The purpose of this study was to investigate myofibrillar mechanisms of depressed contractile function associated with myocardial stunning. We first tested whether the degree of stunning was directly related to changes in myofilament Ca2+ sensitivity. Variable degrees and durations of low-flow ischemia were followed by 30 minutes of reperfusion in an open chest porcine model of regional myocardial stunning (n = 27). Ca2+ sensitivity of isometric tension was measured in skinned myocytes obtained from endocardial biopsies taken during control aerobic flow and after 30 minutes of reperfusion. The degree of stunning, as assessed by percent systolic wall thickening, ranged from 3% to 75% of control but did not correlate (r=.11) with changes in pCa50, ie, pCa for half-maximal tension. Only in the group (n=10) with the most severe level of ischemia was there a significant decrease in pCa50 (from 5.97 ± 0.06 in the control condition to 5.86 ± 0.07 after ischemia, P<.05). Less severe levels of ischemia (n=17) resulted in significant stunning (percent systolic wall thickening, 38 ± 4% of control) but not change in pCa50. To investigate the possibility that alterations in myofibrillar cross-bridge kinetics contribute to depressed function in stunning, maximum velocity of shortening (V(O)) was measured in postischemic myocytes. V(O) in postischemic myocytes was reduced to 56±4% of V(O) in control myocytes and was independent both of the degree of stunning (r=.26) and changes in Ca2+ sensitivity. We conclude that the basis of stunning involves decreased cycling rates of myofibrillar cross-bridges and, after more severe ischemia, a reduction in myofilament Ca2+ sensitivity.
- contractile proteins
- myocardial contraction
- myocardial ischemia
- myocardial reperfusion injury
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine