Calcium Fluxes and Reperfusion Damage: The Role of Mitochondria
Myocardial ischaemia in the absence of reperfusion ultimately leads to cell necrosis and the development of infarction (Mergner and Schaper, 1982; Lucchesi and Mullane, 1986; Smith et al., 1988). While restoration of flow is clearly a prerequisite for tissue recovery, the process of reperfusion itself results in the development of metabolic and functional abnormalities that were not apparent during the ischaemic period and can be regarded as the response of the myocardium to reperfusion. This response encompasses a variety of phenomena, including reperfusion arrhythmias (Woodward and Zakaria, 1985; Manning et al., 1985; Sugiyama and Ozawa, 1987), myocardial stunning (Gross et al., 1986; Bolli et al., 1989), cell lysis (Shen and Jennings, 1972a,b) and an inflammatory component characterized by neutrophil infiltration (Mullane et al., 1984; Lucchesi and Mullane, 1986; Smith et al., 1988). One of the key responses that occur as part of this continuum is the acute cell damage that occurs at the point of reperfusion. A component of this damage has been shown to be dependent on the reintroduction of oxygen to the tissue and on this basis it is frequently referred to as the ‘oxygen paradox’. Perturbations of cell calcium homoeostasis have been implicated in most aspects of reperfusion damage (Shen and Jennings, 1972a,b; Mergner and Schaper, 1982; Sugiyama and Ozawa, 1987), but in this present chapter we shall concentrate on the oxygen paradox and examine the role that calcium plays in this phenomenon.
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