Cholinergic sensitivity of the denervated cannine heart.

We determined whether the extrinsically denervated heart becomes supersensitive to acetylcholine (ACh) and nicotine (NIC). Fifteen mongrel dogs were subjected to total extrinsic cardiac denervation. The negative inotropic responses of their hearts were compared with those of 15 control dogs with respect to ACh (0.005-1.0 pig) and NIC (10-300 fig) administered intracoronary. All dogs were placed on cardiopulmonary bypass, and atrial and ventricular contractility were evaluated using a four-chamber, isovolumic technique. The denervated hearts showed no detectable supersensitivity to ACh. Because the effects of ACh at the doses used are almost completely on the decentralized cardiac muscle cells, the results indicate that the cardiac muscle is an exception to the increased sensitivity usually produced by decentralization. When the positive inotropic effects of NIC were blocked by practolol in the control hearts, the negative inotropic effects of the intrinsic parasympathetic neurons (IPN) are seen clearly. These intrinsic neural elements are specifically activated by NIC. The denervated atria and ventricles displayed NIC dose-response curves that consistently were shifted to the left when compared to control animals after 0,-blockade. These results indicate the IPN, which are denervated by the surgical procedure, do become more sensitive to NIC. The increases in sensitivity to NIC were between 2and 6-fold, comparable to the increased sensitivity to norepinephrine observed in denervated hearts. The postjunctional IPN supersensitivity probably occurs as a result of spreading of nicotinic receptors on the ganglion cell membrane.