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With the technical assistance of Robert D. Campo Animals pretreated with appropriate closes of anticholinesterase agents develop auricular flutter and fibrillation following injection of acetylcholine or vagal stimulation. Depression of normal sinoauricular nodal function facilitates induction of fibrillation. During fibrillation, additional injections of acetylcholine, or vagal stimulation, increase the rate of fibrillation. Atropine in small closes reverts the fibrillation to normal sinus rhythm.T HE production of auricular fibrillation by acetylcholine is well recognized. 1This type of fibrillation is not constant in occurrence and is transient. The present report describes a method for consistently producing auricular fibrillation of extended duration by the use of acetylcholine or vagal stimulation in animals treated with anticholinesterase agents. The report describes a means of regulating the rate of fibrillation, the role of normal sino-auricular node function in the initiation of the fibrillating state, and the abolition of fibrillation by atropine. METHODSThirty-four dogs, four goats and six monkeys were used. Three types of experiments were conducted. The first type used animals anesthetized with chloralose (50 mg./Kg.) in which conventional electrocardiograms were obtained. The second type of experiment used the anesthetized animal under artificial, positive pressure respiration with the chest open ut the sternal midline, and in which action potentials were obtained from electrodes applied directly to the myocardium. The third type of experiment was conducted on unanesthetized animals with normal respiration in which direct cardiac electrodes had been previously implanted using thiopental anesthesia.The preparation of the animals for the first and second type of experiments is a well established procedure. Our method for the preparation of animals for the third type of experiment is as follows:From the Physiology Division, Chemical Corps Medical Laboratories, Army Chemical Center, Maryland.Received for publication February 21, 1955.The animal was anesthetized with sodium thiopental (20 to 25 mg. per Kg.). Suitable incisions were made for insertion of a femoral vein polyethylene cannula and for a tracheal cannula. Both vagi were exposed in the neck. The right vagus was sectioned and shielded electrodes were fixed to the distal stump. The anterior two-thirds of the fourth left rib were exposed and subperiosteally resected. The parietal pleura was incised and positive pressure respiration was started. The pericardium was incised parallel and just anterior to the left phrenic nerve exposing the left auricle and half of the left ventricle. Two spring steel, shielded electrodes were clipped about 5 mm. apart to the upper mid surface of the left auricle. Two additional electrodes were clipped about 5 mm. apart to the mid portion of the left ventricle. The pericardium and pleura were then closed around the lead-in wires with sutures. The lungs were re-expanded and the skin incision closed. Artificial respira...

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Quantitative recovery of drugs from biological samples is important when a response is to be related to the amount of drug present in a tissue sample. Morphine is one drug of interest in this regard because of its widespread use and its chemical peculiarities. Its relatively low dosage, amphoteric nature, and metabolism to a water-soluble product, 3-morphine monoglucuronide [1,2], make morphine relatively difficult to analyze in biological samples. Most quantitative analytical schemes of analysis require that the glucuronide be cleaved to free morphine for extraction into an organic solvent. Acid hydrolysis [3] and enzymatic cleavage [4] are the most popular methods for freeing the morphine. We report here a study of the recoveries of radioactively tagged morphine from biological samples of morphine-treated dogs by using hydrolysis and solvent extraction. It is possible to recover more than 90% of the morphine contained in a sample with acid hydrolysis and about 80% with enzymatic cleavage.