We correlated the effects of high volumes of K+ cardioplegic solution on myocardial structure and function in 16 dogs following open-heart surgery. Eight animals received high volume potassium cardioplegic solution (25 cc/kg body weight, every 30 min) during 90 min of ischemic arrest (HVK-C group). The others received sufficient cardioplegic solution to maintain complete electrical arrest as defined by voltage monitoring criteria (VM group). Cardiac index (CI), left ventricular stroke work index (LVSWI), and myocardial contractility (dp/dt) were determined before arrest and after 90 min of ischemia and 45 min of reperfusion. Biopsies were taken for EM ultrastructure and ATP estimation. Morphometric analysis of EM micrographs found increased volume of damaged mitochondria (DMR) (p less than 0.025), damaged myofibrils (DMF) (p less than 0.001), intermyofibrilar edema (p less than 0.005), T-tubule and sarcoplasmic reticulum (p less than 0.05) in the HVK-C group. Left ventricular (LV) function was more depressed in animals receiving HVK-C. CI decreased by 1.8 +/- 0.4 l/min/square meter (p less than 0.01), LVSWS fell by 3.3 +/- 0.8 gm-m/beat/Kg (p less than 0.01), dp/dt decreased by 684 +/- 135 (p less than 0.0025). ATP decreased by 26% in HVK-C and by 12% in VM group (0.1 less than p less than 0.05). Structural damage (scores of injured volume of mitochondria and myofibrils) correlated with post-ischemic depression of LV function (Cardiac output and myocardial contractility), r = -0.72 and -0.66 (p less than 0.001 and 0.004).