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Effects of Hypoxic-hyperoxic Preconditioning in Cardio-surgical Patients

Effects of Hypoxic-hyperoxic Preconditioning on Myocardial Protection Against Ischemia-reperfusion Injury in Cardio-surgical Patients

Status
Completed
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05354648
Enrollment
120
Registered
2022-04-29
Start date
2015-06-01
Completion date
2016-02-22
Last updated
2026-06-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Coronary Artery Disease, Hyperoxia, Hypoxia, Myocardial Reperfusion Injury

Keywords

myocardial protection, preconditioning, hypoxia, hyperoxia, ischemia-reperfusion injury, cardiopulmonary bypass, oxygen transport

Brief 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.

Interventions

PROCEDUREHypoxic-hyperoxic preconditioning

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.

PROCEDUREPlacebo

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.

Sponsors

Alexander Averyanov
Lead SponsorOTHER_GOV
Tomsk National Research Medical Center of the Russian Academy of Sciences
CollaboratorOTHER
Siberian State Medical University
CollaboratorOTHER
I.M. Sechenov First Moscow State Medical University
CollaboratorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)

Eligibility

Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No

Inclusion criteria

* the need for coronary artery bypass grafting (CABG)

Exclusion criteria

* 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

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants with complications60 daysAny type of complications in postoperative period
Mechanical ventilation60 daysMechanical ventilation time
Rate of spontaneous sinus rhythm recovery14 daysSpontaneous sinus rhythm recovery after surgery

Secondary

MeasureTime frameDescription
Catecholamine support60 daysCatecholamine support time
Troponin T12 hoursTroponin T concentration
Endothelin-11 day before surgeryEndothelin-1 concentrations
Endothelin-1 dynamics 1at the end of surgeryEndothelin-1 concentrations
Endothelin-1 dynamics 224 hours after surgeryEndothelin-1 concentrations
NOx total1 day before surgeryNOx total concentrations
NOx total dynamics 1at the end of surgeryNOx total concentrations
NOx total dynamics 224 hours after surgeryNOx total concentrations
Asymmetric dimethylarginine (ADMA)1 day before surgeryADMA concentrations
ADMA dymanics 1at the end of surgeryADMA concentrations
ADMA dymanics 224 hours after surgeryADMA concentrations

Contacts

PRINCIPAL_INVESTIGATORIrina A Mandel, PhD

Federal Research Clinical Center FMBA Russia

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jun 10, 2026