|Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
A series of in vivo experiments using hypoxemic immature piglets was performed to test the hypotheses that uncontrolled reoxygenation of cyanotic immature hearts when starting cardiopulmonary bypass (CPB) with the conventional high pO2 pmduces a reoxygenation injury that a) is mediated by oxidants derived myocardial lipidperoxidation , and b) is avoidable by controlling pO2 at CPB and additives to the CPB prime (Controlled Reoxygenation).
Immature piglets (<3 weeks old) were placed on 120 minutes of cardiopulmonary bypass, and 5 piglets served as biochemical control without CPB (biochemical Control Group). Five piglets underwent CPB without hypoxemia (CPB control). Twenty eight others were made hypoxic on CPB for 60 minutes by lowering p02 to 20-30mmHg, followed by reoxygenation for 60 minutes at pO2-400mmHg (Hyperoxic REOX Group) or pO2100mmHg (Normoxemic REOX Group). Others were allocated to the treatment groups in which following additives were administered to the CPB: deferoxamine (
50mg/kg total dose); the NO-synthase inhibitor N -nitro-L-arginine methyl ester (L-NAME, 4mg/kg); L-arginine (20 mg/kg); antioxidants (MPG Catalase Coenzyme Q10); Glutamate/ Asparatate (13mMol).
Post CPB myocardial function was evaluated from endsystolic elastance (Ees, conductance catheter) and Starling curv analysis. Myocardial conjugated diene (CD) production, ( a marker of lipidperoxidation) creatine phosphokinase (CPK) leakage were assessed as biochemical markers of injury, and antioxidant reserve capacity determined by measuring malondialdehyde (MDA) in post CPB myocardium incubated in the oxidant, t-butyl hydroperoxide(t-BHP).
CPB without hypoxia caused no oxidant or functional damage. Conversely, reoxygenation (Hyperoxic) raised myocardial conjugated dienes and CPK production, reduced antioxidant reserve capacity, and produced severe postbypass dysfunction. In contrast, deferoxamine, inhibition of NO production by L-NAME, reduction of antioxidants by MPG catalase, coenzyme Q10 equally avoided conjugated dienes production and CPK release, retaine normal antioxidant reserve, and functional recovery was significantly improved in all Rx groups.
We conclude that reoxygenation of the hypoxemic immature heart by initiating the conventional hyperoxic CPB causes oxidant damage characterized by lipid peroxidation and reduced antioxidants, leading to functional depression surgical reoxygenation injury of myocardium . These detrimental effects can be reduced by starting CPB at the physiological pO2 or addition of anti-oxidants agents to the CPB. Less