Suppression of Ouabain‐induced Atrial Arrhythmias by Carotid Sinus Stimulation

Abstract

In dogs anaesthetized with chloralose ectopic atrial arrhythmias were produced by subepicardial injection of ouabain. Stimulation of the right carotid sinus abruptly suppressed the ectopic arrhythmias. They returned on cessation of stimulation and sometimes already during the period of stimulation. It is suggested that in view of its response to carotid sinus stimulation the ouabain-induced arrhythmia resembles paroxysmal atrial tachycardia and that it is distinct from the aconitine-induced arrhythmia which on account of its response to vagal stimulation has been classified as atrial flutter.It is well known to clinicians that attacks of atrial paroxysmal tachycardia can often be terminated by carotid sinus pressure whereas this procedure is ineffective in atrial flutter. It is equally well known that different types of atrial arrhythmias can be produced in animals by local application of various drugs to the epicardial surface of the heart (Scherf, 1944(Scherf, , 1947Kisch, 1944;Scherf & Chick, 1951;Prinzmetal, Corday, Brill, Oblath & Kruger, 1952;Scherf, Blumenfeld, Taner & Yildiz, 1960), but it has never been shown that any of these resemble paroxysmal atrial tachycardia in man by the crucial test of being consistently suppressible by means of carotid sinus stimulation. It has now been found that the arrhythmia produced by subepicardial injection of ouabain is regularly susceptible to carotid sinus stimulation. METHODSDogs weighing between 9 and 14 kg were premedicated with morphine, 1 mg/kg injected subcutaneously, and anaesthetized with chloralose, 0.1 g/kg injected intravenously. The blood pressure was recorded from a femoral artery and a cannula was inserted into the trachea.In all experiments stimulation of the carotid sinus was carried out on the right side with both sinus and aortic nerves intact in order to approximate the effects obtained in man, where pressure on the right carotid sinus is more frequently effective in terminating attacks of atrial paroxysmal tachycardia (Scherf & Schott, 1953). The right carotid sinus was exposed, and stimulating shielded platinum electrodes were applied to the dissected sinus nerve and connected to a transistor stimulator (Joslin, 1959). Stimulation was carried out with impulses of 15 V, 1 msec, 100/sec. In a few experiments the innervated right carotid sinus was isolated, according to the method of Moissejeff (1927), making possible its distension by introducing liquid into it, and at the same time recording the intrasinusal pressure.After dissection of the carotid sinus, the sternum was split, the chest opened in the midline to expose the heart, while artificial respiration was given with a Starling (" Ideal ") pump.

In Silico Molecular Dynamics Docking of Drugs to the Inhibitory Active Site of SARS-CoV-2 Protease and Their Predicted Toxicology and ADME

“…Also used to treat other malignancies such as lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme [93][94][95][96] . Ouabain (Rank 60, BE=-8.6, B01092) is indicated for treatment of atrial fibrillation and flutter and heart failure [97][98][99][100][101][102] , and has been investigated in oncology [93,103] . Indinavir (Rank 91, BE=-8.5, B00224) is an antiretroviral drug for the treatment of HIV infection [104][105][106] .…”

In Silico Molecular Dynamics Docking of Drugs to the Inhibitory Active Site of SARS-CoV-2 Protease and Their Predicted Toxicology and ADME

“…Etoposide is also used to treat other malignancies such as lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme (Nandakumar et al, 2020;McHugh et al, 2020;Martinez et al, 2020;and Marconi et al, 2020). Ouabain (Rank 60, BE = -8.6, B01092) is indicated for treatment of atrial fibrillation and flutter and heart failure (Schott, 1961;Govier, 1965;Yusuf and Gans, 1966;Higgs, 1971;Wongcharoen et al, 2007;, and has been investigated in oncology (Schott, 1961;Govier, 1965;Yusuf and Gans, 1966;Higgs, 1971;Wongcharoen et al, 2007;Nandakumar et al, 2020;McHugh et al, 2020;Martinez et al, 2020;Marconi et al, 2020;Shen et al, 2020;and Rupaimoole et al, 2020). Indinavir (Rank 91, BE = -8.5, B00224) is an anti-retroviral drug for the treatment of HIV infection (Wang et al, 2020;Pollak and Parmar, 2020;and Knudsen et al, 2020).…”