed in controlled experimental setting.
详细描述
The investigators will study:
- Resistance of isolated right atrial pectinate muscle trabeculae to simulated hypoxia/reperfusion in functional organ bath model
- Resistance of isolated right atrial pectinate muscle trabeculae to induction of apoptosis by simulated hypoxia/reperfusion
- Resistance of mitochondria in isolated right atrial pectinate muscle trabeculae to changes induced by simulated hypoxia/reperfusion
Simultaneously we will assess:
- Amount of myocardial necrosis in vivo induced by period of ischemia and reperfusion during coronary artery bypass grafting (CABG) as assessed by postoperative myocardial necrosis markers release profile
- Myocardial function in vivo after the period of ischemia and reperfusion during CABG as assessed by hemodynamic measurements (thermodilution method), oxygen supply/consumption and inotropic support requirements
- Induction of apoptosis and status of mitochondria after the period of ischemia, and reperfusion during CABG as assessed in left ventricular myocardial biopsies The investigators will try correlate the in vitro and in vivo findings from the same patients.
Methodology The study will be conducted both in vivo and ex-vivo. Patients referred for CABG for stable coronary artery disease will be recruited and randomized (1:1) by random digit generator to one of two groups: remote preconditioning or "placebo" intervention. Only patients in who at least 3 coronary artery bypass grafts with use of cardiopulmonary bypass (CPB) are planned will be included. On the day of surgery, after induction of anesthesia and before the skin incision remote preconditioning will be elicited. The "placebo" group will have the pressure cuff placed on the right arm but no inflations will be performed. To obtain blinding, the inflations will occur under surgical drapes, and will be performed by the same person every time, who will be involved in random sequence generation, and remote preconditioning application, but not in the care of the patient, or other research related tasks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, 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 of both genders.
- •Patients with stable coronary artery disease referred for surgical revascularization in who at least 3 coronary artery bypass grafts are planned with use of cardiopulmonary bypass.
排除标准
- •Age below 18 and above
- •Plan to use radial artery as a graft.
- •Plan to perform other concomitant cardiac procedure in addition to CABG.
- •Diabetes mellitus.
- •Troponin T level before surgery in excess of 99th percentile of upper reference limit.
- •Acute coronary syndrome in last 14 days before surgery.
- •Angina pectoris in last 48 hours before surgery.
- •Significant peripheral vascular disease.
- •Renal disease with either creatinine level ≥ 2mg/dl or estimated glomerular filtration rate < 30ml/h/1.73m
- •Renal replacement therapy.
- •Clinically relevant hepatic insufficiency with bilirubin level at least 1.5 times above upper limit of normal or AlAT, AST levels at least 2 times above upper limit of normal.
- •Advanced lung disease with FEV1 < 40% of predicted value.
- •Severe systolic dysfunction of left ventricle (EF<35%).
- •Psychiatric disease.
- •Drug or alcohol abuse.
研究组 & 干预措施
Remote ischemic preconditioning
Left arm blood pressure cuff inflation for 5 min then deflation of cuff for 5 min- cycle repeated 3 times before coronary artery bypass grafting.
干预措施: Remote ischemic preconditioning (Procedure)
Placebo
Deflated cuff on arm for 30 minutes.
干预措施: Placebo (Procedure)
结局指标
主要结局
Troponin-T
时间窗: 72 hours
Troponin-T release over the perioperative 72-hour period and its area under the curve (AUC)
次要结局
- Creatine Kinase isoenzyme MB, full hemodynamic assessment with oxygen metabolic assessment and creatinine clearance (CKD-Epi method)(1 week post surgery)
- Resistance of isolated right atrial pectinate muscle trabeculae to simulated hypoxia/reperfusion in functional organ bath model.(Day 1 of the RICP intervention)
- Resistance of isolated right atrial pectinate muscle trabeculae to induction of apoptosis by simulated hypoxia/reperfusion.(1day at the moment of harvesting)
- Induction of apoptosis and status of mitochondria after the period of ischemia, and reperfusion during coronary artery bypass grafting as assessed in left ventricular myocardial biopsies.(1 day at the moment of harvesting)
- Alveolar-arterial gradient (A-a gradient), S100 concentration, NGAL and zonulin concentration(1st week post surgery)
研究者
Marek Deja
MD PhD
Medical University of Silesia