Textbook of Experimental Surgery

Markowitz, Jacob

doi:10.1097/00000441-193806000-00023

Cited by 2 publications

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“…However, in three dogs given dicumarol two days previously, there was a typical fall in blood pressure after protamine. Removal of the abdominal viscera, including the liver, by the method of Markowitz (1937), did not alter the effect of protamine on blood pressure (M-81; Table 11). …”

Section: Resultsmentioning

confidence: 99%

A Study of the Toxicity of the Protamine, Salmine*

Jaques

1949

British Journal of Pharmacology and Chemotherapy

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The protamine, salmine, has become widely known in the combined form, protamine-insulin. It has been generally assumed that the protamines are non-toxic. Vartiainen and Marble (1941) found that the median lethal dose of salmine subcutaneously in mice and rabbits was 200-300 mg./kg. and concluded that it was non-toxic in ordinary doses-a view supported by its widespread clinical use with no allergic or other side-actions. Reiner, de Beer, and Green (1942) found an LD50 of 94 mg./kg. in mice with protamine (presumably salmine ?). Ahlstrom and von Euler (1946) have reported essentially similar results with rats and guinea-pigs, using salmine and also the related protamines, clupein and scombrin.A second possible clinical use of protamine is as an antidote for heparin, first suggested by Chargaff and Olsen (1937) and reported by Jorpes, Edman, and Thaning (1939). As the protamine for this purpose will probably be given intravenously, it raises the question of possible toxicity by this route. Thompson (1900) reported that the intravenous injection of the protamine, clupein, gave markedly toxic reactions in the narcotized dog, 15-18 mg./kg. killing the animals. The injection ofsmaller amounts of protamine caused a definite and relatively prompt fall in blood pressure, which returned to normal in 25-30 minutes. In addition to the fall in blood pressure, the respirations became markedly increased in rate and depth, and were followed by a period of apnoea. Thompson also noted a delayed clotting of the blood and a leucopenia.Jappelli (1933) confirmed Thompson's results with salmine using the unanaesthetized dog, as did Jaques, Charles, and Best (1938); 5 mg. salmine sulphate per kg. caused a pronounced fall in blood pressure and dyspnoea. However, they found that this protamine had relatively little effect on guineapigs, and this led to the present investigations. Shelley, Hodgkins, and Visscher (1942) reported that intravenous or intracardiac injection of 120 mg./kg.

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Section: Resultsmentioning

confidence: 99%

A Study of the Toxicity of the Protamine, Salmine*

Jaques

1949

British Journal of Pharmacology and Chemotherapy

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“…Insertion of the duodenal cannula utilized standard experimental surgical techniques (34). Between experiments the cannula was closed with a screw-on cap.…”

Section: Animal Preparationmentioning

confidence: 99%

Regulation of the fasting enterohepatic circulation of bile acids by the migrating myoelectric complex in dogs.

Scott¹,

Strasberg²,

El-Sharkawy³

et al. 1983

J. Clin. Invest.

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A B ST R A CT The purpose of this study was to correlate the fasting enterohepatic circulation (EHC) of bile acids with the migrating myoelectric complex. Four dogs were surgically provided with a functional cholecystectomy, a duodenal cannula for direct vision cannulation of the common bile duct, and 12 bipolar electrodes implanted from stomach to terminal ileum. Bile was collected in equal-volume, timed aliquots over 6 to 10 h. Aliquots were sampled and either returned to the duodenum for study of the intact EHC, or collected and retained in order' to study the time course of the bile acid pool washout. In the washout experiments boluses of radiolabeled taurocholic acid were instilled into the duodenum before and after duodenal phase III of the migrating motor or myoelectric complex (MMC). In another group of experiments the bile acid pool was washed out and during a continuous duodenal infusion of taurocholic acid bile was collected to study the pattern of hepatic secretion. Results: (a) In all experiments, a single broad peak of bile flow and bile acid secretion occurred at 35-55% of the MMC migration time. At this time the MMC had migrated to a point 70-85% of the distance along the small intestine. (b) During bile acid pool washout the peak of bile flow and bile acid secretion occurred with the distal migration of the first MMC and then bile flow and bile acid secretion rates decreased to a minimum and stabilized. (c) In bile acid pool washout experiments the radiolabeled bile acids instilled into the duodenum prior to duodenal phase III were secreted and peaked with peak endogenous bile acid secretion. The secretion of radiolabeled bile acids instilled into the duodenum after duodenal phase III was delayed until the subsequent cycle of the MMC. 88% of the bile acid pool collected over 6 h was secreted during the distal migration of the first MMC Address reprint requests to Dr. Scott.

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Textbook of Experimental Surgery

Cited by 2 publications

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A Study of the Toxicity of the Protamine, Salmine*

A Study of the Toxicity of the Protamine, Salmine*

Regulation of the fasting enterohepatic circulation of bile acids by the migrating myoelectric complex in dogs.

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