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 (V(max)). Pacing dogs had an increase in circulating catecholamines during exercise but a lower maximal heart rate (214 +/- 19 vs. 241 +/- 26 beats/min, P < 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 < 0.001) and a decrease in beta-adrenergic signal transduction [isoproterenol-induced adenosine 3',5'-cyclic mono-phosphate (cAMP) production 230 +/- 45 vs. 339 +/- 64 pmol.mg-1.min-1, P < 0.001], V(max) normalized in response to isoproterenol in pacing dogs (2.3 +/- 0.6 vs. 2.2 +/- 0.5 L(max)/s, NS, where L(max) is length at which maximum developed tension occurs). Tension did not normalize (8 +/- 2 vs. 12 +/- 2 g/mm2, P < 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.