The Effect of Stress and Adrenalectomy on the Response to Dicumarol in Rats

Mogenson, Gordon J.; Fisher, Lyman M.; Jaques, L. B.

doi:10.1139/y58-008

Cited by 2 publications

(2 citation statements)

References 6 publications

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“…Chandrasekhar et al (1965) point out that there are conflicting opinions concerning the development of tolerance to dicoumarol by rats. Mogenson, Fisher & Jaques (1958) and Boyd & Warner (1948) concluded that rats developed a tolerance after 1 and 2 weeks dicoumarol treatment respectively, whereas Shitis (1958) found no evidence that rats became tolerant to this anticoagulant following its administration for 5 weeks. Chandrasekhar et al (1965) observed no development of tolerance following short-term administration of dicoumarol but found that tolerance developed during longer term administration.…”

Section: Discussionmentioning

confidence: 99%

The effect of warfarin on plasma clotting time in wild house mice (Mus Musculus L.)

Rowe

Redfern

1968

J. Hyg.

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SUMMARYThe coagulability of the plasma of blood taken from the retro-orbital sinus of untreated and warfarin-treated wild house mice (Mus musculus L.) was determined. Individual differences were observed in the resting clotting times of animals drawn from three different sources, so-called ‘normal’ (N) mice, home-bred warfarin resistant (HBR) mice and field-caught suspected warfarin resistant (FR) mice. Mice from the three sources also showed wide individual variation in response to injected doses of 1, 5 and 50 mg. of warfarin/kg, body weight. The overall response shown by HBR and FR mice, particularly females, was less than that shown by N animals. Some FR females failed to respond to a dose of 100 mg. of warfarin/kg, body weight.Normal mice showed a similar response to two identical doses of warfarin (1, 5 or 50 mg./kg. body weight) given at an interval of 3 weeks. They developed a tolerance to repeated daily injected doses of 1 mg. of warfarin/kg, body weight but not to the higher doses (5 and 50 mg./kg.) to which some HBR animals became tolerant.In comparative 21-day feeding tests with 0·025% warfarin in medium oatmeal, the mortality in N, HBR and FR mice was 100% (27), 64·5% (40/62) and 22·7% (10/44) respectively. Whereas the plasma of all N mice was rendered uncoagulable after 3 days and the animals died within 12 days, the clotting times of the surviving HBR and FR mice (24/59 males and 32/47 females) either were not at any stage appreciably increased or had declined to near normal values by the end of the test period.In similar tests with 0·025% warfarin in oatmeal bait containing 5% mineral oil, it was found that the clotting ability of the plasma of N, HBR and FR mice was impaired earlier and that mortality in HBR and FR animals was significantly higher (62/67, 92·5% and 7/8, 87·5% respectively).Three of seven HBR mice died after prolonged feeding on various warfarin baits but only after 186, 197 and 209 days respectively. The inclusion of mineral oil in bait containing 0-0·25% warfarin was more effective in decreasing the coagulability of the blood of these mice than either increasing the concentration of warfarin (to 0·1 and 0·2%) or including sulphaquinoxaline or corn oil.Studies on mice given warfarin by injection and in feed indicated that in females the level of resistance to warfarin may be assessed on the basis of their response to a single injected dose of warfarin.

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Section: Discussionmentioning

confidence: 99%

The effect of warfarin on plasma clotting time in wild house mice (Mus Musculus L.)

Rowe

Redfern

1968

J. Hyg.

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“…This is usually done by comparison of values for means and standard deviations but as pointed out by Millar et al this may require the use of a log or other transformation to give a normal frequency distribution. Mogenson, Fisher and Jaques (17) concluded that stress generally did not affect the mean prothrombin time of the population but caused an increased variability in individual prothrombin times, which was made more prominent with the increased values after dicumarol.…”

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confidence: 99%

The Effect of Stress and Warfarin on the Adrenal Gland in Relation to Spontaneous Hemorrhage, as Judged by Measurement of Adrenal Ascorbic Acid and Serum Corticosterone

Chattopadhyay¹,

Dd²,

Gj³

et al. 1971

Thromb Haemost

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SummaryRats were subjected to the following procedures: No treatment, Stressor (10% NaCl i.p.), Warfarin for 7 days, Stressor followed by Warfarin; and groups were sacrificed at intervals for assessment of spontaneous hemorrhage and of adrenal ascorbic acid concentration. There was no hemorrhage in the no treatment and stressor groups; some hemorrhage in the warfarin group; profound hemorrhage with Warfarin + Stressor. The adrenal ascorbic acid concentration was found to be lower, 8 h and again 5 days after stress, and remained lower in the warfarin + stress animals. Warfarin had no effect on adrenal ascorbic acid level.In another series of experiments in which the stress consisted of an electric current to the cage floor for 6 sec over 15 min, rats were sacrificed daily for determination of serum corticosterone concentration and occurrence of spontaneous hemorrhage. There was a statistically significant increase of serum corticosterone concentration with stress, warfarin and combined warfarin and stress treatments (P< 0.001 for all three variables). There was a significant correlation (r = 0.96 and 0.89, P< 0.01) for serum corticosterone concentration with hemorrhage score and incidence of hemorrhage in stressed rats receiving warfarin, but not in those receiving only warfarin. The results indicate an activation, rather than an exhaustion, of the pituitary-adrenal axis during the combined action of anticoagulant and stress, which results in the development of spontaneous hemorrhage.

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The Effect of Stress and Adrenalectomy on the Response to Dicumarol in Rats

Cited by 2 publications

References 6 publications

The effect of warfarin on plasma clotting time in wild house mice (Mus Musculus L.)

The effect of warfarin on plasma clotting time in wild house mice (Mus Musculus L.)

The Effect of Stress and Warfarin on the Adrenal Gland in Relation to Spontaneous Hemorrhage, as Judged by Measurement of Adrenal Ascorbic Acid and Serum Corticosterone

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