Effects of β-adrenoceptor stimulation on pacing-induced failure of dog hypertrophic hearts

1. We tested the hypothesis that the transition to pacing-induced failure in hypertrophic hearts would result in reduced functional and metabolic responses to β-adrenoceptor stimulation. 2. Isoproterenol (ISO; 0.1 μg/kg per min) was infused into a coronary artery in five anaesthetized open-chest control, five aortic stenosis-induced left ventricular hypertrophy (LVH) and five LVH pacing-induced failure dogs. 3. In both control and LVH dogs, but not in failure dogs, ISO significantly increased local regional work (1923 ± 665 vs 2656 ± 715, 1185 ± 286 vs 1906 ± 562 and 835 ± 106 vs 849 ± 216 g.mm/min, respectively), force (11.1 ± 1.4 vs 16.9 ± 2.6, 8.6 ± 1.5 vs 13.7 ± 2.3 and 12.2 ± 1.1 vs 11.0±1.8 g, respectively) and myocardial O₂ consumption (7.3 ± 2.0 vs 10.0±1.5, 8.2 ± 1.6 vs 11.6 ± 2.6 and 4.4 ± 1.5 vs 5.5 ± 1.8 mL O₂/min per 100 g, respectively). 4. Isoproterenol also significantly increased cAMP in control and LVH dogs (474 ± 67 vs 600±91 and 473 ± 34 vs 619 ± 53 pmol/g, respectively). In heart failure, cAMP was significantly lower and there was no significant increase in cAMP in response to [SO (245 ± 43 vs 314 ± 40 pmol/g, respectively). 5. We conclude that there were no significant myocardial functional, O₂ consumption or cAMP responses to ISO after the transition from hypertrophy to cardiac failure.