ULTRASTRUCTURE OF MUSCLE CELLS AND CAPILLARIES OF ISOLATED RAT HEARTS AFTER DIFFUSE ISCHEMIA AND HYPERCAPNIA

Studies of diffuse ischemia, hypercapnia and anoxia on 19 isolated and perfused rat hearts yielded the following results: A diffuse ischemia caused minimal clearing of the sarcoplasm and a slight spotty clearing of the mitochondrial matrix with retained cristae. As in anoxia, the mitochondrial granula disappeared. Hypothermia (4° C) reduced myocardial metabolism sharply, preventing loss of the granula. Hypercapnia (20% CO2 with CO2 pp 146 mm Hg) reduced coronary flow by one-third, decreased oxygen consumption by one-half, slowed the heart rate by one-third, and reduced the pH from 7.39 to 6.85. Electron-microscopically, the resulting edema of the capillary endothelial cells narrowed the lumen by 20%. Minimal changes, such as clearing of the sarcoplasm and spotty clearing of the mitochondrial matrix, developed in the myocardial cells. Although decreased in number, mitochondrial granula persisted. Anoxia with hypercapnia (100% CO2) induced severe bradycardia and a constricted coronary flow to less than one-tenth normal, resulting nearly in a diffuse ischemia. The pH fell from 7.34 to 6.21. Electron-microscopically the endothelial cells appeared more edematous than with hypercapnia alone. The capillary lumen narrowed to two-thirds normal. The sarcoplasm of myocardial cells became moderately edematous and glycogen granules disappeared. Transverse tubules and the endoplasmic reticulum widened slightly. A slight spotty clearing of the mitochondrial matrix developed; the cristae remained but all mitochondrial granula disappeared. With aerobic perfusion (reperfusion) after the experimental procedures described above, the heart rate, coronary flow, oxygen consumption and the fine structure of the myocardium returned to normal. Myocardial cells of the Langendorff heart were able to reform granules of the mitochondria and glycogen lost during ischemia, hypercapnia and anoxia. Regions of myocardium in all three experimental groups failed to blacken with osmium fixation by perfusion; they remained clear and revealed collapsed capillaries or capillaries with severely edematous endothelial cells and intense hypoxic damage of myocardial cells. The greatest changes in capillaries and muscle cells developed in anoxia with hypercapnia (100% CO2). On reperfusion the ultrastructure of the clear regions failed to become normal. The results indicate a rise in CO2 tension and a fall in pH are important in causing hypoxic changes in myocardial cells; both occur during ischemia. Quantitative relationships between edema of the capillary endothelial cells and the reduction in the vessel lumen were calculated. The distribution of hypoxic changes in myocardial cells appeared to depend on the microcirculation. The capillary-induced ischemia is an important factor in causing focal disseminated hypoxic necrosis of the myocardium. © 1969 Springer-Verlag.