Alterations in energy metabolism and ultrastructure upon reperfusion of the ischemic myocardium after coronary occlusion.

The effects on myocardial function, metabolism and ultrastructure of 60 minutes of reperfusion, instituted after 30, 60 and 90 minutes of occlusion of the left anterior descending coronary artery, were studied in 48 dogs. Twelve sham-operated dogs served as controls. Coronary occlusion for 60 or 90 minutes caused significant depression in the first derivative of left ventricular pressure (dP/dt) (P less than 0.05) that could not be reversed by reperfusion. Upon reperfusion, creatine phosphate stores in myocardium made ischemic for 30 and 60 minutes, but not for 90 minutes, returned toward control levels, but stores of adenosine triphosphate (ATP) and total nucleotides and the ATP/adenosine diphosphate ratio of myocardium subjected to 60 and 90 minutes of ischemia were further decreased. After 60 and 90 minutes of ischemia, swelling of the sarcoplasmic reticulum and mitochondrial damage (swelling, decreased matrix density and partial loss of cristae) were seen. Myofibrils were relaxed in all these groups. Reperfusion produced gross contraction of myofibrils and aggravated these changes in mitochondria and sarcoplasmic reticulum. In the hearts subjected to 90 minutes of ischemia these changes were gross. The levels of creatine phosphokinase, glutamic oxaloacetic transaminase and lactic dehydrogenase in the coronary sinus blood increased dramatically (P less than 0.05) upon reperfusion after 60 or 90 minutes of occlusion, indicating severe impairment of cell membranes. This secondary rise in serum enzyme activity during reperfusion should be taken into consideration when estimating the size of a myocardial infarct from enzyme changes alone. It appears that 60 and 90 minutes of ischemia cause severe myocardial damage that is not reversed by reperfusion maintained for 1 hour although longer periods of reperfusion may be beneficial.