Clinical trial NCT05354648: Effects of Hypoxic-hyperoxic Preconditioning in Cardio-surgical Patients
Official title: Effects of Hypoxic-hyperoxic Preconditioning on Myocardial Protection Against Ischemia-reperfusion Injury in Cardio-surgical Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Myocardial Reperfusion Injury
Hypoxia
Hyperoxia
Coronary Artery Disease
Keywords: myocardial protection
preconditioning
hypoxia
hyperoxia
ischemia-reperfusion injury
cardiopulmonary bypass
oxygen transport
Lead sponsor: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Sponsor class: OTHER_GOV
Collaborators: name: Tomsk National Research Medical Center of the Russian Academy of Sciences
name: Siberian State Medical University
name: I.M. Sechenov First Moscow State Medical University
First posted: 2022-04-29
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with complications
timeFrame: 60 days
measure: Mechanical ventilation
timeFrame: 60 days
measure: Rate of spontaneous sinus rhythm recovery
timeFrame: 14 days
Secondary outcomes:
measure: Catecholamine support
timeFrame: 60 days
measure: Troponin T
timeFrame: 12 hours
measure: Endothelin-1
timeFrame: 1 day before surgery
measure: Endothelin-1 dynamics 1
timeFrame: at the end of surgery
measure: Endothelin-1 dynamics 2
timeFrame: 24 hours after surgery
measure: NOx total
timeFrame: 1 day before surgery
measure: NOx total dynamics 1
timeFrame: at the end of surgery
measure: NOx total dynamics 2
timeFrame: 24 hours after surgery
measure: Asymmetric dimethylarginine (ADMA)
timeFrame: 1 day before surgery
measure: ADMA dymanics 1
timeFrame: at the end of surgery
measure: ADMA dymanics 2
timeFrame: 24 hours after surgery
Other outcomes:
Locations:
Study officials:
affiliation: Federal Research Clinical Center FMBA Russia
name: Irina A Mandel, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.