Myocardial Reperfusion InjuryNCT05354648
Effects of Hypoxic-hyperoxic Preconditioning in Cardio-surgical Patients
A study testing Hypoxic-hyperoxic preconditioning in people with Myocardial Reperfusion Injury and Hypoxia, run by Alexander Averyanov.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Myocardial Reperfusion Injury, Hypoxia, Hyperoxia
- What is being tested?
- Hypoxic-hyperoxic preconditioning
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2015to 22 Feb 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- the need for coronary artery bypass grafting (CABG)
Who cannot join
- 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
About this study
Official title: Effects of Hypoxic-hyperoxic Preconditioning on Myocardial Protection Against Ischemia-reperfusion Injury in Cardio-surgical Patients
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.
Read the 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.
- Being tested
- Hypoxic-hyperoxic preconditioning, Placebo
- Keywords
- myocardial protection, preconditioning, hypoxia, hyperoxia, ischemia-reperfusion injury, cardiopulmonary bypass, oxygen transport
- Medical subject headings
- Myocardial Reperfusion Injury, Hypoxia, Hyperoxia, Coronary Artery Disease, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypoxic-hyperoxic preconditioningProcedure or surgery
Also called HHP
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.
PlaceboProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Hypoxic-hyperoxic preconditioning (HHP) | Active comparator | 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. Receives: Procedure: Hypoxic-hyperoxic preconditioning |
| Control | Placebo comparator | 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. Receives: Procedure: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with complications
Any type of complications in postoperative period
Measured: 60 days
Mechanical ventilation
Mechanical ventilation time
Measured: 60 days
Rate of spontaneous sinus rhythm recovery
Spontaneous sinus rhythm recovery after surgery
Measured: 14 days
Secondary outcomes (11)
Catecholamine support
Catecholamine support time
Measured: 60 days
Troponin T
Troponin T concentration
Measured: 12 hours
Endothelin-1
Endothelin-1 concentrations
Measured: 1 day before surgery
Endothelin-1 dynamics 1
Endothelin-1 concentrations
Measured: at the end of surgery
Endothelin-1 dynamics 2
Endothelin-1 concentrations
Measured: 24 hours after surgery
NOx total
NOx total concentrations
Measured: 1 day before surgery
NOx total dynamics 1
NOx total concentrations
Measured: at the end of surgery
NOx total dynamics 2
NOx total concentrations
Measured: 24 hours after surgery
Asymmetric dimethylarginine (ADMA)
ADMA concentrations
Measured: 1 day before surgery
ADMA dymanics 1
ADMA concentrations
Measured: at the end of surgery
ADMA dymanics 2
ADMA concentrations
Measured: 24 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2022
- Study start1 Jun 2015
- Primary completion15 Jan 2016
- Study completion22 Feb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial Reperfusion InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexander Averyanov
- Sponsor type
- Other government
- Collaborators
- Tomsk National Research Medical Center of the Russian Academy of Sciences, Siberian State Medical University, I.M. Sechenov First Moscow State Medical University
- Responsible party
- Sponsor-investigator, Alexander Averyanov, Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
- Investigators
- Irina A Mandel, PhD, Principal investigator, Federal Research Clinical Center FMBA Russia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05354648
- Sponsor's protocol ID
- HHP-cardio
- Status last verified
- Jun 2026
- First submitted
- 26 Apr 2022
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Mandel IA, Podoksenov YK, Suhodolo IV, An DA, Mikheev SL, Podoksenov AY, Svirko YS, Gusakova AM, Shipulin VM, Yavorovskiy AG. Influence of Hypoxic and Hyperoxic Preconditioning on Endothelial Function in a Model of Myocardial Ischemia-Reperfusion Injury with Cardiopulmonary Bypass (Experimental Study). Int J Mol Sci. 2020 Jul 27;21(15):5336. doi: 10.3390/ijms21155336.
PubMed 32727110
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Hypoxic-hyperoxic Preconditioning on Myocardial Protection Against Ischemia-reperfusion Injury in Cardio-surgical Patients
- ClinicalTrials.gov ID
- NCT05354648
- Acronym / sponsor ID
- HHP-cardio
- Keywords
- myocardial protection, preconditioning, hypoxia, hyperoxia, ischemia-reperfusion injury, cardiopulmonary bypass, oxygen transport
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Alexander AveryanovOther government
- Collaborators
- Tomsk National Research Medical Center of the Russian Academy of Sciences, Siberian State Medical University, I.M. Sechenov First Moscow State Medical University
- Study start
- 1 Jun 2015 (actual)
- Primary completion
- 15 Jan 2016 (actual)
- Study completion
- 22 Feb 2016 (actual)
- First posted
- 29 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypoxic-hyperoxic preconditioning (HHP) | Active comparator | Procedure: Hypoxic-hyperoxic preconditioningHHP 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. |
| Control | Placebo comparator | Procedure: PlaceboThe 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- the need for coronary artery bypass grafting (CABG)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hypoxic-hyperoxic preconditioningAlso: HHPPatients 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. | Procedure or surgery | Hypoxic-hyperoxic preconditioning (HHP) |
| PlaceboPatients 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. | Procedure or surgery | Control |
Primary outcome
Number of Participants with complications
Time frame: 60 days
Any type of complications in postoperative period
Mechanical ventilation
Time frame: 60 days
Mechanical ventilation time
Rate of spontaneous sinus rhythm recovery
Time frame: 14 days
Spontaneous sinus rhythm recovery after surgery
11 secondary outcomes
Catecholamine support
Time frame: 60 days
Troponin T
Time frame: 12 hours
Endothelin-1
Time frame: 1 day before surgery
Endothelin-1 dynamics 1
Time frame: at the end of surgery
Endothelin-1 dynamics 2
Time frame: 24 hours after surgery
NOx total
Time frame: 1 day before surgery
NOx total dynamics 1
Time frame: at the end of surgery
NOx total dynamics 2
Time frame: 24 hours after surgery
Asymmetric dimethylarginine (ADMA)
Time frame: 1 day before surgery
ADMA dymanics 1
Time frame: at the end of surgery
ADMA dymanics 2
Time frame: 24 hours after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Background: PubMed 32727110Mandel IA, Podoksenov YK, Suhodolo IV, An DA, Mikheev SL, Podoksenov AY, Svirko YS, Gusakova AM, Shipulin VM, Yavorovskiy AG. Influence of Hypoxic and Hyperoxic Preconditioning on Endothelial Function in a Model of Myocardial Ischemia-Reperfusion Injury with Cardiopulmonary Bypass (Experimental Study). Int J Mol Sci. 2020 Jul 27;21(15):5336. doi: 10.3390/ijms21155336.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Irina A Mandel, PhD principal investigator
Federal Research Clinical Center FMBA Russia
Questions about this trial
What is this clinical trial studying?
A study testing Hypoxic-hyperoxic preconditioning in people with Myocardial Reperfusion Injury and Hypoxia, run by Alexander Averyanov.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with complications (time frame: 60 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05354648, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2026.