Quantitative correlation between cell swelling and necrosis in myocardial ischemia in dogs.

Previously, we demonstrated that there were effects of elevated plasma osmolality on both early cell swelling and eventual cell necrosis in ischemic cardiac muscle. The present study quantifies the extent of cell volume derangement, determines whether or not there is a quantitative relationship between cell swelling and eventual necrosis, and defines the time limits of ischemia within which prevention of early swelling by hyperosmotic intervention can reduce eventual necrosis. Computer-assisted analysis of tissue pathology was used for quantification of myocardial cell swelling early during ischemia. The results then were correlated with the extent of eventual necrosis. When canine posterior papillary muscle was sampled for electron microscopy soon after the restoration of blood flow following proximal circumflex artery occlusion, stereological methods revealed a substantial increase in myocardial cell volume. The data define the spectrum of volume gain in ischemic myocardial cells. The effectiveness of an osmotic intervention with mannitol in preventing cell swelling and eventual necrosis was limited to ischemic periods of less than 90 minutes. There was a strong linear correlation between the fractions of cells with increased volume (whether the increase was measured as cytoplasmic space, mitochondrial volume, or overall volume expansion), and the fraction of cells necrotic 12 hours after restoration of blood flow. The pattern of action of osmotic intervention in the prevention of ischemic cell swelling and in diminishing eventual necrosis in this model suggests strongly that there is an important relationship between a failure in cell volume regulation and eventual cell death in myocardial ischemia. Circ Res 47: 653-665, 1980