Cardiac Myofilament Protein Function is Altered During Sepsis

Male Sprague–Dawley rats (350–500 g) were made septic by intraperitoneal injection of 200 mg/kg cecal material in 5% dextrose in water (D5W; 5 ml/kg). Control rats (n=11) received D5W. Preparations were studied on days 1 (n=7), 3 (n=7), and 7 (n=8) of sepsis. In isolated hearts, ventricular function was depressed on days 3 and 7 of sepsis. Densitometric analysis of myofilament proteins from septic rats separated by SDS-PAGE showed no differences in relative amounts of actin, troponin, tropomyosin and myosin light chains compared to control. Myofilament function, assessed by measuring ATPase activities, was altered during sepsis. CA2+-independent Mg-ATPase activity was elevated on days 1 and 3 of sepsis, returning toward control by day 7. Maximal ATPase activity was unchanged on day 1, but was increased on days 3 and 7 of sepsis. Myofibrillar myosin K(EDTA)-, Ca2+-, and Mg2+-ATPase activities were not altered, nor were there any apparent changes in myosin heavy chain isoform populations. Our data are the first to demonstrate alterations in minimal and maximal ATPase activities and myofilament CA2+- sensitivity during chronic peritoneal sepsis. These alterations may contribute to observed changes in ventricular function.