Effects of Hypoxic-hyperoxic Preconditioning in Cardio-surgical Patients
Condition: Myocardial Reperfusion Injury; Hypoxia; Hyperoxia; Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Reperfusion Injury; Myocardial Reperfusion Injury; Hypoxia; Hyperoxia
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Hypoxic-hyperoxic preconditioning; Placebo
Intervention type(s): Procedure; Procedure
Intervention description(s): Patients were intubated and mechanically ventilated with the target values of PaO2 and PaCO2 (80 - 120 mm Hg and 35 - 45 mm Hg, respectively) under the inhalation anesthesia. 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, then a period of breathing with atmospheric air (normoxia and normocapnia) until the cardio-pulmonary bypass is connected.; Patients were intubated and mechanically ventilated with the target values of PaO2 and PaCO2 (80 - 120 mm Hg and 35 - 45 mm Hg, respectively) under the inhalation anesthesia until the cardio-pulmonary bypass is connected.
Other intervention name(s): HHP
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Prevention
Keywords: myocardial protection; preconditioning; hypoxia; hyperoxia; ischemia-reperfusion injury; cardiopulmonary bypass; oxygen transport