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Actions of O-ethyl-S-(2-dimethylaminoethyl)-methylphosphonothioate and some pyridine aldoximes on isolated guinea-pigs heart atria.

1. The effects of acetylcholine and methylfurmetide on isolated guinea-pigs heart atria in the presence or absence of O-ethyl-S-(2-dimethylaminoethyl)-methylphosphonothioate (EDMM) were investigated. The influence of three cholinesterase reactivators on the heart atria pretreated with EDMM has been studied. 2. In the presence of EDMM, the negative inotropic effect of acetylcholine on the isolated heart atria was not significantly increased. This effect of methylfurmetide on heart atria was significantly decreased in the presence of EDMM. 3. EDMM alone caused negative inotropic and negative chronotropic effects depending on its concentration. These pharmacological effects were accompanied with inhibition of acetylcholinesterase activity in the heart muscle. 4. Addition of cholinesterase reactivators normalized the inotropic response of the isolated guinea-pig heart atria altered by EDMM and also increased the acetylcholinesterase activity in the heart.

Acetylcholine

The effects of some cholinesterase reactivators on contractility of the isolated guinea-pig heart atria.

The effect of eight monoquaternary and bisquaternary pyridine aldoxime cholinesterase reactivators was tested on isolated guinea-pig heart atria. 2. Acetylcholine and methylfurthretonium in concentrations ranging from 10(-7) M to 10(-5) M have negative inotropic effects in the electrically stimulated atria and negative chronotropic effects in the spontaneously beating atria. 3. In the presence of higher concentration of cholinesterase reactivators alone, the parameters of heart muscle contractility are significantly altered. 4. Cumulative dose-response curves of methylfurthretonium in the presence of reactivators in the range of concentrations from 10(-5) M to 10(-3) M are shifted parallelly to higher concentrations of the agonist.

Acetylcholine

[The effect increased choline levels on the synthesis and release of acetylcholine in heart atria in white rats].

The paper addresses the problem of (1) the relationship of choline in extracellular fluid and acetylcholine (ACh) synthesis in chambers of the heart of white rats, and (2) the possibility of physiological involvement of this ACh in the control of cardiac activity. Within 60 min after s.c. administration of choline in the dose of 300 mg/kg body weight the ACh content rose to 136% of the control value in isolated heart chambers and after administration of 400 mg/kg body weight to 159% of the control value. Increased ACh synthesis failed to affect the heart rate, nor did it increase the tonic effect of vagus innervation of the heart. Excessive ACh could however be released by electric transmural stimulation of isolated heart chambers as well as by potassium depolarization. The release depended on the presence of calcium ions. The obtained results demonstrate that an increase in the level of choline in extracellular fluid results in increased ACh synthesis in nerve terminals. Enhanced release of this ACh is a precondition for high choline levels to induce an increase in parasympathetic control of cardiac function.

Acetylcholine

[Action potentials of the heart atria and ventricles of Rana temporaria frogs and Cyprinus carpio carp].

Using microelectrode technique, studies have been made on electrophysiological indices (amplitude of AP, amplitude of the plateau, latent period of AP, duration of maximal depolarization, duration of repolarization at different levels) of cells of isolated atrium and ventricles of the carp during both the spontaneous activity and electrical stimulation. The obtained amplitude-temporal parameters were compared to those of the heart in the frog R. temporaria. It was found that the amplitude of AP, the amplitude of the plateau and the duration of the latent period of AP in both the atrium and ventricles of the carp significantly (p less than 0.01) differ from the corresponding indices of the frog. On the contrary, the duration of maximal depolarization and repolarization in cells from homologous parts of the heart is very close in the species investigated.

Action Potentials

[Prognostic value of the state of the heart atria in determination of the time of sinus rhythm preservation after correction of auricular fibrillation].

Data are presented from atrial vectorcardiograms of 130 patients with different forms of auricular fibrillation including an analysis of their parameters and a study of the catamnestic data following the elimination of auricular fibrillation, which permitted to develop prognostic criteria for determining the period of sinus rhythm preservation after this type of arrhythmia had been eliminated.

Adolescent

[Study of the electric activity of the heart atria in auricular fibrillation with the aid of the instrumental correlation analysis].

The autocorrelation funtion of the electrocardiographic signal in the V1 lead is approximated by the formula of an attenuated consinusoid. Parameters are singled out (median period, attenuation factor) to characterize the atrial activity. A procedure for recording the auto correlation function is described and optimal conditions of its registration are studied. First results following clinical application of the method are reported.

Action Potentials

[A comparative study of the stereoselectivity of cholinoreceptors].

Muscarine-sensitive cholinoreceptors (M-ChR) of higher vertebrates exhibit high stereoselectivity which is also revealed with respect to enantiomers of a very potent muscarinomimetic methyldilvasen (F-2268), the stereospecific index (SSI) being about 100. M-ChRs in the neuronal membrane of the gastropod mollusc Planorbarius corneus and in the hearts of the bivalve molluscs Mercenaria stimpsoni and Anadara broughtoni are highly sensitive to methyldilvasen (10(-9)-10(-10) M), but their sensitivity to its enantiomers is identical. In heart atria of the tortoise Testudo horsfieldi, frog Rana temporaria, and fishes Siluris glanis, Cyprinus carpio, as well as in ventricles of tadpoles, high SSI was revealed. These data are consistent with a hypothesis that during evolution of vertebrates no significant changes took place in the active center of M-ChR. Possibly, the lack of stereoselectivity in the investigated molluscan M-ChRs, together with their other peculiarities (they are not blocked by atropine), indicate "immaturity" of these receptors.

Animals

The mechanism of the positive chronotropic action of diethyl ether on rat atria.

Diethyl ether elicited a dose-dependent increase in the intrinsic frequency of contraction of isolated rat atrial preparations. The maximum effect (plus 34 per cent) occurred with 230 mg ether/100 ml medium. This ether concentration corresponds to a partial pressure of 29.2 mm Hg or 3 MAC. The positive chronotropic action of ether was not reduced in atria obtained from rats pretreated with reserpine (4 mg/kg, ip) although this treatment markedly reduced the effect of tyramine on frequency of contraction. The positive chronotropic response to 0.01 muM isoproterenol was inhibited by the beta-adrenergic antagonist 0.3 mgM dl-propranolol but remained unimpaired in the presence of 0.3 mgM d-propranolol (a much weaker antagonist). In contrast, the atrial response to ether was similar in the presence of either d- or dl-propranolol. Atropine, in concentrations that completely blocked the negative chronotropic action of acetylcholine, did not increase the frequency of contraction, suggesting that the positive chronotropic effect of ether is not due to an atropine-like activity of ether. Our results indicate that the positive chronotropic effect of ether on isolated rat atrial preparations is not mediated via catecholamine release, nor does it represent direct stimulation of beta-adrenergic receptors or block of cholinergic receptors. (Key words: Anesthetics, volatile, diethyl ether; Heart, atria, diethyl ether.).

Adrenergic beta-Antagonists

Rat brain natriuretic peptide is localized in atrial granules and released into the circulation.

Rat brain natriuretic peptide (BNP) was detected by radioimmunoassay in heart atria and ventricles and in plasma. We have investigated its localization in atria and the possibility of cosecretion of atrial natriuretic factor (ANF) and BNP into the circulation. BNP was detected by chromatographic analysis and immunoblotting in the isolated atrial granules together with ANF: It consisted of two immunoreactive proteins of 14,000 and 2,500 apparent molecular weight. By immunohistochemical methods, BNP was particularly found in the perinuclear region of atrial cardiocytes. Double-labeling immunocytochemical methods colocalized BNP and ANF in the same atrial secretory granules. Basal plasma BNP levels ranged from 2.6 to 4.4 fmol/ml. After stimuli by morphine injection or an aortocaval shunt, BNP levels increased by 4- and 7-fold, respectively, whereas ANF levels rose by 50- and 6-fold, respectively. Depending on the stimulus, BNP release into the circulation is not necessarily proportional to ANF, indicating that BNP may originate not only from the atrial granules but also from other tissues such as the ventricles. These results suggest that BNP may participate with ANF in blood pressure control and salt and water homeostasis.

Animals

Multiple cerebral aneurysms and cardiac myxoma.

Neurological signs are a frequent manifestation of left atrial myxoma, but the association of cardiac myxoma with multiple cerebral aneurysms is rare. A case of left atrial myxoma was detected in the course of a long-lasting psychiatric and neurological illness. Four-vessel study showed the presence of multiple saccular and fusiform aneurysms, regularly and almost symmetrically distributed. The intracardiac mass was removed, and the patient improved.

Adult

Spinal cord ischemia and left atrial myxoma.

A 62-year-old man had an acute, transient, flaccid paraplegia. Examination showed a primary cardiac tumor with emboli to major branches of the aorta. A myxoma was removed from the left atrium, and normal function returned. Left atrial myxoma should be suspected as a cause for embolism to the CNS.

Embolism

Total anomalous systemic venous drainage.

Total drainage of systemic blood into the left atrium is an exceptional finding in absence of severe intracardiac malformation. In our patient, a boy 3 years and 4 months old, the left superior vena cava, the inferior vena cava, and the coronary sinus drained into the left atrium; there was no right superior vena cava, and the only associated anomaly was a large atrial septal defect. This rare form of cyanotic congenital heart disease was correctly diagnosed and successfully corrected.

Child, Preschool

Right atrial myxoma in a child.

A 12-year-old girl with fatigability, dyspnea, variable murmurs, and chronic congestive failure was treated for chronic myocarditis with medical management for 16 months. Cardiac catheterization and angiography performed to rule out constrictive pericarditis disclosed a right atrial myxoma. Following removal of the mass, this patient became asymptomatic. Since right atrial myxoma rarely occurs in children and can mimic other diseases, the diagnosis depends on a high index of suspicion.

Child