The Cardioprotective Effects of Adding Ozone To Cardioplegic Solution in Adult Cardiac Surgery

forty patients with age ranged between 40-70 years undergoing elective coronary artery bypass graft surgery with cardiopulmonary bypass will be included, they will divided into two groups. Ozone Group: in which Ozone will be added to cold blood cardioplegia. Control Group: in which in which only cold blood cardioplegia Primary outcome: Pattern of recovery of myocardium after declamping of Aorta Time of cardiac rhythm return after declamping. type of cardiac rhythm after declamping and rate of DC use. Secondary outcome: A-cardiac parameters Post operative inotropic score Incidence of post operative cardiac dysrhythmias postoperative ejection fraction (EF) Postoperative parameters of myocardial ischaemia a- Troponin levels b-Pro BNP • Histopathology of myocardial sample for detection of myocyte cellular edema as a marker of ischemic changes. B-non cardiac parameters: inflammatory markers 1. CRP 2. L\N 3. P\N ICU stay hospital stay morbidity and mortality

Ozone Administration Protocol Our procedures for O3T application in CBP surgery conform to international guidelines of the ''Madrid Declaration on Ozone Therapy'' 32 . M-O3T will be carried out as follows: 50mL of blood drawn by vacuum from the patient central catheter into a sterile blood transfusion bag in which 10 mL of 3.8% Na citrate solution (Galenica Senese Industries, Siena, Italy) as an anticoagulant will be previously added so that the blood/citrate volume ratio was 9:1. After blood withdrawal, the bag will momentarily disconnected leaving the venous access open by a saline infusion 33 . A corresponding volume (50 mL) of gas was immediately added with an O3 concentration of 20-50 micrograms/mL gas. Ozone was produced by Medozon compact generator (Herrmann Apparatebau GmbH, Germany). The gas is immediately and continuously mixed with the blood in the bag for at least 5 min and with gentle rotating movement to avoid foaming. Due to the blood viscosity, the gas mixture does not instantaneously come into contact with the whole blood mass, thus this mixing time is necessary. During these 5 min of mixing, the ozone totally reacted with both the potent antioxidants of plasma and the unsaturated lipids bound to albumin, generating asmall amount of hydrogen peroxide and alkenals. These two messengers were responsible for eliciting crucial biochemical reactions on both erythrocytes and within cells. At this point, the hyper-oxygenated ozonated blood will be mixed with the cold cardioplegia (Thomsons cardioplegia) this amount of ozonated blood will be added to each 500 ml of cardioplegic solution Exclusion Criteria: The patient will be excluded from the study if he has any of the following: left ventricular ejection fraction< 40% diabetic or other metabolic disorders, use of left ventricular assist devices, Renal failure or on hemodialysis Hepatic dysfunction Hypothyroidism implanted pacemaker

Our procedures for O3T application in CBP surgery conform to international guidelines of the ''Madrid Declaration on Ozone Therapy'' 32 . M-O3T will be carried out as follows: 50mL of blood drawn by vacuum from the patient central catheter into a sterile blood transfusion bag in which 10 mL of 3.8% Na citrate solution (Galenica Senese Industries, Siena, Italy) as an anticoagulant will be previously added so that the blood/citrate volume ratio was 9:1. After blood withdrawal, the bag will momentarily disconnected leaving the venous access open by a saline infusion 33 . A corresponding volume (50 mL) of gas was immediately added with an O3 concentration of 20-50 micrograms/mL gas. Ozone was produced by Medozon compact generator (Herrmann Apparatebau GmbH, Germany). At this point, the hyper-oxygenated ozonated blood will be mixed with the cold cardioplegia (Thomsons cardioplegia) this amount of ozonated blood will be added to each 500 ml of cardioplegic solution

Inclusion Criteria: patients undergoing elective CABG surgery Exclusion Criteria: • left ventricular ejection fraction< 40% diabetic or other metabolic disorders, use of left ventricular assist devices, Renal failure or on hemodialysis Hepatic dysfunction Hypothyroidism implanted pacemaker