Comparison of in vivo and in vitro cholinergic responses of normal and denervated XXXX hearts.

@entity235 @entity1239 @entity56 @entity3451 @entity934
Ten @entity235 were subjected to total extrinsic cardiac denervation. The negative inotropic responses of their hearts were compared with those of nine normal controls with respect to @entity934 ( @entity3451 ; 0.1-1.0 micrograms) and @entity1239 (0.5-100 micrograms) administered intra-coronary. The @entity235 were on cardiopulmonary bypass and atrial and ventricular contractility were measured by means of a four-chamber isovolumic technique. At the end of this phase of the experiment, atrial strips were removed for in vitro evaluation of negative inotropic responses to @entity3451 (1 X 10(-8) to 1 X 10(-6) M) and @entity1239 (1 X 10(-6) to 1 X 10(-4) M). Both in vivo and in vitro methods demonstrated a leftward shift of the dose-response curve for @entity1239 in denervated hearts, indicative of denervation @entity56 . @entity56 to @entity3451 was seen in atria in vitro but not in vivo. An additional 13 @entity235 were used only for in vitro studies. There was no difference in response between these @entity235 and those which had been used for both in vivo and in vitro studies. The results support the in vivo observation that the intrinsic cardiac neurons become supersensitive to nicotinic activation after extrinsic denervation. In addition, in vitro testing revealed @entity56 to @entity3451 which was not detected by in vivo methods. Inasmuch as the in vivo and the in vitro testing were done on the same animals, a method for determining equivalence for in vivo doses and in vitro concentrations is presented.
