Effects of Hypoxic-hyperoxic Preconditioning in Cardio-surgical Patients

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05354648
• Other study ID #: HHP-cardio
• Status: Completed
• Phase: N/A
• Start date: June 1, 2015
• Est. completion date: February 22, 2016

Study information

• Verified date: April 2022
• Source: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: February 22, 2016
• Est. primary completion date: January 15, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Hyperoxia
• Hypoxia
• Myocardial Reperfusion Injury
• Reperfusion Injury

Intervention

Procedure:
• Hypoxic-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.
• Placebo
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.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Federal Research Clinical Center of Federal Medical & Biological Agency, Russia	I.M. Sechenov First Moscow State Medical University, Siberian State Medical University, Tomsk National Research Medical Center of the Russian Academy of Sciences

References & Publications (1)

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). pii: E5336. doi: 10.3390/ijms21155336. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with complications	Any type of complications in postoperative period	60 days
Primary	Mechanical ventilation	Mechanical ventilation time	60 days
Primary	Rate of spontaneous sinus rhythm recovery	Spontaneous sinus rhythm recovery after surgery	14 days
Secondary	Catecholamine support	Catecholamine support time	60 days
Secondary	Troponin T	Troponin T concentration	12 hours
Secondary	Endothelin-1	Endothelin-1 concentrations	1 day before surgery
Secondary	Endothelin-1 dynamics 1	Endothelin-1 concentrations	at the end of surgery
Secondary	Endothelin-1 dynamics 2	Endothelin-1 concentrations	24 hours after surgery
Secondary	NOx total	NOx total concentrations	1 day before surgery
Secondary	NOx total dynamics 1	NOx total concentrations	at the end of surgery
Secondary	NOx total dynamics 2	NOx total concentrations	24 hours after surgery
Secondary	Asymmetric dimethylarginine (ADMA)	ADMA concentrations	1 day before surgery
Secondary	ADMA dymanics 1	ADMA concentrations	at the end of surgery
Secondary	ADMA dymanics 2	ADMA concentrations	24 hours after surgery