Myocardial beta-adrenergic and mechanical properties in pacing-induced heart failure in dogs

Forty-eight dogs had pacing overdrive at 250 beats/min for 4-6 wk until heart failure developed. Myocardium from pacing dogs had a decrease in tension and maximum unloaded velocity of shortening (Vmax). Pacing dogs had an increase in circulating catecholamines during exercise but a lower maximal heart rate (214 +/- 19 vs. 241 +/- 26 beats/min, P less than 0.05). A blunted chronotropic response to isoproterenol was also found. However, despite a decrease in beta-adrenergic receptor density (80 +/- 14 vs. 122 +/- 14 fmol/mg, P less than 0.001) and a decrease in beta-adrenergic signal transduction [isoproterenol-induced adenosine 3',5'-cyclic monophosphate (cAMP) production 230 +/- 45 vs. 339 +/- 64 pmol.mg-1.min-1, P less than 0.001], Vmax normalized in response to isoproterenol in pacing dogs (2.3 +/- 0.6 vs. 2.2 +/- 0.5 Lmax/s, NS, where Lmax is length at which maximum developed tension occurs). Tension did not normalize (8 +/- 2 vs. 12 +/- 2 g/mm2, P less than 0.001). Thus in this model of heart failure, despite widespread evidence of decreased beta-adrenergic signal transduction, indexes of shortening but not force generation normalize in response to isoproterenol.