SR CA2-ATPASE ACTIVITY AND EXPRESSION IN VENTRICULAR MYOCARDIUM OF DOGS WITH HEART-FAILURE()

The purpose of this study was to examine the activity and expression o f sarcoplasmic reticulum (SR) Ca2+-ATPase in left ventricular (LV) myo cardium of dogs with chronic heart failure (HF). LV and right ventricu lar (RV) tissue specimens were obtained from six normal (NL) control d ogs and six dogs with chronic HF (LV ejection fraction, 23 +/- 2%) pro duced by multiple sequential intracoronary microembolizations. Thapsig argin-sensitive Ca2+-ATPase activity was measured in isolated SR membr ane fractions prepared from LV and RV myocardium. Ca2+-ATPase expressi on, using a specific dog myocardium monoclonal antibody, was measured in sodium dodecyl sulfate (SDS) extract prepared from LV and RV myocar dium. Ca2+-ATPase activity in both ventricles of NL or KF dogs increas ed with increasing Ca2+ concentration and reached a plateau at 3 mu M Ca2+. The maximal velocity (V-max, mu mol P-i released.min(-1).mg(-1)) of Ca2+-ATPase activity was significantly lower in LV of HF dogs comp ared with NL(0.15 +/- 0.01 vs. 0.23 +/- 0.01, P < 0.05), whereas the a ffinity of the Ca2+ pump for Ca2+ was unchanged. LV tissue levels of C a2+-ATPase (densitometric units/5 mu g noncollagen protein) were also significantly lower in LV myocardium of HF dogs compared with NL (3.52 +/- 0.43 vs . 5.53 +/- 0.47, P < 0.05). No significant differences in Ca2+-ATPase activity or expression were observed in RV myocardium of HF dogs compared with NL. We conclude that SR Ca2+-ATPase activity and protein levels are reduced in LV myocardium of dogs with chronic HF. This abnormality of the SR Ca2+ pump of the failed LV can result in im paired Ca2+ uptake and ultimately to Ca2+ overload and global LV dysfu nction.