EFFECTS OF THE REACTIVE OXYGEN SPECIES HYPOCHLOROUS ACID AND HYDROGEN-PEROXIDE ON FORCE PRODUCTION AND CALCIUM SENSITIVITY OF RAT CARDIAC MYOFILAMENTS

Neutrophil activation occurs after myocardial infarction/ischaemia. Th ey produce the reactive oxygen species (ROS) hypochlorous acid (HOCl) and hydrogen peroxide (H2O2) which could contribute to contractile dys function upon reperfusion. The myofilaments of 'skinned' rat cardiac m uscle were exposed to ROS in various states of activation. Isometric f orce was measured at controlled degrees of activation. A single applic ation of 10 mu M HOCl for 1 min increased log [Ca-2+] for half-maximal activation (log K-1/2) from 5.23 to 5.32, initial maximum Ca-activate d force (F-Ca,F- max) was reduced by 18.8+/-5.8% and resting tension i ncreased to 15.4+/-8.0% of F-Ca,F- max At 50 mu M, a 1-min exposure to HOCl produced a greater increase in Ca-sensitivity (log K-1/2 increas ed from 5.23 to 5.47), a greater reduction in F-?(Ca,F- max) (falling by 42.3+/-23.2%) and a greater increase in resting tension (to 25+/-10 .7% of F-Ca,F- max). The nature of the resting tension rise was examin ed by reducing pH before and during exposure to HOCl; the results are consistent with 'rigor-like' cross-bridges being involved. H2O2 was wi thout effect on the myofilaments at physiologically relevant (<10 mu M ) concentrations. These results suggest that ROS associated with infla mmation could contribute to post-ischaemic myocardial dysfunction.