Cell-to-cell interaction: a mechanism to explain wave-front progression of myocardial necrosis.

Histological sections performed 24 h after coronary occlusion in eight pigs displayed compact infarcts extending transmurally with well-defined edges; reconstruction and inspection of the area of necrosis showed a geometric distribution of the infarcts with very irregular, interdigitating edges always in continuity with the main mass of necrosis. Reperfusion in 32 pigs after periods of coronary occlusion of 90, 60, 45, and 30 min exponentially reduced infarct size and transmural extension of the infarct but did not modify its geometry. The two-dimensional size, progression, and geometry of the infarcts could be reproduced by a computer model. In the simulated infarcts, each myocardial cell within the area at risk was represented by a pixel. The algorithm included an inner loop, which determined at random at each iteration a status of reversible or irreversible damage to all pixels. The number of iterations could reproduce infarct of various sizes. With the addition of an index of transmural sensitivity to ischemia, progression of the infarct area could also be reproduced. The only possible means of reproducing the geometry of the infarct was to enter into the program a contiguity condition requiring a direct contact between irreversibly damaged pixels. These observations suggest that the physical interaction between cells is an important determinant of progression of necrosis during coronary occlusion.