Effects of beta-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 beta-adrenoceptor stimulation. 2. Isoproterenol (ISO; 0.1 microg/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 (1,923+/-665 vs 2,656+/-715, 1,185+/-286 vs 1,906+/-562 and 835+/-106 vs 849+/-216g.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+/-1.8g, 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 ISO (245+/-43 vs 314+/-40pmol/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.