Anesthetic Management and Remote Reperfusion Injuries
Condition: Heart Valve Diseases
MeSH terms: Heart Valve Diseases
Study type: Observational

Summary: 
      Ischemia- reperfusion ( IR ) injuries were not only seen in the transplanted organs but also
      the remote organs such as lungs that brings major postoperative complications. Severe
      complications such as pulmonary infiltration and pulmonary edema following reperfusion were
      frequently associated with liver transplantation. Cardiac surgery performed with the use of
      cardiopulmonary bypass ( CPB ) provokes a systemic inflammatory response syndrome that
      affects postoperative pulmonary, myocardiac and renal functions. Previous study about the
      reperfusion injuries was focused on the leukocyte and endothelial activation and the
      following oxidative injuries, however, the alteration on pulmonary function such as dynamic
      compliance and the oxidative/antioxidative balance in erythrocytes and the following effects
      in CPB have not been fully studied. Erythrocytes' reaction to oxidative stress including
      cytoplasma and cell membrane should be studied because RBCs are the major circulating blood
      cells having different types of antioxidant system to capture reactive oxygen species ( ROS )
      thus RBC may be severely injured by ROS or protected ROS injuries during CPB. In these
      three-year study, we plan to explore the extent and pattern of remote oxidative injuries in
      lungs by massive ROS production and the following products released from reperfused organs.
      In the first year, the remote pulmonary injuries from hepatic IR will be focused. We plan to
      establish an animal model for pulmonary function and pulmonary injury assessments including
      dynamic compliance (Cdyn), pulmonary edema wet-to-dry ratio (W/D), malondialdehyde (MDA) and
      histopathological findings under hepatic IR challenge. In the second year, the IR effects
      during and after CPB on circulating blood cells will be fully studied. We plan to investigate
      the magnitude, subtypes and timing on ROS production, the changes of oxidative and
      antioxidant activities of erythrocytes including cytoplasma and cell membrane, the changes on
      leukocytes and plasma to explore the roles of circulating erythrocytes on oxidative stress in
      CPB. In the third year, we plan to try propofol, stated having antioxidant in vivo and in
      vitro, on the remote pulmonary injuries following hepatic IR and CPB.
    

Detailed description: 
      Seven ml blood sample were taken from arterial line after stabilization of anesthesia (T1),
      30 minutes after total CPB (T2), one hour after weaning from CPB (T3) and 24 hours after
      weaning from CPB (T4). One ml blood sample was immediately wrapped in aluminum foil and kept
      in ice to immediate measurements of MetHb, COHb and CL (ROS). CL assay was carried out within
      2 hours of sampling. Six ml samples remained was placed into tubes containing ethylenediamine
      tetraacetic acid. Serum were separated ( at 2000rpm for 10 minutes) immediately after
      sampling and stored at -80℃ for TAS assay, cytokine measurements, malondialdehyde (MDA)
      determination, complements and leukocyte elastase measurements. Those assay and measurements
      were carried out within 4 weeks of surgery.

      Measurements of hemoglobin (Hb), COHb and MetHb: Hb, COHb and MetHb were measured immediately
      with ABL520, Radiometer, Copenhagen, Denmark).

      Measurement of Redox balance: 0.2ml of fresh drawn blood was used to measure ROS production
      by lucigenin Chemiluminescence (CL) (detecting superoxide mainly) and luminal CL (detecting
      H2O2 and HOCl mainly) as previous study.The total antioxidant status in 20 uL of plasma was
      measured with a total antioxidant status (TAS) kit ( TAS CAL, Randox). Hemodilution effects
      with CPB, TAS levels at T2 were corrected with the hematocrits. Lipid peroxidation was
      determined by the thiobarbiturate reaction measuring the formation of MDA in plasma by TBARS
      assay kit (Cayman chemical co. USA) Cytokines analysis: Inflammatory cytokines were analysis
      with RayBio human inflammation antibody array 3 according to the manufacturer's instruction.
      (Cat# AAH-INF-3, RayBiotech Inc. Norcross, GA, USA).29 Measurements of complement activation
      and leukocytes activation: Complement Component 3a (C3a), C5a, and Human Terminal Complement
      Complex C5b-9 (C5b-9) were measured with human C3a EIA kit, human C5a EIA kit, Human Terminal
      Complement Complex C5b-9 kit, Life Science Inc.). Leukocyte elastase were measured by Elisa
      kit for Human Elastase 2,Neutrophil(NE, Life Science Inc.)
    

Intervention name(s): Cardiopulmonary bypass
Intervention type(s): Other
Intervention description(s): sequential changes of oxidative injuries before and after cardiopulmonary bypass
Other intervention name(s): oxidative injuries; inflammatory cytokines; complements; leukocyte elastase
Intervention MeSH terms: Complement System Proteins
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        patients who receive an open heart surgery under cardiopulmonary bypass
      
Biospecimen description: 
      whole blood and plasma
    
Keywords: cardiopulmonary bypass; oxidative injuries