REDUCED H-3 OUABAIN BINDING-SITE (NA,K-ATPASE) CONCENTRATION IN VENTRICULAR MYOCARDIUM OF DOGS WITH TACHYCARDIA-INDUCED HEART-FAILURE

The present study evaluates H-3-ouabain binding site (Na,K-ATPase) con centration in left ventricular myocardium of dogs with heart failure i nduced by tachycardia as a result of ventricular pacing. Samples of le ft ventricle were obtained from 10 dogs exposed to pacing of 240 beats /min for 3 to 4 weeks and eight sham-operated controls. Na,K-ATPase wa s quantified using vanadate facilitated H-3-ouabain binding to intact samples. At time of sacrifice paced dogs showed clinical signs of hear t failure, a significant 257 % increase in left ventricular end diasto lic pressure and a significant 46 % decrease in left ventricular dP/dt compared with control. There was no significant change in left ventri cular mass. H-3-ouabain binding concentration was significantly reduce d by 16 %. Evaluation of 3H-ouabain binding kinetics revealed no signi ficant difference between myocardium from paced and control dogs: Equi librium binding conditions were at the various concentrations used obt ained after similar incubation rime; nonspecific uptake and retention of H-3-ouabain was 0.9-0.8 % of total uptake and retention obtained in the standard assay; apparent dissociation constant (K-D) was 6.5 x 10 (-8)-6.6 x 1O(-8)mol/l; loss of specifically bound H-3-ouabain washout at 0 degrees C occurred with a half-life time (T-1/2) of 120 and 121 h. Hence, total H-3-ouabain binding site concentration in left ventric ular myocardium was (mean +/- SEM) 1110 +/- 56 and 1317 +/- 68 pmol/g wet weight, 8.54 +/- 0.43 and 10.05 +/- 0.52 pmol/mg protein, and the total amount of H-3-ouabain binding sites in the entire left ventricle 121 +/- 6 and 162 +/- 8 nmol in paced (n = 10) and control (n = 8) do gs (p<0.05), respectively. In conclusion, the present study reports a significant reduction in left ventricular myocardium H-3-ouabain bindi ng site concentration in tachycardia induced heart failure. This obser vation supports the concept of a relationship between Na,K-ATPase conc entration and contractile capacity and may be of pathophysiological im portance in tachycardia and heart failure.