Auricular fibrillation

Of the other cinchona bases, the dextrorotatory forms cinchonine and quinidine have been used as anti-malarial drugs in cases of idiosyncrasy to quinine, a subject to which Dawson has given much attention. Quinidine is used to eontrol auricular fibrillation, and its value for this purpose in comparison with dihydroquinidine has been investigated by several workers. Dawes has recently devised a method of testing... 

Shideman EE, Procita L Pharmacology of the monomethyl ethers of mono-, di-, and tripropylene glycol in the dog with observations of the auricular fibrillation produced by these compounds. J Pharmacol Exp Ther 102 79, 1951... 

Gavrilesco S, Streian C, Constantinesco L. Tachycardie ventriculaire et fibrillation auriculaire associees apres vaccination anticholeriques. [Associated ventricular tachycardia and auricular fibrillation after anticholera vaccination.] Acta Cardiol 1973 28(l) 89-94. 

Rokseth R, Storstein O. Quinidine therapy of chronic auricular fibrillation. The occurrence and mechanism of syncope. Arch Intern Med 1963 111 184-9. 

Roelvink M E, Goossens L, Kalsbeek H C et al 1991 Analgesic and spasmolytic effects of dipyrone, hyoscine-/V-butylbromide and a combination of the two in ponies. Veterinary Record 129 378-380 Roos J 1924 Auricular fibrillation in domestic animals. Heart 11 1-7... 

In the auricular arrhythmias (premature auricular systole, auricular paroxysmal tachycardia, auricular flutter, and auricular fibrillation), the auricles contract in chaotic, incomplete fashion and there is inefficient transfer of blood to the ventricles. While the auricular arrhythmias are not fatal, unless a normal rhythm is restored there will be a serious strain on the heart that will contribute to its failure or there is an increased likelihood of lethal emboli formation. The ventricular arrhythmias (ventricular premature systole, ventricular tachycardia, and ventricular fibrillation)... 

The changes produced by drugs on other electrical properties of the heart may also be evaluated. For example, an alkaloid may decrease the electrical excitability of the auricles. Thus, a greater intensity of current would then be required to provoke an extra systole. The time of application of this electric shock must be precisely determined. Following each systole, the heart has a refractory period, during which time it is highly resistant to external stimuli thus, it insures the necessary rest period for the heart. Measurements of the auricular refractory period are commonly made with antifibrillatory alkaloids. If the Thomas Lewis-Mines circus movement theory of auricular fibrillation is to be believed, then any sub-... 

Auricular fibrillation can be established in an isolated rabbit auricle by forming a crush infarct or by application of aconitine in benzene (11). The alkaloids to be examined are added in minute amounts to the bath. 

The first successful therapy of a patient with fibrillation occurred in 1914. Wenckebach (16) reported that a Dutch merchant in Java, who was taking quinine for malaria, stated that he could also control his attacks (paroxysms) of auricular fibrillation with this alkaloid. In 1918 Frey (17) found that the dextro-isomer, quinidine, was superior to quinine, and it has remained the therapeutic agent of choice to the present time. Since that date, a rather massive literature on investigations of quinidine s action on the heart has accumulated. Only a small portion of this literature can be cited here although it is to be regretted that many valuable contributions will be slighted. 

Most of the information concerning an antifibrillatory property for quinine is to be found in clinical trial reports. Frey (17) tried quinine in 1.0-1.5-g. daily doses in patients with auricular fibrillation complicated by mitral insufficiency and congestive failure. In neither case did conversion to normal sinus rhythm occur although subsequent use of quinidine did... 

Grant and Iliescu (23) preferred to evaluate quinine potency by an indirect method. They administered quinine in 0.6-g. doses to patients with auricular fibrillation. These subeffective but safer doses do not eliminate the arrhythmia but do cause a decrease in the auricular rate and an increase in ventricular rate. Again quinine proved to be inferior to quinidine quinine decreased the average auricular rate 86 beats/min. and increased the ventricular rate 15 comparable figures for quinidine are 161 and 45. Gold (2) reports that the maximum limit of reduction of auricular rate is twice as high for quinidine as for quinine quinine, even at 2.0-g. doses, produced only the slowing that quinidine effected at a 0.3-g. dose. 

The classic publication of Frey (17) epitomizes most of the information known today about the therapy of auricular fibrillation with quinidine. He converted to normal sinus rhythm 6 of 10 patients whose auricular fibrillation was complicated by atherosclerosis, mitral stenosis or insufficiency, and rheumatic fever or congestive failure. These patients included other arrhythmias such as auricular flutter or ventricular extra systoles. Some had been digitalized. Conversion occurred after 1.0 to 1.4 g. quinidine given over 2 to 8 days. Frey (33) also distinguished between patients with paroxysmal auricular fibrillation and the more stubborn continuous fibrillation. In this latter group of patients, many of whom had serious cardiac damage, quinidine converted 11/22 to normal rhythm. 

Van Dongen and Sanchez (29) compared the antifibrillatory activity of hydroquinidine with a specially purified quinidine. They present the viewpoint that the activity of commercially prepared quinidine in auricular fibrillation is based entirely on its content of dihydroquinidine. They used the rabbit as a test animal and observed that dihydroquinidine produced an increase in the electrical stimulus thresholds required to provoke premature systoles, tachycardia, auricular fibrillation, and ventricular fibrillation. With dihydroquinidine there was also a decrease in the duration of fibrillation which occurs after the electrical stimulus is ended. Dihydroquinidine, they found, could prevent the heterotropic rhythms (largely ventricular arrhythmias) provoked by the intravenous injection of barium chloride or epinephrine. They also observed that hydroquinidine, at 8 mg./kg., prolonged the auricular conduction time by 50%, the AV conduction time by 30 %, and increased the refractory period by 15%. Pure quinidine was inactive at this dosage. 

Most of the above-reported observations in animals have been confirmed in man. Taquini (47) utilized 80-100-mg. doses of allocryptopine injected intramuscularly in 4 patients with auricular fibrillation and in two with auricular flutter. All but one patient with auricular fibrillation converted to normal sinus rhythm within 30 min. These patients had associated rheumatic mitral stenosis, myocardial infarctions, or hypertension. 

Scherf, Silver, and Weinberg (48) employed allocryptopine intramuscularly in doses of 60-120 mg. for 13 patients with various auricular arrhythmias. Of 10 patients with auricular fibrillation, 8 converted to normal... 

With increases in knowledge of digitalis action in therapy of congestive heart failure the use of sparteine was discarded. Sparteine fell into disuse, but with the successful use of quinidine in auricular fibrillation sparteine was again revived for therapy of stubborn cases of A.F. Sparteine has continued to be employed in auricular arrhythmias for many years and may still be tried occasionally. 

Bohnenkamp and Hildebrandt (71) produced cardiac irregularities in the guinea pig by injections of strophanthin. Sparteine prevented many of these irregularities and kept the animal alive. These extra systoles are not truly like those appearing in man. They, however, suggested that sparteine has an action similar to quinidine in clinical auricular fibrillation. 

Rauwolfia serpentina Benth. is the source of several related alkaloids. Ajmaline, ajmalicine, ajmalinine, serpentine, serpentinine, isoajmaline, and neoajmaline have been identified. Ajmaline and serpentine have been given provisional structural formulas (81, 82). Other members of the Apocynaceae yield alkaloids of similar properties. Although Rauwolfia preparations have been used in Ayurvedic medicine for hypertension, there appear no indications that they have been used in clinical cardiac arrhythmia. Yet, incomplete pharmacologic studies indicate properties for these alkaloids which should prompt additional studies toward their possible use in auricular fibrillation. 

Additional evidence for an antifibrillatory action for ajmaline was supplied by van Dongen (13). He found that in the decerebrate cat 0.5 mg./kg. ajmaline increased the amount of faradic current required to produce auricular fibrillation, ventricular fibrillation, and post-stimulus arrhythmias. This action differs from that of quinidine, which prolonged auricular conduction time and atrioventricular conduction times by 52-100 %, while ajmaline did not alter refractory periods or conduction times. Heterotropic cardiac rhythms were produced by a variety of means (barium chloride, epinephrine, and strophantin-ephedrine) which in all cases may be prevented by ajmaline. 

Quinidine (73), another alkaloid found in Cinchona, is used to treat certain heart conditions in particular, this alkaloid is used to inhibit auricular fibrillation (Fig. 34.19) (Cordell, 1981 Tyler et al., 1981). 

---