Intermittently Hypoxic Myocardium

Adult male Wistar rat hearts subjected to 60-min ischaemia followed by reperfusion using a Langendorff perfusion apparatus showed a moderate (30.2 8%) increase in the production of reactive oxygen species determined by the dihydrorhod-amine 123 method and a significant increase in the production of malondialdehyde (from 1 to 23 2.7 nmol/ml) (Szabados etal. 1999). 

Ischaemic hearts of 7 patients aged 48 to 63 years had increased mtDNA damage and OXPHOS gene expression, suggesting that mtDNA damage is associated with OXPHOS deficiency (Corral-Debrinski et al. 1991). Oxidative phosphorylation defects may also play a role in some other forms of cardiac disease as idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, myocarditis, brown atrophy and coronary aAerosclerosis. 

The lipids that constitute the cell membrane, especially those lipids containing unsaturated double bonds, are susceptible to free radical attack, leading to the formation of lipid peroxides and aldehydes (Kako 1985). A number of short chain fragments produced from peroxidation of polyunsaturated fatty acids as 4-hydroxyperoxy nonenal and 4-hydroxy 2-alkenals react with sulphydryl groups of various enzymes modifying their activities. 

A significant amount of lipid peroxidation associated with depressed Na-K-ATPase activity was observed after 15 min of H2O2 (300 pM) Langen-dorff perfusion of the isolated rat heart, and consequently the cell membrane permeability was greatly increased (Oguro etal. 1992). When N -diphenyl-1,4-phenylenediamine (2.5 mM) a potent antioxidant, was added to the perfusate, the lipid peroxidation was totally inhibited. 

Cell adhesion molecule gene expression is upre-gulated in ischaemia/reperfusion. Kacimi etal. (1998) studied intercellular adhesion molecule (ICAM) response to cytokines and acute hypoxia in cultured myocardial cells. Northern blot analysis and immunoassay showed that the proinflammat-ory cytokines interleukin-ip and tumour necrosis factor-a stimulated concentration dependent in- 

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