Effects of Hypoxic-hyperoxic Preconditioning on Myocardial Protection Against Ischemia-reperfusion Injury in Cardio-surgical Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 主要终点
- Number of Participants with complications
研究概览
简要总结
Coronary artery bypass grafting (CABG) with cardiopulmonary bypass is a common surgical therapy for patients suffering from coronary artery diseases. The heart is subjected to a long period of ischemia due to the occlusion of the aorta. The heavy burden of myocardial ischemia-reperfusion injury (IRI) thus induces cardiomyocyte death, which can paradoxically reduce the beneficial effect of CABG. Preconditioning by moderate hypoxia or hyperoxia serves as an effective drug-free method to increase the organism's resistance to negative effects, including IRI.
详细描述
It has been firmly established that the diminished oxygen delivery to the tissues in response to hypoxia is countered by a combination of the increased regional blood flow and the enhanced functional capillary density in the microcirculation. In experimental studies, exposure to hyperoxia for a limited time before ischemia induces a low-grade systemic oxidative stress evokes a preconditioning-like effect on the myocardium and reduces the infarction area by 20%, and the number of arrhythmias after ischemia-reperfusion. One hundred twenty patients were randomly assigned into two equal groups: hypoxic-hyperoxic preconditioning before the surgery (HHP group) and the control group (without preconditioning). Safety control of the preconditioning procedure included ECG monitoring, invasive blood pressure, cardiac output, pulse oximetry, capnography, cerebral oximetry, measurement of anaerobic threshold; acid-base status and metabolic state of arterial and venous blood were assessed once every 10 min during the preconditioning procedure; oxygen balance parameters were calculated. Seventy-two hours before the surgery, an anaerobic threshold was determined to establish a safe oxygen concentration in the respiratory gas mixture during the hypoxic preconditioning phase from 10 to 14%, followed by 75-80% oxygen concentration during the hyperoxic phase.
The hypoxic-hyperoxic preconditioning with individual parameters selection based on the anaerobic threshold in patients with coronary artery diseases before the main stage of cardiac surgery with a cardiopulmonary bypass should reduce the duration of mechanical ventilation, catecholamine support, and frequency of perioperative complications.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •the need for coronary artery bypass grafting (CABG)
排除标准
- •age over 75 years
- •emergency surgery
- •diabetes mellitus
- •exacerbation of a chronic disease 1 week before surgery
- •any oncological disease at the time of the examination
研究组 & 干预措施
Hypoxic-hyperoxic preconditioning (HHP)
HHP was carried out as follows: breathing with a hypoxic gas mixture for 10 min with the development of hypoxemia, then breathing with a hyperoxic gas mixture for 30 minutes, and at the last stage, a period of breathing with atmospheric air until the cardio-pulmonary bypass is connected. The anaerobic threshold was determined 72 hours before surgery to establish a safe oxygen concentration in the respiratory gas mixture during the hypoxic phase of preconditioning.
干预措施: Hypoxic-hyperoxic preconditioning (Procedure)
Control
The anaerobic threshold was determined, however, patients in the control group were not preconditioned. Mechanical ventilation was carried out with individual settings maintaining the target values of PaO2 and PaCO2 (80 - 120 mm Hg and 35 - 45 mm Hg, respectively), until the cardio-pulmonary bypass was connected.
干预措施: Placebo (Procedure)
结局指标
主要结局
Number of Participants with complications
时间窗: 60 days
Any type of complications in postoperative period
Mechanical ventilation
时间窗: 60 days
Mechanical ventilation time
Rate of spontaneous sinus rhythm recovery
时间窗: 14 days
Spontaneous sinus rhythm recovery after surgery
次要结局
- ADMA dymanics 2(24 hours after surgery)
- Catecholamine support(60 days)
- Troponin T(12 hours)
- NOx total(1 day before surgery)
- Endothelin-1(1 day before surgery)
- Endothelin-1 dynamics 2(24 hours after surgery)
- NOx total dynamics 2(24 hours after surgery)
- Asymmetric dimethylarginine (ADMA)(1 day before surgery)
- Endothelin-1 dynamics 1(at the end of surgery)
- NOx total dynamics 1(at the end of surgery)
- ADMA dymanics 1(at the end of surgery)
研究者
Alexander Averyanov
Professor
Federal Research Clinical Center of Federal Medical & Biological Agency, Russia