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.
Juneau
C
C
Centre de Recherche de l'Hôpital du Sacré-Coeur, Université de Montréal, Quebec, Canada.
Calderone
A
A
Rouleau
J L
JL
D000818:Animals; D002303:Cardiac Output, Low / Q000378:metabolism / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D005080:Exercise Test; D006321:Heart / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol