Selective vagal postganglionic innervation of the sinoatrial and atrioventricular nodes in the non-human primate.

The distribution of parasympathetic postganglionic nerves to the atrioventricular (AVN) and sinoatrial nodal (SAN) regions was investigated in the non-human primate heart. Eight male monkeys (Macaca fascicularis) weighing 5.5-7.0 kg. were anesthetized (alpha-chloralose, 50 mg/kg and urethane, 500 mg/kg) and instrumented to measure arterial pressure, electrocardiogram, atrial and ventricular electrograms. The cervical vagi were electrically stimulated (20 Hz, 4 V, 2 ms) before and after selective denervation (D) of the AVN and/or SAN. Vagal stimulation was repeated during atrial pacing to assess parasympathetic modulation of AVN conduction. Ablation of parasympathetic pathways to the AVN, accomplished by the disruption of the epicardial fat and surface muscle layer at the junction of the inferior vena cava and inferior left atrium eliminated (P less than 0.01) the dromotropic effects of vagal stimulation without affecting the heart rate response (right vagus, before D, paced: atrial rate 218.0 +/- 6.3, ventricular rate 67.1 +/- 23.7; after D: atrial rate 210.3 +/- 6.4, ventricular rate 210.3 +/- 6.4 beats/min, means +/- S.D.). In sharp contrast, surgical dissection of the fat pad overlying the right pulmonary vein-superior vena cava junction significantly (P greater than 0.01) attenuated negative chronotropic effects of vagal stimulation (left vagus, before D the R-R interval increased by 832.7 +/- 146.4 ms, 209.5% increase; after D 37.4 +/- 18.0 ms, 8.8% increase). These data demonstrate discrete vagal efferent pathways innervate both the SAN and AVN regions of the non-human primate heart.

Selective ganglionic blockade of vagal inputs to sinoatrial and/or atrioventricular regions.

Vagal postganglionic neurons to sinoatrial (SAN) and atrioventricular (AVN) nodal regions of the canine heart have been localized surgically around the right pulmonary vein-atrial fat pad and in the fat pad overlying the epicardium at the inferior vena cava-inferior left atrial junction, respectively. Local ganglionic blocking doses (total of 5 mg per injection) of hexamethonium were injected into the pulmonary vein-atrial fat pad to block selectively right and left vagal inputs to the SAN region without interrupting vagal inputs to AVN. Conversely, hexamethonium injected into the inferior vena cava-inferior left atrial pad selectively blocked vagal control of arteriovenous conduction without interfering seriously with vagal control of SAN function. Vagal ganglia situated in pulmonary vein-atrial fat pad also exercise moderate but incomplete control of right atrial contractile force. Lesser vagal control of atrial inotropism is localized in the inferior vena cava-inferior left atrial fat pad. Ganglia situated in a large fat pad on the dorsal epicardial surface of the left atrium (left atrial fat pad) appear to play little or no role in SAN or AVN regulation, although some left preganglionic axons may pass through it en route to the AVN region. Vagal stimulation is associated with prompt and profoundly negative chronotropic and dromotropic responses, but in response to the same stimulation, a negative change in atrial contractile force is much slower in development and is much longer lasting. Such precise anatomical localization and differentiation of the intrinsic vagal regulation of SAN, AVN and contractile force opens new avenues of research on the neural regulation of cardiac performance.

The contribution of Na and K ions to the pacemaker current in sheep cardiac Purkinje fibres.

The ionic components of the pacemaker current are quantitatively analysed in sheep cardiac Purkinje fibres by simultaneous measurements of the intracellular Na activity (alpha iNa) and the membrane current under voltage clamp. The pacemaker current is operationally defined as the Cs inhibited membrane current (ICs) in Ba containing media at clamp potentials negative to -60 mV. At these potentials solutions containing CsCl (0.2-5 mM) shift the holding membrane current into the outward direction and simultaneously decrease alpha iNa. The Cs effects on membrane current and alpha iNa display a similar voltage dependence. A Cs inhibited Na influx contributes to ICs. The ratio ICs/(Cs inhibited Na influx in electrical units) is less than 1 at membrane potentials positive to the potassium equilibrium potential EK and greater than 1 at potentials negative to EK. The ratio is close to 1 at EK suggesting Na ions to be the only carriers of the current at EK whereas K ions contribute to ICs at potentials different from EK. The effects of Cs on the Cs inhibited Na influx and ICs show a very similar dose dependence. The effect is half maximum at approximately 0.2 mM CsCl (in 21.6 mM K; clamp potential: -85 mV). An increase of the external K concentration augments ICs and the Cs inhibited Ca influx. Na and K ions carrying ICs probably cross the membrane via an identical channel. The permeability of the channel for K+ is about 10-20 times larger than for Na+. The ICs reversal potential of a fibre bathed in a medium containing 5.4 mM K is estimated to be -50 to -60 mV.

Atrial demand pacing to protect against vagal overactivity in sympathetic autonomic neuropathy.

The clinical features, investigation and management of a patient with a subacute autonomic neuropathy are described. A series of physiological and biochemical studies indicated severe but selective sympathetic cardiovascular dysfunction, associated with bradycardia. The bradycardia was enhanced by raising blood pressure but there was no other evidence either of cardiac vagal impairment or hyperreactivity. Oral atropine prevented the bradycardia but had to be withdrawn because of intolerable side effects. An atrial demand pacemaker was implanted to elevate basal heart rate and prevent bradycardia. The pacemaker alone did not improve postural hypotension but it enabled the blood pressure to be readily and safely controlled by a combination of drugs.

[Innervation of the atrioventricular portion of the interatrial septum in the rat]. / Innervatsiia atrioventrikuliarnoi chasti mezhpredserdnoi peregorodki u krysy.

A quantitative electron microscopical investigation has revealed reliable differences in contents of muscular, connective tissue and neural elements in the conductive system, on the one hand (in the atrioventricular node and in the internodal specialized pathways) and in the working myocardium of the inferior third of the interatrial septum, on the other hand. Morphometrical analysis of the neuromuscular interrelations, performed separately for every type of specialized conductive myocytes (II, III) and of working cardiomyocytes of the interatrial septum, reveals some differences in size of the neural fibers and their terminals and in distance between them and myocytes. The synaptic vesicles of the efferent terminals are qualitatively different in all types of the myocytes. The afferent terminals situating near specialized cardiac cells are characterized. Criteria for distinguishing small and large granular vesicles in the terminals are discussed. A suggestion is made that the innervational peculiarities revealed reflect certain specificity in regulation the conduction in the atrioventricular area of the heart.

[Role of the autonomic nervous system in early arrhythmias in acute myocardial infarct in the rabbit]. / Influencia del sistema nervioso autónomo sobre las arritmias tempranas en el infarto miocárdico agudo en el conejo.

In order to evaluate the influence of the autonomic nervous system in the incidence and characteristics of the early arrhytmias that follows myocardial infarction, we have developed an experimental myocardial infarction in rabbits by acute occlusion of the left ventricular artery. The influence of adrenergic and cholinergic suppression over rhythm disorders and hemodynamics changes after experimental infarction in the rabbit was also studied. We found that after the acute experimental infarction in the rabbit heart, arose an early stage of rhythm disorders in 60% of the animals. In a group of animals that were injected with Practolol before coronary occlusion, the incidence of arrhythmias was 25% and in a group of animals with vagotomy prior to occlussion none of them developed rhythm disorders. It was concluded that the model is highly steemed for the study of early arrhytmias and that automatic nervous system has an important role in the incidence of such arrhythmias.

[Morphofunctional characteristics of pacemaker formations situated in the atrioventricular valves of the heart]. / Morfofunktsional'naia kharakteristika peismekernykh obrazovanii, raspolozhennykh v atrioventrikuliarnykh klapanakh serdtsa.

By the microelectrode technique and the method of electron microscopy multicellular formations responsible for generation of the automatic pacemaker activity were found in the cusps of the atrioventricular valves in the rabbit heart. Cells of different morphological structure were revealed: P-cells, cells of the Purkinje type and transitional cells. These formations have rich innervation, mainly of cholinergic nature. A certain correlation was established between the morphological and electrophysiological characteristics of these cells.

Temperature effects on pacemaker generation, membrane potential, and critical firing threshold in Aplysia neurons.

Temperature increases cause a regular and reproducible increase in the frequency of generation of pacemaker potentials in most Aplysia neurons specialized for this type of activity which can only be explained as a direct stimulating effect of temperature upon the ionic mechanisms responsible for pacemaker potentials. At the same time all cells in the visceral ganglion undergo a membrane potential hyperpolarization of approximately 1-2 mv/ degrees C warmed. In spite of the marked variation in resting membrane potential the critical firing threshold remains at a constant membrane potential level at all temperatures in the absence of accommodative changes. The temperature-frequency curves of all types of cells are interpreted as a result of the interaction between the effects of temperature on the pacemaker-generating mechanism and resting membrane potential. Previous observations on the effects of temperature on excitability of mammalian neurons suggest that other types of neurons may undergo similar marked shifts in resting membrane potential with temperature variation.