Quantitative effect of a single large dose of methylprednisolone on infarct size in baboons

Despite numerous studies directed at determining the ability of glucocorticoids to minimise myocardial ischaemic damage following acute coronary occlusion, there remains no clear consensus concerning their usefulness. Within an ischaemic region, glucocorticoids produce membrane stabilising effects which decrease the autolytic effects of marked cellular swelling and lysosomal membrane rupture. Their use has also been associated with a decreased cellular lysis due to infiltrating inflammatory cells and with an increase in collateral blood flow. The use of glucocorticoids has remained clinically attractive due to experimental observations regarding these local actions; however, the potential of these actions to enhance long-term viability of ischaemic myocardium has remained uncertain. A major problem in the comparison of the extent of infarction between treated and untreated animals has been the variability in infarct size that results from coronary artery ligation at any given anatomical site. In the experimental baboon model which we have employed, we have previously shown that the ultimate epicardial area of infarction, as well as the volume of infarction as assessed histologically at 7 days post occlusion, shows a good linear relationship to the area of ischaemic injury at 1-hour post occlusion, as assessed by high resolution epicardial ST segment mapping. In this way animals may serve as their own controls and as long as an intervention is initiated at 1 h or later post occlusion, then the epicardial area or transmural volume of histologically assessed infarction at 7 days can be compared with the predicted epicardial area or transmural volume of infarction and hence determine the effect of that intervention in altering infarct size. This experimental model does not rely on a comparison of the absolute magnitude of infarcts between treated and untreated animals and, therefore, avoids the error introduced by the inherent variability in infarct size between animals after coronary occlusion.