EFFECTS OF ISCHEMIA ON SARCOPLASMIC-RETICULUM AND CONTRACTILE MYOFILAMENT ACTIVITY IN HUMAN MYOCARDIUM

The effects of global ischemia on the contractile system and on sarcop lasmic reticulum (SR) function were studied by measuring the isometric tension and the SR Ca2+ release activity of chemically skinned cardia c fiber preparations from seven patients undergoing open-heart surgery . Ten minutes of ischemia caused 1) a decrease in the myofilament sens itivity to Ca2+ (expected Ca2+ concentration giving half-maximal tensi on; from 0.69 +/- 0.04 to 1.38 +/- 0.06 muM, n = 7) and in the coopera tivity index (Hill coefficient; from 2.61 +/- 0.45 to 0.92 +/- 0.15, n = 7), 2) a decrease in myosin light chain phosphorylation, and 3) a 3 00% increase in the threshold caffeine concentration for SR Ca2+ efflu x channel activation, with a 30% reduction in the rate of Ca2+ release by caffeine at threshold concentrations and a 23% reduction in the ra te of release by 20 mM caffeine. After preincubation with 5 muM triflu operazine, a calmodulin antagonist, the caffeine threshold of ischemic and control cardiac muscle became comparable. Most changes were rever sed by reperfusion, while the caffeine threshold was still two times g reater than control. These results indicate that ischemia caused alter ations of the cardiac muscle contractile apparatus and the SR that wer e reversed only after reperfusion.