Intrinsic neural regulation of the heart in the chronic, conscious dog

The present experiments were performed to examine the capability of the intrinsic cardiac nerves (ICN) to modify cardiac performance in the resting chronic, conscious dog. Control and cardiac-denervated dogs were instrumented for recording of left atrial (LA) and ventricular (LV) contractility, heart rate, and atrioventricular (AV) conduction time. Acetylcholine (ACh) and nicotine (Nic) were administered via an indwelling coronary artery catheter. Limited distribution from the injection site only allowed access to the LA, LV, and AV node. Both β-blockade with timolol and cardiac denervation were used to separate direct effects of ICN stimulation from indirect (e.g., reflex) effects. ACh produced the expected negative inotropic and dromotropic changes. ICN stimulation with Nic caused large decreases in LA contractility along with depression of AV conduction but only trivial effects on the LV. We concluded that the ICN has limited effects on cardiac performance in the resting animal under minimal sympathetic drive. It is likely, however, that the ICN is capable of significantly depressing cardiac function under conditions of elevated sympathetic tone as would be encountered in exercise.

Atrioventricular responses of canine heart following chronic unilateral vagotomy

The intrinsic cardiac nerves (ICN) have been shown to develop supersensitivity to nicotine (NIC) following complete extrinsic cardiac denervation. The present experiments were performed to delineate the pattern of ICN distribution in the heart by examining the pattern of NIC supersensitivity after unilateral vagotomy (VGX). Thirty-eight dogs were placed on cardiopulmonary bypass and inotropy evaluated by means of isovolumic pressures from fluid-filled balloons placed in the atria and ventricles. The animals were divided into three groups: group I, sham-operated controls; group II, animals studied 1–2 wk after VGX; and group III, animals studied 8–12 wk after VGX. Chronotropic and inotropic responses were evaluated in terms of NIC and acetylcholine (ACh) dose-response curves as well as frequency-response curves to stimulation of the intact vagus nerve (0.5–30 Hz). No change in NIC sensitivity was observed in group II, and vagal frequency-response curves were identical to group I. In group III dogs, both the right atrium and right ventricle showed significant increases in NIC sensitivity after left vagotomy. All group III animals showed right-shifted frequency-response curves. We conclude that nicotinic supersensitivity of the ICN and inotropic unresponsiveness to vagal stimulation occur but are slow in developing (70–130 days); and preganglionic sprouting does not appear to play a functional role in the adjustment of cardiac control mechanisms to unilateral vagotomy.

Source of intrinsic innervation of canine ventricles: a functional study

Recently it has been suggested that the parasympathetic innervation of the ventricles is by way of postganglionic axones that emanate from ganglion cells in the atria, reaching the ventricles by traversing the atrioventricular (AV) groove. We designed a series of experiments to test this hypothesis. Phenol (89%) was applied to the AV groove and surrounding 5 mm of epicardium in 21 dogs on cardiopulmonary bypass. The effects of intracoronary acetylcholine (ACh; 1-5 micrograms) and intracoronary nicotine (NIC; 25–100 micrograms) on cardiac isovolumic pressures were evaluated after beta-blockade. In another series of experiments, eight dogs were exposed to phenol in the same way and allowed to recover for 7–10 days. Atrial and ventricular responses to NIC were unaffected by phenol application to the AV groove in the acute animals when compared with application of saline alone. However, in the chronic animals, pretreatment with phenol 7–10 days previously reduced the ventricular responses to NIC by 70% while leaving the atrial responses intact. These data indicate that the intrinsic cardiac nerves (ICN) of the canine ventricles consist primarily of postganglionic parasympathetic axones which arise from supraventricular ganglia and cross the AV groove.

Functional integrity of intrinsic cardiac nerves located over an acute transmural myocardial infarction

Acute transmural myocardial infarction has been reported to functionally denervate the normal myocardium distal to the infarcted zone by interrupting neurotransmission in axons coursing in the subepicardial region of the myocardial necrosis. To directly investigate the viability of such neurotransmission, the effects of acute transmural myocardial infarction on conduction in the intrinsic cardiac nerves overlying and distal to an experimentally induced acute transmural myocardial infarction were studied. In eight dogs, during control states electrical stimulation of the epicardium adjacent to a coronary artery produced compound action potentials in the more cranially located cardiopulmonary nerves. Thereafter, in four dogs an acute transmural myocardial infarction was produced by injecting rapidly hardening latex into a major diagonal branch of the left anterior descending coronary artery. Epicardial stimulation over the infarct, as well as proximal or distal to it, produced compound action potentials that conducted at normal velocities for at least 12 h postinfarction. The transmural extent of the infarct was verified with tetrazolium blue staining at the end of the experiment. In the other four dogs, compound action potentials were generated in cardiopulmonary nerves as described above and then ventricular fibrillation was produced to assess the effects of global anoxia on the function of axons coursing in cardiac nerves. Following the onset of ventricular fibrillation, compound action potentials were generated in these nerves in C fibers for up to 2 h, in B fibers for up to 4 h, and in A fibers for at least 12 h. However, the conduction velocities of these axons was gradually reduced over these periods of time, indicating that, in contrast to the function of axons coursing over a transmural myocardial infarction, their function gradually deteriorated. Thus, by directly assessing the function of axons coursing over a transmural infarction, it is concluded that an acute transmural myocardial infarction does not significantly modify the function of intrinsic cardiac nerves coursing over such an infarct.

Altered nicotinic sensitivity of AV node in surgically denervated canine hearts

The responses of normal and cardiac-denervated (DNV) dogs to acetylcholine (ACh) and nicotine (NIC) were examined to determine if the intrinsic cardiac nerves (ICN) that modulate electrical conduction display denervation supersensitivity. Control (n = 18) and DNV (n = 18) animals were placed on cardiopulmonary bypass. Recording of intra-atrial (P-A), intraventricular (H-V), and atrioventricular (AV) nodal (A-H) conduction times were made from the region of the His bundle. ACh (0.1-10 micrograms) was used to produce muscarinic stimulation, whereas NIC (0.1-400 micrograms) was employed to stimulate the ICN. All drugs were administered intracoronary. No supersensitivity to either ACh or NIC was seen in the data from the P-A or H-V intervals of the His electrogram in the DNV animals. However, this group displayed approximately a 10-fold increase in the negative dromotropic effect of NIC on the AV node compared with control. No significant change in muscarinic sensitivity of the AV node was observed in the DNV animals. We conclude that 1) no denervation supersensitivity of the ICN mediating effects on intra-atrial and intraventricular conduction occurs; 2) the AV node itself does not show muscarinic supersensitivity following extrinsic denervation; 3) the ICN do display denervation supersensitivity as shown by a 10-fold increase in the effects of NIC on AV nodal conduction time.