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REVERSIBLE COLD BLOCK OF THE SPECIALIZED CARDIAC TISSUES OF THE UNANAESTHETIZED DOG.

The sinoatrial node and the bundle of His in intact, unanesthetized dogs were subjected to local cooling by means of surgically implanted devices. Impulse formation in the sinoatrial node could thus be suppressed at will and the heart rate regulated within a physiological range by an electrode driving the atrium. Reversible blockage of atrioventricular conduction was easily induced on cooling the region of the bundle of His.

Bundle of His↗

Chronotropic and dromotropic responses to stimulation of intracardiac sympathetic nerves to sinoatrial or atrioventricular nodal region in anesthetized dogs.

We gave atropine intravenously to autonomically decentralized, open-chest, anesthetized dogs and stimulated the discrete intracardiac sympathetic nerve fibers to the sinoatrial (SA) (SAS stimulation) or atrioventricular (AV (AVS stimulation) nodal region. A brief burst of neural stimuli was delivered during each cardiac cycle. SAS stimulation consistently decreased the atrial cycle length but had variable effects on the AV interval. The positive chronotropic response to SAS stimulation increased when the level of stimulation (i.e., stimulus pulse duration, pulse amplitude, and number of pulses per burst) was increased. When the heart rate was held constant by atrial pacing, SAS stimulation did not change the AV interval. AVS stimulation decreased the AV conduction time but did not change the atrial cycle length. The AV conduction response increased when the level of AVS stimulation was increased. A high level of AVS stimulation induced an AV junctional rhythm in seven of eight experiments. When the atrial pacing interval was decreased, the basal AV interval increased, and the decrease in AV interval induced by AVS stimulation was exaggerated. The chronotropic response to SAS stimulation and the dromotropic response to AVS stimulation were abolished by propranolol given systemically and by lidocaine given topically. From these results, we conclude that in anesthetized dogs treated with atropine, activation of the discrete intracardiac sympathetic nerves to the SA and AV nodal regions controls the sinus rate and AV conduction time independently and activation of the discrete sympathetic nerves may shift the dominant pacemaker site to a subsidiary site.

Animals↗

[Effect of electric stimulation of the cerebral cortex on cardiac nociceptive signal conduction].

In acute experiments on cats we studied the influence of the cortex cerebri electric stimulation on potentials in the subcortical structures such as the thalamus, hypothalamus, striatum griseum superficiale. The potentials were provoked by electric irritation of the nodus synuatrialis zone of the heart conducting system. A cortex cerebri depressing effect (mainly the 1st and 2nd zones of somatovisceral sensitivity) on cardiac afferent signals with nociceptive component was determined.

Animals↗

Immunological relationship between different types of bovine intermediate filaments.

In order to examine the relationship between the intermediate filaments from Purkinje fibres of the cow heart conduction system and five proposed subclasses of mammalian intermediate filaments, the gel electrophoresis-derived enzyme-linked immunosorbent assay (GEDELISA) has been used to examine the specificity and crossreactivity of our antibodies against the Purkinje fibre intermediate filament protein, skeletin. Bovine tissues known to contain intermediate filaments of the five main subclasses were examined with antiskeletin and with preimmune serum and the specific antiserum absorbed with pure skeletin as controls. The antibodies raised against Purkinje fibre skeletin reacted with all three polypeptides of the "neurofilament triplet", with glial fibrillary acidic protein (GFAP), with smooth muscle desmin and also slightly with some prekeratin subunits and with endothelial vimentin. From studies with monoclonal antibodies and amino acid sequencing, certain regions of all intermediate filaments are suggested to be structurally related. Here we show that Purkinje fibre skeletin seems to share antigenic determinants with the proposed five main classes of intermediate filaments. Our antibody is the first carefully controlled experimentally induced antibody having such properties. This might be due to the special attributes of the intermediate filament system in Purkinje fibres, which themselves have unique properties.

Animals↗

The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart.

OBJECTIVE: The molecular mechanisms that regulate the formation of the conduction system are poorly understood. We studied the developmental expression pattern and functional aspects of the T-box transcription factor Tbx3, a novel marker for the murine central conduction system (CCS). METHODS: The patterns of expression of Tbx3, and of Cx40, Cx43, and Nppa, which are markers for atrial and ventricular chamber-type myocardium in the developing heart, were analyzed in mice by in situ hybridization and three-dimensional reconstruction analysis. The function of Tbx3 in regulating Nppa and Cx40 promoter activity was studied in vitro. RESULTS: In the formed heart, Tbx3 is expressed in the sinoatrial node (SAN), atrioventricular node (AVN), bundle and proximal bundle branches (BBs), as well as the internodal regions and the atrioventricular region. Throughout cardiac development, Tbx3 is expressed in an uninterrupted myocardial domain that extends from the sinoatrial node to the atrioventricular region. This expression domain is present in the looping heart tube from E8.5 onwards. Expression of the chamber-type myocardial markers is specifically absent from the Tbx3 expression domain. Tbx3 is able to repress Nppa and Cx40 promoter activity and abolish the synergistic activation of the Nppa promoter by Tbx5 and Nkx2.5. CONCLUSION: We identified the T-box transcription factor Tbx3 as a novel and accurate marker for the central conduction system. Our analysis implicates a role for Tbx3 in repressing a chamber-specific program of gene expression in regions from which the components of the central conduction system are subsequently formed.

Animals↗

The heart and cardiac conduction system in thrombotic thrombocytopenic purpura. A clinicopathologic study of 17 autopsied patients.

The relation between the heart lesions of thrombotic thrombocytopenic purpura and clinical cardiac dysfunction was studied in 17 autopsied patients. Thirteen of the 17 patients had extensive small-vessel thromboses and in some instances hemorrhages and focal necroses within the heart. Congestive heart failure was present in nine of the 17 patients. Thrombotic microcirculatory cardiac lesions and anemia-related high cardiac output may have contributed to cardiac dysfunction. Serial histologic sections of the cardiac conducting system in 10 patients showed microthrombi in seven and associated hemorrhages in five. Lesions were localized to the atrioventricular node and His bundle parts of the system with sparing of the sinoatrial node and bundle branches. Two patients had electrocardiographic evidence suggesting lesions within conducting tissues. Thrombi and hemorrhages are common findings in the conducting tissues in thrombotic thrombocytopenic purpura and may account for cardiac arrest or transient rhythm disturbances.

Adolescent↗

THE EFFECT OF INTRA(CEREBRO)VENTRICULAR RESERPINE ON THE ACETYLCHOLINE CONTENT OF THE HEART, ILEUM AND HYPOTHALAMUS OF THE DOG.

The effect of injection of reserpine into the cerebral ventricles on the acetylcholine contents of the sino-atrial node, ileum and hypothalamus of the dog was studied in ten dogs. Another group of five dogs served as a control. The effect of intravenous administration of reserpine, in the same dose as given intracerebroventricularly, was also studied on the acetylcholine content of these tissues in five dogs. General sedation, bradycardia, miosis, salivation, emesis and purgation were looked for. Tissues were removed 1 hr after administration of reserpine for estimation of acetylcholine content, which was increased in all the tissues studied. The increase in the peripheral tissues was greater than in the hypothalamus. The increase in the acetylcholine content was not quantitatively related to the other effects of reserpine. The increase in the acetylcholine content of the sino-atrial node and the ileum and also the peripheral effects observed on intracerebroventricular administration of reserpine can be attributed to its central action. With the same dose of reserpine given intravenously the acetylcholine content of the sino-atrial node was significantly increased, while that of the hypothalamus and ileum was not.

Acetylcholine↗

Beat-by-beat modulation of AV conduction. II. Autonomic neural mechanisms.

We examined the mechanism by which autonomic neural activity associated with respiration and blood pressure modulates atrioventricular (AV) conduction in conscious dogs. Mongrel dogs were anesthetized and instrumented under sterile conditions to record atrial and ventricular electrograms and blood pressure. In the conscious state, electrocardiogram (ECG), respiration, blood pressure, and electrograms were recorded continuously, and heart rate and AV interval were plotted graphically as a function of time. To delineate the role(s) of sympathetic and parasympathetic activity, AV conduction was studied during abrupt and linear changes in heart rate after administration of atropine, propranolol, or both. In the basal state and after propranolol, AV interval oscillated with respiration both in the absence of atrial pacing and at pacing rates 10-100 beats/min above control. Following atropine, oscillations in AV interval associated with respiration were abolished; however, linear and abrupt heart rate increases resulted in AV conduction changes that were associated with fluctuations in blood pressure. In contrast, after both atropine and propranolol, alterations in blood pressure or respiration did not influence AV conduction and rate-dependent prolongation of AV conduction occurred. We conclude that in the basal state, AV conduction is influenced predominately by changes in parasympathetic activity which is the major determinant of respiratory-related AV interval oscillations; after atropine, sympathetic activity produces fluctuations in both AV conduction and blood pressure; and intrinsic rate-dependent properties of the AV node are modulated continually by both divisions of the autonomic nervous system.

Animals↗